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Description / Table of Contents: Abstract. Total intravenous anaesthesia (TIVA) using a combination of a hypnotic and an analgesic agent is gaining increasing popularity as an alternative to balanced anaesthesia with volatile anaesthetics for abdominal surgery. Among the required characteristics of the drugs used in this technique are a good correlation between dose, plasma concentrations, and effect as well as rapid elimination from the circulation, allowing close control of anaesthetic depth. Two hypnotic drugs with similar pharmacokinetic and pharmacodynamic profiles are propofol and methohexitone, both of which can be employed as a component of a TIVA technique. Two TIVA combinations utilising either of these drugs with alfentanil were tested against isoflurane-nitrous oxide in a balanced regimen. Methods. Twenty-seven healthy women undergoing hysterectomy for non-malignant diseases participated in the study after having given written consent. They were randomly allocated to receive either isoflurane (Iso), methohexital-alfentanil (M-A), or propofol-alfentanil (P-A). Blood samples for determination of cortisol, prolactin, catecholamines, glucose, lactate, non-esterified fatty acids, and pharmacon concentrations were drawn repeatedly from before induction until 360 min after surgery. Anaesthesia was induced in group Iso with fentanyl 0.1 mg and M 1.5 mg⋅kg−1 and maintained with Iso-N2O. In the TIVA groups M or P was given in a two-step infusion to load peripheral compartments and then maintain plasma concentrations within the hypnotic range. A was given as a continuous infusion in an identical dose (0.1 mg⋅kg−1 initial, 0.125 mg⋅kg−1⋅h−1 maintenance) in both groups. If signs of insufficient depth of anaesthesia occurred (heart rate or systolic blood pressure 〉25% above baseline), then first A (0.5 – 1 mg), and if that was ineffective, then 50 mg hypnotic was administered. The A infusion was stopped 30 min before the end of surgery, and Iso or the hypnotic was stopped at skin closure. Recovery time was the time until the patients were able to give their birth date after stopping the Iso or hypnotic. Results. The three groups were comparable with regard to age, weight, and duration of surgery. The total doses of M and P were 1,357±125 mg (mean±SEM) and 1,315±121 mg, respectively, and the total A doses were 20.7±2.5 mg (M-A) and 23.4±3.5 (P-A). The peak plasma concentrations were P 10.6±1.5 µg⋅ml−1 and M 12.4±2.6 µg⋅ml−1. At the end of surgery the P concentrations were in the projected range while those of M were somewhat lower than expected (P3.7±0.4 µg⋅ml−1; M 3.5±0.6 µg⋅ml−1). Three patients each in the P-A and M-A groups required supplementary A injections. Five patients in the P-A group required additional bolus injections of the hypnotic as compared to 2 in the M-A group. The median recovery times were Iso 15 min, M-A 50 min, and P-A 25 min (P〈0.05). The incidence of shivering was Iso 3/9, M-A 5/9, and P-A 0/9 (P〈0.05); vomiting occurred with equal frequency in all groups (Iso 33%, M-A 33%, P-A 22%). The patients were somewhat more restless in group M-A. Systolic blood pressure dropped in a similar manner in all groups after induction of anaesthesia (Iso −31%, M-A −37%, P-A −36%) but recovered during surgery. The intraoperative response of cortisol (Iso +216%, M-A +92%, P-A +43%) and catecholamines (noradrenaline Iso +56%, M-A +30%, P-A −21%) was lower in the TIVA groups, whereas prolactin increased after induction in all groups. Plasma concentrations of glucose, lactate, and fatty acids were lower in the TIVA groups than in the Iso group intraoperatively, but increased to comparable postoperative levels. Conclusions. Both TIVA regimens are acceptable alternatives to balanced anaesthesia with Iso N2O. Both are similar with regard to haemodynamic, endocrine, and metabolic changes and are able to reduce the stress response more effectively than Iso N2O. Of the two, P seems to offer the advantage of a somewhat shorter recovery time, less shivering, and calmer patients in the immediate postoperative period, although M might be preferred if economic considerations are important.

Description / Table of Contents: Abstract. Etomidate is a hypnotic with only minor effects on haemodynamics. Although its rapid elimination kinetics would suggest its use in total intravenous anaesthesia (TIVA) and sedation, its administration in higher doses or for a prolonged period has been discouraged due to its inhibitory effects on corticosteroid synthesis. Newer evidence that the suppression of cortisol synthesis might not be total requires a re-evaluation of this drug as a component of a TIVA technique. The effects of high-dose etomidate with fentanyl on spontaneous and stimulated corticosteroid levels as a measure of the magnitude and duration of adrenocortical suppression, as well as on plasma concentrations of adrenocorticotropic hormone (ACTH) β-endorphin, and catecholamines during cardiac surgery were investigated in a prospective, randomised study and compared to those following the administration of midazolam-fentanyl. Patients and methods. Nineteen patients undergoing myocardial revascularisation were assigned to two groups: group 1: etomidate-fentanyl (n=9) and group 2: midazolam-fentanyl (n=10). Anaesthesia was induced with fentanyl 0.5 mg and either etomidate 0.3 mg/kg or midazolam 0.2 mg/kg. Relaxation was achieved with pancuronium 0.1 mg/kg. Anaesthesia was maintained during extracorporeal circulation (ECC) with an infusion of etomidate (0.36 mg⋅kg−1⋅h−1) or midazolam (0.16 mg⋅kg−1⋅h−1) and fentanyl (10 µg⋅kg−1⋅h−1. Blood samples were drawn before induction, before ECC, and 1, 6, and 20 h after surgery. Cortisol secretion was stimulated with 0.25 mg ACTH1 – 24 IV at 6 and 20 h postoperatively. Results. The total drug doses were etomidate 87±3 mg and midazolam 46±2 mg. Plasma cortisol concentrations decreased in the etomidate group from 20 (10 – 31) to 10 (6 – 31) µg⋅dl−1 (median and range) before ECC, but had returned to baseline at 1 h and were significantly increased at 6 h [29 (15 – 47) µg⋅dl−1] and 20 h [46 (29 – 62) µg⋅dl−1]. There was no difference between the groups except at 20 h, when cortisol levels were higher in the etomidate group. The stimulated cortisol increase was markedly impaired in this group at both measuring points. ACTH and β-endorphin were markedly increased in the etomidate group and ACTH concentrations were eight times greater than the corresponding values in the midazolam group after surgery (ACTH 141 vs. 18 pmol⋅l−1). Plasma catecholamine concentrations increased significantly in both groups. Noradrenaline concentrations were greater in the etomidate group at 6 h after surgery. Two patients in the midazolam group and none in the etomidate group required circulatory support with exogenous catecholamines. Discussion. It is concluded that the stress of cardiac surgery can overcome the block in cortisol synthesis caused by the administration of high-dose etomidate by substantially increasing ACTH secretion. The administration of high-dose etomidate was not associated with cardiovascular instability. The use of etomidate as a component of TIVA can therefore not be ruled out on the grounds of insufficient cortisol secretion.