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...     

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.     

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.     

Effects of inhalational anaesthetics in experimental allergic asthma

We evaluated whether isoflurane, halothane and sevoflurane attenuate the inflammatory response and improve lung morphofunction in experimental asthma. Fifty‐six BALB/c mice were sensitised and challenged with ovalbumin and anaesthetised with isoflurane, halothane, sevoflurane or pentobarbital sodium for one hour. Lung mechanics and histology were evaluated. Gene expression of pro‐inflammatory (tumour necrosis factor‐α), pro‐fibrogenic (transforming growth factor‐β) and pro‐angiogenic (vascular endothelial growth factor) mediators, as well as oxidative process modulators, were analysed. These modulators included nuclear factor erythroid‐2 related factor 2, sirtuin, catalase and glutathione peroxidase. Isoflurane, halothane and sevoflurane reduced airway resistance, static lung elastance and atelectasis when compared with pentobarbital sodium. Sevoflurane minimised bronchoconstriction and cell infiltration, and decreased tumour necrosis factor‐α, transforming growth factor‐β, vascular endothelial growth factor, sirtuin, catalase and glutathione peroxidase, while increasing nuclear factor erythroid‐2‐related factor 2 expression. Sevoflurane down‐regulated inflammatory, fibrogenic and angiogenic mediators, and modulated oxidant–antioxidant imbalance, improving lung function in this model of asthma.     

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.     

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.     

Comparison of conventional and rapid inhalational induction of anaesthesia with enflurane

Inhalational induction of anaesthesia using either a conventional method or a vital capacity breath of 4% enflurane in 67% nitrous oxide was compared in 30 adult surgical patients. Induction time was significantly faster in patients who took a vital capacity breath (71, SD 22 versus 132, SD 18 seconds, p less than 0.01). There were no significant differences between groups in respect of systolic blood pressure, heart rate, arterial oxygen saturation or incidences of excitement or coughing. The vital capacity breath method was acceptable to 87% of patients.     

Early intravenous cannulation in children during inhalational induction of anaesthesia

Intravenous cannulation is obtained in almost all patients scheduled for operative intervention under anaesthesia. In our practice, inhalational induction precedes cannulation in children in order to avoid pain and discomfort, and cannulation is delayed until the child is adequately anaesthetized in fear of precipitating laryngospasm due to painful stimulus of venepuncture in the light stage of anaesthesia. This study was performed on 150 patients between two to eight years of age to determine if there is a difference in the incidence of untoward incidents, if cannulation is performed when children are lightly anaesthetized (Early, Group E), as compared to when they are deeply anaesthetized (Late, Group L). In patients randomized to early cannulation, the results showed that there was a significantly shorter time from induction to venous cannulation, the halothane concentration was lower at the time of cannulation, there was a greater incidence of movement on cannulation and a greater incidence of changes in heart rate, blood pressure, and respiratory rate. There was no significant differences in the incidence of laryngospasm or in the success rate of intravenous cannulation between the two groups. We conclude that venous cannulation can be safely performed during the light stages of anaesthesia.     

Pressure support ventilation during inhalational induction with sevoflurane and remifentanil in adults

BACKGROUND AND OBJECTIVE: The purpose of this prospective randomized study was to assess the value of pressure support ventilation during inhalational induction with sevoflurane in adult patients. METHODS: Thirty-five adult patients, ASA I-II and scheduled for ear nose throat surgery were studied. Vital capacity induction with 8% sevoflurane in 8 L min-1 oxygen was performed. Pressure support ventilation was used in Group 1 with pressure set at 15 cmH2O. In Group 2, patients breathed spontaneously. After 2 min, sevoflurane was set to 3% and remifentanil 1 microg kg(-1) was injected over 2 min followed by an infusion of 0.1 microg kg(-1) min(-1). Two minutes after the end of the bolus, intubation was performed. Bispectral index, oxygen saturation, respiratory rate, end-tidal carbon dioxide, expired tidal volume and expired sevoflurane concentration were recorded every minute. RESULTS: Eighteen patients were included in Group 1 and 17 in Group 2. Saturation, respiratory rate and end-tidal carbon dioxide were similar in the two groups. Expired tidal volume was significantly higher and bispectral index values significantly lower in Group 1. Intubating conditions were better in Group 1. CONCLUSIONS: Pressure support ventilation provides both better ventilation and deeper level of anaesthesia during inhalation induction with sevoflurane.