Objective: This study was undertaken to investigate simultaneously the influence of coinduction with propofol and midazolam on sympathoadrenergic and hemodynamic reactions and stress response during the extended induction period of TIVA.
Methods: 2 x 20 patients over the 60th year of life with major visceral surgery were investigated in a prospective randomized design. All patients received about 0.1 mg/kg BW midazolam for oral premedication. In the midazolam-group, induction of TIVA was undertaken with 0.05 mg/kg BW midazolam, 2.5 micrograms/kg BW fentanyl and 1.0 mg/kg BW propofol (1 min later). Controls received 2.5 micrograms/kg BW fentanyl and 2.0 mg/kg BW propofol. After muscle relaxation with 0.1 mg/kg BW vecuronium, TIVA was conducted in both groups with 8-5 mg/kg BW/h propofol and bolus injections of fentanyl with respect to clinical demands. Beyond consumption of anesthetics and recovery, sympathoadrenergic and hemodynamic reactions and SEF90 were investigated at 6 time points before induction of anesthesia and at skin incision. Plasma levels of ADH, ACTH and cortisol were measured twice before induction and at skin incision.
Results: Biometric data of both groups were comparable, and mean age was over 65 years. In the midazolam-group, co-induction with a mean dosage of 3.8 mg midazolam halved the induction dose of propofol and reduced the propofol demand during the following course of anesthesia as well, achieving a significant over all reduction of 200 mg propofol (p = 0.04). With respect to recovery from anesthesia more than 90 min later, no significant differences were found. Plasma concentrations of noradrenaline and adrenaline dropped significantly in both groups (p < 0.0001), as well as mean arterial pressure and heart rate (Fig. 1 and 2). For ADH, ACTH, cortisol and SEF90, no statistical differences were observed. Plasma-concentrations of midazolam were significantly higher in the midazolam-group.
Conclusion: In elderly patients, co-induction with 0.05 mg/kg BW midazolam halved the induction dose of propofol and led to a further dose reduction with maintained hypnotic potency. However, the halvage of propofol induction dose had no effect on the reduction of the sympathoadrenergic tone with decrease of blood pressure and heart rate. The overall moderation of the stress response was comparable as well. Thus, both induction regimens investigated in this study cannot be recommended in patients with severe hemodynamic disorders like hemorrhagic or cardiac shock. The propofol reduction should be primarily considered under economic aspects.