INHALATIONAL ANESTHETICS Nitrous Oxide (N 2 O)

Transcription

1 INHALATIONAL ANESTHETICS Nitrous Oxide (N 2 O) -low molecular weight, clear, odorless, inert, inorganic gas -non-flammable but does support combustion -gas at room temperature, kept as liquid under pressure -low blood solubility (B:G partition coefficient 0.47) "=> rapid induction -low tissue solubility (tissue gas solubility coefficient 1.22) "=> rapid emergence -oil:gas partition coefficient 1.4 -weak anesthetic (MAC 104%) most commonly used in conjunction with a volatile anesthetic or moderate dose narcotic technique -MAC awake approximately 60% -prominent analgesic effects -minimal skeletal muscle relaxation -may play a role in the development of PONV but studies remain inconclusive (E. Eger states that there is no difference in the occurrence of PONV in cases which used N 2 O 50% vs. those which used none) respiratory effects: -minimal at [ ] of 50% or less -does not increase PaCO 2 -produces little ventilatory depression -profoundly depresses the ventilatory response to arterial hypoxemia -*is the only inhalational anesthetic to increase pulmonary vascular resistance, especially in patients with preexisting pulmonary hypertension CV effects: -produces either no change or modest increases in BP, SVR and CO from activation of the SNS -depresses the carotid sinus -produces mild sympathetic stimulation as evidenced by: -increase in plasma catecholamines -mydriasis -increase in body temperature -diaphoresis -increase in RAP

2 -vasoconstriction of the pulmonary and systemic circulations, including cutaneous beds -causes profound circulatory depression in the presence of opioids as evidenced by: -decrease in BP, CO -increases LVEDP and SVR ***lt is possible that opioids inhibit the sympathomimetic effects of N 2 O thereby unmasking a cardiac depressant effect excretion: -eliminated primarily as an expired gas -approximately 0.004% undergoes reductive metabolism to nitrogen from activity of anaerobic bacteria in the Gl tract miscellaneous: -does not potentiate the effects of non-depolarizing muscle relaxants -does not trigger MH ***because it is 34X more soluble than nitrogen in the blood, it diffuses into air containing body cavities and can increase the pressure or expand the volume of gas in these cavities resulting in: -distention of the bowel -expansion or rupture of pulmonary cysts -expansion or rupture of the tympanic membrane in an occluded middle ear -pneumoencephalus -expansion of air emboli in the bloodstream -expansion of pneumothorax -expansion of cuffs of ETT or LMA -causes a negative Ames test but has been implicated in causing an increased incidence of SAB in OR and PACU personnel -irreversibly oxidizes the cobalt atom of vitamin B 12 thereby inactivating it and interfering with the synthesis of these enzymes: -methionine synthase (important in the formation of myelin) -thymidylate synthase (important in the formation of DMA) -may cause megaloblastic changes and agranulocytosis in bone marrow which is directly related to the interference of DMA synthesis-has a deleterious effect on hematopoiesis ***contraindicated for use in pregnancy, the immunosuppressed, and pts with pernicious anemia -overexposure may lead to peripheral neuropathies

3 isoflurane (Forane) F Ci F i i i F-C-C-0-C-H i i i F H F -a halogenated hydrocarbon (methyl ethyl ether); an isomer of enflurane -clear, non-flammable liquid at room temperature -pungent, ethereal odor -extremely stable not degraded by soda lime or light -vapor pressure 240 mm Hg -molecular weight 184 -since it is an isomer of enflurane, it exhibits similar pharmacologic properties -devoid of seizure activity, hepatic, or renal damage -intermediate blood solubility (B:G partition coefficient 1.4) -tissue gas solubility 110 -MAC 1.15% (intermediate potency) -MAC awake approximately 173 rd of MAC -oikgas solubility 91 respiratory effects: -produces significant respiratory depression (dose dependent) CV effects: -cardiac output may increase from SNS response to hypercapnia from hypoventilation -may possess some intrinsic sympathomimetic properties -*most potent vasodilator of the volatile agents; decreases SVR -causes coronary steal in steal-prone pts -does not sensitize the myocardium to catecholamines CNS effects: -same as the other volatiles with regard to CMRO 2) CBF, and ICP renal/hepatic effects: -least deleterious effect on both systems actually best of all the volatiles at preserving hepatic blood flow

4 muscular: -provides profound skeletal muscle relaxation greatest of all of the volatile agents -potentiates the effects of the NDMBs -relaxes uterine smooth muscle -triggers MH excretion: -primarily excreted unchanged as expired gas -undergoes minimal hepatic degradation (approximately 0.2%)

5 desflurane (Suprane) F F F I t i F-C-C-0-C-H i i i F H F -a fluorinated methyl ethyl ether structurally similar to isoflurane with substitution of a fluorine atom on the alpha ethyl carbon -vapor pressure 664 mm Hg must be vaporized through a heater -molecular weight 168 -stable in soda lime -pungent odor; may irritate airways especially at [ ] > than 1 MAC -MAC 4.58% to 6.3% (not extremely potent) -MAC awake approximately I/3" 1 of MAC -insoluble in blood (B:G coefficient 0.42) c >rapid induction/emergence expected -low oil:gas partition coefficient low tissue:gas partition coefficient (35); surrendered quickly as agent dissipates CV, respiratory, CMS, hepatic, renal, muscular effects: -thought to be similar in effects on all systems to isoflurane; may have a slightly greater effect in decreasing SVR -newer studies report that cardiac stimulation (i.e. tachycardia) is noted with rapid increases in [ ] -does not cause coronary steal in canine model; human studies pending -does not sensitize the myocardium to catecholamines -may provide cardiac protection in the face of ischemia -does not bronchodilate may actually cause bronchoconstriction and respiratory irritation (6% or greater) especially in smokers -may impair cerebral autoregulation at [ ] > 0.5 MAC -reports of greater incidence of PONV -recently reported to cause less post-operative delirium in the pedi population -**may cause CO toxicity if administered through desiccated soda lime metabolism: -undergoes minimal biotransformation in the liver (approximately 0.02%)

6 sevoflurane (Ultane) F l F - C - F F H-C-0-C-H F-C-F I F H -a fluorinated methyl ethyl ether -vapor pressure 160 mm Hg -molecular weight 200 -unstable in soda lime leads to formation of Compound A which is nephrotoxic (occurrence primarily in Baralyme) ***fresh gas flows of <2l/min not recommended -odor less pungent; well accepted for inhalation induction -may react with glass; H 2 O added as a preservative; unnecessary in plastic or aluminum containers -insoluble in blood (B:G coefficient 0.69) -tissue:gas solubility 99 -MAC 1.71 (intermediate potency) -MAC awake approximately l/3 rd of MAC -poor lipid solubility (oil:gas partition coefficient 55) CV effects: -similar effects as other volatiles, particularly desflurane -does not cause SNS stimulation with rapid increases in [ ] -does not cause coronary steal -does not sensitize the heart to catecholamines -mildly depresses myocardial contractility CNS effects: -preserves cerebral autoregulation at [ ] up to 1.5 MAC -increase in CBF parallels ICP -recent reports of seizure activity with high [ j in a non-epileptic pt respiratory effects: -depresses respiration like other volatiles -non-irritating to the airways; may reverse bronchospasm, status asthmaticus hepatic, muscular effects: -similar to those of desflurane -triggers MH metabolism: -deflourination exceeds that of enflurane; still only 1/3 rd of potential renal toxic dose -undergoes minimal hepatic degradation (2-3%)