Anaesthetic Adverse Drug Reactions

Anaesthetic Adverse Drug Reactions

INTRODUCTION

Anaesthesia requires the exposure of a patient to a mixture of drugs in a short space of time. The main groups of drugs selectively used for anaesthe-sia include the intravenous anaesthetic agents, the gases and volatile inhalational agents, neuromuscu-lar blocking drugs and selected benzodiazepines and analgesics. For these groups, allergic reactions can be a source of adverse events. In the United Kingdom, the incidence and severity of anaphylactic reactions are unclear. A report of suspected anaphylactic reac-tions associated with anaesthesia from the Association of Anaesthetists of Great Britain and Ireland (AAGBI) and British Society for Allergy and Clinical Immunol-ogy (2003) from 1 January 1995 to 22 June 2001 identified from Medicines and Healthcare Regulatory Agency (MHRA) figures a total of 361 (36 fatal) reactions described as anaphylactic shock, anaphylac-tic reaction or anaphylactoid reaction compared with 2074 (76 fatal) for all reported reactions. Hence, 361 of 2074 (17%) of all reported allergic drug reactions occur in the context of anaesthesia, and 10% are fatal compared with 4% for all drugs. It is possible that the intravenous route for many anaesthetic agents predis-poses patients to these reactions, and more than 90% of reports occurred immediately or soon after induc-tion of anaesthesia. The MHRA yearly average for reported suspected anaphylactic reactions related to anaesthesia is 55 per year compared with 319 for all drugs. Unfortunately, there is no denominator data to calculate the frequency of allergic reactions. However, the report by the AAGBI estimates that in the United Kingdom there are 500 anaphylactic reactions annu-ally by using epidemiological data from France and Australia. Previous estimates for the United Kingdom ranged from 350 to 5000 patients per year (Clarke and Watkins, 1993).

Anaesthetists are also working in intensive care units (ICUs) where similar drugs to those used during surgery are continued for longer periods. A recent USA national survey complied from data in 1998 identified the sedative agents most often used for over 72 hours to be opioids and benzo-diazepines. If mechanical ventilation was main-tained, then neuromuscular blocking drugs were also administered, such as vecuronium and pancuronium (Rhoney and Murry, 2003). Less than half the units in this survey used protocols, and drug selection was based on physician preference. In the United Kingdom in a similar survey, the most commonly used drugs for sedation were opioids (e.g. alfentanil and morphine), benzodiazepines (e.g. midazolam) and propofol (Murdoch and Cohen, 2000). Neuromuscu-lar blocking agents were rarely used but of those that were atracurium was the commonest. For chil-dren, propofol was still being used despite reports of adverse drug effects in this situation. A review of the risks involved in patient care using long-term anaes-thetic infusions has identified the following adverse effects (Riker and Fraser, 2005):

•   propofol infusion syndrome (see below);

•   propylene glycol intoxication (Cawley, 2001);

•   prolonged QTc intervals with analgesics and antipsychotics (Glassman and Bigger, 2001);

•   interference with bone healing with non-steroidal anti-inflammatory drugs (Reuben, Ablett and Kaye, 2005) and

•   delirium/withdrawal after opioid combinations with benzodiazepines (Korak-Leiter et al., 2005)