Halogenated inhalational anaesthetics

The halogenated inhalational anaesthetics halothane, enflurane, isoflurane and desflurane can produce metabolic hepatocellular injury in humans to a variable extent. During metabolism of these anaesthetics, tissue acetylation occurs due to the formation of reactive intermediates. Proteins modified by acetylation may constitute neo-antigens with a potential for triggering an antibody-mediated immune response. The likelihood of suffering post-operative immune hepatitis depends on the amount of the anaesthetic metabolized and is thereby considerably less with enflurane, isoflurane or desflurane compared with halothane. Plasma inorganic fluoride concentrations are regularly increased after sevoflurane. Elevated inorganic fluoride concentrations have been associated with nephrotoxicity following methoxyflurane anaesthesia but not after sevoflurane. Another source of concern is the products of degradation from reactions with carbon dioxide absorbents. Most important is compound A, which has been shown to exhibit nephrotoxicity in rodents. However, no significant changes in renal function parameters have been reported in surgical patients.     

Occupational hazards of inhalational anaesthetics

Occupational exposure to inhalational anaesthetics has often been associated with health hazards and reproductive toxicity, but the available evidence is weak and comes mostly from epidemiological studies that have been criticized. Studies based on registered data generally showed no association between occupational exposure to inhalational anaesthetics and reproductive effects. Animal studies also showed a lack of carcinogenicity, organ toxicity and reproductive effects with trace concentrations, as observed in operating rooms. The exception may be nitrous oxide, which in some, but not all, studies showed teratogenicity in rats chronically exposed to concentrations of 1000 p.p.m. and higher, such as may occur in unscavenged operating rooms lacking a mechanical ventilation system. Occupational exposure has also been associated with impairment of psychological functions, but these effects do not occur with trace concentrations. All in all, the scientific evidence for hazards is weak. Nonetheless, it is good practice to limit levels of exposure.     

Drug interactions with inhalational anaesthetics

The literature concerning the interactions between volatile anaesthetics, nitrous oxide and other compounds is reviewed. The majority are well known and most can be managed by careful dosage of the anaesthetics. The following interactions should be stressed since these are less predictable or potentially fatal. Of the cardiovascular drugs mainly the Ca+ + channel blockers require attention. The volatile anaesthetics act synergistically with these drugs on the inhibition of cardiac conduction and may induce cardiac arrest. Aminoglycoside therapy should prompt an alternative to enflurane because of increased nephrotoxicity with this combination. Thiopentone induction makes the dog heart more susceptible to arrhythmias, especially during anaesthesia with volatile anaesthetics. Probably pentobarbitone, etomidate or a benzodiazepine should be preferred as an alternative to thiopentone when the use of adrenergic drugs peroperatively is anticipated. Nitrous oxide augments the sequelae after coronary air emboli and impaired cerebral perfusion in animals. The necessity of this drug should therefore be considered when anaesthetizing patients undergoing open heart surgery and patients with severe carotic or cerebral arteriosclerosis.     

Biotransformation and toxicity of inhalational anaesthetics

Canadian Journal of Anesthesia/Journal canadien d'anesthésie - In summary, anaesthetics and drugs used perioperatively are all xenobiotics and can be metabolized mainly by microsomal...     

The effect of inhalational anaesthetics on QTc interval

BACKGROUND AND OBJECTIVE: The aim of this study was to assess time dependent cumulative effects of three different inhalation anaesthetics on QTc interval during the maintenance of anaesthesia. METHOD: Seventy-five ASA I-II male patients undergoing inguinal herniorrhaphy were randomly allocated into three groups. No premedication was given. Anaesthesia was induced with thiopental and tracheal intubation was facilitated by vecuronium in all groups. Anaesthesia was maintained with 0.8% halothane (Group I) (n = 25), 1% isoflurane (Group II) (n = 25), or 2% sevoflurane (Group III) (n = 25) and 66% nitrous oxide in oxygen. Three lead electrocardiogram recordings were taken before induction, 2, 5, 10, 15, 30 and 45 min after induction and after extubation. Heart rate, systolic, diastolic, mean arterial pressure and SpO2 were recorded at the same time. Heart rate and corrected QT interval were evaluated by using Bazett's formula. Multivariate analysis of variance for repeated measures was used to determine intergroup and intragroup differences. RESULTS: There was no statistically significant difference in the baseline QTc values of the groups. There was no difference between QTc values with halothane and sevoflurane. There was a difference between QTc values with isoflurane and those with the other two inhalation anaesthetics (P < 0.05). Although QTc values in the isoflurane group were higher at all times, the critical value of 440 ms was not exceeded. CONCLUSION: We conclude that halothane 0.8%, isoflurane 1% and sevoflurane 2% do not prolong QTc interval.     

Interaction of inhalational anaesthetics with CO2 absorbents

We review the currently available carbon dioxide absorbents: sodium hydroxide lime (=soda lime), barium hydroxide lime, potassium-hydroxide-free soda lime, calcium hydroxide lime and non-caustic lime. In general, all of these carbon dioxide absorbents are liable to react with inhalational anaesthetics. However, there is a decreasing reactivity of the different absorbents with inhalational anaesthetics: barium hydroxide lime > soda lime > potassium-hydroxide-free soda lime > calcium hydroxide lime and non-caustic lime. Gaseous compounds generated by the reaction of the anaesthetics with desiccated absorbents are those that threaten patients. All measures are comprehensively described to--as far as possible--prevent any accidental drying out of the absorbent. Whether or not compound A, a gaseous compound formed by the reaction of sevoflurane with normally hydrated absorbents, is still a matter of concern is discussed. Even after very high loading with this compound, during long-lasting low-flow sevoflurane anaesthesias, no clinical or laboratory signs of renal impairment were observed in any of the surgical patients. Finally, guidelines for the judicious use of different absorbents are given.     

Action guidance for addressing pollution from inhalational anaesthetics

Climate change is a real and accelerating existential danger. Urgent action is required to halt its progression, and everyone can contribute. Pollution mitigation represents an important opportunity for much needed leadership from the health community, addressing a threat that will directly and seriously impact the health and well-being of current and future generations. Inhalational anaesthetics are a significant contributor to healthcare-related greenhouse gas emissions and minimising their climate impact represents a meaningful and achievable intervention. A challenge exists in translating well-established knowledge about inhalational anaesthetic pollution into practical action. CODA is a medical education and health promotion charity that aims to deliver climate action-oriented recommendations, supported by useful resources and success stories. The CODA-hosted platform is designed to maximise engagement of the global healthcare community and draws upon diverse experiences to develop global solutions and accelerate action. The action guidance for addressing pollution from inhalational anaesthetics is the subject of this article. These are practical, evidence-based actions that can be undertaken to reduce the impact of pollution from inhalational anaesthetics, without compromising patient care and include: removal of desflurane from drug formularies; decommissioning central nitrous oxide piping; avoidance of nitrous oxide use; minimising fresh gas flows during anaesthesia; and prioritising total intravenous anaesthesia and regional anaesthesia when clinically safe to do so. Guidance on how to educate, implement, measure and review progress on these mitigation actions is provided, along with means to share successes and contribute to the essential, global transition towards environmentally sustainable anaesthesia.     

Exposure of operating personnel to inhalational anaesthetics in paediatric surgery

High flows of halothane and N₂O are commonly used in children during induction of anaesthesia. We prospectively evaluated the efficiency of a double mask system in children, during inhalational induction with photoacoustic infrared spectroscopy. Thirty-two children 5 days to 8.5 years of age were studied. Anaesthesia was induced with inspired halothane concentrations of 2–3% and N₂O 50–70% in 6–8 litres of freshgas flow via a Jackson-Rees breathing system. Children were randomly assigned into two groups. Anaesthesia was induced in group 1 using a Rendell-Baker mask with a regular scavenging device (25 1·min^?1). In group II a double-mask system was connected to an active scavenging system (580 1 min^?1). Halothane and N₂O were measured at 10 cm below the chin of the anaesthesiologist. We could demonstrate that the use of double-mask system with a regular scavenging device substantially reduced the exposure of the anaesthesiologist to halothane by 89% and to N₂O 80% respectively during inhalational induction.     

A primigravida allegedly allergic to local anaesthetics

Pregnant patients may give a history of allergy to local anaesthetics, but many of these supposed allergies have not been investigated. There is cross-reactivity between the amide local anaesthetics, which are the only group available in the UK for regional analgesia. We report the management of a primigravida who gave a history of allergy to two local anaesthetics, lidocaine and prilocaine. She was admitted to the labour ward at 38 weeks' gestation for challenge testing to the amide local anaesthetic bupivacaine, with full resuscitation and delivery facilities available. The tests proved negative and she was allowed home. She was re-admitted at term in labour and requested epidural analgesia. Epidural bupivacaine with fentanyl was used without incident for labour and forceps delivery. Subsequent allergy testing to lidocaine also proved negative.     

Inhalational anaesthetics in the ICU: theory and practice of inhalational sedation in the ICU, economics, risk-benefit

ICU sedation poses many problems. The action and side-effects of intravenous drugs in the severely ill patient population of an ICU are difficult to control. The incidence of post-traumatic stress disorder after long-term sedation is high. The recent focus on propofol infusion syndrome entails restrictions in the use of this drug. On the other hand, volatile anaesthetics very selectively suppress consciousness but leave many autonomic functions intact. In the absence of perception and disturbed information processing the number of adverse experiences should be lower, leading to a better psychological outcome. Respiration and intestinal motility are not depressed, facilitating modern therapeutic concepts such as early enteral feeding and augmentation of spontaneous breathing. Awakening after inhalational ICU sedation is quick and predictable, extubation can be planned and organized, and the time during which the patient needs very close observation will be short. Technological advances have greatly simplified the application of inhalational anaesthetics. New anaesthesia ventilators offer ventilatory modes and high flow generation comparable to ICU ventilators. However, they are not yet licensed for stand-alone use. The introduction of a volatile anaesthetic reflection filter for the first time enables the concept of inhalational sedation to be performed with very little effort by many ICUs. This 'anaesthetic conserving device' (AnaConDa) is connected between the patient and a normal ICU ventilator, and it retains 90% of the volatile anaesthetic inside the patient just like a heat and moisture exchanger. In this chapter possible advantages of the new concept and the choice of the inhalational agent are discussed. The technical prerequisites are explained, and the practice and pitfalls of inhalational ICU sedation in general and when using the AnaConDa are described in detail.     

Effects of inhalational anesthetics on verapamil pharmacokinetics in dogs

Six dogs were chronically instrumented in order to collect aortic blood samples and record mean arterial pressure, cardiac output and heart rate. Each animal received verapamil 200 micrograms X kg-1 by 10-min intravenous infusions on four occasions in random sequence: awake, and during halothane 1.2%, enflurane 2.5%, and isoflurane 1.6% anesthesia. Rate of initial distribution of verapamil was reduced during anesthetic exposure. Verapamil intercompartmental clearance from the central compartment to the peripheral compartment was decreased during exposure to halothane and isoflurane, and tended to decrease during enflurane exposure as well. Verapamil terminal volume of distribution at steady-state was reduced by halothane, enflurane, and isoflurane exposure as compared with awake: 65 +/- 10, 80 +/- 9, and 93 +/- 191, respectively, versus 132 +/- 121 (mean +/- SEM; P less than 0.05). Verapamil total clearance was also reduced by halothane, enflurane, and isoflurane as compared with awake: 37 +/- 4, 39 +/- 2 and 41 +/- 31 X h-1, respectively, versus 64 +/- 71 X h-1 (P less than 0.05). Verapamil administered to awake animals resulted in a decrease from baseline in mean arterial pressure; 95 +/- 8 mmHg versus 108 +/- 4 mmHg (P less than 0.05): and an increase in cardiac output; 2.60 +/- 0.33 1 X min-1 versus 1.93 +/- 0.22 1 X min-1 (P less than 0.05). During halothane, enflurane, and isoflurane anesthesia, verapamil administration resulted in a similar decrease in mean arterial pressure; however cardiac output decreased, in contrast to the increase noted in awake animals.(ABSTRACT TRUNCATED AT 250 WORDS)