Terms in this set (155)

Addison's disease, or primary adrenal insufficiency, is distinguished from other types of adrenal insufficiency in that the primary problem comes from the inability of the adrenal glands to produce sufficient levels of cortisol, and at times, aldosterone. Primary adrenal insufficiency is usually not apparent until 90% of the adrenal cortex has been destroyed. The most common cause of Addison's disease is idiopathic adrenal insufficiency secondary to autoimmune destruction of the adrenal cortex. Symptoms include: chronic fatigue, muscle weakness, anorexia, wt loss, nausea, vomiting and diarrhea. Diffuse hyperpigmentation occurs secondary to a compensatory increase in ACTH and beta-lipotropin. Mineralocorticoids are usually deficient resulting in a reduction in urine sodium concentration (and can be accompanied by life threatening hyperkalemia).
Diagnosis involves an ACTH stimulation test during which the blood and/or urine cortisol levels are measured before and 30 minutes and 60 minutes after the IV administration of 250 micrograms of synthetic ACTH. A normal test reveals a rise in plasma cortisol of at least 7mg/dl sixty minutes after the ACTH injection. Patients with adrenal insufficiency demonstrate no or little adrenal response.
Patients on chronic steroids therapy can also develop an "Addisonian Crisis" upon abrupt discontinuation of the steroids or the failure to provide additional (or "stress dose steroids") during periods of stress, such as surgery or critical illness. It is important to note that, unlike patients with primary Addison's Disease, these patients have suppression of the hypothalamic—pituitary axis and will not have symptoms of ACTH excess (such as hyperpigmentation).
Hyponatremia occurs as a result of both the loss of sodium and volume caused by mineralocorticoid deficiency and increased vasopressin secretion due to cortisol deficiency. This at times results in significant salt craving. Hyperkalemia is often associated with a mild hyperchloremic acidosis due to a deficiency in mineralocorticoids.
1. General - predominantly iatrogenic complication - atmospheric gas is introduced into the systemic venous system - mostly associated with neurosurgical procedures conducted in the sitting position. - now, associated with (1) central venous catheterization (2) penetrating and blunt chest trauma, (3) high-pressure mechanical ventilation, (4) thoracocentesis (5) hemodialysis and several other invasive vascular procedures
2. Pathophysiology A. What FAVORS air embolus? TWO preexisting Conditions a. DIRECT communication btn source of air and vasculature b. Pressure gradient favoring passage of air
B. What determines MORBIDITY AND MORTALITY? VERY HIGH Mortality( 80%) a. volume of air entrained: as little as 20 mL of air can be fatal!, but typical 5mL/kg is bad b. rate of accumulation-->puts BIG strain on RV and increases PA pressures-->decreases pulmonary venous return-->secreases CO--> circulatory collapse--> tachyarrhythmia(sometimes brady's occur)--> cardiac arrest c. pt's position: Fowlers/sitting
C. Tissue Level changes occur: -inflammatory change in pulmonary vessels - direct endothelial damage: accumulation of plt, fibrin, and lipid droplets -activation of complement and release of free radicals -->capillary damage and non-cardiogenic pulmonary edema
-all these changes lead to V/Q mismatching --> intrapulmonary r to l shuntinginc in alveolar dead space -arterial HYPOXEMIA and hypercapnea
3. Dx - most go unrecognized, b'c s/s can mimic other cardiopulmonary dz - Hx: recent neurosurgery, indwelling catheter presence, blunt/penetrating trauma, positive pressure ventilation - Sx: dyspnea, N/V, dizziness, substernal CP - Signs: a) Mill WHEEL murmur: constant machine like sound, late sign, heard over precordium b) Dysrhythmias: either tachy or brady c) Myocardial Ischemia d) Circulatory/Cardiovascular collapse e) Hypotension f) rales, wheezing g) hemoptysis h) tachypnea i) pulmonary edema - L/S: a) ABG can show metabolic ACIDOSIS as a result of hypoxemia
b) TEE: highest SENSITIVITY for detecting AIR in RV and pulmonary vessels
c) Precordial Doppler: most SENSITIVE NON-invasive test
d) CT: HCT can reveal air, chest CT can show blunt trauma/penetrating of chest wall
e) MRI: NOT reliable for detecting gas emboli
f) EKG: low sensitivity, can show RV strain pattern, ST depression
g) ETCO2: look for it to DECREASE, nonspecific finding
h) SPO2: late finding
4. Rx a. 100% O2, intubate if there are any signs of respiratory distress b. Durant Maneuver: place pt in L Lat decubitus and T-berg c. one MAY attempt to remove air via aspiration with CVC d. Supportive: CPR(can break big small bubbles), Hyperbaric Oxygen therapy, fluid resuscitation, pressors

There are an estimated 50-200 operating room fires annually in the United States including airway and non-airway fires. A fire requires three components known as the "fire triad" including: an oxidizer, ignition source, and fuel. Oxidizers in the OR include oxygen and nitrous oxide, which increase the likelihood and intensity of combustion. Ignition sources include elecrosurgical devices, lasers, burrs and drills, and fiberoptic scopes. Fuels include tracheal tubes, sponges/gauzes, alcohol containing solutions, drapes, masks, and nasal cannulae. A surgical fire is defined as a fire that occurs on or in a patient. An airway fire is a surgical fire that occurs in a patient's airway and may or may not include a fire in the attached breathing circuit.


If possible, avoid using ignition sources near oxidizer-enriched environments. Configure the drapes to avoid oxidizer pooling or accumulation. Allow flammable skin prepping solutions to completely dry. Sponges and gauzes should be moistened if they are to be used near ignition sources. For laser procedures in the airway, it is recommended to use laser-resistant cuffed tubes, and to fill the cuff with saline tinted with methylene blue to identify a cuff puncture by the laser. Before an ignition source is used the surgeon should announce the intent to use the device upon which the oxygen concentration should be reduced to the minimum needed to avoid hypoxia, and nitrous oxide should be stopped. The surgeon should not begin until all of the above criteria are met.


In the case of an airway fire immediately, without hesitation, halt the procedure and remove the tracheal tube. Stop the flow of all airway gases. Remove sponges or any other flammable material from the airway, and pour saline into the airway. Once the fire is extinguished, re-establish ventilation either with the circuit or a self-inflating resuscitation bag. If possible, ventilate with room air. Examine the integrity of tracheal tube to make sure no fragments may have been left in the airway. Consider bronchoscopy (preferably rigid) to assess injury and, especially, to locate and remove tracheal tube fragments and other debris. Assess the patient and then devise a management plan.
When anemia develops chronically, over a prolonged period of time, and blood volume is maintained, there are four primary mechanisms of compensation.
1) Increased cardiac output: The two principal determinants of SVR are vascular tone and viscosity of blood and in isovolemic hemodilution from chronic anemia, the hematocrit decreases and reduces SVR through decreased viscosity of blood. The decrease in SVR then increases stroke volume and therefore cardiac output and blood flow to tissues. Oxygen delivery usually remains constant at a hematocrit between 30 and 45%. Further reductions in hematocrit are accompanied by increases in cardiac output (up to 180%) baseline as hematocrit nears 20%.
2) Redistribution of cardiac output: When isovolemic hemodilution occurs in chronic anemia, blood flow is redistributed to the tissues with higher extraction ratios (brain and heart, for example). This blood is redistributed to the coronary circulation in a healthy heart and coronary blood flow can increase up to 600% of baseline. When the heart reaches the point at which it can no longer increase either cardiac output or coronary blood flow, then it is subjected to possible myocardial injury from decreased oxygen delivery.
3) Increased oxygen extraction: In times when the hematocrit reaches less than 25%, the oxygen extraction ratio increases in multiple tissue beds, leading to an increase in the total body oxygen extraction ratio and to a decrease in mixed venous oxygen saturation. The brain and heart already have a high extraction ratio and are unable to increase oxygen delivery by this mechanism, but tissues such as the kidney, skeletal muscle, and skin compensate in this manner.
4) Changes in oxygen-hemoglobin affinity: The oxyhemoglobin dissociation curve relates the partial pressure of oxygen in the blood to the percent saturation of hemoglobin with oxygen. The P50 at 37 degrees celcius and a pH of 7.4 is 27mmHg. When anemia develops over a long period of time, the oxyhemoglobin dissociation curve is shifted to the right, whereby hemoglobin has a decreased affinity for the oxygen molecule and releases oxygen to the tissues at higher partial pressures. Since this process occurs only after increased 2,3 DPG, it occurs only with chronic anemia and NOT when patients undergo isovolemic hemodilution(see below).
Isovolemic hemodilution is a process in which a patient's blood is drawn during the perioperative and replaced with an equal volume of colloid. The autologous blood is then saved and transfused back to the patient at the end of the procedure.
The nerve supply of the foot is primarily from the sciatic nerve:
1) The superficial peroneal nerve is located lateral to the extensor digitorum longus Sensory-dorsum of foot and toes except b/w the great and second toes (deep peroneal n.) Technique-see below, blocked with deep peroneal n. and saphenous n.
2) The deep peroneal nerve is located lateral to the extensor hallicus longus Sensory-between the great and second toes Motor-extends the toes Technique-see below, blocked with superficial peroneal n. and saphenous n.
3) The sural nerve is located superficially between the lateral malleolus and the Achilles tendon Sensory-posterolateral leg, lateral foot, 5th toe Technique- Needle is inserted lateral to the tendon and is directed toward the malleolus as 5-10 ml of local anesthetic is injected subcutaneously.
4) The tibial nerve is posterior to the medial malleolus Sensory-plantar surface of the foot Motor-flexes the toes Technique-the posterior tibial artery is palpated and a needle is inserted posterolateral to the artery at the level of the medial malleolus. A paresthesia is often elicited at which time 2-5 mL of local should be injected. If no paresthesia, 7-10 ml should be injected as the needle is slowly withdrawn back from the posterior aspect of the tibia.
The femoral nerve contributes one nerve to the ankle:
5) The saphenous nerve is just anterior to the medial malleolus Sensory-anteromedial side of the leg, medial side of foot Technique-see below, blocked with deep peroneal n. and superficial peroneal n.
The deep peroneal, superficial, peroneal, and saphenous nerves can be blocked through a single needle entry site. A line is drawn across the dorsum of the foot connecting the malleoli and local anesthetic is infiltrated along this line across the anterior aspect of the foot.
Note-the three nerves that start with the letter S (superficial peroneal, sural, saphenous) are all Sensory only. The other 2 nerves, deep peroneal and tibial, are motor + sensory
Tumors of the anterior mediastinum cause obstruction of three structures: the tracheobronchial tree, the main PA (and atria) and the SVC. If the patient can tolerate the supine position, a CT scan should be obtained to define the involvement of each structure.
Obstruction of the tracheobronchial tree usually occurs at the level of the carina (in most cases, distal to the end of the ET tube). Flow volume loops will show a pattern characteristic of variable intrathoracic obstruction - forced expiration will increase pleural pressure, causing narrowing of the airway lumen and obstruction to flow. A plateau flow will occur as the airway is maximally narrowed. During inspiration, pleural pressure is negative, the airways distend, and the flow volume loop may appear normal.
Loss of spontaneous ventilation is thought to predispose patients to airway collapse due to loss of the tone of the chest wall and distending forces of active inspiration. Muscle relaxation may also alter the extrinsic support of the airway and lead to airway obstruction.
Compression of the main PA and atria is much less common because the PA and atria are usually somewhat shielded by the aorta. Position change is thought to precipitate deterioration. Maintenance of preload, PA pressure, and cardiac output may attenuate compression of the main PA.
Compression of the SVC may cause SVC syndrome, resulting in venous distention of the upper body, edema of the head and neck, and cyanosis. In addition, respiratory symptoms may result from venous engorgement of the airways and mucosal edema. A change in mentation secondary to cerebral venous engorgement may occur in severe cases.
1. Preprocedure evaluation Relevant history (major organ systems, sedation-anesthesia history, medications, allergies, last oral intake). Focused physical examination (to include heart, lungs, airway. Laboratory testing guided by underlying conditions and possible effect on patient management. Findings confirmed immediately before sedation.
2. Patient counseling Risks, benefits, limitations, and alternatives
3. Preprocedure fasting Elective procedures—sufficient time for gastric emptying. Urgent or emergent situations—potential for pulmonary aspiration considered in determining target level of sedation, delay of procedure, protection of trachea by intubation.
See ASA Guidelines for Preoperative Fasting2
4. Monitoring Data to be recorded at appropriate intervals before, during, and after procedure. Pulse oximetry. Response to verbal commands when practical. Pulmonary ventilation (observation,auscultation, exhaled carbon dioxide monitoring considered when patients separated from caregiver. Blood pressure and heart rate at 5-min intervals unless contraindicated. Electrocardiograph for patients with significant cardiovascular disease.
For deep sedation: Response to verbal commands or more profound stimuli unless contraindicated. Exhaled CO2 monitoring considered for all patients. Electrocardiograph for all patients.
5. Personnel Designated individual, other than the practitioner performing the procedure, present to monitor the patient throughout the procedure. This individual may assist with minor interruptible tasks once patient is stable.
For deep sedation: The monitoring individual may not assist with other tasks.
6. Training Pharmacology of sedative and analgesic agents. Pharmacology of available antagonists Basic life support skills—present. Advanced life support skills—within 5 min.
For deep sedation: Advanced life support skills in the procedure room.
7. Emergency Equipment Suction, appropriately sized airway equipment, means of positive-pressure ventilation. Intravenous equipment, pharmacologic antagonists, and basic resuscitative medications. Defibrillator immediately available for patients with cardiovascular disease.
For deep sedation: Defibrillator immediately available for all patients
8. Supplemental Oxygen Oxygen delivery equipment available Oxygen administered if hypoxemia occurs
For deep sedation: Oxygen administered to all patients unless contraindicated
9. Choice of Agents Sedatives to decrease anxiety, promote somnolence. Analgesics to relieve pain.
10. Dose Titration Medications given incrementally with sufficient time between doses to assess effects Appropriate dose reduction if both sedatives and analgesics used. Repeat doses of oral medications not recommended.
11. Use of anesthetic induction agents (methohexital, propofol) Regardless of route of administration and intended level of sedation, patients should receive care consistent with deep sedation, including ability to rescue from unintended general anesthesia.
12. Intravenous Access Sedatives administered intravenously—maintain intravenous access. Sedatives administered by other routes—case-by-case decision. Individual with intravenous skills immediately available
13. Reversal Agents Naloxone and flumazenil available whenever opioids or benzodiazepines administered.
14. Recovery Observation until patients no longer at risk for cardiorespiratory depression. Appropriate discharge criteria to minimize risk of respiratory or cardiovascular depression after discharge.
15. Special Situations Severe underlying medical problems—consult with appropriate specialist if possible. Risk of severe cardiovascular or respiratory compromise or need for complete unresponsiveness to obtain adequate operating conditions—consult anesthesiologist
What are indications for Mechanical Ventilation?

clinical or laboratory signs that the patient cannot maintain an airway or adequate oxygenation or ventilation.
include respiratory rate > 30/min
inability to maintain arterial O2 saturation > 90% with fractional inspired O2 (Fio2) > 0.60
PCO2 of > 50 mm Hg with pH < 7.25
A little about Lung Mechanics and Ventilators
when you breathe normally, your lungs SUCK AIR Into the lung, this creates a NEGATIVE pressure gradient btn the lung and intrapleural space
when your breathing depends on a machine, the ventilator creates the pressure gradient artificially by BLOWING air into your lungs via POSITIVE pressure
Here are some interesting things about Pressure and the waveforms we look at on the ventilator:
Peak airway pressure(PAP): measures pressure at the airway
It represents the total pressure needed to overcome the inspiratory flow resistance (resistive pressure), the elastic recoil of the lung and chest wall (elastic pressure), and the alveolar pressure present at the beginning of the breath
PAP= Presistive + Pelastic + Palveolar

Resistive pressure: product of
circuit resistance
airflow: IN Mechanically Ventilated patient depends on
ventilator circuit
endotracheal tube
patient's airways
NOTE: even when these factors are constant, an increase in airflow increases resistive pressure.
Elastic pressure : product of
elastic recoil of the lungs
chest wall (elastance)
volume of gas delivered
NOTE: anything that makes it harder to distend the alveoli(ie stretch the lungs) will increase elastic pressure
eg. Inc lung stiffness: pulmonary fibrosis
eg. Chest wall/diaphragm restriction: tense ascites, obesity
elasticity: measures lung recoil
compliance: measures lung stretchability
elasticity and compliance are inversely proportional to one another
.End-expiratory pressure: normally the same as atmospheric pressure.
INTRINISIC PEEP/AUTO PEEP: when the alveoli fail to empty completely because of
airway obstruction
airflow limitation, or shortened expiratory time
NOTE: you can ADD PEEP to the Mechanically Ventilated patient , this is therapeutic PEEP

What are signs of BRONCHOSPASM in the Mechanically Ventilated patient?

elevated resistive pressure (eg, > 10 cm H2O) suggests
kinked ETT, ETT plugging
intraluminal mass
increased intraluminal secretions
intrinsic PEEP suggests:
airflow obstruction (eg, airway secretions, bronchospasm)

Carcinoid tumors typically secrete excessive amounts of the hormone serotonin (although they may secrete many hormones). They arise from neuroendocrine cells throughout the body. Most commonly from organs derived from the primitive gut (90% come from distal ileum or appendix)
Serotonin causes vasodilation, increased blood clotting (stimulation of platelet aggregation)
Malignant Carcinoid Syndrome typically occurs when tumor spreads to liver - vasoactive substances escape hepatic degradation, excessive production of serotonin both lead to red hot flushing of face, severe and debilitating diarrhea, and asthma attacks (tachykinins)

Surgical Treatment

May offer complete and permanent cure
• Hepatic resection for accessible areas of liver
• Distal ileum - Right hemicolectomy
• Appendix - Tumors < 1.5 cm appendectomy
• Rectum - <1.5 cm local resection, >1.5 cm abdominoperineal resection
• Chemoembolization of liver lesions

Anesthetic Considerations


• Some develop right heart problems due to tricuspid stenosis from serotonin action
• Other common problems - Asthma, wheezing, palpitations, hypotension, dizziness


• Pay attention to: heart murmur, asthma-like symptoms, pellagra, electrolyte deficieny/dehydration from diarrhea, hepatomegaly (from metastasis)
• Carcinoid heart disease
• Typically right side of heart
• Fibrous deposits on valvular endocardium
• Thickening of endocardium of cardiac chambers


• Measurement of serotonin metabolite 5-HIAA in 24 hr urine
• 25 mg/day of 5-HIAA is diagnostic


Prevention of Mediator release
• Preoperative Stress (use anxiolytic without histamine relating properties
• Response to intubation
• Inadequate analgesia
• Hypotension / Hypertension
• Intraoperative handling of tumor
• Histamine releasing drugs
• Severe hypotension/hypertension
• Flushing
• Bronchospasm
• Hypercoagulability

• Octreotide (Somatostatin) immediately available- high affinity for somatostatin receptor that may help relieve vasoactive symptoms and restore hemodynamic stability
• Ondansetron - Anti-serotonin action with potential benefit
• Immediate availability of vasopressors (ephedrine and phenylephrine), vasodilators
Note: consider invasive monitoring
CEA requires temporary clamping of the carotid artery being worked on rendering the ipsilateral hemisphere dependent on collateral flow from the vertebral arteries and the contralateral carotid artery through the Circle of Willis. Neurologic monitoring is used to verify adequate perfusion of bilateral regions of the brain and to guide decision making in regards to shunting, BP control, and surgical technique. Also competing needs for increased BP vs. reducing myocardial workload, neurologic monitoring allows for aiming for lowest BP to maintain perfusion while reducing myocardial workload. Monitoring options include an awake patient under local anesthesia, EEG, SSEPs, and less often transcranial doppler(TCD), cerebral oximetry and stump pressures with reliability in that order.
Advantages of an awake patient: The most effective in detecting ischemic episodes, less post-op hypertension when done under field block, easy post-op neurologic exam. Disadvantages of an awake patient: Requires very cooperative patient. Patient may panic, while draped in sterile field if he/she becomes aphasic or hemiplegic intraoperatively, and could require immediate GA and a secured AW. Anxious patients will have increased sympathetic response increasing risk for myocardial ischemia in patients already prone to cardiac events. And not all surgeons can work quickly enough to make a field block practical or tolerable for older arthritic patients.
EEG records spontaneous electrical activity of cortical surface cells, an area more prone to decreased perfusion. It is a sensitive parameter for ischemia since electrophysiologic activity accounts for 60% of cerebral metabolic demand. EEG changes occur in about 20% of patients during carotid occlusion and are indicative of potentially serious ischemia. Changes lasting more than 10 minutes correlate strongly with post-op neurologic deficits, and thus EEG changes of greater than a mild degree are an indication for shunt placement or induced hypertension. Typical regional cerebral blood flow is 50-55ml/min/100gm brain tissue. Ischemia typically occurs around 18-20 ml/min/100gm and tissue death at 8-10. EEG deterioration begins around 15-20ml/min/100gm, and manifests as frequency slowing or amplitude attenuation, severe ischemia may be isoelectric. Limitations are that deep structures are not monitored, preexisting deficits or EEG changes reduce predictive value (may not show intraop changes), may miss regional ischemic events, especially if using only 4-channel, and are affected by changes in temperature, BP, PaCO2, and anesthetic depth, however, these are more likely to be b/l. Focal embolic events may also be missed. 16 lead EEG is the gold standard- responds quickly and detects regional changes, but requires a skilled technician and continuous observation, thus processed EEGs with fewer leads, 2-4 channels, are available and widely used. Need electrodes covering bilateral anterior and posterior regions of brain.
SSEPs are based on detection of cortical potentials after electrical stimuli are presented to a peripheral nerve. Advantages: also evaluates deep brain structures vs. EEG and cortical function only, and may be better for patients with previous CVA and EEG changes. Disadvantages: Not felt to be as sensitive or specific for ischemic injury during CEA. Requires considerable expertise. Also effected by choice of anesthesia and need constant light plane to be maintained to accurately interpret changes in EPs.
Transcranial doppler is not a good sole intraoperative monitor. Measures mean blood flow velocity in MCA and detects emboli. Emboli account for up to 65% of postop deficits. Can detect acute thrombotic occlusion and microemboli and is much more useful in this aspect especially in helping surgeons modify their technique. Does not evaluate functional changes. Also useful for predicting postop hyperperfusion syndrome and help in reducing BP to avoid complications.
Carotid stump pressure Estimates hemispheric blood flow by measuring pressure in stump distal to the clamp. Stump pressure is more often used to determine whether or not a shunt should be placed intraop. Problem with this is it doesn't indicate perfusion to all regions of the brain. A stump pressure of 60mmHg is usual threshold, however, in some patients this may not be adequate for compromised areas and in others perfusion is adequate at pressures well below this resulting in unnecessary shunting. On a scientific basis there is no correlation between stump pressure and regional or global blood flow. None of these have been shown to improve outcome since postoperative emboli and not intraoperative hypoperfusion are most likely cause of periop stroke, but do aid in decision to shunt and BP maintenance.
Very safe, can be used to provide peri and postoperative analgesia, Can be sole anesthetic or can be combined with GA
1. Indications a. Anesthesia and analgesia below the umbilicus - the very young a caudal block may be adequate to carry out urgent procedures such as reduction of incarcerated hernias -superficial operations such as skin grafting, perineal procedures, and lower limb surgery. GA may be required in addition Pain relief will extend into the post operative period. The duration of the block can been prolonged by the addition of an opiate (pethidine 0.5 mg/kg) to the local anaesthetic.
b. Obstetric analgesia for the 2nd stage or instrumental deliveries. Care should be taken as the fetal head lies close to the site of injection and there is real risk of injecting local anaesthetic into the fetus c. chronic pain problems such as leg pain after prolapsed intervertebral disc, or post shingles pain below umbilicus.
2. Contraindication a. Infection at site b. Pilonidal cyst c. Coagulopathy d. Congenital anomaly of spine or meninges 3. Anatomy caudal epidural space: lowest portion of the epidural system and is entered through the sacral hiatus. The sacrum is a triangular bone that consists of the five fused sacral vertebrae (S1- S5). It articulates with the fifth lumber vertebra and the coccyx. The sacral hiatus is a defect in the lower part of the posterior wall of the sacrum formed by the failure of the laminae of S5 and/or S4 to meet and fuse in the midline. There is a considerable variation in the anatomy of the tissues near the sacral hiatus, in particular, the bony sacrum. The sacral canal is a continuation of the lumbar spinal canal which terminates at the sacral hiatus.
The volume of the sacral canal can vary greatly between adults.
4. Drugs - 0.25 percent marcaine, preservative free at 2 mg/kg - adults usually get 20 to 30cc for analgesia for lower extremity

5. Technique - can be done in prone or semiprone or lateral position - find landmarks: The sacral hiatus can be located by first palpating the coccyx, and then sliding the palpating finger in a cephalad direction (towards the head) until a depression in the skin is felt. - Once the sacral hiatus is identified the area above is carefully cleaned with antiseptic solution, and a 22 gauge short bevelled cannula or needle is directed at about 45° to skin and inserted till a "click" is felt as the sacro-coccygeal ligament is pierced. The needle is then carefully directed in a cephalad direction at an angle approaching the long axis of the spinal canal. - The needle should be aspirated looking for either CSF or blood. A negative aspiration test does not exclude intravascular or intrathecal placement. Care should always be taken to look for signs of acute toxicity during the injection. The injection should never be more than 10 ml/30 seconds - A small amount of local anaesthetic should be injected as a test dose (2-4mls). It should not produce either a lump in the subcutaneous tissues, or a feeling of resistance to the injection, nor any systemic effects such as arrhythmias, peri-oral tingling, numbness or hypotension. If the test dose does not produce any side effects then the rest of the drug is injected, the needle removed and the patient positioned for surgery
6. Complications
• Intravascular or intraosseous injection. This may lead to grand mal seizures and/or cardio-respiratory arrest.
• Dural puncture. Extreme care must be taken to avoid this as a total spinal block will occur if the dose for a caudal block is injected into the subarachnoid space. If this occurs then the patient will become rapidly apnoeic and profoundly hypotensive. Management includes control of the airway and breathing, and treatment of the blood pressure with intravenous fluids and vasopressors such as ephedrine.
• Perforation of the rectum. While simple needle puncture is not important, contamination of the needle is extremely dangerous if it is then inserted into the epidural space.
• Sepsis.
• Urinary retention.
• Absent or patchy block
• Hematoma
This is a test used to evaluate an hypothesis by comparing measured results to theoretically expected results (i.e. the Null hypothesis). This test is designed to convert the differences between "expected" and "measured" results into the probablility of their occuring by chance. After using the conversion calculations, it basically compares a calculated value X2 with an expected value X2 (Chi-Square value) and tells the observer if the difference was "significant" enough to reject the expected result (null hypothesis). It takes into account both the sample size and the number of variables. As the number of variables increase, so does the complexity.
For example, suppose that the overall male to female ratio of UVA Anesthesiology Faculty was 1:1, but over the past 5 years the Critical Care/ Anesthesiology faculty had 8 males and 4 females. You might want to know if this would be considered a significant difference from the expected 1:1 ratio for the departement?
To test this question, first bulid a table showing observed numbers (O), expected numbers (E). Then you subtract each "expected" value from the corresponding "observed" value (O-E), then square the "O-E" values, and divide each by the relevant "expected" value to give (O-E)2/ E. Add all the (O-E)2/E values and call the total "X2"
Male Female Total
Observed # (O) 8 4 12
Expected # (E) 6 6 12
O - E 2 -2 0
(O-E)2 4 4
(O-E)2/ E 0.6667 0.6667 1.3334= X2
Now you compare the X2 value (1.3334) with a X2 (chi squared) value in a standard table (see below) of X2 values and "degrees of freedom". Degrees of freedom = n-1 (n= # of categories, in this case 2: male and female). Thus, our example has 1 degree of freedom.
Degrees of Freedom Probability, p
0.99 0.95 0.05 0.01 0.001
1 0.000 0.004 3.84 6.64 10.83
2 0.020 0.103 5.99 9.21 13.82
3 0.115 0.352 7.82 11.35 16.27
4 0.297 0.711 9.49 15.09 18.47
Back to the original question of: "is the male: female ratio of 2:1 for Critical Care/ Anesthesiology faculty significant"? A sigificant difference from the 1:1 faculty ratio hypothesis (null hypothesis) would be found if the calculated X2 value was greater than the expected X2 value (3.84) shown for 0.05 column. If so, it would mean that there was a 95% chance of some unknown bias towards male faculty entering Critical Care/ Anesthesia and only a 5% probability that our calculated X2 value would have occurred by chance. Thus, finding a significant difference would give a reason to reject the null hypothesis of a 1:1 male to female ratio.
For our example, looking at the chart, for a p= 0.05, the X2 expected value is 3.84. Our X2 value (1.3334) was NOT greater than 3.84, thus the finding of 8 males and 4 female Critical Care/ Anesthesiology faculty would NOT be considered a significant departure from the 1:1 ratio in the entire department. Thus, the null hypothesis of a 1:1 ratio is still reasonably true.
To carry this further, if the calculated X2 value was equal to or less than the expected X2 for the p = 0.95 column, the results give no reason to reject your hypothesis that the faculty has a 1:1 ratio. Rarely, a calculated X2 value lower than the X2 value in the p =0.95 or 0.99 column gives evidence that the calculated results actually agree well with the "null" hypothesis.
On the other hand, if our calculated X2 value exceeded the value of 10.83 in the "p = 0.001" column, not only would it be significant, but it would have given us 99.9% confidence that some factor leads to a "bias" towards males entering the Critical Care/ Anesthesiology field at UVA, and only a 0.1% chance the difference was caused by chance.
In summary, the Chi-square test for categorical variables determines whether there is a difference in the population proportions between two or more groups.
What type of Local? ESTER MOA: blocks the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse and by reducing the rate of rise of the AP
METABOLISM Plasma cholinesterases(just like esmolol, sux), also elimination will be impaired in hepatic/renal disease
TOXICITY Cardiac depression: decrease CO, and HR, contractility, vasodilation
CNS: seizures, depression of medulla coma, resp depression,death

How do locals cross placenta? - passive diffusion - the rate and degree of diffusion det by: (1) the degree of plasma protein binding - since only the free, unbound drug is available for placental transfer - increase protein binding means less drug can xfer across placenta and harm baby, makes sense?? (2) the degree of ionization: more nonionization means xfer (3) lipid solubility: the more fat soluble means more xfer

EFFECTS ON FETUS • Fetal bradycardia -heart rate of less than 120 per minute w/ doses of chloroprocaine of 120 mg to 400 mg of chloroprocaine -effect may NOT be dose related
• Fetal acidosis -limited data -demonstrated by blood gas monitoring around the time of bradycardia or afterwards.
• No intact chloroprocaine and only trace quantities of a hydrolysis product, 2-chloro-4-aminobenzoic acid, have been demonstrated in umbilical cord arterial or venous plasma following properly administered paracervical block with chloroprocaine.
• The role of drug factors and non-drug factors associated with fetal bradycardia following paracervical block are unexplained at this time
Unlike benign pain, usage of opioids in chronic pain management elicits little controversy. Nevertheless, there is significant disagreement in drug choice, timing, and dosage leading to significant practice variance. In one large series, 95% of patients with advanced cancer have pain, only 50% report that it is well treated and 25% were rated as having died in severe pain. Treatment is directed at the cause of the pain, if known. Pain can be caused from a direct tumor effect (invasion causing visceral pain, bony metastasis), from treatment (neuropathic pain from chemo) or preexisting pain exacerbated from the disability of cancer and/or its treatment.
Opioids are a mainstay of cancer pain treatment but should be used in a multimodal approach which may include pharmacologic adjuncts (NSAIDs, corticosteroids, anti-convulsants, bisphophonates, etc), non-pharmacologic interventions (PT, TENS, acupuncture, supportive psychotherapy, cognitive-behavioral interventions, etc) and invasive interventions where appropriate (spinal cord stimulators, intrathecal pumps, neurolytic blocks, etc). Estimates suggest that 90% of chronic cancer pain can be treated with simple interventions.
Like all pain management, initial therapy should be conservative, but with a lower threshold for beginning narcotics. With end-stage disease upward titrations are often swift. Best therapy is usually achieved with long acting agents (Sustained release oral morphine, methadone, Oxycontin, fentanyl patches). Shorter-acting medications (oxycodone, trans-buccal fentanyl) should be provided for breakthrough.
Severe uncontrolled cancer pain is a medical emergency. If patients have failed oral therapy, inpatient or home/hospice parental therapies are used, typically IV but sometimes with SQ infusion pumps. Home PCA can have basal rates set with on-demand dosing. For many with severe untreated pain, intraspinal opioids, particularly for those with excessive side effects from oral/iv forms, is an attractive option. Infusions can be mixed with local anesthetics, clonidine and/or baclofen for synergistic effects. Because implants come with their own set of complication (bleeding, infection, equipment failure) and high costs, they are usually reserved for those judged to have at least 3 months to live.
Addictive behavior (drug craving/seeking, behavioral problems) is rare in cancer patients.
Management of Cancer Pain: Guideline Overview. Agency for Health Care Policy and Research, Rockville, MD. J Natl Med Assoc. 2004
Bonica JJ. Cancer pain. In: Bonica JJ, ed. The Management of Pain. 3nd ed. Philadelphia, Pa: Lea & Febiger; 2001:400-460.
The power of a statistical test is the probability that the test will reject a false null hypothesis (that it will not make a Type II error). As power increases, the chances of a Type II error decrease. The probability of a Type II error is referred to as the false negative rate (β). Therefore power is equal to 1 − β.
Power analysis can either be done before (a priori) or after (post hoc) data is collected. A priori power analysis is conducted prior to the research study, and is typically used to determine an appropriate sample size to achieve adequate power. Post-hoc power analysis is conducted after a study has been completed, and uses the obtained sample size and effect size to determine what the power was in the study, assuming the effect size in the sample is equal to the effect size in the population.
The power of a test is the probability that the test will find a statistically significant difference between two populations, as a function of the size of the true difference between those two populations. Note that power is the probability of finding a difference that does exist, as opposed to the likelihood of declaring a difference that does not exist.
Power increases with:
- Sample size (n): sample reliability always depends upon its size (the smaller the sample, the larger the error). Thus, it is intuitively obvious that increases in sample size will increase statistical power.
- Effect size : The degree to which a specified alternative hypothesis deviates from the null hypothesis
- The statistical significance criterion used in the test (p-value)

The diagnosis of CO poisoning is made by a history of exposure (internal combustion engine exhaust, fire, improperly adjusted gas or oil heating, charcoal or gas grills, or exposure to paint stripper containing methylene chloride, which is metabolized by the liver to CO). Confirmation of the diagnosis is made by finding elevated COHb in either arterial or venous blood. The COHb concentration in anticoagulated blood samples is stable for several days. Therefore, if COHb determination is not available at a referring facility, the diagnosis can be confirmed with a blood sample obtained at the time of initial evaluation and transported with the patient. Fetal hemoglobin (hemoglobin F) can produce a falsely elevated reading for COHb on certain four-wavelength laboratory co-oximeters. In the first few weeks of life, blood from normal infants may therefore falsely indicate 7% to 8% COHb.
Actual COHb levels measured on arrival at the emergency department correlate poorly with clinical status and should not be used as the sole criterion to determine the need for treatment. Because of the lower intracellular PO2, elimination of CO from intracellular binding sites occurs more slowly. Significant mental obtundation, vomiting, and headache may remain even in the face of a normal COHb level.
Brain imaging may reveal a variety of abnormalities in patients with CO poisoning, including hypodensities in the globus pallidus and subcortical white matter, cerebral cortical lesions, cerebral edema, hippocampal lesions, loss of gray-white differentiation, and white matter hyperintensities.


"Initial treatment is directed at providing immediate oxygen to a patient who may be suffering from relative hypoxia. A 100 per cent non-rebreather face mask should be used. In addition to promoting cellular respiration, 100 per cent oxygen will reduce the elimination half-life of COHb from an average 4 to 5 hours to 1 to 2 hours. Initial stabilization of the patient includes a blood glucose determination with correction of hypoglycemia or hyperglycemia. Extremes of glucose should be avoided because of the potential to exacerbate neuronal cell death. Treatment with oxygen should continue until the patient is asymptomatic, usually when COHb levels are less than 10 per cent."

Hyperbaric Oxygen (HBO)

In case of persistent severe symptoms or markers of severe toxicity, consideration should be given to treatment with HBO. Many researchers advocate HBO for definitive treatment of severe symptomatic CO poisoning. The most obvious benefit of HBO is enhanced elimination of COHb, with a half-life average of 20 minutes at 3 atmospheres absolute. However, in reality most dissociation of COHb occurs with administration of normal pressure oxygen before HBO treatment. Therefore, the real benefit of HBO may be in regeneration of cytochrome oxidase and inhibition of leukocyte adherence to the microvascular endothelium. All this prevents the cascade of events that leads to ischemic reperfusion injury, the process thought to be responsible for lipid peroxidation of the brain and delayed neurologic sequelae.
Clear indications include 1) any loss of consciousness and 2) seizures, coma, or altered mental status. HBO should be considered 1) in patients with persistent neurologic symptoms, 2) in pregnancy, and 3) in patients with persistent cardiac ischemia. There are ways to optimize HBO treatment for CO poisoning. The first is that treatment should be performed as early as possible. In the only clinical series that retrospectively examined this factor, both mortality and delayed neurologic sequelae were substantially less in patients treated within 6 hours of discovery. Two recent controlled studies showed no benefit of HBO in poisoned patients when the average time to treatment was 6 hours. In contrast to these findings, a recent randomized trial showed a reduction in delayed sequelae from 33 per cent to zero, when patients were treated within 6 hours with HBO as opposed to routine oxygen.
The chemical control of breathing is based on a negative feedback loop and chemoreflex. Thus, when the central and peripheral chemoreceptors sense an increase in [H+], breathing is stimulated by a chemoreflex that includes the central nervous system, respiratory muscles, and changes in alveolar ventilation, resulting in correction of the [H+], hence the negative feedback designation of the system. However, in addition to chemical stimuli, non-chemical drives to breathe also contribute to the level of ventilation, independently of the chemoreflexes. These drives include the central nervous system "state" of the subject, which is referred to as the "waking neural drive," because it is withdrawn during sleep.
Inspiration of carbon dioxide in healthy, awake subjects increases minute ventilation by approximately 3 L/min per 1 mm Hg of arterial carbon dioxide tension. All inhaled anesthetics depress the ventilatory response to hypercarbia in a dose-dependent fashion. High concentrations of volatile anesthetics may almost entirely eliminate hypercarbia-induced increases in ventilatory drive. The slope of the minute ventilation-arterial carbon dioxide tension relation returns toward normal after 6 hours of halothane anesthesia, but ventilatory responsiveness to carbon dioxide remains profoundly depressed despite this observation.
The effects of small doses of inhaled anesthetics on ventilatory responses to hypercarbia remain somewhat controversial despite intense investigation. Several studies have demonstrated that subanesthetic concentrations (e.g., 0.1 MAC) of inhaled anesthetics (with the exception of desflurane and nitrous oxide) depress the peripheral chemoreflex loop by approximately 30% to inhibit the ventilatory response to hypercarbia. The response was also attenuated during administration of desflurane when a level of sedation comparable with sleep was achieved. At higher concentrations of volatile agents, other sites, including the central chemoreceptors, may also be affected.
Anitfibrinolytics are frequently used in patients placed on CPB. The two available lysine analogs, ε-aminocaproic acid and tranexamic acid, bind to lysine binding sites on plasminogen and fibrinogen and thereby inhibit plasminogen activator and plasmin release. When administered before CPB, these agents clearly inhibit fibrinolysis, decrease mediastinal bleeding, and depending on the study, may or may not decrease transfusion requirements.
Aprotinin is a nonspecific protease inhibitor, and its inhibitory action includes the intrinsic coagulation cascade, complement activation, fibrinolysis, and bradykinin and kallikrein formation. It is a naturally occurring compound extracted from beef lung and as such has the potential to induce antibody formation. Aprotinin clearly decreases bleeding and transfusion requirements. However, it is not used as widely as it might be because of cost, immunogenicity, and possible side effects.
IgG antibody formation has been demonstrated after aprotinin exposure. However, this does not necessarily translate into a clinical problem. A recent study in pediatric patients demonstrated reactions to protamine in 1% of patients on first exposure and 1.3% of patients on re-exposure. Moreover, some evidence suggests that antibody levels change over time and are highest and the risk greatest if re-exposure occurs within 6 months.
Aprotinin is excreted by the kidney, and one study of patients subject to deep hypothermic circulatory arrest suggested that aprotinin had a negative impact on renal function. However, their controls were historical, and lesser doses of heparin were used in the patients who received aprotinin. Recent studies suggest that aprotinin does not have a negative influence on renal function. Concern regarding the prothrombotic effects of aprotinin remains unresolved, but the preponderance of clinical data suggests that such concern may not be justified. However, recent laboratory data suggest that aprotinin may inhibit endothelial NOS in the coronary circulation. In contrast to concerns regarding thrombosis in the coronary circulation, aprotinin may exert a salubrious effect on neurologic injury. Pooled, double-blind, multicenter data in 1721 patients demonstrated a reduction in the stroke rate from 2.4% in the control group to 1% in the aprotinin group. If real, the underlying mechanisms responsible for this decrease are likely to extend beyond aprotinin's effects on the coagulation and fibrinolytic cascades. A "high-dose" regimen of aprotinin was used in this study, and it is likely that to derive maximal effect from this nonspecific protease inhibitor, one should use a higher dose to inhibit pathways that have very different affinities and binding properties for this protein. As a corollary, it is possible to demonstrate a benefit from lower doses of aprotinin, depending on the specific end point one measures."
In regards to the safety of aprotinin, a 2006 prospective study of over 4000 patients by Mangano, et al published in the NEJM demonstrated increased adverse outcomes when aprotinin was used in cardiac surgery. Specifically, they observed a doubling in the risk of renal failure requiring dialysis, a 55% increase in the risk of MI or heart failure, and a 181 percent increase in risk of stroke or encephalopathy when aprotinin was used as compared with aminocaproic acid, tranexamic acid, or no antifibrinolytic therapy [Mangano et al. NEJM 354: 353, 2006]. This study influenced many subsequent clinical practices, and the routine use of aprotinin in cardiac surgery has since fallen out of favor
Sitting Position

The sitting position for cranial surgery is associated with a high incidence of air embolism (25%-45%). This situation occurs because noncollapsible venous channels, such as diploic and emissary veins, can be violated during craniotomy; this, in turn, leads to air entrainment in the sitting position because of the negative pressure gradient between the surgical site and the heart. The sitting position can result in hypotension, especially if not attained gradually and not preceded by adequate hydration. Hypotension seemed to be particularly an issue in patients who are classified as ASA III or IV.
Cardiac output decreases because of a reduction in venous return and the inability for cardiovascular reflexes to compensate. Peripheral and pulmonary vascular resistance increases but only incompletely compensates for the decrease in cardiac output, and cerebral perfusion pressure decreases. In fact, orthostatic blood pressure decreases are common (76%) in the first 60 minutes after induction of anesthesia. Hence, direct arterial pressure must be followed closely on attaining the sitting position, with the transducer leveled at the head.
Other reported complications include midcervical quadriplegia (thought to be attributable to a combination of preexisting cervical spine disease and low perfusion pressure); airway, tongue, and facial swelling (exacerbated by placement of oral airways for lengthy surgery); obstruction of the endotracheal tube (ETT; usually the result of overzealous flexion in the absence of a bite-block); brachial plexus stretch injuries (caused by inadequate arm support); and cardiovascular instability during tumor dissection. Airway obstructing supraglottic edema has also been reported after prolonged posterior fossa surgery conducted with the head in forced flexion. Although 100% of patients undergoing sitting craniotomies develop pneumocephalus, the contributory role of nitrous oxide (N2O) is in doubt. Its elimination from the anesthetic regimen at the time of dural closure has not been found to be efficacious. To date, experts are aware of at least 20 cases of paraplegia after acoustic neuroma resection in the sitting position.

Beach Chair Position

This position is frequently used for shoulder arthroscopic surgery. Patients are positioned 30° to 60° head-up. This technique has recently been associated with hypotensive episodes and consequent severe neurologic dysfunction, including brain stem infarction from cerebral hypoperfusion and visual loss. The incidence of hypotensive or bradycardic events has been reported to be 5.7% under propofol target-controlled anesthesia and up to 28% with an interscalene brachial plexus block. Prophylactically administered metoprolol (up to 10 mg) but not glycopyrrolate decreases the incidence of hypotensive or bradycardic events.
In rare cases, what is thought to be an activation of the Bezold-Jarisch reflex has resulted in full cardiac arrest. Cerebral perfusion pressure should be maintained at a level of 70 to 80 mm Hg. It is important to realize that the blood pressure cuff or arterial catheter is situated substantially below the level of the head and that cerebral perfusion pressure calculations need to be adjusted for the blood pressure readings obtained from these devices. For example, if mean arterial pressure (MAP) by cuff is 70 mm Hg and the cuff is positioned 12.5 cm below the foramen magnum, cerebral perfusion pressure is only 60 mm Hg, because there is a decrease in 1 mm Hg for each 1.25-cm gradient in height between the cuff and head. As is true for other sitting position variants, arm support is important to avert stretch injury to the brachial plexus. An elevated contralateral arm position was associated with fewer episodes of venous thrombophlebitis from intravenous catheter placement for arthroscopic surgery.

The Prone Position

Important position injuries in the prone position include eye injury (eg, corneal abrasion, retinal ischemia); brachial plexus stretch injuries; and pressure injury to the face, elbows, knees, breasts, and male genitalia. Brachial plexus injury can occur when the head is severely rotated toward the contralateral side or extended, stretching nerve roots; excessive pressure on the clavicle can compress the neurovascular bundle against the first rib; and the head of the humerus can likewise press into the brachial plexus when the arms are hyperabducted and the shoulder is not sufficiently mobile and relaxed. The arms should be abducted no more than 90°. Pressure on the femoral nerve or lateral femoral cutaneous nerve may be experienced, especially with post-type positioning devices (eg, the Relton-Hall or Jackson frame). In addition, ulnar nerve damage may occur from pressure against hard OR table edges or leaning by the surgical team.

Postoperative visual loss in the prone position

Faulty positioning only accounts for a small fraction of postoperative visual loss (POVL). An example is the occurrence of central retinal artery occlusion (CRAO), which is known to be a consequence of direct or indirect pressure on the globe. There is periorbital and scleral edema; funduscopic examination reveals the hallmark "cherry red spot" of CRAO. An orbital compartment syndrome has also been reported in which increased orbital venous pressure and external compression from the silicone headrest were implicated as potential causes. Intraocular pressure increases progressively with time in the prone position, although a causal relation between this phenomenon and postoperative blindness has not been established. Such anatomic features as exophthalmos and a small nasal bridge may predispose to excess pressure on the eyes during prone positioning.
Still, most POVL (89% in the ASA POVL registry) is diagnosed as ischemic optic neuropathy (ION), which, to date, remains an enigmatic idiopathic disease. ION is associated with the prone position, Mayfield pin headholder use, anesthetic duration greater than 6 hours, or high blood loss greater than 1000 mL. Association with other conditions, such as diabetes, hypertension, smoking, atherosclerosis, anemia, ulcerative colitis, and preexisting retinal disease, has been reported. It is not thought to be the result of optic globe compression or specific prone position-related factors. ION occurred in patients who were positioned on the Wilson frame , the Jackson table, or chest rolls; Mayfield head pinning was not protective, and ION occurred in patients positioned on foam or gel pads whether or not regular eye checks were documented during the case.
Complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy (RSD), is a regional, posttraumatic, neuropathic pain problem that most often affects 1 or more limbs. Like most medical conditions, early diagnosis and treatment increase the likelihood of a successful outcome. Accordingly, patients with clinical signs and symptoms of CRPS after an injury should be referred immediately to a physician with expertise in evaluating and treating this condition. Physical therapy is the cornerstone and first-line treatment for CRPS. Mild cases respond to physical therapy and physical modalities. Mild to moderate cases may require adjuvant analgesics, such as anticonvulsants and/or antidepressants. An opioid should be added to the treatment regimen if these medications do not provide sufficient analgesia to allow the patient to participate in physical therapy. Patients with moderate to severe pain and/or sympathetic dysfunction require regional anesthetic blockade to participate in physical therapy. A small percentage of patients develop refractory, chronic pain and require long-term multidisciplinary treatment, including physical therapy, psychological support, and pain-relieving measures. Pain-relieving measures include medications, sympathetic/somatic blockade, spinal cord stimulation, and spinal analgesia.


CRPS-1 is a syndrome where chronic pain (normally in an extremity) appears to be associated with sympathetic nervous system dysfunction after trauma. No single theory has explained sympathetic nervous system dysfunction in CRPS-1 and the pathophysiology is poorly understood. In general, the patient must meet the following criteria for diagnosis:
1. There must be some initial noxious event (contusion, crush, or laceration, surgery, sprain, fracture, or dislocation). This initial event normally involves any kind of discrete nerve injury and may indeed be occult.
2. There must be involvement distal to the site of injury.
3. Pain, allodynia, and/or hyperalgesia must be present.
4. Pain is always disproportionate to injury.
5. Pain is never limited to a single nerve.
6. The patient must have symptoms associated with sympathetic nervous system dysfunction (i.e. edema, changes in skin blood flow, sudomotor activity, etc...)
Patients complaining of pain in an area of decreased sensation, pain without cutaneous hyperalgesia or allodynia, pain only in a specific nerve distribution, or only proximal symptoms do NOT have CRPS-1. Finally, three phases of CRPS (acute, dystrophic, and atrophic) can often be identified:
Acute Dystropic Atropic
Pain Localized, severe, and burning More diffuse, throbbing Less severe, can involve other extremities
Extremity Warm Cold, cyanotic, and edematous; muscle wasting Severe muscle atropy; contractures
Skin Dry and red Sweaty Glossy and atropic
X-ray Normal Osteoporosis Severe osteoporosis; ankylosis of joints
Duration 1-3 months 3-6 months Indefinite


For an excellent algorithm for the treatment of CRPS (I & II), see Mayo Clin Proc. 2002;77:174-180
CRPS is essentially a result of autonomic nervous system dysfunction. It can be categorized as CRPS Type 1 (formally Reflex sympathetic dystrophy) or CRPS Type 2 (formally Causalgia). It may or may not involve the sympathetic nervous system, hence the phrase sympathetically independent pain. Only one thing is certain about CRPS and that is the unpredictability of the condition. The cause is obscure and elusive, although we may identify sympathetic nervous system involvement in a subset of this population, hence the phrase sympathetically maintained pain.
Multimodal treatment is often necessary (and what I typically employ in my practice): Physical Therapy, anticonvulsants, antidepressants, occasional opioids, sympathetic nerve blocks, epidural infusions, bier blocks, intravenous infusions, radiofrequency ablation of sympathetic nervous system, and spinal cord stimulation. Also, CBT (Cognitive Behavioral Therapy) may be necessary.
The category of phases may be considered as an older way to view CRPS, however, currently CRPS may or may not have some or many of those features listed above.
"Administration of large volumes of fluid deficient in platelets and clotting factors will predictably lead to the development of a coagulopathy as a consequence of dilution." There has been much research into whether patients first become deficient in platelets of clotting factors during massive volume resuscitation. In the end, this question is not likely to be important. What is important is that after massive volume resuscitation, whether it be with PRBCs, crystalloid or colloid, your patient is likely to be thrombocytopenic and or deficient in clotting factors.
Most of the clotting factors are stable in stored blood except for factors V and VIII. These tend to decrease by up to 50% after 21 days of blood storage. PRBC's have fewer of all the clotting factors.
Total platelet activity is only 50% to 70% of the original in vivo activity after 6 hours of storage in bank blood at 4°C. After 24 or 48 hours of storage, platelet activity is only about 10% or 5% of normal, respectively. Infusion of bank blood stored for longer than 24 hours dilutes the available platelet pool.
Clinically significant dilution of fibrinogen occurs after 1.4 blood volumes, factors II, V, and VII after 2 blood volumes and platelets after 2.3 blood volumes.
Platelets should not be given to treat laboratory evidence of thrombocytopenia unless clinical coagulopathy is also present. When the platelet count is less than 50,000 to 75,000/mm3, a bleeding problem is likely and is probably a combination of dilutional thrombocytopenia and DIC.
Cylinders stored on the back of anesthesia machines are E cylinders. The height of an E cylinder is 24.9 inches, the diameter of the base is 4.38 inches, and the empty weight is 5.90 kg. Both air and oxygen are stored as compressed gasses, and therefore the volume can be calculated if the pressure in the cylinder is known. In contrast, nitrous oxide is stored as both liquid and compressed gas. As vaporized nitrous leaves the cylinder, more nitrous is vaporized. Therefore, the pressure in the cylinder remains the same as long as there is any nitrous remaining in the cylinder. When the pressure begins to decrease, approximately 400 L of nitrous remain in the cylinder.
Characteristics of Compressed Gases stored in E sized Cylinders
Characteristics Oxygen Nitrous Oxide Air
Physical State Gas Liquid and Gas Gas

Cylinder contents, L 625 1590 625
Cylinder Weight, empty, kg 5.90 5.90 5.90
Cylinder Weight, full, kg 6.76 8.80 (missing)
Cylinder Pressure, full, kg 2000 750 1800
There are many other sizes of oxygen cylinders available for medical use:
Table 1
Aluminum Cylinder
Name Dia. (") H.t (") Capac. (L) Wt. (lb.)**
M-2 3.21 5.37 34 0.7
A or M-4 3.21 8.4 113 1.6
B or M-6 3.21 11.6 164 2.2
ML-6 4.38 7.68 165 2.8
M-7 4.38 9.18 198 3.3
C or M-9 4.38 10.7 255 3.7
D or M-15 4.38 16.5 425 5.3
E or M-24 4.38 24.9 680 7.9
*Specifications vary slightly among manufacturers
**Empty weight--without valve or oxygen
Source: Catalina Cylinders at wwwcatalinacylinders.com
There are two classifications used. Cylinders may be labeled A-E (from smallest to largest), or may be labeled with an alpha-numeric designation (m for medical, followed by a number denoting the number of cubic feet of compressed gas contained in a cylinder). Larger cylinder (such as those that supply building supply) may be very large, but are still labeled in the same manner (H-cylinder is the most common). To convert cubic feet to liters, multiply by 28.33.
Differential diagnosis of delayed emergence can be classified into one of three causes: drug effects, metabolic disorders, or neurologic disorders. If a patient doesn't "wake" after an anesthetic you have to go down these three in that particular order.

Drug Effects

Included under drug effects are:
1) Residual anesthetic (volatile, propofol, barbituates, ketamine)
2) Excess narcotics - can be reversed by naloxone - remember it's short acting
3) Preoperative sedatives - too much midazolam? - reversed by flumazenil
4) Inadequate reversal or no reversal of muscle relaxation or rarely pseudocholinesterase deficiency - give muscle relaxation or wait
5) Acute alcohol intoxication or other illicit drugs rendering unconciousness extending the length of the anesthetic

Metabolic Disorders

Included under metabolic disorders are:
1) Hypercarbia - check a gas, may need to ventilate postoperatively until the patient resumes adequate spontaneous ventilation
2) Hypoxemia - may require mechanical ventilation or supplemental oxygen
3) Acidosis - correct the underlying disorder (metabolic/respiratory)
4) Hypoglycemia/Hyperglycemia - check a gas, correct as indicated
5) Hyponatremia - correct slowly such as not to create central pontine myelinolysis
6) Hypothermia/Hyperthermia - correct as indicated
7) Underlying metabolic disorder - e.g. liver disease

Neurologic Disorders

Included under neurologic disorders are:
1) New ischemic event
2) Cerebral Hemorrhage
3) Seizures or post-ictal state
4) Increased ICP or pre-existing obtundation
Remember if the patient is unable to protect airway reflexes then it is best to maintain a secure airway (keep them intubated) until the patient is awake and able to protect their away.
What causes vWD?
-abnormality, either quantitative or qualitative, of the von Willebrand factor
What is vWF?
-a large multimeric glycoprotein that functions as the carrier protein for factor VIII functions: 1. required for normal platelet adhesion
2. primary hemostasis involving platelet adhesion, attaches to platelets by its specific receptor to glycoprotein Ib on the platelet surface and acts as an adhesive bridge between the platelets and damaged subendothelium at the site of vascular injury
3. secondary hemostasis, protects FVIII from degradation and delivers it to the site of injury Types of vWD • Type 1
-70-80% of cases
- characterized by a partial quantitative decrease of qualitatively normal von Willebrand factor and FVIII
-mild Sx
-AD inheritance, varied penetrance

• Type 2
- either autosomal dominant or autosomal recessive
- Of the 4 described type 2 von Willebrand disease subtypes (ie, 2A, 2B, 2M, 2N), type 2A von Willebrand disease is by far the most common.
• Type 3
- most severe form
- In the homozygous patient, type 3 von Willebrand disease is characterized by marked deficiencies of both von Willebrand factor and FVIIIc in the plasma, the absence of von Willebrand factor from both platelets and endothelial cells, and a lack of response to DDAVP
- autosomal recessive trait
Dx: 1. H and P:
-Increased or easy bruising -Recurrent epistaxis
-postoperative bleeding (particularly after tonsillectomy or dental extractions)
-Family history of a bleeding diathesis
-Bleeding from wounds
-Gingival bleeding
-Postpartum bleeding
-Mucosal bleeding and bruises
2. xs bleeding time, prolonged PTT in some cases
3. low vwF assays
Rx: - Minor bleeding problems in patients with von Willebrand disease, such as bruising or a brief nosebleed, may not require specific treatment - More serious bleeding, o desmopressin (1-deamine-8-D-arginine vasopressin [DDAVP]) - causes a 2-fold to 5-fold increase in plasma von Willebrand factor and FVIII concentrations in individuals who are healthy and patients who are responsive.

- can be used to treat bleeding complications or to prepare patients with von Willebrand disease for surgery.
- type IIB von Willebrand disease, DDAVP may cause a paradoxical drop in the platelet count and should not be used in a therapeutic setting without prior testing to see how the patient responds.

Route:IV, intranasal, sc
The dose for hemostasis is approximately 15 times the dosage used to treat individuals with diabetes insipidus. The regular intranasal preparation (0.1 mg/mL), which is used to treat persons with diabetes insipidus, is too dilute to elicit a hemostatic response. A high-concentration intranasal preparation (ie, Stimate 1.5 mg/mL) has been licensed and has shown a similar response as the intravenous form.
I. What is DI? A. Central DI - decreased secretion of antidiuretic hormone (ADH, aka AVP) - results in polyuria and polydipsia by diminishing the patient's ability to concentrate urine - defect in one or more sites involving the hypothalamic osmoreceptors, supraoptic or paraventricular nuclei, or the supraopticohypophyseal trac
B. Nephrogenic DI -decrease in the ability to concentrate urine due to a resistance to ADH action in the kidney. - seen in chronic renal insufficiency, lithium toxicity, hypercalcemia, hypokalemia, and tubulointerstitial disease
-rare hereditary form of nephrogenic diabetes insipidus is transmitted as an X-linked genetic defect of the V2receptor gene
ADH: Actions are mediated through at least 2 receptors V1 mediates vasoconstriction, enhancement of corticotrophin release, and renal prostaglandin synthesis V2 mediates the antidiuretic response
C. ETIO -can result from trauma or CNS tumor(craniopharyngioma, pinealoma), CNS surgery(particularly to pituitary or hypothalamus) -10-20% of patients get DI following transsphenoidal removal of an adenoma,which increases to 60-80% with large tumors. Not all cases of diabetes insipidus are permanent. The most common causes of postoperative polyuria are excretion of excess fluid given during surgery and an osmotic diuresis as a result of treatment for cerebral edema
D. Manifestation: one of 3 patterns can be exhibited
1. Transient
2. Permanent
3. Triphasic: more often clinically observed
-1st: polyuric, lasts 4-5days, ADH is inhibited -immediate increase in urine produced -2nd : antidiuretic phase, lasts 5-6days, stored ADH is released -3rd: permanent DI, ADH stores are exhausted, cells that produce more ADH are absent or unable to produce it
E. DDx: psychogenic polydipsia, osmotic diuresis
F. L/S: usually clinical dx -urine specific gravity of 1.005 or less and a urine osmolality less than 200 mOsm/kg is the hallmark of diabetes insipidus. -Random plasma osmolality generally is greater than 287 mOsm/kg. -water deprivation test (ie, Miller-Moses test), a semiquantitative test to ensure adequate dehydration and maximal stimulation of ADH for diagnosis, is performed in ambiguous clinical circumstances, typically with more chronic forms of diabetes insipidus -mri Brain
G. Rx: desmopressin, IVF if pt is not drinking enough
EMLA (Eutectic Mixture of Local Anesthetics) is a eutectic mixture of lidocaine 2.5% and prilocaine 2.5% formulated as an oil in water emulsion developed to anesthetise intact skin. This eutectic mixture has a melting point below room temperature and therefore both local anesthetics exist as a liquid oil rather than as crystals. EMLA Cream is indicated as a topical anesthetic for use on:1) normal intact skin for local analgesia; and 2) genital mucous membranes for superficial minor surgery and as pretreatment for infiltration anesthesia. To provide sufficient analgesia for clinical procedures such as intravenous catheter placement and venipuncture, EMLA Cream should be applied under an occlusive dressing for at least 1 hour. To provide dermal analgesia for clinical procedures such as split skin graft harvesting, EMLA Cream should be applied under occlusive dressing for at least 2 hours. Satisfactory dermal analgesia is achieved 1 hour after application, reaches maximum at 2 to 3 hours, and persists for 1 to 2 hours after removal. Absorption from the genital mucosa is more rapid and onset time is shorter (5 to 10 minutes) than after application to intact skin.
EMLA Cream is contraindicated in patients with a known history of sensitivity to local anesthetics of the amide type. Patients treated with class III anti-arrhythmic drugs (eg, amiodarone, bretylium, sotalol, dofetilide) should be under close surveillance and ECG monitoring considered, because cardiac effects may be additive. Studies in laboratory animals have shown that EMLA Cream has an ototoxic effect when instilled into the middle ear. EMLA Cream should not be used in patients with congenital or idiopathic methemoglobinemia and in infants under the age of twelve months who are receiving treatment with methemoglobin-inducing agents. There have been reports of significant methemoglobinemia (20-30%) in infants and children following excessive applications of EMLA Cream. Neonates and infants up to 3 months of age should be monitored for Met-Hb levels before, during, and after the application of EMLA Cream.
Epiglottitis (supraglottic inflammation) vs croup (subglottic inflammation)
Inflammation of the epiglottis, vallecula, arytenoids, and aryepiglottic folds.
Can rapidly progress to complete airway obstruction and requires early intervention. Mortality as high as 10% in unintubated children, and less than 1% after intubation.
Most commonly seen in ages 2-7 years, now rare in children since the introduction of the HiB vaccine in 1985. Also uncommon in adults and less severe when encountered.
Present with sore throat, drooling-can't handle secretions, stridor, and in tripod position- sitting up on hands with the tongue out and the head forward. These are late and ominous signs.
No lab studies should be attempted, especially throat swabs until protected airway established. Lateral neck films can help in diagnosis if unsure.
Direct visualization should never be attempted, as acute obstruction may occur. Avoid agitating the patient with acute epiglottitis. Let the patient take a position in which he or she feels most comfortable. Humidified O2 if possible, but do not force patient as agitation will worsen obstruction.
Securing airway is #1 priority. Mask induction is best way to accomplish this if no IV available. Mask induction will avoid agitation of placing an IV in the child and will help with maintenance of spontaneous respirations.
Transport them to the OR in their most comfortable position with airway equipment available at all times. Allowing parents to accompany the child to the OR is calming for the patient and may help with mask induction and cooperation of the child. Once the patient becomes sleepy the parent should be escorted from the OR before proceeding. Have OR set up for DL, bronchoscopy, tracheostomy-along with ENT surgeons, ASA monitors as usual. Induce with 100% O2 and volatile agents, Sevoflurane best choice, with child in their most comfortable position. A quiet, calm, controlled environment is a must. Once induced, lie the child down gently and gain IV access, while assisting gently with ventilation. However, positive pressure mask ventilation can cause obstruction by the edematous epiglottis. Avoid muscle relaxants if possible, but assure mask ventilation if you do relax. Lidocaine 1mg/kg can help attenuate cough and laryngospasm. DL and intubate with ETT 0.5-1.0mm smaller than normal for age. If unable to intubate by DL be prepared for bronchscopy, emergent cricothyroidotomy or tracheostomy.
Mask induction is a risk for aspiration especially if full stomach, but hypoxia is bigger risk if unable to intubate or ventilate after RSI, plus will need to place IV. Also a spontaneously breathing patient may help with finding the glottic opening.
Glycopyrrolate10mcg/kg as antisialogogue may also help.
If child unable to cooperate with mask induction IM ketamine is option, but obviously will cause agitation, may accentuate airway reflexes, and cause increased secretions, all of which are already a problem. Other last resort techniques for ventilation include transtracheal ventilation with 16G PIV catheter, by attaching 3.5ETT adapter and bag ventilating, or can attach 3cc syringe to catheter, then 6.5ETT adapter and bag ventilate, or use of jet ventilation through catheter.
Once airway is controlled cultures can be taken and antibiotics started. Racemic epi and steroids have shown no benefit.
Pathophysiology- 2 theories 1. mechanical theory: large fat droplets are released into the venous system. These droplets are deposited in the pulmonary capillary beds and travel through arteriovenous shunts to the brain. Microvascular lodging of droplets produces local ischemia and inflammation, with concomitant release of inflammatory mediators, platelet aggregation, and vasoactive amines. 2. biochemical theory: hormonal changes caused by trauma and/or sepsis induce systemic release of free fatty acids as chylomicrons. Acute-phase reactants, such as C-reactive proteins, cause chylomicrons to coalesce and create the physiologic reactions described above. The biochemical theory helps explain nontraumatic forms of fat embolism syndrome.
Mortality: 10 to 20%
HISTORY: trauma to long bone/pelvis, recent orthopedic procedure, recent lipid infusion
PE: Major criteria Respiratory symptoms, signs or radiologic disease; cerebral signs without other etiologies; petechial rash
Minor criteria: A pulse that is over 110 beats/min, fever over 38.5 º C, retinal changes of fat globules or petechiae, renal dysfunction, jaundice, acute drop in hemoglobin and/or platelets, elevated sedimentation rate
One major and 4 minor criteria, plus fat microglobulinemia, must be present to formally diagnose fat embolism syndrome. • Cardiopulmonary o Early persistent tachycardia may herald the onset of the syndrome. o Patients become tachypneic, dyspneic, and hypoxic due to ventilation-perfusion abnormalities 12-72 hours after injury. o Patients become febrile with high-spiking temperatures. • Dermatologic o Alert clinicians may notice reddish-brown nonpalpable petechiae developing over the upper body, particularly in the axillae, within 24-36 hours of insult or injury. These petechiae occur in only 20-50% of patients and resolve quickly, but they are virtually diagnostic in the right clinical setting. o Subconjunctival and oral hemorrhages and petechiae also appear. • Neurologic o Central nervous system dysfunction initially manifests as agitated delirium but may progress to stupor, seizures, or coma and frequently is unresponsive to correction of hypoxia. o Retinal hemorrhages with intra-arterial fat globules are visible upon funduscopic examination.
Workup: a. Labs 1. ABG: increase in pulmonary shunt fraction alveolar-to-arterial oxygen tension difference, especially if it occurs within 24-48 hours of a sentinel event 2. Hematocrit, platelet count, fibrinogen: Thrombocytopenia, anemia, and hypofibrinogenemia are indicative of fat embolism syndrome 3. Urine studies: Urinary fat stains are not felt to be sensitive or specific enough for diagnosing fat embolism or for detecting a risk of it.
b. imaging 1. Chest radiography: increasing diffuse bilateral pulmonary infiltrates within 24-48 hours of onset of clinical findings. 2. Noncontrast head CT: diffuse white-matter petechial hemorrhages consistent with microvascular injury. 3. Nuclear medicine ventilation/perfusion imaging of the lungs: Performed for suspicion of pulmonary embolus, the findings from this scan may be normal or may demonstrate subsegmental perfusion defects. 4. Helical chest CT for pulmonary embolism: 5. MRI: Scant data exist regarding MRI findings in patients with this syndrome; however, in one small patient group, multiple, nonconfluent, hyperintense lesions were seen on proton-density- and T2-weighted images. 6. Transcranial Doppler sonography: In a small case study, 5 patients with trauma were monitored with intracranial Doppler sonography, 2 during intraoperative nailing of long bone fractures. Cerebral microembolic signals were detected as long as 4 days after injury. 7. Transesophageal echocardiography (TEE): TEE may be of use in evaluating intraoperative release of marrow contents into the bloodstream during intramedullary reaming and nailing. The density of the echogenic material passing through the right side of the heart correlates with the degree of reduction in arterial oxygen saturation. Repeated showers of emboli have been noted to increase right heart and pulmonary artery pressures. Embolization of marrow contents through patent foramen ovale also has been noted. However, evidence of embolization by means of TEE is not correlated with the actual development of FES.
c.Procedures Bronchoalveolar lavage (BAL) with staining of alveolar macrophages for fat
BAL specimens have been evaluated in trauma patients and sickle cell patients with acute chest syndrome, and the results have been mixed. Lipid inclusions commonly appear in patients with traumatic and nontraumatic respiratory failure; the standard cut-off of 5% fat-containing macrophages in the BAL studies results in a low specificity for the test. Some authors suggest increasing the cut-off to 30% to improve specificity. Presently, using BAL to aid in the diagnosis or to predict the likelihood of fat embolism syndrome is controversial.
RX : supportive, steroids don't currently have a role in treatment
What is FFP?

Fresh frozen plasma is the liquid component of blood, and must be frozen within 6 hours of collection to be considered "fresh." It is stored at -30 degrees C. FFP contains all coagulation factors and has traditionally been used to treat surgical blood loss, for urgent reversal of warfarin, and to treat heparin resistance (because FFP also contains antithrombin)

Uses of FFP

ASA Recommendations
As stated in Murray's "Critical Care Medicine," the ASA recommendations for FFP are the following:
ASA recommendations for the administration of FFP (recommended dose = 10-15 cc/kg)
1. Urgent reversal of warfarin (only requires 5-8 cc/kg). Note, however, the prothrombin complex concentrate has been shown to be more
effective {Makris et. al. Br J Haematol 114: 271, 2001}
2. Correction of known coagulation factor deficiencies for which specific concentrates are unavailable
3. Correction of microvascular bleeding in the presence of INR > 1.5 (debatable efficacy, see below)
4. Correction of microvascular bleeding in the presence of massive transfusion (> 1 blood volume)

Criticisms of FFP

Mechanistic Considerations
"For many clinicians, coagulation is envisioned as proceeding through either an intrinsic pathway (triggered by a negatively charged surface) or by an extrinsic pathway (triggered by tissue factor). But the reality is that in vivo the coagulation processes are more interrelated, with initiation of coagulation occurring through the extrinsic pathway (dependent on the tissue factor-FVIIa complex) and propagation through factors in the intrinsic pathway (the intrinsic factor tenase and the prothrombinase complexes)" {Stanworth. Hematology 2007: 179, 2007}

Paucity of Data
According to Barash, "there is remarkably little systematically derived evidence of efficacy {Stanworth et. al. Br J Haematol 126: 139, 2004}"

Infection Risk
Similar to the risk of PRBCs, as both are kept below room temperature but neither of which are heated. The risk of bacterial sepsis/endotoxin reaction for PRBCs is 1/30,000, and the risk of hepatitis B is 1/350,000 (HIV and hepatitis C are closer to 1/2,000,000), all of which are likely similar for FFP. Platelets, by contrast, carry a 1/2000 risk of bacterial infection, as they are kept at room temperature

Decreased Bleeding Risk?
Studies evaluating bleeding following central venous line placement {Fisher et. al. Intensive Care Med 25: 481, 1999; DeLoughery et. al. Transfusion 36: 827, 1996}, liver biopsy {Ewe et. al. Dig Dis Sci 26: 388, 1981} thoracentesis and paracentesis {McVay et. al. Transfusion 31: 164, 1991}, and lumbar puncture {Howard et. al. JAMA 284: 2222, 2000} have all failed to show a correlation between the risk of bleeding and mild abnormalities in preprocedure PT, partial thromboplastin time (PTT), or platelet (PLT) values

Data on FFP for INR < 1.85 (the MGH study)
Abdel-Wahab prospectively audited all FFP transfusions for an INR of 1.1-1.85 at Massachusetts General Hospital over 13 months (324 transfusions had the necessary follow up data). Transfusion of FFP resulted in normalization of PT-INR values in 0.8 percent of patients and decreased the INR halfway to normalization in 15% of patients (furthermore, there was no significant relationship between pretransfusion INR and likelihood of achieving 50 percent correction of the INR after FFP transfusion). There was no dose-response effect, and increasing amounts of FFP did not appear to result in larger decrements in INR. Median decrease in INR was 0.07 [Abdel-Wahab et. al. Transfusion 46: 1279, 2006]

A study by Deitcher showed that over the INR range of 1.3-1.9, mean factor levels ranged from 31% to 65% (FII), 40% to 70% (FV), and 22% to 60% (FVII), all of which were consistent with adequate concentrations of factors to support hemostasis {Deitcher SR. Lancet. 359: 47, 2002}, further suggesting that FFP is not indicated for INR < 1.85
Garlic Inhibition of platelet aggregation, Increased fibrinolysis, Equivocal anti-HTN activity May ↑ risk of bleeding, especially when combined with other meds that inhibit platelet aggregation At least 7 days before surgery
Ginkgo Inhibition of platelet-activating factor May ↑ risk of bleeding, especially when combined with other meds that inhibit platelet aggregation At least 36 hours before surgery
Ginseng Inhibition of platelet aggregation, ↑ PT/PTT in animal studies, ↓ blood glucose May ↑ risk of bleeding, Hypoglycemia At least 7days before surgery
Saw Palmetto Inhibition of cyclooxygenase May ↑ risk of bleeding No data
Garlic is used for its potential to prevent atherosclerosis by reducing blood pressure, thrombus formation, and serum lipid and cholesterol levels. The development of concentrated garlic preparations has made it possible for patients to take otherwise unachievable high doses, which may increase the risk of adverse effects.
The pharmacologic effects of garlic are primarily attributed to organosulfur compounds. Several of these compounds inhibit platelet aggregation in a dose-dependent manner. The inhibition of platelet aggregation appears to be irreversible and may potentiate the effect of other compounds such as prostacyclin and indomethecin. The mechanism by which these effects occur is unknown, although some studies have implicated the cyclooxygenase pathway and direct interaction with the platelet fibrinogen receptor
The potential for irreversible inhibition of platelet function warrants the discontinuation of garlic at least 7 days before surgery, especially if intraoperative or postoperative bleeding is a concern or other platelet inhibitors are used.
Ginkgo is used by patients with cognitive disorders, peripheral vascular disease, age-related macular degeneration, vertigo, tinnitus, erectile dysfunction, and altitude sickness. The compounds believed to be responsible for ginkgo's pharmacologic effects are the terpenoids and flavonoids. These compounds alter vasoregulation, act as antioxidants, modulate neurotransmitter and receptor activity, and inhibit platelet-activating factor.
Based on the pharmacokinetic data and the risk of bleeding, ginkgo should be discontinued at least 36 hours before surgery.
Ginseng has been used for virtually every purpose, including to promote health, immune function, endocrine function, athletic performance, and cognitive function and to treat cardiovascular disease, diabetes mellitus, cancer, impotence, and viral infections.
Most pharmacologic effects of ginseng are attributed to the ginsensosides, a group of compounds that act as steroid hormones. It is not known, however, whether long-term use of ginseng can cause the well-described complications of long-term steroid use.
Ginsenosides inhibit platelet aggregation in vitro and prolong the PT and PTT in animal studies. They also lower postprandial blood glucose in patients with type 2 diabetes mellitus. Although it has great therapeutic potential, it can also create unintended hypoglycemia. (patients fasting preoperatively)
The pharmacokinetics of ginsenosides suggest that patients should discontinue ginseng use at least 24 hours before surgery, but discontinuation at least 7 days before surgery is preferred because of the potential for irreversible platelet inhibition.
Saw Palmetto is used to treat symptoms associated with BPH.
The pharmacologic activity of saw palmetto has not been attributed to a single compound. Multiple mechanisms of action have been proposed to explain its therapeutic effects: inhibition of estrogen receptors, blocking prolactin receptor signal transduction, interference with fibroblast proliferation, induction of apoptosis, inhibition of α1-adrenergic receptors, and anti-inflammatory effects. Saw Palmetto has been associated with excessive intraoperative bleeding. This is attributed to saw palmetto's anti-inflammatory effects, specifically the inhibition of cyclooxygenase and subsequent platelet dysfunction.
Because there are no pharmacokinetic data for saw palmetto, specific recommendations for preoperative discontinuation cannot be made.
Maternal primary infection with HSV before pregnancy does not usually impact the intrauterine development of the fetus. Increased rates of miscarriage and IUGR following primary HSV infection during pregnancy have been reported.
Intrauterine HSV infections are rare (1 in 200,000 deliveries). Manifestations in such cases include skin vesicles, eye disease, microcephaly or hydranencephaly. The greatest risk to infants exposed perinatally to HSV is the development of neonatal herpes infection. There are three categories of neonatal HSV infections: local (skin, eye and mouth) disease, encephalitis, and disseminated infection. There is significant neonatal mortality with disseminated disease (60 percent), and a neonatal mortality rate of 15 percent with encephalitis. Neonatal HSV infection is treated with intravenous acyclovir.
Neonatal HSV infection complicates approximately 1 in 3,500 deliveries. The estimated risk of neonatal HSV during primary maternal infection is 50 percent, and in cases of recurrent HSV infection, the risk of neonatal HSV ranges from 0 to 3 percent. Thus, neonatal HSV infection is most often caused by primary maternal HSV infection, rather than recurrent infection. Factors predicting neonatal HSV transmission include: cervical HSV shedding, invasive monitoring, preterm delivery, maternal age less than 21 years of age, and HSV viral load.
Elective cesarean delivery is recommended for women with demonstrable genital herpes lesions or prodromal symptoms in labor to reduce the incidence of neonatal HSV infection. The risk of neonatal HSV infection in cases of nongenital, maternal HSV lesions ( thigh, buttock, mouth) is low; therefore, cesarean delivery is not recommended for these women.
Hypertension is the most significant modifiable risk factor for stroke, and stroke incidence is proportional to the level of the blood pressure. Decreasing systolic blood pressure by approximately 10mmHg reduces the relative risk of stroke by 35% to 40.
Causes of Hypertension
• Essential Hypertension
• Chronic renal parenchymal disease
• Acute glomerulonephritis
• Renovascular hypertension
• Withdrawal from hypertensive agents (clonidine)
• Encephalitis, meningitis
• Pheochromocytoma
• Sympathomimetic agents (cocaine, amphetamines, phencyclidine [PCP], lysergic acid diethylamide [LSD])
• Eclampsia and preeclampsia
• Head trauma
• Collagen vascular disease
• Autonomic hyperactivity
• Vasculitis
• Ingestion of tyramine-containing foods or tricyclic antidepressants in combination with monoamine oxidase inhibitors
Intracerebral Hemorrhage Chronic hypertension causes fibrinoid necrosis in the penetrating and subcortical arteries, weakening of the arterial walls, and formation of small aneurysmal outpouchings that predispose the patient to spontaneous ICH. Bleeding usually arises from the deep penetrating arteries of the circle of Willis. Acute increases in blood pressure and blood flow can also precipitate ICH even in the absence of preexisting severe hypertension.
ICH is a major cause of morbidity and death and accounts for 10% to 15% of all strokes in whites and approximately 30% in individuals of African or Asian origin. Pregnancy may increase the risk of ICH. Eclampsia accounts for more than 40% of ICHs in pregnancy, and ICH is a common cause of death from eclampsia. Locations of hypertensive ICHs are the putamen (40%), cerebral lobes (22%), thalamus (15%), pons (8%), cerebellum (8%), and caudate (7%).
Spontaneous ICH can also occur in association with bleeding diatheses, especially the prescription of anticoagulants, primary or metastatic brain tumors or granulomas, and use of sympathomimetic drugs.
Location Motor/Sensory Eye Movements Pupils OTHER SIGNS
Putamen or internal capsule Contralateral hemiparesis and hemisensory loss Ipsilateral conjugate deviation Normal Left: aphasia
Right: left-sided neglect
Thalamus Contralateral hemisensory loss Down and in upgaze palsy Small; react poorly Somnolence, decreased alertness; left: aphasia
Frontal Contralateral limb weakness Ipsilateral conjugate gaze Normal Abulia
Temporal None None Hemianopia Left: aphasia
Occipital None None Hemianopia
Parietal Slight contralateral hemiparesis and hemisensory loss Hemianopia; left: aphasia; right: left neglect; poor drawing and copying
Caudate None or slight contralateral hemiparesis None Normal Abulia, agitation, poor memory
Pons Quadriparesis Bilateral horizontal gaze paresis, ocular bobbing Small; reactive Coma
Cerebellar Gait ataxia, ipsilateral limb hypotonia Ipsilateral gaze or cranial nerve VI paresis Small Vomiting, inability to walk, tilt when sitting
Prognosis depends on the location, size, and rapidity of development of the hematoma. If the patient survives the initial changes in ICP, blood is absorbed over several weeks and a cavity or slit forms that may disconnect brain pathways. Recurrence rate of hypertensive ICH is approximately 2% per year. The site of the subsequent ICH usually differs from the first one. Diastolic blood pressure (DBP) is the most critical factor for recurrence, with the average DBP at 90mmHg (10% if DBP > 90mmHg; less than 1.5% if DBP < 90mmHg).
Subarachnoid Hemorrhage
The cause of SAH is a ruptured aneurysm in 85% of cases and a variety of rare conditions such as vascular malformations in 15%. Aneurysms are probably caused by a combination of congenital defects in the vascular wall and degenerative changes. Aneurysms usually occur at branching sites on the large arteries of the circle of Willis at the base of the brain.
Risk factors include smoking, hypertension, heavy alcohol use, and genetic factors predispose only a minority. Patients with degenerative elongation and tortuosity of arteries, fibromuscular dysplasia, polycystic kidney disease, and connective tissue diseases have a higher incidence of aneurysms. Infected materials from endocarditis (bacterial or fungal) or cardiac myxoma can embolize to the intracranial arteries and can cause mycotic aneurysms.
Most patients are younger than 60 years of age. The incidence of SAH increases with age (mean age of approximately 50 years) and is higher in women than in men. Blacks are at higher risk than whites. Population-based incidence rates for SAH vary from 6 to 16 per 100,000, with the highest rates reported in Finland and Japan.
Cerebral vasospasm, which develops in approximately one-half of patients with SAH, is the delayed narrowing of large capacitance arteries at the base of the brain and often leads to diminished brain perfusion in the territory of the constricted arteries. Angiographic vasospasm runs a typical temporal course: onset between 3 and 5 days after hemorrhage, maximal narrowing between 5 and 14 days, and gradual resolution over 2 to 4 weeks. Once ischemia has occurred, triple H therapy: hypertension, hypervolemia, and hemodilution is recommended. Transluminal angioplasty can be tried in patients for whom conventional therapy has failed. To reduce the risk of delayed cerebral ischemia, patients are treated with supply of fluids, avoidance of antihypertensive drugs, and administration of the calcium antagonist nimodipine.
Acute obstructive hydrocephalus following SAH complicates approximately 20% of cases. Ventriculostomy is recommended in severe cases, but this intervention may be associated with increased chance of rebleeding and infection.
Case fatality is approximately 50% overall (including prehospital deaths) and one-third of survivors remain dependent.
Brain Stem Syndromes
Hemorrhage (hypertensive, SAH, ruptured AV malformation), tumors, infarctions, demyelinating disease (multiple sclerosis), infections, encephalitis, and inflammatory conditions such as tuberculosis or sarcoidosis may affect brain stem function.
Injury within the brain stem commonly affects the trigeminal system. Brain stem syndromes may be characterized by sensory paresthesias, numbness, or pain in the distribution of V1 to V3, along with combinations of cranial nerve palsies and distinct motor, sensory, and cerebellar system signs.
Cerebrovascular disease is the most common cause of dysautonomia associated with brain stem dysfunction. Hemorrhage in the basilar artery territory may present with paroxysmal hypertension before any focal neurological deficit becomes apparent. Lateral medullary injury (Wallenberg's syndrome) produces Horner's syndrome and, occasionally, more severe autonomic abnormalities, such as profound bradycardia, supine hypotension, or central hypoventilation.
Background: Glucagon was originally thought to be a "contaminant" that caused hyperglycemia found in pancreatic extracts in studies from 1923. Looking for the hyperglycemic mechanism of this "contaminant" led to the nobel prize-winning discovery of cyclic adenosine monophosphate (c-AMP) in the 1960s. Full understanding of this hormone did not come until the 1970s, when somatostatin was discovered and found to inhibit the action of Glucagon.
Glucagon is a peptide hormone, synthesized and secreted by Alpha cells of the pancreas. Its main action is to stimulate glycogenolysis, i.e. release of stored glucose (glycogen) from the liver. It also inhibits glycogen synthesis thus averting further storage of glucose in the liver, and increases gluconeogenesis in the liver from protein and fat. Other actions include transiently paralyzing the smooth muscles of the intestines. After a 12-16 hour fast, arterial and venous concentrations range between 25 and 150 pg/ mL and, the normal human pancreas contains approximately 700- 1000 micrograms of glucagons.
Manufacturing: Synthetic Glucagon is manufactured by genetically engineering E. coli. It is prepared as a powder and freeze-dried.
Route: IV, IM, SQ
Preparation: It is administered by mixing with 1mL of glycerin.
Dosage: [Children < 44 pounds] 0.03-0.1 mg/kg/dose IV/IM q20min prn; not to exceed 0.5 mg/dose; not to be administered at concentrations >1 mg/mL. [Adults & Children >44 pounds] 1mg (1unit). After mixing, the solution should appear clear and without floating particles and should not be discolored. Metabolism: Kidney (23-39%) > Liver. ↓ catabolism of Glucagon seen in renal failure and starvation. No changes seen in diabetics or liver disease.
Major Stimulation of Glucagon Secretion: Hypoglycemia, exercise, trauma, infection, and other stress. Hypoglycemia both directly (stimulates Alpha cells) and indirectly (↓ insulin secretion which otherwise tonically inhibits Glucagon) increases Glucagon release. Other contributions come from: NorEpi (autonomic adrenergic), acetylcholine (cholinergic), and peptidergic neural & epinephrine (adrenomedullary signals). ***In Diabetics (type 1&2), alpha cells can become dysfunctional and not secrete Glucagon in response to hypoglycemia, predisposing diabetics to severe hypoglycemia. Similar problems occur in chronic pancreatitis and in pts s/p pancreatectomy.
Interactions: Effects of anticoagulants may be enhanced by glucagon (although onset may be delayed); monitor prothrombin activity and for signs of bleeding in patients receiving anticoagulants; adjust dose accordingly.
Pregnancy: B- no studies in pregnant women, some risk seen in animals.
Side effect: N/V
Contraindications: Not to be administered to patients with little to no glycogen stores: starvation (including chronic alcoholics), adrenal insufficiency, pheochromocytomas or chronic hypoglycemia.
Mechanisms of Action: [figure needed]
Effects: Glucagon dose, in appropriate patients, will produce maximal glucose effects 5-20min (IV) and approximately 30 min for IM/ SQ.
Hyperventilation by positive pressure ventilation can lead to oliguria through a number of different mechanisms:
1) Decreased cardiac output secondary to the increased intrathoracic pressure and an increase in right ventricular afterload - the decrease of cardiac output and BP caused by PPV results in a baroreceptor mediated increase in SNS with subsequent renal vasoconstriction. Volume receptors in the atria respond to decreased filling by decreasing the production of ANP, increasing sympathetic tone, increasing renin activity and ADH production.
2) Increase of IVC pressure → decreased renal perfusion
3) Increase of renal venous pressure → decreased renal drainage
Through the above mechanisms, PPV can lead to a decrease in renal blood flow, GFR, Na excretion and urine flow rate. This impairment of renal function can be prevented or attenuated by preserving normal circulatory status, ie appropriate hydration.
Keep in mind that while hyperventilation caused by PPV can lead to oliguria, there are other situations in the OR in which you may see both hyperventilation and oliguria.
1) Neuroendocrine stress response. Sympathetic outflow from the celiac and renal plexus (T4-L1) result in alpha 1 mediated renal vasoconstriction. Circulating catecholamines also result in a redistribution of renal blood flow to the renal medullary → clinically associated with Na retention. Stress - hyperventilation.
2) Pneumoperitoneum. Oliguria secondary to abdominal compartment like state. Mechanisms include venous compression (IVC and renal veins), renal parenchymal compression, decreased cardiac output and increased levels of renin, aldosterone and ADH. These effects are generally proportional to insufflation pressures. Increased minute ventilation is due to the absorbtion of CO2 from insufflation.
3) Metabolic Acidosis with Respiratory Compensation. Many causes of metabolic acidosis will also be associated with oliguria. For example, lactic acidosis secondary to sepsis or hypovolemia also be associated with oliguria.

The interscalene nerve block is performed at the C6 level (level of the cricoid cartilage) between the anterior and middle scalene muscles.
1) Place the patient supine with head turned to the opposite side to be blocked.
2) Identify the SCM. By having the patient slightly raise his head, the scalene muscles behind the SCM tense and you can identify and mark the groove between the anterior and middle scalenes (posterior and lateral to the SCM).
3) Mark the level of the cricoid thyroid, C6.
4) Place needle perpendicular to all planes at the C6 level within the groove and advance until you get nerve localization you want, usually a motor response in the deltoid or biceps. If you hit tubercle, withdraw needle and redirect in an anteroposterior plane.


1) Distal shoulder
2) Arm
3) Elbow surgery
Ulnar distribution is the most commonly missed!


Related to inadvertently hitting structures located in the vicinity
1) Pneumothorax - if needle directed too caudad; should be considered if patient has chest pain, SOB or cough.
2) Spinal or epidural anesthesia - if needle directed too medially and enters the intervertebral foramina.
3) Intravascular injection - the vertebral artery lives in the canal of the transverse process
4) Hematoma formation

Side Effects

Related to the spread of local anesthetic to nearby structures
1) Diaphragm paralysis - due to phrenic nerve blockade
2) Horner's Syndrome - due to spread to the sympathetic chain. Ptosis, anhidrosis and miosis. May also see nasal congestion due to the sympathectomy.
3) Hoarse voice - due to spread to the recurrent laryngeal nerve
Muscle Metabolism

Muscle metabolism --> creatine --> creatinine (nonenzymatically converted). Creatinine production is constant, related to muscle mass (20-25 mg/kg males, 15-20 mg/kg females). Filtered but not reabsorbed in kidneys. Therefore, directly related to muscle mass, inversely related to glomerular filtration. More reliable than BUN because body muscle mass is fairly constant for a given individual. Normal values: 0.8-1.3 males, 0.6-1.0 females. Double serum creatinine = 50% reduction of GFR

Variables which affect creatinine levels

Cimetidine, large meat meals, ketoacidosis all elevate creatinine without changing GFR.

GFR changes with aging

GFR decreases 5% per decade after age 20, but muscle mass also declines, therefore serum levels remain normal although creatinine production decreases. Therefore, in elderly, small increase in creatinine = large change in GFR.

Lab Assessment

BUN/creatinine ratio

Ratio increases above 10:1 during low renal tubular flow states (decreased renal perfusion, urinary tract obstruction, etc). Also increases during increases in protein catabolism. BUN:creatinine ratios greater than 15:1 seen in volume depletion, CHF, cirrhosis, nephrotic syndrome, and obstructive uropathies.

Creatinine clearance

Most accurate study to evaluate renal function (GFR) (Urine creatinine x Urine flow rate)/(Serum creatinine). Usually calculated via 24 hour urine, but 2 hour tests are reasonably accurate in critically ill patients. Normal values: males 97-137, females 88-128. Mild renal impairment -> CCR 40-60, CCR 25-40 = moderate impairment and almost always causes symptoms.
Progressive renal disease enhances creatinine secretion in proximal tubules. Therefore, with progressively worsening renal disease, CCR progressively overestimates true GFR.

Perioperative assessment of renal function

Urine flow rate, specific gravity, and osmolality are all poor indicators of renal dysfunction because they are influenced by nonrenal factors.
BUN and creatinine are good screening tools, but poor tools to predict renal dysfunction because they are late warning signs of declining renal function.
Again, CCR is the best study to monitor renal function and predict potential ARF.
Intro: Electrocution

To receive a shock, persons need body contact with two separate conductive materials at different voltage potentials to complete a circuit. The most common scenario in which a shock occurs is where a grounded ("neutral voltage") patient touches a "hot" wire which exists at a non-zero voltage potential - the electrical current that subsequently passes through the patient can be described as I = V/R, where V is the difference in voltage potential between the "ground" (0) and the "hot" line (~ 120V for a standard wall outlet).

Primary vs. Secondary Wiring

Primary wiring in an operating room (from the main alternating current power supply) is normally grounded. Equipment used in the OR is NOT normally grounded, but the equipment casing is- this configuration protects this patient, as the secondary wiring system, which is not grounded, requires two faults in order to shock the patient (fault no. 1 = grounded, fault no. 2 = patient touching the secondary wiring system). An electrical wire which is not grounded is thus considered an "isolated" line - if an ungrounded patient were to touch an "isolated" ie ungrounded line, nothing would happen. In order for a piece of equipment to take advantage of this safety mechanism, it must be connected to the primary wiring system (which is grounded) via an isolation transformer (for a schematic diagram, see Morgan and Mikhail Figure 2.7, page 25)

What the Line Isolation System Does

In summary, line isolation systems (isolation transformer + line isolation monitor) protect persons from electrocution by turning a normal "grounded system" (that exists outside the operating room) which only needs a single fault to cause electrocution into a "protected" system in which two faults are needed to deliver a shock. The line isolation monitor determines the degree of isolation between the two power wires and the ground and predicts how much current could flow if a second short-circuit were to develop. An alarm goes off if an unacceptably amount of current to the ground is possible.

What the Alarm Means
When the monitor is alarming, there is a single fault in the system, but there still needs to be another one in order to deliver a shock. If the alarm is going off, the last piece of equipment plugged in is usually suspect and should be unplugged.

Regulations Post-1984

Isolated power systems are no longer required in operating rooms as of 1984, thus some modern equipment may offer the potential for electrocution, although this risk is reduced by the use of ungrounded batteries for power, double insulating equipment, and isolating patients from equipment (Morgan and Mikhail 23-23)
Introduction and Controversy

Introduction to Liposuction and Tumescent Fluid

Howard Solbel, in an editor's response to Yoho's article (see below), state the following - "Let us first understand the difference between the tumescent technique and the tumescent solution. The tumescent technique involves using the tumescent solution (lidocaine 0.05%, epinephrine 1:1,000,000) anywhere from 1:1 up to 2:1 tumescent solution to aspirate, with less than 55 mg/kg of lidocaine injected. Most important, the procedure as described by Dr. Jeffrey Klein is performed strictly under local anesthesia, without general anesthesia or I.V. sedation." {Yoho. IHCSAD 3: 1, 2001}
The use of tumescent solution allows liposuction to be performed under conscious or deep sedation, although some surgeons will still use a tumescent technique in conjunction with general anesthesia, especially if large volumes (> 2000 mL) are to be removed.
While most of the tumescent solution is removed along with the fat, a significant amount of the solution may be absorbed and several cases of fluid overload and pulmonary edema have been reported {Plast Reconstr Surg 1997; 99:215, Plast Reconstr Surg 1997; 100:1363, N Engl J Med 1999; 340:1471}. Although the concentration of lidocaine present in the tumescent solution is very low and the absorption of lidocaine is attenuated by epinephrine-induced vasoconstriction, patients can nonetheless be exposed to significant quantities of lidocaine: 70 - 80 mg/kg, well above the 7 mg/kg toxic dose of lidocaine when it is co-administered with epinephrine.

Controversy Surrounding Lidocaine Toxicity

In a recent article, Gorney stated that "lidocaine toxicity... is probably the second or third most common cause of fatal outcome in lipoplasty... such deaths occurred in the surgical suites of nonsurgeons)" {Gorney, M. Aesthet Surg J 20: 226, 2000} however, Yoho, in a guest editorial to the International Journal of Cosemetic Surgery and Aesthetic Dermatology {Yoho. IHCSAD 3: 1, 2001}, replied that there no literature references to back up Gorney's claim, and that furthermore, a contemporary study of > 100 deaths during liposuction did found no death related to lidocaine toxicity {Grazer et. al. Plast Reconstr Surg 105: 436, 2001}

Signs and Symptoms of Toxicity During Liposuction

The signs and symptoms of Lidocaine Toxicity may not be apparent during or immediately following the procedure and serum concentrations of lidocaine may continue to rise for 16 hours or longer (N Engl J Med 1999; 340:1471). Lidocaine toxicity (and all local anesthetic toxicity) can cause circumoral numbness, facial tingling, restlessness, vertigo, tinnitus, slurred speech, and tonic-clonic seizures.

Guidelines on Maximum Lidocaine Dose in Liposuction

The American Academy of Dermatology has published guidelines for liposuction ( J Am Acad Dermatol 2001; 45:438) which indicate a maximum safe of lidocaine of 55 mg/kg; however, this remains an area of significant controversary. Some experts note that 35 mg/kg is a more reasonable limit noting that the hepatic metabolism of lidocaine by means of CYP3A4 is saturable and once saturation occurs, absorption exceeds elimination, and plasma lidocaine concentrations increase precipitously (N Engl J Med 1999; 340:1471). Administration of other drugs that are metabolized by or inhibit CYP3A4 can also alter lidocaine metabolism. Indeed, death with toxic postmortem levels of lidocaine levels has been reported after only 10 mg/kg of tumescent lidocaine [Textbook of Cosmetic Dermatology, p 624] - in this particular instance, however, the post-mortem serum lidocaine level was 5.2 mg/L, significantly higher than what would be expected based on the literature (ex. one published report of 4 patients receiving 60 mg/kg of lidocaine in tumescent solution showed plasma concentratinos of 1.7 - 2.2 mg/L).
Pharmacologic Data

Esters Max Dose (mg/kg) Duration (h)

Chloroprocaine 12 0.5-1
Procaine 12 0.5-1
Cocaine 3 0.5-1
Tetracaine 3 1.5-6


Lidocaine 4.5/(7 with epi) 0.75-1.5
Mepivacaine 4.5/(7 with epi) 1-2
Prilocaine 8 0.5-1
Bupivacaine 3 1.5-8
Ropivacaine 3 1.5-8

Effects on Organ Systems

Central nervous system

The initial CNS symptoms are tinnitus, blurred vision, dizziness, tongue parathesias, and circumoral numbness. Excitatory signs such as nervousness, agitation, restlessness, and muscle twitching are the result of blockade of inhibitory pathways. Muscle twitching heralds the onset on tonic-clonic seizures. The early signs/symptoms advance to CNS depression with slurred speech, drowsiness, unconsciousness, and then respiratory arrest. Patients who have received CNS depressant drugs may present with only CNS depression without any preceding excitatory signs.
The effects on the CNS depend on various clinical factors including:
Hypercarbia - Increased PaCO2 lowers the seizure threshold with local anesthetic administration. There is a concomitant increase in cerebral blood flow which allows more local anesthetic to be delivered to the CNS. An increase in intracellular pH leads to ion-trapping of the local anesthetic. The acidosis caused by hypercarbia decreases the protein binding of local anesthetics making more drug available to the CNS.
CNS Depression - Conscious patients receiving CNS depressant drugs such as benzodiazepines or IV anesthetic drugs will have higher seizure threshold, and may not manifest seizure activity before complete CNS depression results.

Cardiovascular system

Local anesthetics have directs effects on the heart and peripheral blood vessels. They block the fast sodium channels in the fast-conducting tissue of Purkinje fibers and ventricles resulting in a decrease rate of depolarization. The effective refractory period and action potential duration are also reduced by local anesthetics. High concentrations can decrease conduction times leading to prolonged PR intervals and widened QRS complexes, and even sinus brady/arrest. Ventricular arrhythmias, including fibrillation, are more likely to occur with bupivacaine than lidocaine. Local anesthetics have a dose-dependent negative inotropic effect. This depressant effect is directly proportional to the drugs relative potency (see chart). Patients with acidosis and/or hypoxia are at a greater risk for the cardiac depressant effects of local anesthetics. Cardiotoxicity of local anesthetics can be compared using the CC/CNS dose ratio that is the ratio of the dose causing cardiac collapse (CC) to the dose causing seizure/convulsions. The lower the number the more cardiotoxic the drug (ex. The CC/CNS for bupivacaine is approximately 3 versus 7 for lidocaine). It is important to note that patients under general anesthesia will typically present with cardiotoxicity as the first sign of local anesthetic toxicity.
Local Anesthetic Relative Potency
Procaine 1
Chloroprocaine 1
Cocaine 2
Lidocaine 2
Prilocaine 2
Mepivacaine 2
Etidocaine 6
Bupivacaine 8
Tetracaine 8

Peripheral vascular effects

Low doses of local anesthetics may cause vasoconstriction, where as, moderate or high doses result in vasodilation and decreased SVR. Cocaine is the only local anesthetic that causes vasoconstriction at all doses.

Different nerve blocks

Generally speaking, after a given injection with the same amount of local anesthetic, serum levels are highest following intercostal blocks followed by epidural/caudal blocks, followed by brachial plexus and femoral/sciatic nerve blocks, followed by subcutaneous injections. This order parallels the vascular supply of each tissue. See Keyword below.


Bupivacaine has been shown to have increased cardiotoxicity in pregnant women resulting in a decreased CC/CNS dose ration.


A side effect unique to prilocaine is methemoglobinemia at doses of at least 600mg. The liver metabolizes prilocaine to O-toluidine which oxidizes hemoglobin to methemoglobin. Methemoglobinemia is readily treated with methylene blue

Lidocaine: A Focus

Criticisms of Current Recommenations

"The current recommendations regarding maximum doses of local anesthetics presented in textbooks, or by the responsible pharmaceutical companies, are not evidence based (ie, determined by randomized and controlled studies). Rather, decisions on recommending certain maximum local anesthetic doses have been made in part by extrapolations from animal experiments, clinical experiences from the use of various doses and measurement of blood concentrations, case reports of local anesthetic toxicity, and pharmacokinetic results" {Rosenberg PH. Reg Anesth Pain Med 29: 564, 2004}

Signs and Symptoms

Lidocaine toxicity (and all local anesthetic toxicity) can cause circumoral numbness, facial tingling, restlessness, vertigo, tinnitus, slurred speech, and tonic-clonic seizures. Local anesthetics are actually CNS depressants, thus tonic-clonic seizures are thought to be caused by depression of inhibitory pathways.

Lidocaine Toxicity in Various Clinical Scenarios

Spinal Anesthesia

There is evidence that lidocaine, when used for spinal anesthesia, can be neurotoxic [Drasner Reg Anesth Pain Med 27: 576, 2002], even in single-injection doses [Drasner Anesthesiology 87: 469, 1997]

Local Injection
The maximum recommended single dose of lidocaine is 300 mg (or 500 mg when combined with epinephrine)

The American Academy of Dermatology has published guidelines for liposuction {J Am Acad Dermatol 45: 438, 2001} which indicate a maximum safe of lidocaine of 55 mg/kg; however, this remains an area of significant controversary. Some experts note that 35 mg/kg is a more reasonable limit noting that the hepatic metabolism of lidocaine by means of CYP3A4 is saturable and once saturation occurs, absorption exceeds elimination, and plasma lidocaine concentrations increase precipitously {NEJM 340: 1471, 1999}
Magnesium sulfate is used as a tocolytic and anticonvulsant in parturient patients with preeclampsa/eclampsia. Although it is a very effective medication in this setting it has severe adverse effects at supratherapeutic levels requiring regular monitoring of the patient for sign/symptoms of magnesium toxicity.
Some minor side effects of magnesium are feeling warm/flushed, nausea or vomiting, sedation, dizziness, injection site irritation, and muscle weakness. As the plasma levels increase the muscle weakness becomes more pronounced and there is a marked reduction and then loss of deep tendon reflexes eventually leading to flaccid paralysis and respiratory arrest. This is the result of both decreased release of presynaptic acetylcholine and decreased motor end-plate sensitivity to acetylcholine. This end-plate effect results in an increased sensitivity to both depolarizing and non-depolarizing muscle relaxants. NMDBs have a reduced ED50 and onset time, and increased duration of action. Muscle relaxant doses should be reduced by 25-50%. Fasciculations will likely be absent with succinylcholine administration. Magnesium has cardiovascular effects ranging from hypotension and bradycardia to complete heart block/cardiac arrest. A prolonged PR interval and widened QRS may be seen on EKG. Magnesium administration also increases the risk of post-partum hemorrhage.
mg/dL mEq/L Effect

1.8-2.4 1.2-2 Normal
4.8-9.6 4-8 Therapeutic
6-12 5-10 EKG changes (prolonged PR interval, widened QRS)
12 10 muscle weakness; loss of deep tendon reflexes
18 15 SA/AV node block; respiratory paralysis
24 20 Cardiac arrest
Neonates born to parturients receiving magnesium may have magnesium toxicity at the time of delivery resulting in flaccidity, respiratory depression, and apnea. The treatment for magnesium toxicity, in all patients, is intravenous calcium (note: there is approximately three times more calcium in calcium chloride than calcium gluconate). Loop diuretics such as furosemide increase the renal excretion of magnesium
In the resting state, the electrical potential of the inside of a nerve cell is negative with respect with the outside. When the action potential depolarizes the nerve terminal, an influx of calcium diffuse into the cell via channels. The entry of calcium facilitates the release of acetylcholine (ACh). These ACh molecules then diffuse across the synaptic cleft and bind to the nicotinic cholinergic receptors at the motor end-plate. This depolarizes the end-plate generating an action potential propagating the activation of sodium channels throughout the muscle fiber.
Neuromuscular blocking agents work at the neuromuscular junction. There are two types, depolarizing and nondepolarizing. Depolarizing muscle relaxants acts as ACh receptor agonists. They bind to the ACh receptors and generate an action potential. However, because they are not metabolized by acetylcholinesterase, the binding of this drug to the receptor is prolonged resulting in an extended depolarization of the muscle end-plate. As the muscle relaxant continues to bind to the ACh receptor, the end plate cannot repolarize, resulting in a phase I block. The ACh receptor can also undergo conformational and ionic changes after a period of time, resulting in a phase II block. Nondepolarizing muscle relaxants act as competitive antagonists. They bind to the ACh receptors but unable to induce ion channel openings. They prevent ACh from binding and thus end plate potentials do not develop.
When there is a compensatory increase in the number of ACh receptors extrajunctional isoforms of the receptor such as in certain disease states, there is an increased sensitivity to depolarizing relaxants and resistance to nondepolarizers. In states where there are fewer ACh receptors, the opposite occurs where there is resistance to the depolarizers and increased sensitivity to the nondepolarizers.

Neonates are especially prone to apnea following surgery. The younger the neonate at delivery (i.e. preterm vs. term) the more likely they are to develop apnea following a general anesthetic. Regional anesthesia decreases the risk of apnea but regional anesthesia with sedation has an increased risk of apnea, though not equal to a general anesthetic.

Ex-Premature Infant

Post-operative apnea is always a concern, however it is impossible to fully develop a monitoring protocol [Cote et. al. Anesthesiology 82: 809, 1995]. Apnea is rare after 48 weeks of conceptual age, but the incidence is not zero. The decision of whether or not to admit an ex-premature infant s/p surgery must be individualized. The most conservative approach would be to admit all infants younger than 60 weeks post-conception but this is often impractical. Note that many of these children have chronic lung conditions that last as many as ten years (mostly secondary to reactive airway disease). Hepatic and renal function, as well as developmental delay may also occur.
Cote combined data from eight prospective studies (255 patients) to develop an algorithm based on gestational age, post-conceptual age, apnea at home, size at gestational age, and anemia [Cote CJ et. al. Anesthesiology 82: 809, 1995]. Cotes data showed that the incidence of apnea following inguinal hernia repair did not fall below 5% until gestational age reached 35 weeks and post-conceptual age reached 48 weeks, and that the incidence of apnea following inguinal hernia repair did not fall below 1% until gestational age reached 32 weeks and post-conceptual age reached 56 weeks (or post-gestational 35 weeks with post-conceptual 54 weeks). Any infant that exhibits apnea, has a history of apnea, or is anemic, should not undergo outpatient surgery



The conservative approach is to monitor the child for 24 hours postoperatively as apnea may not appear within the first 6-8 hours, especially if treated with caffeine.


A treatment for apnea is caffeine (10mg/kg) or theophylline (metabolized to caffeine). Caffeine can be given 4 times daily and its effectiveness is for approximately 6 hours.
One lead of the low-output nerve stimulator is attached to a needle and the other lead is grounded somewhere on the patient. Lower current is required when a negative lead is attached to the needle. The reason for this phenomenon is that when the stimulating electrode is negative, the current flow alters the resting membrane potential adjacent to the needle, producing an area of depolarization which then spreads across the nerve. When the electrode adjacent to the nerve is an anode(positive), the current causes an are hyperpolarization adjacent to the needle and a ring of depolarization distal to the needle tip. This arrangement is less efficient in propagating the stimulus. The needles used are ins.ulated and only allow current flow at the tip so nerve localization is precise. Muscle contraction occurs and is of increased intensity as the needle approaches the nerve and diminishes and the needle moves away from the nerve. Optimal needle positioning produces evoked contrations with 0.5 mA or less. The evoked contraction rapidly fades after injection of 1-2 cc of local anesthetic.
Ability to electrically stimulate a peripheral nerve depends upon many variables: 1) conductive area at the electrode, 2) electrical impedance, 3) electrode-to-nerve distance, 4) current flow (amperage), and 5) pulse duration. Electrode conductive area follows the equation R-pL/A, where R-electrical resistance, p- tissue resistivity, L-electrode-to-nerve distance, and A-electrode conductive area. Therefore resistance varies to the inverse of the electrode's conductive area Tissue electrical impedance varies as a function of the tissue composition. In general, tissues with higher lipid content have higher impedances. Modern electrical nerve stimulators are designed to keep current constant, in spite of varying impedance. The electrode-to-nerve distance has the most influence on the ability to elicit a motor response to electrical stimulation. This is governed by Coulomb's law: E=K(Q/r2) where E-required stimulating charge, K-constant, Q=minimal required stimulating current, and r-electrode-to-nerve distance. Therefore, ability to stimulate the nerve at low amperage (e.g. <0.5 mA), indicates an extremely close position to the nerve. Similarly, increasing current flow (amperage) increases the ability to stimulate the nerve at a distance. Increasing pulse duration increases the flow of electrons during a current pulse at any given amperage. Therefore, reducing pulse duration to very short times (e.g. 0.1 or 0.05 ms) diminishes current dispersion, requiring the needle tip to be extremely close to the nerve to elicit a motor response.
After parenteral injection, sodium nitroprusside enters red blood cells, where it receives an electron from the iron (Fe2+) of oxyhemoglobin. This nonenzymatic electron transfer results in an unstable nitroprusside radical and methemoglobin (Hgb Fe3+). The former moiety spontaneously decomposes into five cyanide ions and the active nitroso (NO) group. The cyanide ions can be involved in one of three possible reactions: binding to methemoglobin to form cyanmethemoglobin; undergoing a reaction in the liver and kidney catalyzed by the enzyme rhodanase (thiosulfate + cyanide; or binding to tissue cytochrome oxidase, which interferes with normal oxygen utilization. Its principal toxicity results from this inactivation of cytochrome oxidase (at cytochrome a3), thus uncoupling mitochondrial oxidative phosphorylation and inhibiting cellular respiration, even in the presence of adequate oxygen stores. Cellular metabolism shifts from aerobic to anaerobic, with the consequent production of lactic acid. Consequently, the tissues with the highest oxygen requirements (brain and heart) are the most profoundly affected by acute cyanide poisoning.
The last of the above reactions is responsible for the development of acute cyanide toxicity, characterized by metabolic acidosis, cardiac arrhythmias, tachycardia, hypertension, CNS dysfunction and increased venous oxygen content (as a result of the inability to utilize oxygen). Another early sign of cyanide toxicity is the acute resistance to the hypotensive effects of increasing doses of sodium nitroprusside (tachyphylaxis).
Thiocyanate is slowly cleared by the kidney. Thiocyanate toxicity is associated with long-term infusions (usually more than 6 days) in patients simultaneously treated with sodium thiosulfate. It may develop with shorter infusions in patients with renal insufficiency. Manifestations include abdominal pain, weakness, tinnitus, vomiting, tremor, agitation, disorientation, progressing to lethargy, seizures and coma in severe cases. The risk of cyanide toxicity is not increased by renal failure, however. Methemoglobinemia from excessive doses of sodium nitroprusside or sodium nitrate can be treated with methylene blue, which reduces methemoglobin to hemoglobin.
Cyanide toxicity is a clinical diagnosis, because cyanide blood concentrations are usually not available in time to help treatment of acute toxicity. Monitor serum electrolytes, serum lactate, arterial blood gases (looking for metabolic acidosis) and mixed venous oxygen saturation (which would be elevated) if cyanide toxicity is a concern. Monitor thiocyanate levels in patients with prolonged infusions, those with renal insufficiency and those receiving simultaneous thiosulfate infusions.

Afferent Limb

Trigeminal Nerve (ciliary ganglion to ophthalmic division of trigeminal nerve to gasserian ganglion to the main trigeminal sensory nucleus). Also afferent tracts from maxillary and mandibular divisions of trigeminal nerve have been documented.

Efferent Limb

Vagus Nerve (afferents synapse with visceral motor nucleus of vagus nerve located in the reticular formation and efferents travel to the heart and decrease output from the sinoatrial node).

Triggering Stimuli

Triggered by traction on the extraocular muscles (especially medial rectus), direct pressure on the globe, ocular manipulation, ocular pain.
Also triggered by retrobulbar block, ocular trauma, manipulation of tissue in orbital apex after enulcleation.
Reflex fatigues with repeated stimulation.


Most commonly leads to sinus bradycardia, but may also lead to junctional rhythm, ectopic beats, atrioventricular block, ventricular tachycardia, and asystole.

Risk Factors

Neonates and infants undergoing strabismus surgery.
Hypoxia, hypercarbia, acidosis, and light anesthesia can worsen the severity of the OCR.

Intraoperative Management

May occur during both local and general anesthesia.
The retrobulbar block may prevent arrythmias by blocking the afferent limb, but may also stimulate the OCR with local injection.
Notify the surgeon to stop orbital stimulation.
Optimize oxygenation and ventilation. Prevent light anesthesia.
If arrythmia/bradycardia does not resolve consider atropine 20 mcg/kg IV (or glycopyrrolate).

Postoperative Management

The OCR may occur as much as 1.5 hours after a retrobulbar
Retrobulbar hemorrhage can result in delayed OCR as persistent bleeding gradually increases periocular pressure.
Monitor carefully in the PACU if suspected retrobulbar hemorrhage.
Odds: the ratio of the probability that an event will occur versus the probability that the event will not occur, or probability / (1-probability). For example, if you are normally on call 2 out of 7 days in a week, then the odds of you being on call on a certain day of the week is [(2/7)/(5/7)] = 0.40. Note that this differs from risk (or probability): the risk of being on call is equal to (# of call days )/ (total # of days in a week) = 2/7 = 0.285.
Odds ratio: a ratio of odds; in general they refer to the ratio of the odds of an event occurring in the exposed group versus the unexposed group. For example, lets say you want to compare the differences between PONV in women undergoing total abdominal hysterectomy receiving Drug X and those who do not, controlling for all other variables. You compare 100 different cases.
PONV No PONV Total # cases
Drug X 20 80 100
No Drug X 40 60 100

The odds of PONV having received Drug X is 20/80 or 0.25.
The odds of PONV without Drug X is 40/60 or 0.67.
Therefore, the odds ratio for PONV with Drug X vs. PONV without Drug X is 0.25/0.67 or 0.37.
The probability of PONV having received Drug X is 20/100 or 0.20.
The probability of PONV with no Drug X is 40/100 or 0.40.
Therefore, the relative risk for PONV with Drug X vs. PONV without Drug X is 0.20/0.40 = 0.5.
Odds ratios are used instead of relative risk for case-control studies. To be able to calculate relative risk, we compare the risks of outcome in different groups. In case-control studies, we already know what the outcome is and we separate groups into those with the outcome vs. controls. Our objective in such studies is to try to identify risk factors that are more strongly associated with one group than the other; thus, risk and therefore relative risk cannot be calculated from these studies. We use odds ratios instead, which can give us a measure of how strongly the risk factor is associated with the outcome.
For example, if we suspect that Drug X is associated with less PONV, then we could take 100 patients with out PONV to 100 patients with PONV and see how many in each group received Drug X. Since we select the outcome in both groups, we cannot calculate the relative chance (risk) of less PONV in the Drug X group because we do not know the chance of no PONV in the general population (who are not Drug X users), and therefore we have no comparison group. However, we can compare the odds of the use of Drug X in those who had no PONV vs. those who had PONV by calculating the odds ratio. So for example:
Drug X No Drug X
No PONV 40 60
PONV 20 80

Odds of Drug X use in those without PONV = 40/60 = 0.67.
Odds of Drug X in those with PONV = 20/80 = 0.25.
Odds ratio of Drug X without PONV vs. with PONV = 0.67/0.25 = 2.7.
You can say that the odds of use of Drug X were 2.7 times greater in non PONV patients vs. PONV patients in this study. This implies an association between use of Drug X and preventing PONV. However, many other things could have contributed to this apparent association: chance alone could have accounted for this difference (helpful to know the 95% CI for the OR); the sample selected for both groups could have been skewed to favor Drug X use in the non-PONV group.
Odds = Probability / (1-probability).
Odds ratio (OR) = ratio of odds of event occurring in exposed vs. unexposed group.
Odds ratio are used to estimate how strongly a variable is associated with the outcome of interest; in prospective trials, it is simply a different way of expressing this association than relative risk.
In case-control studies, we separate groups by their outcomes and retrospectively try to identify variables that appear to be more associated with one outcome than another. Therefore, we cannot deduce a calculable risk because the outcome has already been predetermined. We therefore use odds ratios instead to estimate the strength of association of the variable with the outcome of interest.
In a prospective study, either a Randomized Clinical Trial or a Cohort study, use Relative Risk
Organophosphate compounds are used as commercial insecticides (isulfoton, phorate, dimethoate, ciodrin, dichlorvos, dioxathion, ruelene, carbophenothion, supona, TEPP, EPN, HETP, parathion, malathion, ronnel, coumaphos, diazinon, trichlorfon, paraoxon, potasan, dimefox, mipafox, schradan, sevin, and dimetonor) in chemical warfare (nerve gases such as tabun and sarin) and are applied as aerosols or dusts. They can be rapidly absorbed through skin and mucous membranes or by inhalation.
Organophosphates are also used in opthomology - echothiopate is used to treat glaucoma.
Organophosphate mechanism of toxicity:
• Anticholinesterase inhibitors that form a stable irreversible covalent bond to the enzyme.
• Occurs at cholinergic junctions of the nervous system including postganglionic parasympathetic junctions (sites of muscarinic activity), autonomic ganglia and the neuromuscular junctions (sites of nicotinic activity) and certain synapses in the CNS.
• Acetylcholine is the neurohumoral mediator at the cholinergic junctions junctions. Since acetylcholinesterase is the enzyme that degrades acetylcholine following stimulation of a nerve, by inhibiting acetylcholinesterase, organophosphates allows acetylcholine to accumulate and result in initial excessive stimulation followed by depression.

Signs and Symptoms

Muscarinic signs

(SLUDGE) salivation, lacrimation, urination, diaphoresis, gastrointestinal upset, emesis and progressing to bronchospasm, bronchorrhea, blurred vision, bradycardia or tachycardia, hypotension, confusion, and shock.

Nicotinic effects

Skeletal muscle initially exhibits fasciculation (involuntary irregular, violent muscle contractions) followed by the inability to repolarize cell membranes resulting in weakness and paralysis. Severe reactions can lead to ventilatory failure and death (cholinergic crisis).


• Termination of the exposure including removing all soiled clothing. Gently clense with soap and water to hydrolyze organophosphate solutions.
• Airway control and adequate oxygenation. Intubation may be necessary in cases of respiratory distress due to laryngospasm, bronchospasm, bronchorrhea, or seizures. Immediate aggressive use of atropine may eliminate the need for intubation. Succinylcholine should be avoided because it is degraded by AChE and may result in prolonged paralysis.
• Continuous cardiac monitoring and pulse oximetry should be established; an ECG should be performed. Torsades de Pointes should be treated in the standard manner. The use of intravenous magnesium sulfate has been reported as beneficial for organophosphate toxicity. The mechanism of action may involve acetylcholine antagonism or ventricular membrane stabilization.
• Irrigate the eyes of patients who have had ocular exposure using isotonic sodium chloride solution or lactated Ringer's solution. Morgan lenses can be used for eye irrigation.

Pharmacologic Treatment

• Atropine - The endpoint for atropine is dried pulmonary secretions and adequate oxygenation. Tachycardia and mydriasis must not be used to limit or to stop subsequent doses of atropine. The main concern with OP toxicity is respiratory failure from excessive airway secretions. Start with a 1-2 mg IV bolus, repeat q3-5min prn for desire effects (drying of pulmonary secretions and adequate oxygenation). Consider doubling each subsequent dose for rapid control of patients in severe respiratory distress. An atropine drip titrated to the above endpoints can be initiated until the patient's condition is stabilized.
• Pralidoxime - Nucleophilic agent that reactivates the phosphorylated AChE by binding to the OP molecule. Used as an antidote to reverse muscle paralysis resulting from OP AChE pesticide poisoning but is not effective once the OP compound has bound AChE irreversibly (aged). Current recommendation is administration within 48 h of OP poisoning. Because it does not significantly relieve depression of respiratory center or decrease muscarinic effects of AChE poisoning, administer atropine concomitantly to block these effects of OP poisoning. Start with 1-2 g (20-40 mg/kg) IV in 100 mL isotonic sodium chloride over 15-30 min; repeat in 1 h if muscle weakness is not relieved; then repeat q3-8h if signs of poisoning recur; other dosing regimens have been used, including continuous drip.
Mechanism of hypoxia during one lung ventilation

• In the lateral decubitus position the dependent lung is under ventilated as it is compressed by the compression of the abdominal contents and the weight of the mediastinum. The nondependent lung is relatively over ventilated secondary to increased compliance as the corresponding hemithorax is opened.
• There is also a difference in perfusion in the lateral decubitus position. Perfusion is higher in the dependent lung secondary to the effects of gravity. This mismatch of ventilation and perfusion contributes to hypoxia while in the lateral decubitus position.
• During one lung ventilation in the lateral decubitus position there is mixing of unoxygenated blood from the collapsed nondependent lung with oxygenated blood from the still-ventilated depended lung widening the P(A-a) gradient and leading do hypoxemia.

Factors Affecting oxygenation during one lung ventilation

• The degree of HPV (hypoxic pulmonary vasoconstriction). HPV is an adaptive mechanism unique to the pulmonary circulation that allows redirection of blood flow to alveoli with higher oxygen tension, thereby reducing ventilation/perfusion mismatch. HPV has been shown to be of greatest benefit when 30-70% of the lung is made hypoxic.
• Factors known to inhibit HPV and worsen right-to-left shunting and oxygenation include: (1) most systemic vasodilators (nitroglycerin, nitroprusside, dobutamine, calcium channel antagonists, beta-2 receptor agonists), (2) inhalational volatile anesthetics, (3) very high or very low pulmonary artery pressures, (4) hypocapnia, (5) high or very low mixed venous PO2, (6) pulmonary infection.
• Factors that decrease blood flow to the ventilated lung can counteract the effects of HPV and worsen oxygenation by indirectly directing blood to the collapsed unventilated lung: (1) high mean airway pressures in the ventilated lung secondary to high levels of PEEP, hyperventilation, or high peak inspiratory pressures, (2) a low FIO2 leading to HPV in the ventilated lung, (3) vasoconstrictors (dopamine, epinephrine, phenylephrine) that will vasoconstric normoxic vessels greater than hypoxic ones, (4) intrinsic PEEP from inadequate expiratory times.

Mechanisms to improve oxygenation during one lung ventilation

• Adequate FIO2. An FIO2 of 1.0 has been shown to help protect against hypoxemia and is associated with PaO2 values from 150-250 mm Hg during OLV. A high FIO2 also promotes vasodilation in the dependent, ventilated lung to accept blood flow redistribution from the hypoxic nondependent lung. However, high FIO2 may contribute to absorption atelectasis, oxygen toxicity, and bleomycin induced injury. So maintaining an adequate but not excessive FIO2 is recommended.
• Most advise protective lung ventilation strategies with smaller tidal volumes of 6-8 ml/kg. Very high tidal volumes can lead to increased peak and mean airway pressures and PVR that may shunt blood flow to the nonventilated lung and may also contribute to barotrauma. However, very low tidal volumes may cause decreased FRC and atelectasis in the dependent lung which should also be avoided.
• Adequate ventilation. The respiratory rate should be adjusted to maintain a normal PaCO2 of 40 mm Hg. This may require increasing the respiratory rate if tidal volumes are reduced. Hypocarbia can cause vasodilation that would inhibit HPV. Hypercarbia can cause increases in PVR to the worsening perfusion to the ventilated lung.

Interventions once a patient undergoing OLV develops hypoxia:

• Increase FIO2.
• Recheck positioning of double lumen tube for correct placement using fiberoptic bronchoschope.
• Suction both lumens of double lumen tube for secretions or mucous plugs
• May need to notify surgeons to stop and return to two lung ventilation. Or at least ask for periodic reinflation/recruitment maneuvers of the nondependent collapsed lung.
• Consider CPAP (5-10 cm H2O) to the collapsed, nondependent lung. This maintains patency of the nondependent alveoli allowing gas exchange to occur and will divert blood away from the collapsed lung.
• Consider PEEP (5-10 cm H2O) to the ventilated, dependent lung. This can increase FRC and improve gas exchange in the dependent lung. However, high levels can increase PVR and shunt blood flow to the nondependent lung.
• Ultimately may need to ligate or clamp the ipsilateral pulmonary artery (i.e. during pneumonectomy) so that all blood flow directed to ventilated lung.
• Last resort (as in patient undergoing a lung transplant) may need to go on cardiopulmonary bypass to improve oxygenation.
The oxyhemoglobin dissociation curve shows the relationship between the hemoglobin saturation (SO2) at different oxygen tensions (PO2).
The P50 is the oxygen tension at which hemoglobin is 50% saturated. The normal P50 is 26.7 mm Hg.
Shifting the curve to the left or right has little effect on the SO2 in the normal range where the curve is fairly horizontal; a much greater effect is seen for values on the steeper part of the curve.

Shifting of the oxyhemoglobin dissociation curve

• A rightward shift increases P50 and lowers hemoglobin's affinity for oxygen, thus displacing oxygen from hemoglobin and releasing it to the tissues.
• A leftward shift decreases P50 and increases hemoglobin's affinity for oxygen, thus reducing its availability to the tissues.

Factors affecting the oxyhemoglobin dissociation curve

• A decrease in pH shifts the standard curve to the right, while an increase shifts it to the left. This is known as the Bohr effect.
• Carbon dioxide affects the curve in two ways: first, it influences intracellular pH (the Bohr effect), and second, CO2 accumulation causes carbamino compounds to be generated through chemical interactions. Increasing CO2 has the effect of shifting the curve to the right and decreasing shifts the curve to the left.
• 2,3-diphosphoglycerate is created in erythrocytes during glycolysis. The production of 2,3-DPG is likely an important adaptive mechanism, because the production increases for several conditions in the presence of diminished peripheral tissue O2 availability, such as hypoxemia, chronic lung disease, anemia, and congestive heart failure, among others. High levels of 2,3-DPG shift the curve to the right, while low levels of 2,3-DPG cause a leftward shift, seen in states such as septic shock and hypophosphatemia.
• Temperature does not have so dramatic effect as the previous factors, but hyperthermia causes a rightward shift, while hypothermia causes a leftward shift.
• Hemoglobin binds with carbon monoxide 240 times more readily than with oxygen, and therefore the presence of carbon monoxide can interfere with the hemoglobin's acquisition of oxygen. In addition to lowering the potential for hemoglobin to bind to oxygen, carbon monoxide also has the effect of shifting the curve to the left. With an increased level of carbon monoxide, a person can suffer from severe hypoxemia while maintaining a normal PO2.
• Methemoglobinemia causes a leftward shift in the curve.
• Fetal hemoglobin (HbF) is structurally different from normal hemoglobin (Hb). The fetal dissociation curve is shifted to the left relative to the curve for the normal adult. Typically, fetal arterial oxygen pressures are low, and hence the leftward shift enhances the placental uptake of oxygen.
Components of Oxygen in Blood

Oxygen delivery to the periphery depends on the oxygen content of blood and tissue blood flow. The oxygen content of blood has two components: oxygen bound to hemoglobin and oxygen dissolved in plasma. Oxygen bound to hemoglobin is generally the much greater contributor to oxygen content. (One notable exception when oxygen dissolved in plasma is a major contributor is carbon monoxide poisoning: hemoglobin has 230 times greater affinity for carbon monoxide than oxygen.) Tissue blood flow is equal to cardiac output.

Oxygen Delivery

Therefore, oxygen delivery can be calculated:
DO2 = CaO2 x CO

Oxygen Content

Oxygen content can be calculated as: CO2 = (1.39 x Hb x O2Sat/100) + (0.003 x PO2)

Oxygen Consumption

Oxygen consumption can be calculated by the Fick principle as the difference between arterial and venous oxygen content: VO2 = CO x (CaO2 - CvO2)

Oxygen Dissociation

The oxyhemoglobin dissociation curve relates oxygen saturation at varying oxygen tensions. The oxyhemoglobin dissociation curve is S shaped, reflecting subunit cooperativity. Using the dissociation curve and the equations above it is possible to calculate oxygen delivery and consumption.
(A decent dissociation curve)
Under normal conditions, the oxygen tension of arterial blood is 95 mmHg (oxygen tension at the pulmonary capillaries is 104 mmHg, but pulmonary capillary blood then mixes with bronchial blood to reach an arterial oxygen tension of 95 mmHg), and is fully saturated. Using the oxygen content equation and a hemoglobin concentration of 15 g/dL the amount of oxygen this blood caries is 21.14 mL/dL. If cardiac output is 5 L/min, then total oxygen delivery is 1057 mL/min. This blood then travels to the periphery where the PO2 is 40 mmHg. From the oxyhemoglobin dissociation curve, it is evident that a PO2 of 40 is equal to an oxygen saturation of 75%. Using the equation for oxygen content again, the amount of oxygen in venous blood is 15.76 mL/dL. Using the Fick principle, oxygen consumption is calculated as 269 mL/min
The S shape of the oxyhemoglobin dissociation curve allows blood to unload oxygen where it is needed most, thus in the periphery small changes in the partial pressure of O2 lead to large changes in the % saturation.

Shifts in the Dissociation Curve

Shifts of the oxyhemoglobin dissociation curve result from changes in pH, temperature, 2,3-DPG, type of hemoglobin, and also interestingly: some inhaled anesthetics cause a rightward shift {Kambam, LJ. Isoflurane and oxy-hemoglobin dissociation. Anesthesiology 1982; 57:A496}

Leftward Shifts (increased release)
Leftward shifts are caused by alkalosis, decreased temperature, and decreased 2,3-DPG

Rightward Shifts (increased binding)
Rightward shifts are caused by acidosis (Bohr Effect), increased temperature, increased 2,3-DPG, and inhaled anesthetics.

Bohr Effect
The Bohr effect is the shift of the oxyhemoglobin dissociation curve due to CO2 entering and leaving the blood at the periphery and the lungs. As CO2 enters the blood at the periphery, the pH decreases and the curve shifts to the right facilitating unloading of oxygen, whereas the reverse is true in the lungs. 2,3-DPG decreases the affinity of hemoglobin for oxygen. 2,3-DPG in red cells is increased by anemia and high altitude.
As a rough guide: blood unloads about 25% of delivered oxygen to the periphery,
97% of O2 is transported bound to hemoglobin, 3% is dissolved in plasma.
Solutions: Many solutions are commonly used. Electrolytes can be added to meet the patient's needs. Patients who have renal insufficiency and are not receiving dialysis or who have liver failure require solutions with reduced protein content and a high percentage of essential amino acids.
-For patients with heart or kidney failure, volume (liquid) intake must be limited. -For patients with respiratory failure, a lipid emulsion must provide most of non-protein calories to minimize CO2 production by carbohydrate metabolism. -Neonates require lower dextrose concentrations (17 to 18%).
Beginning TPN administration: Require CVP line Solution is started slowly at 50% of the calculated requirements, using 5% dextrose to make up the balance of fluid. Energy and nitrogen should be given simultaneously. The amount of regular insulin given (added directly to the TPN solution) depends on the blood glucose level; if the level is normal and the final solution contains the usual 25% dextrose concentration, the usual starting dose is 5 to 10 units of regular insulin

Complications: With close monitoring by a nutrition team, the complication rate may be < 5%..
1.Glucose abnormalities are common. a. Hyperglycemia can be avoided by monitoring blood glucose b. Hypoglycemia can be precipitated by suddenly discontinuing constant concentrated dextrose infusions. Treatment, depending on the degree of hypoglycemia, may consist of 50% dextrose IV or infusion of 5 or 10% dextrose for 24 h before resuming TPN via the central venous catheter.
2.Abnormalities of serum electrolytes and minerals Elevated BUN may reflect dehydration, which can be corrected by giving free water as 5% dextrose via a peripheral vein.
3. Volume overload
4. Metabolic bone disease, or bone demineralization (osteoporosis or osteomalacia), develops in some patients receiving TPN for > 3 mo. The mechanism is unknown
5. Adverse reactions to lipid emulsions (eg, dyspnea, cutaneous allergic reactions, nausea, headache, back pain, sweating, dizziness)
-are uncommon
-can occur if lipids are given at > 1.0 kcal/ kg/h.
6. Hepatic complications - liver dysfunction, painful hepatomegaly, and hyperammonemia. - Contributing factors probably include cholestasis and inflammation. Progressive fibrosis occasionally develops. Reducing protein delivery may help. Painful hepatomegaly suggests fat accumulation; carbohydrate delivery should be reduced. Hyperammonemia can develop in infants. Signs include lethargy, twitching, and generalized seizures. Correction consists of arginine
7.Gallbladder complications include cholelithiasis, gallbladder sludge, and cholecystitis. These complications can be caused or worsened by prolonged gallbladder stasis. Stimulating contraction by providing about 20 to 30% of calories as fat and stopping glucose infusion several hours a day is helpful. Oral or enteral intake also helps. Treatment with metronidazole
definition: presence of uterine contractions of sufficient frequency and intensity that causes progressive effacement and dilation of the cervix prior to term gestation (between 20 and 37 wk) - the earlier it occurs, the less the odds of survival of the fetus
What exactly causes it? Nobody really knows, but there are certain things that can predispose pts to it
RF's - decidual hemorrhage o abruption o mechanical factors such as uterine overdistension from multiple gestation or polyhydramnios), - cervical incompetence/short cervix o trauma o cone biopsy - uterine distortion: fibroids, müllerian duct abnormalities - cervical inflammation/infection - maternal inflammation/fever : UTI - nonwhite race, - extremes of maternal age (<17 y or >35 y), - low socioeconomic status - low prepregnancy weight. - hormonal changes (eg, mediated by maternal or fetal stress) - uteroplacental insufficiency o HTN o IDDM o IVDU o Tobacco/ETOH.
How to assess pt? -check integrity of cervix w/ serial digital exams -transvaginal US of cervix -Labs: GC/CL, RPR, APTT, whiff test for BV, lupus anticoagulant -Hysterosalpingogram(preconceptual) Management 1. TOCOLYSIS a. MgSO4 -check CBC, follow urine output in mom, -watch Mom for toxicity: respiratory depression or even cardiac arrest, flushing, nausea, headache, drowsiness, and blurred vision -watch BABY for toxicity: it CROSSES PLACENTA, respiratory and motor depression of neonate - dc magnesium sulfate therapy after 48 hours in most patients unless the gestational age is less than 28 weeks when a gain of an additional 3-4 days may significantly reduce neonatal morbidity and mortality
b. INDOMETHACIN -first-line tocolytic for the pregnant patient in early preterm labor (<30 wk) or preterm labor associated with polyhydramnios. - PG inhibitor - cross placenta and can impair fetal renal function,oligohydramnios - can cause fetal ductus arteriosus to close after 32weeks, so it is not usually given after that - if fetal anuria persistm increases odds of fetal DEMISE
C. NIFEDIPINE -ccb, inhibits uterine contraction - SFx: maternal tachycardia, palpitations, flushing, headaches, dizziness, and nausea
-beta agonists are no longer used b'c of adverse maternal and fetal effects: tachycardia, pulmonary edema,palpitations, hyperglycemia
Tocolytics : side effects
What are tocolytics? Rx which stop labor contractions Why are they used? Mainly to buy time to allow fetal lung maturity, stabilize mom/fetus Does this requiring monitoring? It depends; for certain drugs, yes especially for BP and HR in mom
CONTRAINDICATIONS to using TOCO's 1. fetal death/distress/demise 2. IUGR 3. fetus older than 37 wks 4. chorioamnionitis 5. cervical dilation of 4 cm 6. MOM has : PIH, eclampsia, active bleeding, cardiac dz
The RX a. MgSO4: blocks neuromuscular transmission and prevents release of ACH i. Muscle weakness ii. Respiratory depression iii. Low bp, tachycardia
b. BETA agonists: MOA relax smooth muscle a. RITODRINE: inc HR, hyperglycemia, inc BP, pulmonary edema b. TERBUTALINE: inc HR, hyperglycemia, inc BP, pulmonary edema, fetal tachycardia and hypoglycemia c. NIFEDIPINE: constipation, HA, hypotension, lightheadedness d. INDOMETHACIN: PG inhibitor--> inh renin-->inhibit aldosterone--> hyperNatremia, hyperKalemia, edema, HTN, in more severe cases: renal failure/nephritis
Pregnancy is known to be a state of "physiologic anemia" due to the disproportionate increase in plasma volume relative to red blood cell volume. This increase in blood volume is necessary to supply the fetus and placenta and begins very early in pregnancy. The plasma volume is already increased by 10-15% at 6 weeks of gestation and increases to 30-50% greater than pre-pregnancy volume by term. The red cell volume, in contrast to this, is only increased by 20-30% at term. This increase is prompted by a higher level of erythropoietin. Thus, despite a higher red cell volume, the hematocrit will fall during pregnancy. The greatest time of disproportion between the plasma volume and red cell volume changes will be at 28-36 weeks. Anemia during pregnancy is defined differently than someone who is not pregnant. To be considered anemic during pregnancy the hemoglobin needs to be less than 11g/dL in the 1st or 3rd trimesters.
Other hematologic changes in pregnancy include an increase in white blood cells, particularly neutrophils, and a slight decrease in platelet count. The average white cell count during pregnancy is about 9-15k. It increases up to term, and can go as high as 25k during labor. Platelets, on the other hand, remain in the normal non-pregnant range but mean platelet counts may be slightly lower than in healthy non-pregnant women. The "low normal" range is considered to be about 106-120k.
There are also many changes in blood chemistries during pregnancy as well, mostly by the same dilutional mechanism as the hematocrit. Important among these are albumin, total protein and creatinine. Both albumin and total protein decrease by about 1g/dL by mid-pregnancy and creatinine decreases by about 0.3mg/dL. For other chemistry changes, see chart (below).
Important Laboratory Values in Pregnancy

Test Nonpregnant Range Pregnant Effect Gestational Timing
Serum chemistries
3.5-4.8 g/dL 1 g/dL By midpregnancy
Calcium 9.0-10.3 mg/dL 10% Falls gradually
Chloride 95-105 mEq/L No change
Cholesterol 200-240 mg/dL 50% Progressive
Creatinine 0.6-1.1 mg/dL 0.3 g/dL By midpregnancy
Fibrinogen 200-400 mg/dL 600 mg/dL By term
Glucose, fasting
65-105 mg/dL 10% Gradual fall
Potassium (plasma) 3.5-4.5 mEq/L 0.2-0.3 mEq/L By midpregnancy
Protein (total) 6.5-8.5 g/dL 1 g/dL By midpregnancy
Sodium 135-145 mEq/L 2-4 mEq/L By midpregnancy
Urea nitrogen 12-30 mg/dL 50% First trimester
Uric acid 3.5-8 mg/dL 33% First trimester
Urine Chemistry
Creatinine 15-25 mg/kg/d No change
Protein Up to 150 mg/d Up to 250-300 mg/day By midpregnancy
Creatinine clearance 90-130 mL/min/1.73 m2
40-50% By 16 weeks
Serum Enzymes
Alkaline phosphatase 30-120 U/L 3- to 5-fold By 20 weeks
Amylase 60-180 U/L Controversial
Creatinine phosphokinase 26-140 U/L 2- to 4-fold After labor (MB bands as well)
Lipase 10-140 U/L No change
Aspartate aminotransferase (AST) 5-35 mU/mL No change
alanine aminotransferase (ALT) 5-35 mU/mL No change
Formed Elements of Blood
Hematocrit 36-46% 4-7% Nadir at 30-34 weeks
Hemoglobin 12-16 g/dL 1.4-2.0 g/dL Nadir at 30-34 weeks
Leukocyte count 4.8-10.8 x 103/mm3
3.5 x 103/mm3
Gradual increase to term, as high as 25 x 103/mm3 in labor

Platelets 150-400 x 103/mm3
- there is an increased propensity for tachydysrhythmias (usually SUPRAventricular) during pregnancy - WHY? 1. increases hyperdynamic circulation; some women become more aware of HR changes, skipped beats
What is the mechanism? 1. change in Ca ion channel conduction 2. increase in cardiac size(atrial stretch, increased EDV) 3. change in autonomic tone 4. hormonal changes
- dysrhythmias are MORE common if pt has underlying structural cardiac dz(ie VSD, ASD,) or unabnormal conduction pathway(WPW), Long QT syndrome) - SVT w/ reentry is more common in pregnancy
Sx: Palpitations,dizziness ,Lightheadedness,DOE,syncope

Fetus: vulnerable to effects to maternal dysrhythmias and rx of it as well
Which Supraventricular dysrhythmias? PAD>nonconducted P waves>ectopic atrial tachycardia> WAP> sinus pause> retrograde P waves -overall though, sinus tach/brady are more common than SVdysrhythmias
Dx -hx, PE - ekg, holter - cxr( not routine, but can be done w/ fetal shield) -echo -cardiac cath(caveat: increase in rads xposure to fetus)
Are there Hd changes? Is the dysrhythmia sustained?
- if the answer is Y to either above, then TREAT, otherwise reassure
Dysrhymias 1. PSVT -HR 140 to 220 - increased p waves RX: slow AV conduction 1. vagal maneuvers( can terminate 20 to 25% of reentry svt): carotid massage,sinus massage, valsalva, gagging 2. drugs: adenosine, CCB(verapamil>diltiazem), Bblockers(not as effective as ccb) 3. cardioversion w/ 50J, usually done for HD instability 4. anticholinergic rx : edrophonium 5. rapid atrial pacing: in refractory cases
2. PAD a. Skipped beats b. VERY common c. Rx: reassure pt, avoid caffeine 3. A flutter a. Types i. Type One: AR 300, VR 150 ii. Type Two: AR >350 b. Rx : rapid atrial pacing(type one -Drugs(type two) -cardioversion
4. A fib - AR 350 to 600 - VR 100 to 200 - Irregular, no p waves - Rx: slow VR w/ drugs and prevent recurrence w/ rx
Review of Documented Cases: Habib et. al.

The FDA warning is based on 10 reported cases from 1997-2002 [Habib et. al. Anesthesia and Analgesia 96: 1377, 2003] - these 10 cases were all with 1.25 mg or less, but in none of them could a definitive cause-effect relationship be described, and in five of them there were substantial confounding factors. Assuming that droperidol sales averaged 11 MM ampules per year, and that these events were truly related to droperidol, the authors estimated that the incidence of associated events was 1:150,000.

Smaller Studies

Charbit et. al.

A small study compared QT prolongation with droperidol alone, ondansetron alone, and both combined. Both droperidol and ondansetron significantly prolonged QT interval as expected (droperidol>ondansetron), but when combined did not prolong QT significantly more than droperidol alone {Charbit et. al. Anesthesiology 109: 206, 2008}

Chu et. al.

Another small study (400 total patients, randomized, prospective, controlled) studied haloperidol plus dexamethasone on PONV versus placebo and droperidol alone in vaginal hysterectomy patients. Haloperidol plus dexamethasone produced the greatest reduction in PONV when compared to placebo, either drug alone, or droperidol alone. There was no difference in QT prolongation in the haloperidol plus dexamethasone vs. droperidol alone {Chu et. al. Anesth Analg 106: 1402, 2008}

Nuttal et. al.

Lastly, a retrospective study in Anesthesiology studied whether or not droperidol (low dose) administration increased the incidence of torsades during a 3 year period before and after the FDA placed the black box warning on the drug. They determined that there was no change in the incidence of torsades with the use of low dose droperidol versus none used. The incidence of torsades in droperidol exposure was found to be 1:16791, and the one incident may not have actually been due to droperidol {Nuttal et. al. Anesthesiology 107: 531, 2007}

5HT-3 antagonists

Known to cause QT prolongation, ex. ondansetron (Zofran), granisetron (Kytril), and dolasetron (Anzemet). These drugs have been reported to widen the QRS complex and prolong JT, QT, and PR intervals. Dolasetron (1.2-4mg/kg IV) can prolong QRS by 5-20% whereas Ondansetron has been shown to increase QT and JT intervals by an average of 2-5%. The QRS widening is likely due to blockade of sodium channels while the QT prolongation is caused by blocking potassium channels. In a study done with human myocytes, all of the drugs in this class where shown to block human cardiac Na+ channels probably by interacting with the inactivated state. This could lead to clinically relevant blockade, especially with high heart rates or depolarized/ischemic tissue, potentially leading to ventricular arrhythmias. The rank order of potency for Na+ blockade is granisetron>dolasetron>ondansetron. For blockade of the K+ channel (QT prolongation), the order of potency is ondansetron>granisetron>dolasetron

PONV Guidelines

The Guidelines state that only moderate/high risk patients should receive PONV prophylaxis, and that these patients should receive combination therapy. Interesting, the ambulatory surgery Guidelines suggest haldol, which at 0.5-2 mg IM or IV has been shown on meta-analysis to reduce PONV with a NNT of 4-6 [Buttner et. al. Anesthesiology 101: 1454, 2004], however it does cause QTc prolongation as well. If not for the black box warning, the committee would have made droperidol the first choice.

Radicular pain is sharp, lancinating, radiating pain, often shooting from the low back down into the lower extremity in a radicular distribution. It is the result of a nerve root lesion or of inflammation. Clinically, it can be associated with pain, dermatomal hypesthesia, weakness of muscle groups innervated by the involved nerve roots, diminished deep tendon reflexes, and positive straight-leg raising tests. Inflammation at the epidural space and nerve roots provoked by a herniated disk is a significant factor in causing radicular pain. Other mechanisms include compression of the nerve root vasculature and irritation of dorsal root ganglia from spinal stenosis.
Epidural steroid injections (ESIs) can deliver steroids in a more localized fashion to the area of affected nerve roots, thereby decreasing the systemic effect of the administered steroids. ESIs can be both therapeutic and diagnostic. Diagnostically, ESIs help to identify the region of pain generation through pain relief after local anesthetic injection to the site of presumed pathology, and if the patient experiences more prolonged pain relief, it can be assumed that an element of inflammation was involved. This more prolonged pain relief is presumed to result from a reduction in an inflammatory process, during which time one can also presume that the nerve roots are relatively protected from the effects of inflammation.

Indications for ESIs

Lumbar: lumbosacral disk herniation (the primary indication), spinal stenosis with radicular pain (central canal stenosis, foraminal and lateral recess stenosis), compression fracture with radicular pain, facet or nerve root cyst with radicular pain Cervical: pain associated with acute disk herniation and radiculopathy, postlaminectomy cervical pain, cervical strain syndromes with associated myofascial pain, postherpetic neuralgia Thoracic: acute disk pathology, postherpetic neuralgia, trauma, diabetic neuropathy, degenerative scoliosis, compression fracture


Absolute contraindications

➢ systemic infection or local infection at the site of planned injection
➢ bleeding disorder or fully anticoagulated
➢ history of significant allergic reaction to injected solutions (contrast, local anesthetic, steroid)
➢ acute spinal cord compression
➢ patient refusal

Caution with

➢ pregnant patients (due to fluoroscopy used for procedure)
➢ patients with poorly controlled diabetes (steroids may increase blood glucose levels)
➢ patients with a history of immunosuppression
➢ patients with congestive heart failure (due to the risk of fluid retention due to steroids)


Studies have shown a positive efficacy when lumbar ESIs are used for radiculopathy in well-selected patients in conjunction with fluoroscopic guidance and radiographic confirmation. Benefits include relief of radicular pain and LBP (with leg pain generally relieved more than back pain), facilitation of ability to participate in physical therapy, improvement in quality of life, reduction of analgesic consumption, and improvement in the maintenance of work status. Studies have also shown that ESIs are most effective in the presence of acute nerve root inflammation. In general, patients who have had symptoms for less than 3 months have response rates of 90%. When patients have had symptoms for less than 6 months, the response rate decreases to 70% and further to 50% when symptoms have gone on for over 1 year. Patients with symptoms of shorter duration have more sustained relief than those with chronic pain. Patients with chronic back pain will have a better response if they develop an acute radiculopathy. Favoring the use of ESIs: those who have not had previous back surgery, who are not on workers' compensation, who are younger than 60, and who are nonsmokers.
Despite efficacy, patients must be educated that ESI alone may not be the only solution. It is just one of many non-operative methods to treat LBP and/or radicular symptoms. Other treatments may include short-term bed rest, medications (analgesics, muscle relaxants), physical therapy, and the management of any psychological, financial, marital, and work-related problems. The experts recommend ESIs be performed in combination with "a well-designed spinal rehabilitation program."


Similar to other neuraxial anesthesia techniques

Most common risks

Backache, postural headache, nausea, vomiting, dizziness, and vasovagal reaction.

Rare, but serious

Bleeding along the trajectory of the injection, including epidural hematoma (0.01-0.02% of procedures); infection (more common in immunosuppressed patients) including epidural abscess formation and meningitis, nerve root injury, anterior cord syndrome, spinal cord trauma (cervical/thoracic injections, or compression from hematoma or abscess)
Muscles do not respond in a uniform fashion to neuromuscular blocking drugs. There are differences in the onset time, maximum blockade, and duration of action. These differences become important clinically when looking for a muscle to monitor as a surrogate for those muscles of physiologic importance, such as the abdominal muscles during surgery or the respiratory and airway muscles postoperatively. Common sites of monitoring neuromuscular blockade are the facial nerve around the eye (a good indicator of intubating conditions) and the adductor pollicis at the wrist (a good indicator of upper airway muscle recovery). Other sites include other muscles of the hand, muscles surrounding the eye, and muscles of the foot.
Complete return of neuromuscular function should be achieved at the end of surgery unless post-operative ventilation is planned. The effectiveness of reversal agents depends directly of the degree of recovery present when they are given. Ideally, they should be given only when 4 twitches are visible, preferably measured at the adductor pollicis. The presence of spontaneous ventilation is not a sign of adequate neuromuscular recovery. The diaphragm recovers earlier than the much more sensitive upper airway muscles, such as the geniohyoid, which recovers, on average, at the same time as the adductor pollicis. To prevent upper airway obstruction after extubation, it is preferable to use the adductor pollicis to monitor recovery, instead of the more resistant muscles of the hypothenar eminence or those around the eye. Normal respiratory and upper airway function does not return to normal unless the train-of-four ratio at the adductor pollicis is 0.9 or more.
Typically, hemophilia A and B are treated with replacement of the missing factor (ie, factor VIII or factor IX concentrates). However, patients can develop factor inhibitors, which are IgG antibodies directed against the deficient factor. This usually occurs soon after replacement therapy has been started and is more common in patients with hemophilia A than in those with hemophilia B. As many as 25-40% of patients with severe hemophilia A are reported to have factor VIII inhibitors. It is often not possible to neutralize high titer inhibitors even with administration of very high levels of replacement therapy. Inhibitors are suspected when an increase in the frequency of bleeding occurs. This may be seen when a mild or moderately deficient patient is converted to a more severe state due to inhibitor development. Diagnosis is made by measuring the factor VIII inhibitor activity by the Bethesda assay, which both establishes the diagnosis of factor VIII inhibitor and quantifies the antibody titer.
Treatment of factor inhibitors include the use of agents other than factor VIII (bypass products) and/or inhibitor ablation via immune tolerance induction. In patients with usual bleeding who have high titers of inhibitors, bypass products are generally used. These include prothrombin complex concentrates and recombinant human factor VIIa. Prothrombin complex concentrates and activated prothrombin complex concentrates contain proteases that account for their procoagulant activity. They are partially purified mixtures of the vitamin K-dependent clotting factors prepared from plasma. The proteases are short-lived, therefore, initial hemostasis may be followed by breakthrough bleeding between doses. In addition, there is a risk of thrombosis, the most common of which is myocardial infarction. Prothrombin complex concentrates and activated prothrombin complex concentrates are expensive, carry a risk of significant complications, and provide unpredictable hemostasis.
Another bypass product used for "refractory" patients is factor VIIa. It is effective in as many as 90% of patients. There are many theories about how factor VIIa works in this setting, one of which involves binding to the platelet surface and restoring platelet surface- factor X activation. This interaction is deficient in hemophiliacs due to the absence of factor VIII/IX complexes. There is a smaller risk of systemic activation of coagulation, compared to prothrombin complex concentrates and activated prothrombin complex concentrates. If factor VIIa activity is localized to the platelet surface, it would be subject to normal control mechanisms of coagulation which may explain the lower rate of systemic thrombotic complications. Studies have shown no statistical difference in efficacy between factor VIIa and prothrombin complex concentrates.
Immune tolerance induction involves exposure to repetitive doses of factor VIII. Usually this illicits an initial rise in antibody titers, followed by a progressive reduction to low or undetectable titers. Immune tolerance usually needs to be maintained by continued exposure to factor VIII. Immune tolerance induction may also be used in patients with factor IX deficiency, however, it may be associated with nephrotic syndrome.
Respiratory alkalosis is due to increased alveolar ventilation relative to carbon dioxide production. Causes include problems which decrease carbon dioxide elimination, such as asthma, COPD, OSA, scoliosis, obesity, residual effects of neuromuscular blocking drugs, and pneumonia. In addition, anything which leads to increased carbon dioxide production can lead to respiratory alkalosis. Examples include: malignant hyperthermia, hyperthyroidism, exhausted soda lime, incompetent one-way valve, and carbon dioxide absorption from pneumoperitoneum (laparoscopy). Acute hypocapnia causes a reduction of serum levels of potassium and phosphate secondary to increased cellular uptake of these ions. Often, calcium is decreased secondary to increased binding to albumin. During prolonged respiratory alkalosis, bicarbonate ions are actively transported out of CSF, which causes central chemoreceptors to reset to a lower PaCO2.
The expected change in serum bicarbonate is:
- Acute - [HCO3-] falls 1-2 mEq/L for each 10 mm Hg decrease in the PaCO2
- Chronic - [HCO3-] falls 4-5 mEq/L for each 10 mm Hg decrease in the PaCO2
After a period of 2-6 hours, renal compensation begins and bicarbonate reabsorption from renal tubules is decreased. The expected change in pH with respiratory alkalosis is:
- Acute respiratory alkalosis - Change in pH = 0.008 X (40 - PaCO2)
- Chronic respiratory alkalosis - Change in pH = 0.017 X (40 - PaCO2)
Treatment of chronic respiratory alkalosis is aimed at correcting the underlying disorder. More acute respiratory alkalosis can be corrected during anesthesia by increasing minute ventilation

Respiratory distress syndrome is caused by a deficiency of surfactant, a phospholipid responsible for stabilizing alveolar surfaces and reducing surface tension. Surfactant is 70% lipid (phosphatidylcholine) combined with proteins. When surfactant is deficient, it is more difficult to generate the inspiratory pressure needed to inflate alveoli, resulting in progressive atelectasis. In addition, surfactant deficiency leads to lung inflammation, with resulting pulmonary edema and increased airway resistance. Diffuse atelectasis results in high resistance and low compliance in small airways. Hypoxemia results primarily from V/Q mismatch in atelectatic areas as blood flow continues through poorly ventilated regions of lung.
According to LaPlace's law, the pressure (P) necessary to keep a sphere (alveolus) open is proportional to the surface tension (T) and inversely proportional to the radius (R) of the sphere, shown by the formula: P = 2T/R
If the alveolar volume is small (radius), as occurs at end expiration, and the surface tension is high, the pressure necessary to maintain the alveolus open is high. If this increased pressure cannot be generated, the alveolus collapses.

Risk Factors

Prematurity, infants born to diabetic mothers, infants with mutations in the genes encoding surfactant proteins (SP-B and SP-C)


Respiratory distress and cyanosis occur at birth. Infants have tachypnea and labored breathing, as well as grunting. Grunting is a compensatory response to prevent end-expiratory alveolar collapse. Nasal flaring and intercostals retractions may also be seen. Chest x-ray is characterized by low long volumes. Atelectasis results in diffuse, ground glass appearance with air bronchograms.


Diagnosis is primarily based on clinical signs and symptoms discussed above. ABG shows hypoxemia that responds to supplemental oxygen, with normal to slightly elevated PaCO2. Hypercarbia can occur as the disease worsens.


Any intervention to prevent preterm birth is the best intervention for RDS. This includes cervical cerclage, use of tocolytic agents, smoking cessation, etc. If premature birth cannot be prevented, tests of fetal lung maturity performed on amniotic fluid prior to delivery can be used to assess the risk of development of RDS in a preterm infant. Lecithin and sphingomyelin are the primary phospholipids which make up surfactant. In early pregnancy, the concentration of lecithin is very small, while that of sphingomylin is much greater. Lecithin begins to be secreted into amniotic fluid by the developing fetal lung between 24 and 26 weeks gestation. At 32 to 33 weeks gestation, lecithin and sphingomyelin concentrations are about equal. Subsequently, lecithin begins to increase, with an abrupt rise around 35 weeks. In the mature lung, lecithin comprises 50-80% of the total surfactant lipid. Fetal lung maturity is present when the L/S ratio increases to 2.0 or more. Antenatal steroids reduce the risk of development of RDS. They are typically given to all women at risk for preterm delivery prior to 34 weeks gestation.


Initial management consists of supplemental oxygen and ventilator support, if needed. Often infants have increased levels of vasopressin, which results in low urine output, even if cardiac output is normal. In addition, lung injury may cause increased fluid filtration into the pulmonary circulation; therefore, fluid restriction is often part of the initial management. Surfactant improves survival in infants with RDS. Surfactant may be given prophylactically in the delivery room in infants at significant risk of RDS (those less than 30-32 weeks gestational age), or it may be given early within two hours of birth for infants who are intubated secondary to respiratory distress. It can be used later as a rescue therapy for infants who are not high risk for RDS at birth, but show signs and symptoms later. When mechanical ventilation is required, low tidal volumes should be used. High frequency oscillatory ventilation may also be used, although it does not seem to be superior to conventional ventilation with low tidal volumes.

Prophylactic Surfactant

There is a general concensus that infants less than 30 weeks gestation should be intubated at delivery and given prophylactic surfactant. If the infant is active and is breathing spontaneously, extubation and CPAP support can be considered
Surgery involving the cornea, anterior chamber, and lens can be performed with a retrobulbar or peribulbar block. Retrobulbar block involves depositing local anesthetic inside the muscle cone. It aims to block the ciliary nerves, the ciliary ganglion, and cranial nerves II, III, and VI. Cranial nerve IV is not affected since it lies outside the muscle cone. The ciliary ganglion is a parasympathetic ganglion, which lies about 1 cm from the posterior boundary of the orbit between the lateral surface of the optic nerve and the ophthalmic artery.
Peribulbar block involves injections above and below the orbit, with local anesthetic deposited in the orbicularis oculi muscle. This technique blocks the ciliary nerves, as well as CN III and VI, but does not block the optic nerve (CN II). There is less potential for intraocular or intradural injection since the local anesthetic is deposited outside the muscle cone. This block is technically easier to place and the risk of hemorrhage within the muscle cone and direct injury to the optic nerve is decreased. It is more difficult to get a complete, dense block with peribulbar technique, but it is still widely used, given its lower complication rate.
[edit]Complications of retrobulbar blocks

1. Allergic reactions - usually occur with ester-type local anesthetics
2. Retrobulbar hemorrhage - This is the most common complication seen. It is characterized by a motor block, closing of the upper lid, and simultaneous sudden rise in intraocular pressure causing proptosis. Retrobulbar hemorrhage can lead to central retinal artery occlusion and stimulation of the oculocardiac reflex. Usually surgery is postponed. Hemorrhage is rare with peribulbar block.
3. Central retinal artery occlusion - Can result from retrobulbar hemorrhage or if the dura is penetrated and local anesthetic is injected into the subarachnoid space.
4. Subconjunctival edema (chemosis) - Can be minimized by slowing rate of injection, can interfere with suturing.
5. Penetration or perforation of the globe - more likely to occur in a myopic eye which is longer, but also thinner than normal. Symptoms include pain at the time the block is performed, sudden loss of vision, hypotonic, or a poor red reflex.
6. Central spread of local anesthetic - due to either direct injection into the dural cuff near the optic nerve or retrograde arterial spread. Symptoms include drowsiness, vomiting, contralateral blindness, convulsions, respiratory depression, and cardiac arrest within 5 minutes of injection.
7. Oculocardiac reflex - bradycardia which can follow traction on the eye. Retrobulbar or peribulbar block ablates the oculocardiac reflex by blocking the afferent pathway (ciliary ganglion to ophthalmic division of trigeminal nerve), but this reflex can occur with block placement. It can also occur several hours later if it is secondary to an expanding hemorrhage. Therefore, patients with hemorrhage should be closely monitored.
8. Optic nerve atrophy - Caused by direct damage to the optic nerve secondary to injection into the optic nerve sheath or hemorrhage within the nerve sheath. Symptoms include partial or complete visual loss.
[edit]Complications of peribulbar block

1. Spread of local anesthetics to the contralateral eye
2. Periorbital ecchymoses
3. Transient blindness
[edit]Contraindications to Peribulbar and Retrobulbar Block

a.) Age less than 15
b.) Procedures lasting more than 90-120 minutes
c.) Uncontrolled cough or tremors
d.) Disorientation or mental impairment
e.) Excessive anxiety or claustrophobia
f.) Language barrier or deafness
g.) Bleeding or coagulopathies
h.) Perforated globe
Intended Use

Uterine Relaxant

Mechamism of Action

Ritodrine is a selective beta-2 receptor agonist that developed specifically for use as a uterine relaxant. Ritodrine suppress premature uterine contractions through their effects on increase in intracellular cyclic adenosine monophosphate (cAMP) and relaxes uterine smooth muscles.

Side Effects

Cardiac Effects (Tachycardia)

Tachycardia is a common adverse effect of systemically administered receptor agonists. Stimulation of heart rate occurs primarily via beta-1 receptors. It is uncertain to what extent the increase in heart rate also is due to activation of cardiac beta-2 receptors or to reflex effects that stem from beta-2 receptor-mediated peripheral vasodilation. However, during a severe asthma attack, heart rate actually may decrease during therapy with a agonist, presumably because of improvement in pulmonary function with consequent reduction in endogenous cardiac sympathetic stimulation. In patients without cardiac disease, agonists rarely cause significant arrhythmias or myocardial ischemia; however, patients with underlying coronary artery disease or preexisting arrhythmias are at greater risk. The risk of adverse cardiovascular effects also is increased in patients who are receiving MAO inhibitors. In general, at least 2 weeks should elapse between the use of MAO inhibitors and administration of beta-2 receptor agonists or other sympathomimetics. Tremor is also notable along with other beta-1 effects with ritadrine

Pulmonary Edema

Pulmonary edema from ritodrine in Obsetrics anesthesia has been well noted, but its mechanism is not completely known, putative theories include increase in ADH that aggravate the already expanded intravascular volume of pregnancy. Instances of tocolytic related pulmonary edema with normal pulmonary occlusion pressures, however, argue against this mechanism. It is also possible that fluid infusions used to manage the systemic vasodilation of drug therapy with beta-agonists present a volume overload when vasoconstriction occurs after discontinuation of tocolytic therapy. A pulmonary capillary leak phenomenon may also participate in pathogenic mechanisms. Although exact mechanisms remain elusive, pulmonary edema may occur from varying degrees of heart failure, pulmonary vasoconstriction, capillary leak syndrome, intravascular volume overload, and reduced serum oncotic pressure.

Theoretical Concerns re: long term beta-2-selective receptor agonists
Long use of beta-2-selective receptor agonists have been known to cause death or near-death from asthma possibly through downregulation of receptors in some tissues and decreased pharmacological responses and through increased bronchial hyperreactivity and deterioration in disease control, but this concept is not well know with the use of ritodrine as it is only administered on a temporary basis.


Ritodrine may also increase the concentrations of glucose through gluconeogenesis, this has to be noted in diabetic patients, as higher doses of insulin may be required.

Effects on Potassium (Hypokalemia)

Decrease in the concentration of potassium is also well known. The decrease in potassium concentration may be especially important in patients with cardiac disease, particularly those taking digoxin and diuretics.
AT3 is known to slowly break up fibrin and factor X. When heparin binds to AT3, AT3 will break up fibrin and factor X faster. AT3 is not dependent on vitamin K so unlike warfarin, giving vitamin K will not reverse the effects of heparin.
Types 1. Type I antithrombin deficiency
a. complete loss of the mutant antithrombin protein result in immunologic and functional levels that are 50% or less than normal.
b. major gene deletions or point mutations, which cause a quantitative reduction in antithrombin
c. Homozygous type I antithrombin deficiency (AT deficiency) is almost always fatal in utero.
2. Type II antithrombin deficiency
a. single amino acid changes that result in functional deficits in a molecule that is otherwise synthesized and secreted into the plasma in a normal fashion.
b. The variant antithrombin molecules may have abnormalities at the reactive site or the heparin binding site.
c. Heterozygous
3. Acquired
a. Liver or renal failure
b. Pregnancy
c. Bone marrow tumor
d. Ards
e. Sepsis
-Gene assay
-Looking for underlying cause in acquired cases

Medical Care
a. pt w/ inherited AT deficiency:
- intravenous heparin
- if iv heparin doesn't work , antithrombin concentrate
- LMWHs also require antithrombin for their antithrombotic action. Not much is known about the use of LMWHs in these patients.
- synthetic anti-factor Xa pentasaccharide

b. pts w/ DVT and whose antithrombin deficiency has been recognized : lifelong oral anticoagulation therapy - synthetic direct thrombin inhibitors that do not require antithrombin for their anticoagulant effect (eg, argatroban)

c. Antithrombin supplementation has been suggested to be useful in patients with the following conditions or those undergoing the following procedures:
1.Malignancies 2.Sepsis 3.Shock 4.Open heart surgery 5.Orthopedic procedures

Surgical Care
Replacement with antithrombin concentrate is necessary in patients with known antithrombin deficiency (AT deficiency). In patients with acute severe trauma, some studies suggest a beneficial effect with prophylactic replacement. The frequency of antithrombin replacement depends on the half-life of the product, but in the presence of active bleeding, more frequent replacement should be based on antithrombin levels.
In acquired disorders, correction of antithrombin levels allows heparin to exert its full antithrombotic effect. Such replacement is necessary to maintain a minimum of 80% antithrombin activity until the full therapeutic effect of oral anticoagulants is obtained. Serial assessment of antithrombin levels is necessary to assure the adequacy of the dosing.
- Aprotinin ,a third antifibrinolytic drug obtained from bovine lung, is a nonhuman protein inhibitor of several serine proteases, including plasmin. It is approved by the FDA for use in patients undergoing open heart surgery to reduce operative blood loss
Sensory Evoked Potentials (SEPs)

Described in terms of site of origin (stimulus), latency, and amplitude.


Generally originate near the median/ulnar nerves or posterior tibials. Recording electrodes are on the scalp or spinal cord. Note that volatile anesthetics increase SSEP latency and decrease SSEP amplitude - nitrous oxide decreases SSEP amplitude but does not affect latency [Banoub et. al. Anesthesiology 99: 716, 2003]. The threshold for usefulness of SSEPs during volatile anesthesia is at ~ 0.5 - 0.75 MAC. Barbiturates, benzodiazepines, and opiates may interfere with SSEPs but to a much lesser extent than volatile anesthetics. SSEPs are controversial because their sensitivity is unestablished - it is clear that SSEPs showing prolonged increase in latency can be associated with severe neurologic injury, however the actual threshold (both in terms of duration and amount of latency) is not known [Kumar et. al. Anaesthesia 55: 225, 2001]. According to Barash, a 50% reduction in amplitude in response to a surgical maneuver and while the anesthetic regimen is held constant, is significant.

How Changes in Physiology Affect SSEPs
Temperature, SBP, PaO2, and PaCO2 all affect SEPs and must be controlled during surgery [Baoub et. al. Anesthesiology 99: 716, 2003]. Room temperature irrigation fluids can also affect SSEPs, thus body temperature fluids should be used for irrigation in neurosurgical cases


Similar to SSEPs, visual evoked potentials are highly sensitive to the use of anesthetic agents


More resistant to anesthetic influences than SSEPs and VEPs. According to Barash, a 1 ms increase in latency while the anesthetic regimen is held constant is considered significant.

Selection of an Anesthetic Agent

All volatile agents depress evoked potentials. Nitrous oxide added to other volatile agents profoundly depresses the amplitude of both SSEPs and VEPs. Barash recommends using TIVA or at least above average IV opiates because they produce minimal changes in SEP waveforms. Dexmedetomidine can be added to the anesthetic regimen and will reduce MAC requirements while having essentially no effect on SSEP amplitude. That said, sevoflurane and desflurane have less effect on SEPs than earlier anesthetic agents, with Barash stating that desflurane

Motor Evoked Potentials (MEPs)

Not widely practiced - requires placement of a stimulating scalp electrode or magnetic coil (requires lower voltages) and an intramuscular recording electrode. MEPs are both difficult to obtain and have questionable accuracy. Still, they are sometimes used for intramedullary spinal tumors, scoliosis surgery, and intracranial tumors near the motor strip. Subject to the same effects on physiologic derangements as SEPs. Also profoundly affected by volatile anesthetic agents, less-so by nitrous oxide. Opiates have almost no effect. Nitrous oxide/opiate techniques have been successful with MEPs. Full paralysis makes the MEP essentially useless, however a continuous IV infusion titrated to 1-2 twitches will allow accurate MEP use
Also called a cervicothoracic sympathetic block and used primarily to treat Complex Regional Pain Syndrome. It has also been used to treat refractory angina, phantom limb pain and vascular insufficiency (such as Raynaud's or frostbite), hyperhydrosis and other things. The stellate ganglion is formed by the fusion of the inferior cervical and first thoracic sympathetic ganglia anterior to the vertebral body of C7. It lays under the SCM/carotid, above the lung, lateral to the esophagus/c7 vertebral body/thoracic duct and in front of the vertebral art/brachial plexus.
The block is done supine, usually at C6 between the trachea and the carotid, at the level of the cricoid. Blocking at C7, it normal anatomical location, risks nicking the pleura. The goal is to hit the C6 transverse process (Chassignac's tubercle) then direct med/inf toward the C6 body. Once there, the needle is withdrawn 1-2 mm and contrast is injected. You are hoping for contrast spread cephalad and caudad between tissue planes. Pooling means you're likely in the muscle (longus colli) and immediate disappearance of contrast means you're in a vessel. Usually a very small local/epi 0.5 cc test dose is advocated (although be aware that even this amount straight into the vertebral or carotid artery can cause seizures). Ten or 15 ml with frequent aspiration is then injected. Horner's syndrome is proof of a job well done. Other side effects seen are horseness, (recurrent laryngeal nerve) and elevated hemidiaphragm (phrenic nerve)
Complications are rare but with so many important neighbors, you can imagine the list is long: Hematoma from carotid/IJ trauma, brachial plexus injury, pneumothorax, hemothorax, chylothorax (thoracic duct injury), esophageal perforation (this may be more common than we think but usually of no significance unless it leads it infection/abcess), intravascular/intrathecal/epidural injection, meningitis.
SAH: refers to extravasation of blood into the subarachnoid space between the pial and arachnoid membranes. SAH comprises half of spontaneous atraumatic intracranial hemorrhages, the other half consist of bleeding that occurs within the brain parenchyma. Intracranial hemorrhage as a whole comprises 20% of all strokes.
- hi morbidity and mortality, usually associated with head trauma - associiated with aneurysm and avm rupture -Aneurysms usually occur at the branching sites on the large cerebral arteries of the circle of Willis. The early precursors of aneurysms are small outpouchings through defects in the media of the arteries. These defects are thought to expand as a result of hydrostatic pressure from pulsatile blood flow and blood turbulence, which is greatest at the arterial bifurcations.
Nimodipine -calcium channel blocker -shown to reduce the incidence of ischemic neurological deficits, and nimodipine has been shown to improve overall outcome within 3 months of aneurysmal SAH. Although the mechanism is unproved, it appears that nimodipine may prevent the ischemic complications of vasospasm by the neuroprotective effect of blockading the influx of calcium into damaged neurons

a. General: dihydropyridipine CCB, used to treat cerebral vasospasm 2/2 to SAH b. MOA: works on L type Ca channels, no one actually knows how it prevents vasospasm
i. Theory: may prevent the ischemic complications of vasospasm by the neuroprotective effect of blockading the influx of calcium into damaged neurons
c. Usage i. It is selective for cerebral vasculature ii. Given within 4 days of SAH and cont'd for 3 weeks
d. Pharmacokinetics i. Absorption: given orally, peak [ ]plasma takes 1.5 hrs ii. Metabolism: 1st pass metabolism by the liver, CYP450 iii. Excretion: urine
e. Side Effects: flushing, thrombocytopenia, CHF, DVT
Subdurals happen in the potential (or traumatically created, there is no consensus to what truly happens) space between the dura and the arachnoid. Radiologists find this space occasionally under fluoroscopy and note that when fluid is injected here it ascends against gravity. Secondly, once it is found (or created) it probably becomes a permanent defect making it more difficult to find the subarachnoid space, either at the time or subsequently. It can happen if the needle pokes through the dura or if the epidural catheter is threaded or/and migrates there. In one series of over 2000 epidurals, the incidence was 0.82%. Because it is tough to diagnosis, the true number is likely higher. Subdural injection may be the cause of failed spinals despite free aspiration of fliud. (A few theories as to why: Arachnoid defects allow flow of CFS into the subdural space? Bevel changes directions and puts some medicine in both compartments? A previous pass has damaged the dura and allowed CSF to enter subdurally?)
Classic presentation is delayed and gradual. It usually occurs when your epidural seems to have gone perfectly well. Onset is in 10-30 minutes and starts with an unexpectedly extensive sensory block after negative test dose/aspiration. Motor block is typically minimal, though it can be extensive. Why? The subdural space is thought to be bigger posteriorly and the anesthetic tracks there, minimizing anterior (motor) block. Anteriolateral sympathetic fibers are hit, causing hypotension that is more than expected from epidural placement but less than a total spinal, and it is relatively easy to treat with fluids and small doses of ephedrine/phenyleprine. If the subdural injection continues to track cephalad, it can pool intracranially and cause slow-onset dyspnea and loss of consciouness.
Succinylcholine in Guillain Barre

Should be avoided due to a significant risk of hyperkalemia.
Ferguson et al described four patients with chronic/relapsing polyneuropathy who developed life-threatening arrhythmias following succinylcholine administration, although in this instance SCh was presumed, but not documented to be the cause {Ferguson et. al. Suxamethonium is dangerous in polyneuropathy. BMJ 1981;282:298-99}. Reilly and Hutchinson described a case {Reilly et. al. J Neurol Neurosurg Psychiatry 54: 1018, 1991} in which a 51 year old man developed unstable V-tach leading to cardiac arrest (K increased from 4.3 to 8.6) and death following SCh administration for an intubation during a GBS relapse. Most recently an occurence was documented in Belgium {Dalman et. al. Acta Neurol Belg 94: 1994}
Note that this risk may persist even after the disorder has run its course, as has been documented in at least one case report {Feldman. Anesthesiology 72: 942, 1990}, in this case of a pregnant woman one month post-recovery. Vecuronium and rocuronium, both of which have minimal cardiovascular effects (unlike pancuronium, which does), are recommended. Unfortunately, these patients may be either overly or under sensitive to non-depolarizing NMBDs

Other Anesthetic Considerations in Guillain Barre

Impaired swallowing and ventilatory difficulty are common. Vital capacity should be assessed frequently, and if < 15 cc/kg, mechanical intubation is indicated. There is a substantial correlation between the rapidity of paralysis and the need for mechanical ventilation, with rapidly deteriorating patients being more likely to require support

Cardiovascular System

Autonomic dysfunction can create wide swings in cardiovascular variables, thus alpha and beta blockade may be indicated, however some patients will manifest by lack of compensatory responses and will overreact to positional changes, blood loss, etc (and may require pressors)
Central Nervous System (CNS)

Induction doses of ketamine are generally considered to increase cerebral blood flow (CBF), cerebral metabolism (CMRO2), and intracranial pressure (ICP); however, there is evidence that ketamine administered to anesthetized and mechanically ventilated patients does not increase ICP and has little impact on cerebral hemodynamics. For example, ketamine, in doses up to 5 mg/kg IV, did not increase ICP in intubated, sedated head-injury patients [Albanèse J et al. Anesthesiology 87: 1328, 1997, PMID: 9416717]. On electroencephalogram (EEG) ketamine's effects are characterized by the abolition of alpha rhythm and the dominance of theta activity.

Cardiovascular System

Despite possessing a direct negative cardiac inotropic effect, ketamine causes dose dependent direct stimulation of the CNS that leads to increased sympathetic nervous system outflow. Consequently, ketamine produces cardiovascular effects that resemble sympathetic nervous system stimulation. Ketamine is associated with increases in systemic and pulmonary blood pressures, heart rate, cardiac output, cardiac work, and myocardial oxygen requirements. Systemic vascular resistance and left ventricular end diastolic pressure are normally unchanged. It is important to recognize that critically ill patients may occasionally respond to ketamine with unexpected decreases in blood pressure and cardiac output. This represents depletion of endogenous catecholamines and exhaustion of sympathetic compensatory mechanisms, unmasking ketamine's direct negative inotropic effects.

Pulmonary and Airway

Ketamine does not produce any significant depression of ventilation when used alone. In addition, upper airway skeletal muscle tone is maintained airway reflexes remain intact. Ketamine also possesses bronchodilatory activity but has been shown to increases salivary and tracheobronchial mucous gland secretions.

Hepatic and Renal Function

Ketamine does not alter any laboratory test that reflects hepatic or renal function
TEE and Perfusion Distribution

TEE is an evaluation of Ventricular functions and has been crucial in the OR - goal of intraoperative ventricular function monitoring provides:

Goals of Ventricular Function Monitoring

a. continuous global function assessment
b. volume status information
c. regional function assessment as a reflection of acute coronary ischemia
d. left atrial pressure estimation
In concentrating on TEE's role in assessing acute coronary ischemia and since active ischemia can be seen on a TEE much earlier than any changes in EKG, interpretation of any wall motion abnormalities and how they correlate to coronary artery distribution can be crucial to intraoperative management for an anesthesiologist.


Transgastric Short-Axis View

The short-axis view at the midpapillary muscle level is a commonly used view for evaluating global and segmental ventricular performance. All three coronary territories are represented in this view, making it useful for detecting acute ischemia.

Transgastric Long-Axis View

The transgastric long-axis view is also useful, as the left ventricular apex is imaged most readily in this plane. This is especially important when isolated abnormalities confined to the apex are sought by TEE. This view is also useful in measuring cardiac output through continuous wave Doppler interrogation of the aortic valve. Estimations of cardiac output with this approach correlate well with more direct measures of global function.

Midesophageal Four-Chamber View

The midesophageal four-chamber view allows simultaneous visualization of the left and right ventricles and is analogous to the identically named apical transthoracic echocardiographic view. Segmental function of the lateral and the septal walls is best assessed in this view.

Orthopedic procedures in the arm may be performed under a variety of brachial plexus blocks, with intravenous regional anesthesia, or by using combinations of individual nerve blocks in the arm. The selection of a particular technique depends on the need for a tourniquet and on the site of anticipated surgery.

Shoulder Surgery

The deep structures of the shoulder are largely innervated by the C5 and C6 dermatomes. This is why shoulder surgery can be done under an interscalene block alone. Skin infiltration may be necessary to anesthetize the contribution of the intercostobrachial nerve for the posterior portal for shoulder or if the skin incision extends toward the axilla.

Side Effects of the Beach Chair Position

Open shoulder surgery or arthroscopy performed in the sitting position under interscalene block may be complicated by episodes of bradycardia or hypotension, or both, which occurs in up to 20% of cases. These are believed to be vasovagal reactions that are best prevented by fluid loading and pretreatment with intravenous atropine or beta-blockers.
It has been postulated that this vasovagal reaction is related to venous pooling (caused by the sitting position and epinephrine-induced beta-adrenergic effect) and increased inotropy (also beta-adrenergic effects of epinephrine). Increased epinephrine may occur endogenously from decreased venous return and carotid baroreceptor stimulation, as well as exogenously from epinephrine administered with the local anesthetic for interscalene block, direct wound infiltration, and the irrigation solution. These conditions are similar to those incurred during tilt-table testing in patients with unexplained syncope. Exogenous epinephrine in our patients may play a role similar to isoproterenol infusions in tilt testing, which has been shown to increase the frequency with which vasovagal reactions are induced. In this setting, syncope is preceded by a low-volume hypercontractible ventricle, and there is increased sympathetic tone. This causes stimulation of intramyocardial mechanoreceptors C fibers, which is followed by an abrupt withdrawal of sympathetic outflow with vasodilation and an increase in vagal tone with resultant bradycardia, hypotension. Prophylactic use of beta-blockers has been compared with prophylactic glycopyrrolate administration. Prophylactic beta-blockade, but not prophylactic glycopyrrolate, reduced the frequency of hypotensive bradycardic events. Regardless of the choice to use hydration or pharmacologic prophylaxis, the anesthesiologist must be extremely vigilant and intervene early to prevent progression to asystole. Treatment may include use of ephedrine, atropine, and glycopyrrolate and positioning the patient supine until stable.

Elbow Surgery

Elbow surgery can be performed by interscalene or axillary blocks or by a combination of both. Alkalinization of local anesthetics has been shown to more effectively anesthetize the C8-T1 dermatomes during interscalene blocks. Intercostobrachial blocks (T1-2) in the axilla may be necessary as a supplement to axillary blocks if medial incisions are performed in the upper arm. Hand and forearm surgery can be performed with the use of any of the previous techniques. Axillary blocks may be preferable for surgery of the medial aspect of the hand and forearm (C7-8, T1) because this area is sometimes incompletely blocked by the interscalene approach. The coracoid block is also effective for surgery of the elbow, forearm, or hand. This infraclavicular block has prominent bony landmarks, making it easier to perform with less likelihood of pneumothorax compared with other infraclavicular approaches to the brachial plexus. The site is also ideal for securing a catheter to the anterior chest wall. Continuous axillary blocks may also be used for prolonged cases. Intravenous regional anesthesia is most applicable for shorter cases.

Hand/Wrist Surgery

Peripheral nerve blocks at the wrist or hand can be performed with a long-acting anesthetic such as bupivacaine or ropivacaine to provide postoperative pain relief and facilitate discharge after ambulatory surgery.
Definition of vapor pressure: In a closed container, molecules from a volatile liquid escape the liquid phase and become vapor. These gaseous molecules strike the wall of the container, exerting what's known as vapor pressure. Vapor pressure is directly proportional to temperature. Increasing temperature will increase the ratio of gas:liquid molecules, thereby increasing vapor pressure.
Vapor pressure of volatile agents at 20 degrees C (mmHg):
- Sevoflurane: 157
- Desflurane: 669
- Isoflurane: 238
- Enflurane: 172
- Halothane: 243
- N2O: 38,770

Boiling point

Boiling point is defined as the temperature at which vapor pressure equals atmospheric pressure (760mmHg). Boiling points are listed below (celsius):
Boiling point (C)
- Sevoflurane: 58.5
- Desflurane: 22.8
- Isoflurane: 48.5
- Enflurane: 56.5
- Halothane: 50.2
- N20: -88

Latent heat of vaporization

Latent heat of vaporization: Energy is required when a molecule changes from liquid to gas. Latent heat of vaporization is the number of calories required to change 1 gram of liquid into vapor without changing temperature. Thus, in the absence of an outside temperature source, volatile liquids will cool significantly and lead to decreasing vaporization. The latent heats of vaporization among the common volatile anesthetic gases are similar. However, desflurane is notable for being less potent than the other agents. Thus, more desflurane molecules are required to achieve a given level of anesthetic depth than with the other agents, leading to greater temperature loss and decreasing vapor pressure.


Desflurane's unique characteristics (high volatility/moderate potency) require the use of a special vaporizer for proper utilization of this gas. Desflurane vaporizers are heated to 39 degrees C, which increases the vapor pressure in the sump to 1300mmHg, preventing the possibility of boiling in warm OR rooms. Providing an external heat source compensates for the significant heat loss associated with desflurane vaporization. And unlike stand variable bypass vaporizers that pass fresh gas through the vaporizing chamber, desflurane vaporizers add agent directly to the gas stream.
The definition of MAC is the concentration of the vapor (measured as a percentage at 1 atmosphere, i.e the partial pressure) that prevents the reaction to a standard surgical stimulus in 50% of subjects. Since most of us work at about 1 atmosphere, we can still think in terms of % concentration, but what is physiologically important is the partial pressure (mm Hg), not the concentration.
Modern conventional vaporizers (for halothane, isoflurane, sevoflurane) are agent specific, temperature compensated, variable bypass vaporizers. They automatically compensate for changes in altitude because they put out a partial pressure that is determined by the position of the dial. Even though the units on the dial are percentages, it's actually partial pressure that is determined. The partial pressure of the anesthetic agent is what determines whether a patient is anesthetized, and it does not change at different altitudes. So if you are doing anesthesia with isoflurane at high altitude, setting the dial to 1% will have the same effect as it would at sea level.
However, if the question relates to volume concentration then use equation:
Where VO=vapor output (ml), CG= carrier gas flow(mL.min), SVP=saturated vapor pressure (mm Hg) at room temp, and Pb is barometric pressure (mm Hg)
At a higher altitude where the barometric pressure is ½ that at sea level, the amount of isoflurane vapor output increases due to the lower barometric pressure. Therefore, the settings that delivered 2% isoflurane now deliver 4% isoflurane. However, according to Dalton's law, the partial pressure of isoflurane delivered would be the same at both altitudes since 2% isoflurane at 760mm Hg (15.2 mm Hg) is the same as 4% isoflurane at 380mm Hg (15.2 mm Hg)
Alternatively, the desflurane vaporizer is electrically heated to 39 degrees centigrade, which creates a vapor pressure of 2 atmospheres inside the vaporizer, regardless of ambient pressure. The number on the dial reflects the percentage that will be delivered. So at any altitude, when you dial 5%, it will give you 5%. But when that 5% desflurane leaves the vaporizer at high altitude, what is delivered to the patient is 5% of a decreased ambient pressure, so the partial pressure of desflurane in the alveoli will be much less that it would be at sea level. Thus, you will need to dial a higher concentration at high elevation to attain the same clinical effect as at sea level with desflurane (Tec-9) vaporizer.
General anesthesia causes an increase in intrapulmonary shunt, which may impair oxygenation, and the magnitude of shunt is correlated with the formation of atelectasis. The atelectasis appears within minutes after anesthesia induction in nearly 90% of patients. The degree of atelectasis is larger with obese patients and when a higher fraction of inspired oxygen (FI02) is used. Using lower FIO2 (30%) during induction can effectively decrease the amount of atelectasis, however this is associated with a lower safety margin is patient's who may be difficult to intubate. Another option is the use of positive end expiratory pressure (PEEP) after a recruitment breath during induction that prevents recurrence of atelectasis when high FIO2 is used. Complications of PEEP include decreasing cardiac output (reduced venous return, reduced ventricular compliance, increased RV outflow impedence, and ventricular external constraint by hyperinflated lungs) and well as lung injury/alveoli rupture when used in patients with localized lung disease.
During mechanical ventilation (positive pressure ventilation), atelectasis may occur when lungs are underinflated due to low tidal volumes, or when compression occurs (such as patient position or obesity). Use of volume control ventilation (A/C, IMV) will deliver a preset volume (normally 6-8mL/kg) and the pressure generated in the lung will then be dependent on the resistance and compliance of the respiratory system. In pressure controlled ventilation , a constant pressure is used to inflate the lungs, and the tidal volume delivered will be dependent on the resistance and compliance of the respiratory system. Either of these modes may contribute to atelectasis if the pressure or volume delivered to the lungs is insufficient to prevent the alveoli from collapsing.
Another method to decrease atelectasis is the use of inverse ratio ventilation (IRV) during pressure controlled ventilation. In this mode, PCV is combined with a prolonged inflation time, and the usual I:E ratio (1:2) is reversed (2:1). The prolonged inflation time can help prevent alveolar collapse. However, use of IRV is associated with inadequate emptying of the lungs which can lead to hyperinflation and auto-PEEP, that can decrease cardiac output.