• DOI:10.1111/j.1365-2044.2005.04325.x
• Corpus ID: 27825801

Etomidate for emergency anaesthesia; mad, bad and dangerous to know?

@article{Morris2005EtomidateFE,
  title={Etomidate for emergency anaesthesia; mad, bad and dangerous to know?},
  author={C. Morris and Catherine McAllister},
  journal={Anaesthesia},
  year={2005},
  volume={60}
}

• C. Morris, C. McAllister
• Published 1 August 2005
• Medicine
• Anaesthesia

In the United Kingdom over the period 2001 ⁄ 02, a total of 20 130 deaths within 30 days of surgery were reported to NCEPOD (National Confidential Enquiry into Patient Outcomes and Deaths) [1]. Of these deaths, 15.8% followed non-elective surgery (i.e. urgent or emergency), although this proportion was nearer 25% for certain specialties such as trauma, orthopaedics, vascular and neurosurgery. Similarly, in the placebo limb of a recent study of high risk patients undergoing major elective surgery, mortality rates were 17% [2]. Many factors have been implicated as contributing to peri-operative mortality and morbidity, but has the anaesthetic induction agent etomidate largely escaped scrutiny? For many anaesthetists, and increasingly emergency physicians and prehospital paramedic teams, etomidate is the drug of choice in ‘high risk patients’. We seriously question whether its reputation for safety in emergency anaesthesia is justified and if it should continue to be used in any practice. The carboxylated imidazole anaesthetic agent etomidate was synthesised in 1964 and introduced into practice in 1972. It rapidly gained a reputation as an agent for use in shocked or haemodynamically unstable patients; the ideal or at least the least hazardous induction agent for use in emergency anaesthesia. Etomidate is most commonly used in Europe but it has been withdrawn in the United States, Australia, Canada and the Republic of Ireland, and concerns have been raised previously regarding its use in anaesthesia [3–5] and in the intensive care unit [6]. Countries with licence for use of etomidate include Albania, Austria, Belgium, Brazil, Chile, Colombia, Croatia, Czechia, Denmark, Estonia, Finland, France, Germany, Greece, Jordan, Lebanon, Macedonia, Malaysia, Mexico, Netherlands, Paraguay, Poland, Portugal, Slovenia, Slovakia, South Africa, Spain, Taiwan, Turkey and United Kingdom (personal communication Anuca Somasekaram, Medical Information Assistant, Jansen Cilag UK). While soluble in water, etomidate is chemically unstable as such and was formulated in the United Kingdom in 35% propylene glycol (Hypnomidate , Janssen Cilag, High Wycombe, UK). This hyperosmolar formulation has been associated with thrombophlebitis and pain on injection in approximately one quarter of patients [7] and with haemolysis [8]. A lipid formulation (Lipuro, Braun, Sheffield, UK) has been developed to reduce these effects and has renewed interest in the drug [6, 9]. Following intravenous bolus administration (0.3 mg.kg), onset of anaesthesia is compatible with rapid sequence induction and securing the airway in an emergency. Clinical duration is short, principally due to re-distribution, but this may be prolonged with concurrent use of fentanyl. Other adverse effects are common and include myoclonus, dystonic reactions and nausea and vomiting (in up to one-third of patients). Despite these problems, which have limited its use in elective circumstances, etomidate has been popular due to its relative cardiovascular stability. Following bolus administration for induction of anaesthesia, cardiac output and inotropy, systemic vascular resistance and arterial pressure are all well maintained [10, 11]. However, it is well recognised that etomidate inhibits the mitochondrial 11 b hydroxylase enzyme of the adrenal steroid synthesis pathway [12, 13]. In the elective situation and among otherwise healthy patients who do not subsequently develop critical illness, adrenal suppression is relatively short lived and has not been associated with adverse outcomes, although there are limited data to confirm this [14, 15]. However, insights into the full implications of these effects come from studies suggesting suppression persisting for at least 24 h following cardiac surgery [16] and amongst critically ill patients, where a single dose of etomidate suppressed a cortisol increment > 200 nmol.l for 24 h [17] and in the emergency room where etomidate suppressed early corticotrophin testing [18]. Among elective patients undergoing gynaecological surgery the cortisol response to surgery was absent at 48 h after a single bolus of etomidate [19]. While prolonged infusions of etomidate have been evaluated as a sedative regimen in the ICU, a moratorium has been placed on this practice following a substantial increase in mortality (28% to 77%, p < 0.0005) among multiply injured trauma patients; mortality returned to 25% when etomidate was discontinued [20]. Among patients who survived beyond 5 days, a clear relationship between depressed cortisol levels and etomidate use emerged, with all patients having at least one random cortisol concentration < 260 nmol.l and 10 ⁄ 17 (58.8%) having at least one < 100 nmol.l. By contrast, all 170 patients not receiving etomidate achieved random cortisol concentrations > 260 nmol.l. Similarly, inotrope requirements were four times higher in the etomidate group (20% vs. 81%) and, in the same unit, cortisol replacement in severely stressed patients on etomidate infusions was found to improve outcome [21]. Perhaps less well known is the use of etomidate as therapy for Cushing’s syndrome; not only is etomidate associated with impaired production in times of critical illness, but it is so effective that it can suppress ectopic hypersecretion [22, 23]. The understanding of the adrenal axis during critical illness has undergone considerable developments in recent years. Following ‘stress’, i.e. shock, trauma, sepsis and surgery itself, elevated levels of cortisol (> 500 nmol.l) are seen almost universally, with the Anaesthesia, 2005, 60, pages 737–740 .....................................................................................................................................................................................................................