Anaesthetic Ether/Etomidate 1901
anaesthesia. Ether also possesses analgesic and muscle 400 micrograms/kg). Opioid analgesics or benzodiazepines berequired. The dose of etomidate should also be reduced in relaxant properties. Premedication with an antimuscarinic as premedication reduce myoclonic muscle movements; patients with hepatic cirrhosis. Caution may be appropriate such as atropine is necessary to reduce salivary and opioids also reduce injection site pain. A neuromuscular in patients with pre-existing epilepsy. bronchial secretions. blocker is necessary if intubation is required. See also Adverse Effects and Precautions for General Solvent ether is described on p. 2212.3. Anaesthetics, p. 1896.3. Administration in children. Etomidate is used in children Adverse Effects for the induction of anaesthesia; for details of doses, Effects on the endocrine system. Etomidate used for seda which may be proportionately larger than in adults, see tion in an intensive care unit was implicated in an Ether has an irritant action on the mucous membrane of the Uses and Administration, above. US licensed product increase in mortality. 1 However, there is considerable con respiratory tract; it stimulates salivation and increases information does not recommend the use of etomidate troversy about the effects of etomidate on mortality in cri bronchial secretion. Laryngeal spasm may occur. Ether below 10 years of age. In the UK, etomidate emulsion is tically-ill patients (such as those with severe trauma or causes vasodilatation which may lead to a severe fall in licensed for use in those aged over 6 months, although it sepsis) when given as a single bolus dose for induction.2 blood pressure and it reduces blood flow to the kidneys; it may be given to younger patients in emergencies, and One systematic review' concluded that the use of etomi also increases capillary bleeding. The bleeding time is other formulations do not specify a minimum age; the date for rapid tracheal intubation in ctitically-ill patients unchanged but the prothrombin time may be prolonged. BNFC suggests all etomidate products may be used for was associated with an increased risk of mortality; how Ether may cause malignant hyperthermia in certain induction from I month of age. ever, another review" that included patients receiving rou individuals. Alterations in kidney and liver function have tine surgical anaesthesia found this effect to be statistically been reported. Convulsions occasionally occur. Hyperglyc Administration in theelderly. A study1 in elderly patients insignificant. aemia due to gluconeogenesis has been noted. has shown that although reducing the rate of intravenous The UK CSM agreed that etomidate could cause a Recovery is slow from prolonged ether anaesthesia and injection of etomidate reduces the speed of induction, the significant fall in circulating plasma-cortisol concentrations, postoperative vomiting is common. Acute overdosage of dosage required is also reduced. Giving etomidate 0.2% umesponsive to corticotropin stimulation.' Other regulators ether is characterised by respiratory failure and cardiac solution at a rate of !Omg/minute induced. anaesthesia in have taken similar views in restricting the use of etomidate, arrest. a mean of 89.6 seconds and required a mean dose of which is now not given by prolonged infusion, essentially Dependence on ether or ether vapour has been reported. II 0 micrograms/kg. Corresponding values for a rate of limiting its licensed use to induction of anaesthesia. Prolonged contact with ether spilt on any tissue produces 40 mg/minute were 47.7 seconds and 260micrograms/kg, Licensed product information advises that the postoperative necrosis. respectively. See also Adverse Effects of General Anaesthetics, rise in serum-cortisol concentration, which has been noted 1. Berthoud MC, et al. Comparison of infusion rates of three i.v. anaesthetic after thiopental induction, is delayed for about 3 to 6 hours p. 1896.3. agents for induction in elderly patients. Br J Anaesth 1993; 70: 423-7. when etomidate is used for induction, A study comparing the effects of etomidate with those of Anaesthesia. Etomidate might be useful for induction if Precautions methohexital on the adrenocortical function of neonates rapid tracheal intubation is required with a competitive Ether anaesthesia is contra-indicated in patients with borne by mothers who received these agents for induction neuromuscular blocker as it has been shown to reduce the diabetes mellitus, impaired kidney function, raised CSF of anaesthesia before caesarean section indicated that there time to onset of block with vecuronium.l.2 Indeed, etomi pressure, and severe liver disease. Its use is not advisable in was no evidence to preclude the use of etomidate in such date has been suggested2•3 by some to be the agent of hot and humid conditions in patients with fever, as patients. However, regardless of which anaesthetic agent choice for rapid sequence induction of anaesthesia in convulsions are liable to occur, particularly in children and was used, early feeding was recommended to avoid emergency settings; advantages include rapid onset and in patients who have been given atropine. neonatal hypoglycaemia. short duration of action, predictable clinical effect, and 6 See also Precautions for General Anaesthetics, p. 1897.3. The inhibitory effect of etomidate on adrenocortical haemodynarnic stability. However, there is considerable function has been used to control episodes of hypercorti controversy about its use in critically-ill patients, see Interactions solaemia; for details, see Cushing's Syndrome, above. Effects on the Endocrine System, below. Ether enhances the action of competitive neuromuscular 1. Ledingham Watt I. Influence of sedation on mortality in critically ill 1. Gill RS, Scott RPF. Etomidate shortens the onset time of neuromuscular 1M. multiple trauma patients. Lancet 1983; i: 1270. blockers to a greater degree than most other anaesthetics. block. Br J Anaesth 1992; 69: 444-6. 2. Kulstad EB, et al. Etomidate as an induction agent in septic patients: red 2. Bergen JM, Smith DC. A review of etomidate for rapid sequence However, it does not potentiate the arrhythmogenic effect flags or false alarms? West J Emera Med2010 ; 11: 161-72. intubation in the emergency department. J of sympathomimetics, including adrenaline, as much as Bmero Med 1997; 15: 221-30. 3. Albert SG, et al. The effect of etomidate on adrenal function in critical 3. Nestor NB, Burton JH. ED use of etomidate for rapid sequence induction. other inhalational anaesthetics. illness: a systematic review. Intensive Care Med 2011; 37: 901-10. Am J Emero Med 2008; 26: 946-50. See also Interactions of General Anaesthetics, p. 1897.3. 4. Hohl CM, et al. The effect of a bolus dose of etomidate on cortisol levels, mortality, and health services utilization: a systematic review. Ann Emero Cushing's syndrome. There have been reports1·4 of benefit Med 2010; 56: 105-13.e5. P.��P.�������� . with the use of etomidate for acute control of hypercorti 5. Goldberg A. Etomidate. Lancet 1983; ii: 60. . - - ...... 6. Crozier TA, et al. Effects of etomidate on the adrenocortical and (details are given in Volume B) solaemia associated with Cushing's syndrome (p. 2559.1), ProprielaryPreparations metabolic adaptation of the neonate. Br J Anaesth 1993; 70: 47-53. particularly if the oral route is not available. Single-ingredient Preparations.S.Afr. : Hoffmans Druppels. I. Greening JE, et a!. Efficient short-term control of hypercortisolaemia by Fr. : Ger.: Hypersensitivity. Reactions involving innnediate wide Homoeopathic Preparations. Strophantus Compose; low-dose etomidate in severe paediatric Cushing's disease. Horm Res Angioton H; Angioton St; Corselect N; Crataegus comp; Dia 2005; 64: 140-3. spread cutaneous flushing or urticaria attributed to etomi date have been described.' There have also been reports2•3 card. 2. Johnson TN, Canada TW.Etomidate use for Cushing's syndrome caused by an ectopic adrenocorticotropic hormone-producing tumor. Ann of anaphylactic reactions after injection of etomidate. Pharmacother 2007; 41: 350-3. 1. Watkins J. Etomidate: an 'immunologically safe' anaesthetic agent. 3. Dabbagh A, et al. Etomidate infusion in the critical care setting for Anaesthesia 1983; 38 (suppl): 34-8. suppressing the acute phase of Cushing's syndrome. Anesth Anala 2009; Etomidate tBAN, usAN, rtNNJ 2. Krumholz W, et al. Ein fall von anaphylaktoider reaktion nach gabe von 108: 238-9. etomidat. Anaesthesist 1984; 33: 161-2. 4. Mettauer N, Brierley J. A novel use of etomidate for intentional adrenal 3. Sold M, Rothhammer A. Lebensbedrohliche anaphylaktoide reaktion suppression to control severe hypercortisolemia in childhood. Pediatr Crit nach etomidat. Anaesthesist 1985; 34: 208-10. Care Med 2009; 10: e37-e40.
Status epilepticus. General anaesthesia may be used to Interactions control refractory tonic-clonic status epilepticus (p. 510.2). A reduced dose of etomidate may be necessary in patients A short-acting barbiturate such as thiopental is usually who have received antipsychotics, sedatives, or opioids. The used, but other anaesthetics including etomidate have also hypnotic effect of etomidate has been potentiated by other been tried1 for intractable convulsive status epilepticus. sedative drugs. However, like several other anaesthetics there have been See also Interactions of General Anaesthetics, p. 1897.3. reports of seizures associated with its use in anaesthesia, 23 NOTE. Do not confuse with edetate; see Inappropriate especially in patients with epilepsy. Administration under Sodium Edetate, p. 155!.2. Calcium-channel blockers. Prolonged anaesthesia and 1. Yeoman P, et al. Etomidate infusions for the control of refractory status Cheyne-Stokes respiration after etomidate injection has Pharmacopoeias. In Chin., Bur. (see p. vii) and US. epilepticus. Intensive Care Med 1989; 15: 255-9. been reported in 2 patients also given verapami/.1 Ph. Eur. 8: (Etomidate). A white or almost white powder. 2. Nicoll K, Callender J. Etomidate-induced convulsion prior to electro convulsive therapy. Br J Psychiatry 2000; 177: 373. I. Moore CA. et al. Potentiation of etomidate anesthesia by verapamil: a M.p. about 68 degrees. Very slightly soluble in water; freely 3. Sen H, et al. Epileptic seizure during anaesthesia induction with report of two cases. Hosp Pharm 1989; 24: 24-5. soluble in alcohol and in dichloromethane.. Protect from etomidate. Middle East J Anesthesiol 2010; 20: 723-5. light. General anaesthetics. For a report of synergy between USP 36: (Etomidate). A white or almost white powder. Very Adverse Effectsand Precautions propofo / and etomidate, see p. 1912.2. slightly soluble in water; freely soluble in alcohol and in Excitatory phenomena (especially involuntary myoclonic dichloromethane. Protect from light. muscle movements, which are sometimes severe) are Pharmacokinetics common after injection of etomidate, but may be reduced After injection, etomidate is rapidly redistributed from the Uses and Administration by giving an opioid analgesic or a short-acting benzodia CNS to other body tissues, and undergoes rapid metabolism Etomidate is an intravenous anaesthetic used for the zepine beforehand. Pain on injection may be reduced by in the liver and plasma. Pharmacokinetics are complex and induction of general anaesthesia (p. 1896.1). Anaesthesia is giving etomidate into a large vein in the arm rather than have been described by both 2- and 3-compartment models. rapidly induced and may last for 6 to 10 minutes with a into the hand, or, again, by premedication with an opioid Etomidate is about 76% bound to plasma proteins. It is single usual dose. Recovery is usually rapid without analgesic. Convulsions may occur -rarely, as may mainly excreted in the urine, but some is excreted in the hangover effect. Etomidate has no analgesic activity. laryngospasm and cardiac arrhythmias. Hypersensitivity bile. It may cross the placenta and is distributed into breast For the induction of anaesthesia, etomidate is available reactions including anaphylaxis have been reported. milk. as a conventional or an emulsion injection formulation. The Etomidate is associated with less hypotension than other usual dose is 300 micrograms/kg of etomidate given slowly, drugs commonly used for induction. References. preferably into a large vein in the arm, although a lower Because etomidate inhibits adrenocortical function 1. Levron JC, Assoune P. Pharmacoctnetique de l'etomidate. Ann Fr Anesth Reanim 1990; 9: 123-6. dose of ISO micrograms/kg of the emulsion formulation during maintenance anaesthesia (see below) its use is 2. Sfez M, et al. Comparaison de Ia pharmacocinetique de retomidate chez may be sufficient. An initial dose of !50 to 200 micr limited to induction of anaesthesia. Supplementary I' enfant et chez l'adulte. Ann Fr Anesth Reanim 1990; 9: 127-31. ograms/kg is recommended in the elderly, subsequently corticosteroid therapy should be considered in at-risk 3. Esener Z, et al. Thiopentone and etomidate concentrations in maternal and umbilical plasma, and in colostrum. J adjusted according to effects (see also below). Dosage should patients, particularly those with adrenocortical dysfunction. Br Anaesth 1992; 69: 586-8. 4. Kaneda K, et al. Population pharmacokinetics and pharmacodynamics of also be reduced in hepatic cirrhosis. Children may require Etomidate should be used with care in the elderly, who brief etomidate infusion in healthy volunteers. J Clin Pharmacol201 1; up to 30% more than the usual adult dose (i.e. up to may be more prone to cardiac depression; lower doses may 51: 482-9 1.
The symbol t denotes a preparation no longer actively marketed 1902 Genera l Anaesthetics
�r�p?r?lic:>n.� Incompatibility. In the presence of moisture, halothane with injected adrenaline is lower with halothane than iso _ ...... reacts with many metals. Rubber and some plastics dete flurane or enflurane. (details are given in Volume B) ProprietaryPreparations riorate when in contact with halothane vapour or liquid. Arrhythmias are considered to be very common in children anaesthetised with halothane and in the UK it is Single-ingredient Preparations. Austria: Hypnomidate; Belg.: Hypnomidate; Braz. : Hypnomidate; China: Pu Er Li (;f�;J\5fV); Stability, Halothane contains 0.01% wlw of thymol as a recommended that it should not be used for dental Cz. : Hypnomidate; Fr.: Hypnomidate; Ger.: Hypnomidate; Gr.: stabiliser; some commercial preparations may also contain procedures outside hospital in those under 18 years old. Hypnomidate; Mex. : Hypnomidate; Neth.: Hypnomidate; Pol.: up to 0.00025% wlw of ammonia. Thymol does not volati A review1 of the mechanisms involved suggested that at Hypnomidate; Port.: Hypnomidato; S.Afr. : Hypnomidate; lise with balothane and therefore accumulates in the physiologically relevant concentrations, halogenated anaes Spain: Hypnomidate; Turk. : Hypnomidate; UK: Hypnomidate; vaporiser. It may give a yellow colour to any remaining thetics interact mainly with the repolarising potassium USA: Amidate. liquid; halothane that has discoloured should be dis- channels hERG and IKs, as well as with calcium and sodium carded. channels at slightly higher concentrations. Inhibition of Pharmacopoeial Preporafions these produces proarrhythrnic changes such as slowing of USP 36: Etomidate Injection. repolarisation and conduction. Other mechanisms, in dud Uses and Administration ing. alteration of catecholamine-induced signal transduction Halothane is a volatile halogenated anaesthetic given by and possibly effects on neuronal pathways may also Fospropofol Sodium (riNNM! inhalation. It has a minimum alveolar concentration (MAC) contribute to arrhythmogencsis. value (see Uses of General Anaesthetics, p. 1896.1) ranging l. Fbspropofol Himmel HM. Mechanisms involved in cardiac sensitization by volatile Fo.spropofo! o•sodfurn (USANl: s6dico.;F()spro from 0.64% in the elderly to 1.08% in infants. It is anesthetics: general applicability to halogenated hydrocarbons? Grit Rev Sodiq
All cross-references refer to entries in Volume A