Following the withdrawal of methohexitone from the market place psychiatrists and anaesthetists have been forced to seek out alternative anaesthetic agents for ECT. We report a case of etomidate-induced seizure-like activity. We review the literature on ECT and anaesthetic agents and discuss the alternatives available in accordance with a statement by The Royal College of Psychiatrists.

Etomidate is a sedative–hypnotic chemically unrelated to other induction agents. The pharmacological and safety profile of etomidate offers many advantages for induction during rapid sequence intubation (RSI) in the emergency department (ED). Its onset of action is within 5 to 15 seconds, and its duration of action is 5 to 15 minutes. Unlike thiopental, propofol, midazolam and, to a lesser extent, ketamine, etomidate has minimal respiratory or cardiovascular effects and can be safely used in patients with hemodynamic instability or cardiac ischemia. Etomidate is cerebroprotective, with the ability to decrease intracranial pressure and maintain cerebral perfusion, making it an ideal agent for patients with head injuries. Of the currently available induction agents, etomidate offers the most favourable safety profile and is the least likely to produce adverse effects in patients with unknown or untreated medical conditions. Etomidate may cause pain on injection, myoclonic movements on induction, hiccups, nausea and vomiting. Transient adrenal suppression has been reported, but not to a clinically significant degree, after single induction doses for ED RSI. Etomidate has been well studied in the ED and should be adopted for RSI in specific ED patient groups.

Background and objective: This prospective, randomized, double-blinded study was designed to compare the effects of remifentanil or fentanyl on anaesthetic induction characteristics of propofol, thiopental or etomidate.

Methods: Seventy-two patients were enrolled in six groups of 12 individuals each. In three groups, fentanyl was given as a bolus dose of 1.5 μg kg−1, whereas the others received a remifentanil infusion at 0.5 μg kg−1 min−1. Five minutes later, propofol, thiopental or etomidate were titrated to a state of unresponsiveness. Assessment included the amounts of drug necessary for induction, haemodynamics and the times to apnoea, loss of eyelash reflex, and the release of a water-filled syringe held in the patient's hand.

Results: Induction times to loss of the eyelash reflex were significantly shorter in the remifentanil than in the fentanyl groups: with propofol 50.7 ± 13.6 s (mean ± SD) versus 74.9 ± 27.0 s (P < 0.01), with thiopental 42.9 ± 16.8 s versus 77.2 ± 27.8 s (P < 0.01) and with etomidate 54.7 ± 17.6 s versus 72.3 ± 24.0 s (P < 0.05). The times to respiratory arrest or for the syringe to fall were significantly shorter with remifentanil than with fentanyl for propofol and for thiopental, but not for etomidate. In terms of dosages per kg body weight necessary to achieve unresponsiveness, less propofol (−29%, P < 0.05), thiopental (−25%, P < 0.05) or etomidate (−32%, P < 0.01) was necessary with remifentanil than with fentanyl. Haemodynamic responses to tracheal intubation were controlled more effectively with remifentanil. However, within the remifentanil groups, mean arterial pressure significantly decreased during induction: −26% with propofol,−18% with thiopental and −14% with etomidate (all P < 0.01).

Conclusions: During anaesthetic induction, a remifentanil infusion of 0.5 μg kg−1 min−1 over 5 min is a suitable alternative to a 1.5 μg kg−1 bolus dose of fentanyl: induction times are shorter with reduced amounts of propofol, thiopental or etomidate.

Background and objective In the present study, we investigated the combination of etomidate and s-ketamine with regard to its suitability for modified rapid-sequence induction using rocuronium for muscle relaxation.

Methods In a prospective, randomized and double-blinded study, 90 patients were assigned to one of three groups for induction of anaesthesia in combination with etomidate (0.3 mg kg−1) and muscle relaxation with rocuronium (0.6 mg kg−1). The groups were as follows: (a) control, i.e. placebo; (b) fentanyl, fentanyl (1.5 μg kg−1); (c) ketamine, s-ketamine (0.5 mg kg−1). Tracheal-intubating conditions after 1 min were classified as excellent, good or poor. During the induction of anaesthesia, arterial pressure and heart rate were measured every 60 s.

Results Intubating conditions were best using etomidate and s-ketamine (23 excellent, 7 good, 0 poor) compared with the control (8, 16, 6 respectively) and fentanyl groups (7, 21, 2 respectively) (P < 0.01). While heart rate and arterial pressure remained stable in the control and fentanyl groups during induction, both significantly increased in the ketamine group (P < 0.01).

Conclusions The combination of etomidate and s-ketamine for anaesthesia induction produces mostly excellent intubating conditions after 60 s using only 0.6 mg kg−1 of rocuronium. This combination of drugs may be a useful alternative, if succinylcholine needs to be avoided, for modified rapid-sequence induction.

Background and objective Polymorphonuclear leucocytes make a decisive contribution to defence against bacterial infections. In particular, the effects of anaesthetics on non-oxidative bactericidal mechanisms have previously only been superficially examined. Although the influence of anaesthetic agents on oxi-dative bactericidal activity has been thoroughly examined, our study concentrated on the effect on non-oxidative processes, which appears to have been a neglected field of research.

Methods The effects of methohexital, etomidate, ketamine, fentanyl and morphine on the activity of lysozyme and β-glucuronidase released from polymorphonuclear leucocytes have been studied in vitro. The activity of lysozyme was determined by recording the changes in the turbidity of a suspension of micro-coccus lysodeicticus caused by the enzymatic action of lysozyme. β-glucuronidase activity was photometrically measured by the enzymatic cleavage of phe-nolphthalein glucuronic acid.

Results High concentrations of methohexital inhibited lysozyme activity; however, etomidate and morphine caused an increase of β-glucuronidase activity in therapeutic plasma concentrations. While there was no effect of etomidate on lysozyme activity, all concentrations tested significantly stimulated β-glucuronidase activity. This result was unexpected because intravenous anaesthetics have previously shown a tendency to suppress polymorphonuclear leucocyte functions. Whereas the inhibition of lysozyme activity by the high concentration of methohexital was no surprise, the increase of β-glucuronidase activity caused by etomidate, ketamine, fentanyl and morphine was quite unexpected.

Conclusions At present, the underlying mechanism for the increase of β-glucuronidase activity caused by etomidate, ketamine, fentanyl and morphine is unknown. The fact that there was no influence of these agents on lysozyme activity possibly suggests that the anaesthetic agents have different effects on azurophilic and specific granules. Since in vitro investigations have their limitations, it is too early to draw practical consequences from our study. Moreover, at present it is unclear whether an increase of β-glucuronidase activity in vivo is an advantage or not. In any case, we think it advisable to perform further investigations on the influence of anaesthetic agents on oxygen-independent bactericidal mechanisms.

In a double-blind randomized study, the incidence and severity of postoperative nausea and vomiting was investigated with a new formulation of etomidate (Etomidate-®Lipuro, B. Braun Melsungen AG, Germany) compared with propofol for induction of a balanced anaesthesia with isoflurane/fentanyl in air.

The incidence and intensity of nausea was examined by use of a visual analogue scale (VAS; 0–100 mm) at 1, 2, between 6 and 8, and 24 h postoperatively. One-hundred-and-sixty-four patients undergoing orthopedic procedures were studied. For etomidate vs. propofol, 14.6% vs. 14.2% male and 26.8% vs. 27.5% female patients were nauseated during the first two postoperative hours. The median rating for nausea remained below 5 mm at any time in both groups, i.e. the intensity of nausea was very low. The incidence of vomiting was higher in women receiving etomidate (26.8% vs. 10%).

We conclude that etomidate does not increase nausea during the early postoperative period.

We studied the direct effect of intravenous anaesthetics, local anaesthetics and premedication drugs in common use for major surgery, on the spontaneous versus lectin induced proliferation of cultured normal rat peripheral blood mononuclear cells, not exposed to surgical or any other trauma prior to culture. Peripheral blood mononuclear cells were incubated in cell-culture medium in the presence or in the absence of propofol, ketamine, fentanyl, midazolam, thiopental sodium, lidocaine or etomidate. The cells proliferated either spontaneously or under stimulation with a lectin phytohaemagglutinine P for 72 h. The proliferation rate was evaluated by 2H-Thymidine incorporation. Fentanyl, thiopental sodium, lidocaine and etomidate significantly inhibited phytohaemagglutinine P induced 3H-Thymidine incorporation in cultured rat peripheral blood mononuclear cells. Counts per minute of the cultures treated with these drugs were 1667.80±745.72, 1614.1±615.00, 1688.0±615.0 and 1549±560.41, respectively, compared with the phytohaemagglutinine P stimulated positive control counts per minute, 13488±4305.6 (P<0.001 in each comparison). Propofol, ketamine and midazolam inhibited the lectin-induced cell proliferation to levels not statistically different from the baseline. Counts per minute of these cultures were 1361.90±745.73; 1108.90±751.33 and 1518.10±848.88, respectively. Compared either with the baseline 972.57±356.73 counts per minute or to the positive control culture counts per minute, 13488±4305.6 the difference was statistically significant (P<0.001) in each comparison. All the substances tested in this study proved capable of exerting direct inhibitory effect on circulating immunocompetent cells, because the latter were not subjected to any other immunosuppressive factor, be it operative trauma, blood transfusion, malnutrition, drug abuse, prior to culture. The possible theoretical and practical implications are discussed in this study.

The direct cardiac effects of morphine, alfentanil, ketamine, etomidate, thiopentone, midazolam and propofol were measured in isolated Wistar rat hearts. Experiments were performed using a multiple conlumnar Langendorff apparatus and the hearts were perfused with a modified Tyrode solution under constant pressure. Each drug was applied from a different column in rising concentrations at 5-min intervals. Dose ranges were chosen to compare effects at sub-clinical, clinically relevant and more than clinical concentrations. Six rat hearts were chosen at random for each drug. Only thiopentone reduced contractile force at a clinically relevant concentration: measured as g contractility per g heart weight−1 (mean±standard deviation), base-line contractility was 8.8±2.4, and contractility at 10−4 mol litre−1 thiopentone was 7.1±1.5 (P<0.01). Alfentanil was the only drug to have no significant effect on the isolated heart at any concentration. Propofol was not cardiodepressant at clinically relevant concentrations, but had a lower therapeutic range than the other drugs.

Reports about post-operative infections associated with the use of propofol prompted us to investigate the in-use contamination of lipid-formulated intravenous (i.v.) anaesthetics used for general anaesthesia or for sedation of intensive care patients in this department. The level and incidence of extrinsic contamination of propofol (‘Diprivan’) and of another intravenous anaesthetic, etomidate, formulated in lipid solution (‘Etomidat-lipuro’) was found to be low during two study periods. However, the need to observe strict aseptic precautions in handling these intravenous drugs must be emphasized.

Etomidate-induced suppression of cortisol biosynthesis is a result of a blockade of 11-beta-hydroxylation in the adrenal gland, mediated by the imidazol radical of etomidate. Since the generation of steroids requires reductive and energy rich equivalents, the present study examined whether supplementation with ascorbic acid or xylitol, a major source of NADPH, could attenuate adrenal suppression by etomidate in human subjects by promoting the turnover rate of 11-beta-hydroxylase. During continuous etomidate/alfentanil anaesthesia for pelviscopic surgery 30 female patients received either Ringer's lactate, xylitol (0.25 g kg−1 h−1) or ascorbic acid (0.5 g h−1) intravenously (i.v.). The plasma concentrations of cortisol, aldosterone and dehydroepiandrosterone (DHEA) were recorded for 5 h after end of surgery and a stimulation with synthetic ACTH was performed. The results showed no evidence of a clinically relevant attenuating effect of ascorbic acid or xylitol on etomidate-induced adrenocortical suppression. However, the observed suppression of cortisol levels was not enough to allow an attenuating affect to be measured.