Clinical Pharmacokinetics of the Inhalational Anaesthetics

Abstract

At present, the most widely used inhalational anaesthetics are the halogenated, inflammable vapours halothane, enflurane, isoflurane and the gas nitrous oxide. The anaesthetic effect of these agents is related to their tension or partial pressure in the brain, represented at equilibrium by the alveolar concentration. The minimum alveolar concentration for a specific agent is remarkably constant between individuals. The uptake and distribution of inhalational anaesthetics depends on inhaled concentration, pulmonary ventilation, solubility in blood, cardiac output and tissue uptake. Inhalational anaesthetics are mainly eliminated by pulmonary exhalation, but significant amounts of halothane are removed by hepatic metabolism. Inhalational agents currently in use have acceptable pharmacokinetic characteristics, and clinical acceptance depends on their potential for adverse effects. Induction of anaesthesia with halothane is rapid and relatively pleasant and it is the agent of choice for paediatric anaesthesia. Between 20 and 50% is metabolised, and the parent drug is a potent inhibitor of drug metabolism. Post-operatively enzyme induction may follow. The major disadvantages of halothane are myocardial depression, propensity to evoke cardiac arrhythmias and the rare but serious halothane hepatitis. Induction and recovery from enflurane anaesthesia is rapid. Metabolism accounts for 5 to 9% of the elimination. The metabolic product inorganic fluoride may in rare cases cause renal toxicity. Enflurane is a weak inhibitor of drug metabolism at anaesthetic concentrations. Enflurane depresses circulation more than halothane by reducing both myocardial contractility and systemic vascular resistance, but cardiac rhythm is stable. Enflurane anaesthesia may, unlike the other agents, induce epileptic activity. Enflurane is widely used as replacement for halothane in adults. Despite its low blood-gas solubility, the airway irritability of isoflurane precludes a faster induction of anaesthesia than with halothane. Isoflurane is almost resistant to biodegradation. Myocardial contractility is maintained during isoflurane anaesthesia and cardiac rhythm is stable except for the occurrence of tachycardia in some patients. Isoflurane is the inhalational agent of choice for neurosurgical operations. Sevoflurane is an experimental ether vapour: induction and recovery is fast and pleasant. It is metabolised to the same extent as enflurane and subnephrotoxic concentrations of inorganic fluoride may result. Sevoflurane has fewer respiratory and cardiovascular depressant effects than halothane and may be a future alternative for paediatric anaesthesia.(ABSTRACT TRUNCATED AT 400 WORDS)

Investigation of the metabolic fate of 2‐, 3‐ and 4‐bromobenzoic acids in bile‐duct‐cannulated rats by inductively coupled plasma mass spectrometry and high‐performance liquid chromatography/inductively coupled plasma mass spectrometry/electrospray mass spectrometry

“…This indicates the presence of inorganic bromide. The probable source for this is either bromide originating from the diet16 or from the halothane used to anaesthetise the rats 3 days prior to dosing, as bromide is a known halothane metabolite 17. Analysis by HPLC/ICPMS/ESI‐MS failed to detect any bromine isotope patterns in the solvent front, but, since the scan was performed over the range m/z 100–600, inorganic bromide at m/z 79 and 81 would not be detected.…”

Environmental Implications of Anesthetic Gases

“…Because N 2 O is minimally metabolized in humans (with an approximate rate of 0.004%), it retains its pharmacological effect when exhaled into the room by the patient, and can pose an intoxicating and prolonged exposure hazard to operating room personnel if the room is poorly ventilated. 8 It has been estimated that more than 250,000 health care professionals in the United States who work in hospitals, operating rooms, dental offices, and veterinary clinics are potentially exposed to WAGs and are at risk of an occupational illness. 9 These agents are also a recognized greenhouse gas, accounting for around 6% of the heating effect of greenhouse gases in the atmosphere.…”

Intrathoracic fire during preparation of the left internal thoracic artery for coronary artery bypass grafting

“…In such cases we must understand that high oxygen concentrations in closed spaces could increase a risk of fire [8,9,12]. It is important to note that under normal circumstances, modern inhalation anesthetics are not ignitable [13]. …”