The purpose of this study was to compare etomidate in a lipid emulsion (Etomidat-Lipuro; Braun, Melsungen) and in propylene glycol (Hypnomidate, Janssen Pharmaceutica) in 90 patients in terms of anaesthetic induction characteristics with special reference to injection side effects, haemodynamic changes, and quality of induction. Adrenocortical hormones were determined in 30 patients who received either Etomidat-Lipuro, Hypnomidate, or propofol (Diprivan, ICI Pharma) for induction of anaesthesia.
Methods: One hundred twenty patients gave their informed consent to the study. In the first part, 90 patients were assigned at random to two groups in which induction of anaesthesia was performed either with Etomidat-Lipuro or Hypnomidate. Anaesthesia was started by i.v. injection of 25 micrograms/kg alfentanil (Rapifen, Janssen Pharmaceutica). One minute later, the hypnotic agent was injected into a freely running i.v. line (18 Gcannula) that was used only for the hypnotic and was removed 15 min later. During injection, the patients were asked to inform the anaesthesiologist spontaneously and on request about their sensations at the injection site. The time from the beginning of anaesthesia until the disappearance of the eyelash reflex was measured. The patients were ventilated and vecuronium was administered to allow good intubation conditions 2-3 min later. For the first 10 min, blood pressure and heart rate were measured every minute. Postoperatively, the same investigator made rounds once a day and examined the injection sites. Signs of pain, redness, swelling, induration, thrombophlebitis, or thrombosis were noted. In the second part of the study, 30 patients were investigated for endocrinological changes after induction of anaesthesia with Etomidat-Lipuro, Hypnomidate, or Diprivan. The patients were allocated to the groups at random. A radial artery catheter was inserted in every patient. Sampling took place 30 min before and 1 and 2 h after induction. Additional samples were drawn 30 min and 1, 2, and 22 h after i.v. administration of 0.25 mg ACTH (Synacthen, Ciba-Geigy). The plasma concentrations of cortisol, 17 alpha-OH-progesterone, and aldosterone and the renin activity were determined by high-performance liquid chromatography.
Results: The loss of the eyelash reflex occurred 42.9 +/- 8.7 and 42.2 +/- 11.0 s after the administration of Etomidat-Lipuro and Hypnomidate. The haemodynamic changes were minimal in both groups. After administration of alfentanil, local side effects of the hypnotics were scarce, with a tendency to be weaker and more seldom after Etomidat-Lipuro (3/55 versus 8/55). The postoperative vein reactions were generally mild and occurred in 17 out of 55 patients after Etomidat-Lipuro and 15 out of 55 patients after Hypnomidate. In most cases these signs were no longer present on the 2nd day after the procedure. Cortisol levels were depressed initially by all the hypnotic drugs used. While there was spontaneous recovery in the Diprivan group after 2 h combined with a positive overshooting response to ACTH stimulation, in the etomidate groups cortisol could not be stimulated; it normalized slowly during the following 24 h. The 17 alpha-OH-progesterone increase was significant in the etomidate groups after the administration of ACTH. The aldosterone levels decreased after etomidate injection and had not normalized 24 h later, while there was a normal response to ACTH in the propofol group. There was a normal decrease in renin activity in all three groups after the administration of ACTH.
Conclusion: Local side effects are minimal after the administration of Etomidat-Lipuro and Hypnomidate. Alfentanil reduces the injection pain of etomidate induction agents. Cortisol and aldosterone are depressed by etomidate, but the clinical relevance is minimal after a single bolus injection.