General Anesthetics

1. General Anesthetics Chapter 25

2. Isoflurane Chemistry and Physical Properties. Isoflurane (FORANE, others) is 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether. It is a volatile liquid at room temperature and is neither flammable nor explosive in mixtures of air or oxygen.Pharmacokinetics. Isoflurane has a blood:gas partition coefficient substantially lower than that of halothane or enflurane. Consequently, induction with isoflurane and recovery from isoflurane are relatively rapid. Changes in anesthetic depth also can be achieved more rapidly with isoflurane than with halothane or enflurane. More than 99% of inhaled isoflurane is excreted unchanged via the lungs. Approximately 0.2% of absorbed isoflurane is oxidatively metabolized by CYP2E1. The small amount of isoflurane degradation products produced is insufficient to produce any renal, hepatic, or other organ toxicity. Isoflurane does not appear to be a mutagen, teratogen, or carcinogen.Clinical Use. Isoflurane is a commonly used inhalational anesthetic worldwide. It is typically used for maintenance of anesthesia after induction with other agents because of its pungent odor, but induction of anesthesia can be achieved in less than 10 minutes with an inhaled concentration of 3% isoflurane in O2; this concentration is reduced to 1% to 2% for maintenance of anesthesia. The use of other drugs such as opioids or nitrous oxide reduces the concentration of isoflurane required for surgical anesthesia.

3. Isoflurane • Cardiovascular System • Cardiac output is well maintained • Decreased systemic vascular resistance • Coronary steal • Compensatory mildly elevated heart rate • Rapid increase • Sympathetic stimulation • Tachycardia and hypertension

4. Isoflurane • Respiratory System • Concentration-dependent depression of ventilation • Normal respiration rate but a reduced tidal volume • Reduced alveolar ventilation and increased arterial CO2 • Depressed response to hypercapnia and hypoxia • Bronchodilator • Airway irritant • Can stimulate airway reflexes during induction of anesthesia, producing coughing and laryngospasm.

5. Isoflurane • Nervous System • Dilates cerebral vasculature • Less than enflurane or halothane • Increased intracranial pressure • Hyperventilation to reduce • Does not have to be prophylaxis, unlike halothane • Reduced O2 consumption • Muscle • Relaxation • Enhances depolarizing and nondepolarizing muscle relaxants • More potent than halothane in potentiation of neuromuscular blocking agents • Relaxes uterine smooth muscle • Not recommended for analgesia or anesthesia for labor and vaginal delivery

6. Isoflurane • Kidney • Reduced renal blood flow and glomerular filtration rate • Small volume of concentrated urine • Rapidly reversed • No long-term renal sequelae or toxicities • Liver and Gastrointestinal Tract • Concentration dependent splanchnic and hepatic blood flow reduction • LFTs minimally affected by isoflurane • No reported incidence of hepatic toxicity

7. Enflurane • Chemical and Physical Properties. Enflurane (ETHRANE, others) is 2-chloro-1,1,2-trifluoroethyl difluoromethyl ether. It is a clear, colorless liquid at room temperature with a mild, sweet odor. Like other inhalational anesthetics, it is volatile and must be stored in a sealed bottle. It is nonflammable and nonexplosive in mixtures of air or oxygen.Pharmacokinetics. Because of its relatively high blood:gas partition coefficient, induction of anesthesia and recovery from enflurane are relatively slow. Enflurane is metabolized to a modest extent, with 2% to 8% of absorbed enflurane undergoing oxidative metabolism in the liver by CYP2E1. Fluoride ions are a by-product of enflurane metabolism, but plasma fluoride levels are low and nontoxic. Patients taking isoniazid exhibit enhanced metabolism of enflurane with significantly elevated serum fluoride concentrations.Clinical Use. As with isoflurane, enflurane is primarily utilized for maintenance rather than induction of anesthesia.

8. Enflurane • Cardiovascular System • Concentration dependent hypotension • Depressed myocardial contractility • Peripheral vasodilation • Minimal effect on heart rate • Neither the bradycardia seen with halothane nor the tachycardia seen with isoflurane

9. Enflurane • Respiratory System • Similar to halothane • Rapid, shallow breathing • Minute ventilation decreased • PaCO2 of 60 mm Hg with 1 MAC • Greater depression of the ventilatory responses to hypoxia and hypercarbia than halothane or isoflurane • Bronchodilator

10. Enflurane • Nervous System • Cerebral vasodilator • Increase intracranial pressure • Reduced cerebral O2 consumption • Produces electrical seizure activity • High concentrations or profound hypocarbia result in EEG changes • Seizure activity may be accompanied by peripheral motor manifestations of seizure activity • Self-limited • Not thought to produce permanent damage • Epileptic patients are not particularly susceptible • Generally is not used in patients with seizure disorders.

11. Enflurane • Muscle • Skeletal muscle relaxation • Enhances the effects of nondepolarizing muscle relaxants • Relaxes uterine smooth muscle • Not widely used for obstetric anesthesia

12. Enflurane • Kidney • Reduced renal blood flow, glomerular filtration rate, and urinary output • Rapidly reversed upon drug discontinuation • High plasma levels of fluoride ions (20 to 40 mmol) and can produce transient urinary-concentrating defects following prolonged administration • Scant evidence of long-term nephrotoxicity • Safe in renal impairment, provided that the depth of enflurane anesthesia and the duration of administration are not excessive • Liver and Gastrointestinal Tract • Reduces splanchnic and hepatic blood flow • Does not appear to alter liver function or to be hepatotoxic

13. Desflurane • Chemistry and Physical Properties.Desflurane (SUPRANE) is difluoromethyl 1-fluoro-2,2,2-trifluoromethyl ether. It is a highly volatile liquid at room temperature (vapor pressure = 681 mm Hg) and thus must be stored in tightly sealed bottles. Delivery of a precise concentration of desflurane requires the use of a specially heated vaporizer that delivers pure vapor that then is diluted appropriately with other gases (O2, air, or N2O). Desflurane is nonflammable and nonexplosive in mixtures of air or oxygen.Pharmacokinetics. Desflurane has a very low blood:gas partition coefficient (0.42) and also is not very soluble in fat or other peripheral tissues. For this reason, the alveolar (and blood) concentration rapidly rises to the level of inspired concentration. Indeed, within five minutes of administration, the alveolar concentration reaches 80% of the inspired concentration. This provides for a very rapid induction of anesthesia and for rapid changes in depth of anesthesia following changes in the inspired concentration. Emergence from anesthesia also is very rapid with desflurane. The time to awakening following desflurane is half as long as with halothane or sevoflurane and usually does not exceed 5 to 10 minutes in the absence of other sedative agents.Desflurane is metabolized to a minimal extent, and more than 99% of absorbed desflurane is eliminated unchanged via the lungs. A small amount of absorbed desflurane is oxidatively metabolized by hepatic CYPs. Virtually no serum fluoride ions are detectable in serum after desflurane administration, but low concentrations of trifluoroacetic acid are detectable in serum and urine.

14. Desflurane • Clinical Use. Desflurane is a widely used anesthetic for outpatient surgery because of its rapid onset of action and rapid recovery. The drug is irritating to the airway in awake patients and can provoke coughing, salivation, and bronchospasm. Anesthesia therefore usually is induced with an intravenous agent, with desflurane subsequently administered for maintenance of anesthesia. Maintenance of anesthesia usually requires inhaled concentrations of 6% to 8%. Lower concentrations of desflurane are required if it is coadministered with nitrous oxide or opioids.

15. Desflurane • Cardiovascular System • Concentration dependent decrease in blood pressure • Cardiac output well preserved as is blood flow to the major organ beds (splanchnic, renal, cerebral, and coronary) • Increased heart rate often noted during induction and during abrupt increases • Greater than Isoflurane • Unlike some inhalational anesthetics, hypotensive effects do not wane with increasing duration of administration

16. Desflurane • Respiratory System • Concentration-dependent increase in respiratory rate and decrease in tidal volume • At low concentrations (less than 1 MAC) the net effect is to preserve minute ventilation • Greater than 1 MAC minute ventilation is depressed • Elevated arterial CO2 tension (PaCO2) • Greater than 1.5 MAC will have extreme elevations of PaCO2, may become apneic • Bronchodilator • Strong airway irritant, can cause coughing, breath-holding, laryngospasm, and excessive respiratory secretions • Because of its irritant properties, desflurane is not used for induction of anesthesia

17. Desflurane • Nervous System • Decreases cerebral vascular resistance and cerebral metabolic O2 consumption • Increased cerebral blood flow • Increased intracranial pressure • Hyperventilation to decrease

18. Desflurane • Muscle • Direct skeletal muscle relaxation • Enhanced effects of nondepolarizing and depolarizing neuromuscular blocking agents • Kidney • No reported nephrotoxicity • Liver and Gastrointestinal Tract • Not known to affect liver function tests or to cause hepatotoxicity

19. Sevoflurane • Chemistry and Physical Properties. Sevoflurane (ULTANE) is fluoromethyl 2,2,2-trifluoro-1-[trifluoromethyl]ethyl ether. It is a clear, colorless, volatile liquid at room temperature and must be stored in a sealed bottle. It is nonflammable and nonexplosive in mixtures of air or oxygen. • Sevoflurane can undergo an exothermic reaction with desiccated CO2 absorbent (BARALYME) to produce airway burns or spontaneous ignition, explosion and fire. Care must be taken to ensure that sevoflurane is not used with an anesthesia machine in which the CO2absorbent has been dried by prolonged gas flow through the absorbent. Sevoflurane reaction with desiccated CO2absorbent also can produce CO, which can result in serious patient injury.

20. Sevoflurane • Pharmacokinetics. The low solubility of sevoflurane in blood and other tissues provides for rapid induction of anesthesia, rapid changes in anesthetic depth following changes in delivered concentration, and rapid emergence following discontinuation of administration.Approximately 3% of absorbed sevoflurane is biotransformed. Sevoflurane is metabolized in the liver by CYP2E1, with the predominant product being hexafluoroisopropanol. Hepatic metabolism of sevoflurane also produces inorganic fluoride. Serum fluoride concentrations peak shortly after surgery and decline rapidly. Interaction of sevoflurane with soda lime also produces decomposition products. The major product of interest is referred to as compound A and is pentafluoroisopropenyl fluoromethyl ether (see Kidney, below). • Clinical Use. Sevoflurane is widely used, particularly for outpatient anesthesia, because of its rapid recovery profile. It is well-suited for inhalation induction of anesthesia (particularly in children) because it is not irritating to the airway. Induction of anesthesia is rapidly achieved using inhaled concentrations of 2% to 4% sevoflurane.

21. Sevoflurane • Cardiovascular System • Concentration dependent decrease in arterial blood pressure • Systemic vasodilation • Decrease in cardiac output • Does not produce tachycardia • May be a preferable agent in patients prone to myocardial ischemia

22. Sevoflurane • Respiratory System • Concentration dependent reduction in tidal volume and increase in respiratory rate • Reduction in minute ventilation and an increase in PaCO2 • Not irritating to the airway and is a potent bronchodilator • Most effective clinical bronchodilator of the inhalational anesthetics

23. Sevoflurane • Nervous System • Decreased cerebral vascular resistance • Decreased cerebral O2 consumption • Increased cerebral blood flow • Increase intracranial pressure • Prevented by hyperventilation • Muscle • Skeletal muscle relaxed • Enhanced effects of nondepolarizing and depolarizing neuromuscular blocking agents. • Similar to those of other halogenated inhalational anesthetics

24. Sevoflurane • Kidney • Production of compound A • May produce renal toxicity • Large clinical studies have shown no evidence of increased serum creatinine, blood urea nitrogen • The current recommendation of the FDA is that sevoflurane be administered with fresh gas flows of at least 2 L/min to minimize accumulation of compound A • Liver and Gastrointestinal Tract • Not known to cause hepatotoxicity or alterations of hepatic function tests.

25. Nitrous Oxide • Chemical and Physical Properties. Nitrous oxide (dinitrogen monoxide; N2O) is a colorless, odorless gas at room temperature. It is sold in steel cylinders and must be delivered through calibrated flow meters provided on all anesthesia machines. Nitrous oxide is neither flammable nor explosive, but it does support combustion as actively as oxygen does when it is present in proper concentration with a flammable anesthetic or material.Pharmacokinetics. Nitrous oxide is very insoluble in blood and other tissues. This results in rapid equilibration between delivered and alveolar anesthetic concentrations and provides for rapid induction of anesthesia and rapid emergence following discontinuation of administration. The rapid uptake of N2O from alveolar gas serves to concentrate coadministered halogenated anesthetics; this effect (the "second gas effect") speeds induction of anesthesia. On discontinuation of N2O administration, nitrous oxide gas can diffuse from blood to the alveoli, diluting O2 in the lung. This can produce an effect called diffusional hypoxia. To avoid hypoxia, 100% O2 rather than air should be administered when N2O is discontinued.Nitrous oxide is almost completely eliminated by the lungs, with some minimal diffusion through the skin. Nitrous oxide is not biotransformed by enzymatic action in human tissue, and 99.9% of absorbed nitrous oxide is eliminated unchanged. Nitrous oxide can be degraded by interaction with vitamin B12 in intestinal bacteria. This results in inactivation of methionine synthesis and can produce signs of vitamin B12 deficiency (megaloblastic anemia and peripheral neuropathy) following long-term nitrous oxide administration. For this reason, N2O is not used as a chronic analgesic or as a sedative in critical care settings.

26. Nitrous Oxide • Clinical Use. Nitrous oxide is a weak anesthetic agent and produces reliable surgical anesthesia only under hyperbaric conditions. It does produce significant analgesia at concentrations as low as 20% and usually produces sedation in concentrations between 30% and 80%. It frequently is used in concentrations of approximately 50% to provide analgesia and sedation in outpatient dentistry. Nitrous oxide cannot be used at concentrations above 80% because this limits the delivery of an adequate amount of oxygen. Because of this limitation, nitrous oxide is used primarily as an adjunct to other inhalational or intravenous anesthetics. Nitrous oxide substantially reduces the requirement for inhalational anesthetics. For example, at 70% nitrous oxide, the MAC for other inhalational agents is reduced by about 60%, allowing for lower concentrations of halogenated anesthetics and a lesser degree of side effects.One major problem with N2O is that it will exchange with N2 in any air-containing cavity in the body. Moreover, because of their differential blood:gas partition coefficients, nitrous oxide will enter the cavity faster than nitrogen escapes, thereby increasing the volume and/or pressure in this cavity. Examples of air collections that can be expanded by nitrous oxide include a pneumothorax, an obstructed middle ear, an air embolus, an obstructed loop of bowel, an intraocular air bubble, a pulmonary bulla, and intracranial air. Nitrous oxide should be avoided in these clinical settings.

27. Nitrous Oxide • Cardiovascular System • Cardiac function generally preserved • When administered with halogenated inhalational anesthetics, it generally produces an increase in heart rate, arterial blood pressure, and cardiac output • When administered with an opioid, it generally decreases arterial blood pressure and cardiac output • Increased venous tone in both the peripheral and pulmonary vasculature • Pulmonary vascular resistance can be exaggerated in patients with pre-existing pulmonary hypertension and the drug generally is not used in these patients

28. Nitrous Oxide • Respiratory System • Modest increases in respiratory rate and decreases in tidal volume • Minute ventilation is not significantly changed and PaCO2 remains normal • Depressed ventilatory response to hypoxia • Monitor arterial O2 saturation directly in patients receiving or recovering from nitrous oxide

29. Nitrous Oxide • Nervous System • Increased cerebral blood flow and intracranial pressure • Administered with intravenous anesthetic agents, increases in cerebral blood flow are attenuated or abolished • Administered with halogenated inhalational anesthetic, vasodilatory effect on the cerebral vasculature is slightly reduced • Muscle • Does not relax skeletal muscle • Does not enhance neuromuscular blocking drugs • Does not trigger malignant hyperthermia • Kidney, Liver, and Gastrointestinal Tract • Neither nephrotoxic nor hepatotoxic

30. Xenon • Xenon is an inert gas that first was identified as an anesthetic agent in 1951. It is not approved for use in the United States and is unlikely to enjoy widespread use because it is a rare gas that cannot be manufactured and must be extracted from air. This limits the quantities of available xenon gas and renders xenon very expensive. Despite these shortcomings, xenon has properties that make it a virtually ideal anesthetic gas that ultimately may be used in critical situations.Xenon is extremely insoluble in blood and other tissues, providing for rapid induction and emergence from anesthesia. It is sufficiently potent to produce surgical anesthesia when administered with 30% oxygen. Most importantly, xenon has minimal side effects. It has no effects on cardiac output or cardiac rhythm and is not thought to have a significant effect on systemic vascular resistance. It also does not affect pulmonary function and is not known to have any hepatic or renal toxicity. Finally, xenon is not metabolized in the human body. Xenon is an anesthetic that may be available in the future if limitations on its availability and its high cost can be overcome.

31. Structures of IV General Anesthetics

33. Induction of Anesthesia • Parenteral anesthetics • Rapid onset and short duration after a single bolus dose • Accumulate in fatty tissue • Prolonging recovery if multiple doses or infusion are given • Particularly for drugs with lower rates of clearance • Each has its own unique set of properties and side effects • Propofol most commonly used parenteral agent • Thiopental slightly reduced hypotension, good track record • Etomidate usually is reserved for patients at risk for hypotension and/or myocardial ischemia • Ketamine is best suited for patients with asthma or for children undergoing short, painful procedures

34. Pharmacokinetics • Small, hydrophobic, substituted aromatic or heterocyclic compounds • Hydrophobicity is the key factor governing their pharmacokinetics • Partition into the highly perfused and lipophilic tissues of the brain and spinal cord • Produce anesthesia within a single circulation time • Blood levels fall rapidly • Diffuses into less perfused tissues such as muscle and viscera • Finally, the poorly perfused but very hydrophobic adipose tissue

35. Pharmacokinetics • Redistribution out of the CNS back into the blood • Termination of anesthesia after single boluses primarily reflects redistribution out of the CNS rather than metabolism • After redistribution, blood levels fall according to a complex interaction between the metabolic rate and the amount and lipophilicity of the drug stored in the peripheral compartments • Half-lives are "context-sensitive”

36. For example, after a single bolus of thiopental, patients usually emerge from anesthesia within 10 minutes; however, a patient may require more than a day to awaken from a prolonged thiopental infusion. Most individual variability in sensitivity to parenteral anesthetics can be accounted for by pharmacokinetic factors. For example, in patients with lower cardiac output, the relative perfusion of and fraction of anesthetic dose delivered to the brain is higher; thus, patients in septic shock or with cardiomyopathy usually require lower doses of anesthetic. The elderly also typically require a smaller anesthetic dose, primarily because of a smaller initial volume of distribution.

38. Barbiturates • Chemistry and Formulations. Anesthetic barbiturates are derivatives of barbituric acid (2,4,6-trioxohexahydropyrimidine), with either an oxygen or sulfur at the 2-position. The three barbiturates used for clinical anesthesia are sodium thiopental, thiamylal, and methohexital. Sodium thiopental (PENTOTHAL) has been used most frequently for inducing anesthesia. The barbiturate anesthetics are supplied as racemic mixtures despite enantioselectivity in their anesthetic potency. Barbiturates are formulated as the sodium salts with 6% sodium carbonate and reconstituted in water or isotonic saline to produce 1% (methohexital), 2% (thiamylal), or 2.5% (thiopental) alkaline solutions with pHs of 10 to 11. Once reconstituted, thiobarbiturates are stable in solution for up to 1 week, methohexital for up to 6 weeks if refrigerated. Mixing with more acidic drugs commonly used during anesthetic induction can result in precipitation of the barbiturate as the free acid; thus, standard practice is to delay the administration of other drugs until the barbiturate has cleared the intravenous tubing.

39. Barbiturates: Thiopental and Thiamylal • Produces unconsciousness in 10 to 30 seconds with a peak effect in 1 minute and duration of anesthesia of 5 to 8 minutes • Neonates require higher dose • Elderly/pregnant require lower dose • Doses can be reduced by 10% to 50% after premedication with benzodiazepines, opiates, or a2 adrenergic agonists • Thiopental produces garlic taste prior to induction • Intra-arterial injection of thiobarbiturates can induce a severe inflammatory and potentially necrotic reaction and should be avoided

40. Barbiturates: Methohexital • More potent • Pain in injection • Can produce excitement phenomena such as muscle tremor, hypertonus, and hiccups • Rapid clearance

41. Barbiturates: PK • Primarily eliminated by hepatic metabolism • Renal excretion of inactive metabolites • Small fraction of thiopental undergoes desulfuration to the longer-acting hypnotic pentobarbital • Highly protein bound • Hepatic disease or other conditions that reduce serum protein concentration will increase the initial free concentration and hypnotic effect of an induction dose

42. Barbiturates • Nervous System • Dose dependent reduction of cerebral O2 consumption • Cerebral blood flow and intracranial pressure are similarly reduced • Thiopental has been used as a protectant against cerebral ischemia • At least one human study suggests that thiopental may be efficacious in ameliorating ischemic damage in the perioperative setting • Reduced intraocular pressure • Anticonvulsant • Thiopental in particular is a proven medication in the treatment of status epilepticus

43. Barbiturates • Cardiovascular • Dose-dependent decrease in blood pressure • Vasodilation, particularly venodilation • Direct decrease in cardiac contractility • Heart rate increases as a compensatory response to a lower blood pressure • Baroreceptor reflex blunted • Hypotension can be severe in patients with an impaired ability to compensate for venodilation such as those with hypovolemia, cardiomyopathy, valvular heart disease, coronary artery disease, cardiac tamponade, or b adrenergic blockade • Not contraindicated in patients with coronary artery disease • None of the barbiturates has been shown to be arrhythmogenic

44. Barbiturates • Respiratory • Respiratory depression • Decreased minute ventilation and tidal volume with a smaller and inconsistent decrease in respiratory rate • Reflexes to hypercarbia and hypoxia are diminished • Little effect on bronchomotor tone and can be used safely in asthmatics

45. Barbiturates • Other Side Effects • Short-term administration of barbiturates has no clinically significant effect on the hepatic, renal, or endocrine systems • Single induction dose of thiopental does not alter tone of the gravid uterus, but may produce mild transient depression of newborn activity • True allergies to barbiturates are rare; however, direct drug-induced histamine release is occasionally seen • Can induce fatal attacks of porphyria in patients with acute intermittent or variegate porphyria and are contraindicated in such patients.

46. Propofol • Chemistry and Formulations Propofol now is the most commonly used parenteral anesthetic in the United States. The active ingredient in propofol, 2,6-diisopropylphenol, is essentially insoluble in aqueous solutions and is formulated only for IV administration as a 1% (10 mg/ml) emulsion in 10% soybean oil, 2.25% glycerol, and 1.2% purified egg phosphatide. In the United States, disodium EDTA (0.05 mg/ml) or sodium metabisulfite (0.25 mg/ml) is added to inhibit bacterial growth. Nevertheless, significant bacterial contamination of open containers has been associated with serious patient infection; propofol should be either administered or discarded shortly after removal from sterile packaging.

47. Dosage and Clinical Use. The induction dose of propofol (DIPRIVAN) in a healthy adult is 1.5 to 2.5 mg/kg and it has an onset and duration of anesthesia similar to thiopental. As with barbiturates, dosages should be reduced in the elderly and in the presence of other sedatives and increased in young children. Because of its reasonably short elimination half-life, propofol often is used for maintenance of anesthesia as well as for induction. For short procedures, small boluses (10% to 50% of the induction dose) every 5 minutes or as needed are effective. An infusion of propofol produces a more stable drug level (100 to 300 mg/kg per minute) and is better suited for longer-term anesthetic maintenance. Infusion rates should be tailored to patient response and the levels of other hypnotics. Sedating doses of propofol are 20% to 50% of those required for general anesthesia. However, even at these lower doses, caregivers should be vigilant and prepared for all of the side effects of propofol discussed below, particularly airway obstruction and apnea. Propofol elicits pain on injection that can be reduced with lidocaine and the use of larger arm and antecubital veins. Excitatory phenomena during induction with propofol occur at about the same frequency as with thiopental, but much less frequently than with methohexital.

48. Propofol: PK • Onset and duration of anesthesia similar to thiopental • Recovery much faster after propofol than after thiopental or even methohexital • Very high clearance • Slow diffusion from the peripheral to the central compartment • Less severe hangover compared with barbiturates • Metabolized in the liver to less active metabolites that are renally excreted • Clearance exceeds hepatic blood flow, and anhepatic metabolism has been demonstrated • Highly protein bound, and its pharmacokinetics, like those of the barbiturates, may be affected by conditions that alter serum protein levels

49. Propofol • Nervous System • Decreased cerebral O2 demand, cerebral blood flow, and intracranial and intraocular pressures by about the same amount as thiopental • Has been used in patients at risk for cerebral ischemia • No human outcome studies have been performed to determine its efficacy as a neuroprotectant • Anticonvulsant effects of propofol have been mixed • Some data even suggest it has proconvulsant activity when combined with other drugs

50. Propofol • Cardiovascular • Dose dependent decrease in blood pressure significantly greater than that of thiopental • Vasodilation and mild depression of myocardial contractility • Blunted baroreceptor reflex or is direct vagotonic activity • Smaller increases in heart rate are seen for any given drop in blood pressure after doses of propofol