[Analgesic dosage with (S)-ketamine/propofol vs. (S)-ketamine/midazolam: sedation, stress response and hemodynamics--a controlled study of surgical intensive care patients]

Abstract

Objective: The study was undertaken to investigate the influence of two different regimens of analgosedation on control and quality of sedation, stress response and haemodynamic parameters.

Methods: After ethical approval, 30 surgical intensive care patients were investigated in an open, controlled design. Patients with initial cardiocirculatory stability received 0.33-1.0 mg/kg BW/h (S)-ketamine together with 1-3 mg/kg BW/h propofol (SK/P-group), whereas patients with impaired cardiocirculatory stability received 0.33-1.0 mg/kg BW/h (S)-ketamine and 0.033-0.1 mg/kg BW/h midazolam (SK/M-group). Analgosedation was titrated until tolerance of respirator treatment was achieved and the patient was asleep, but able to respond to simple commands. At least 12 h after beginning of analgosedation, a simple neurological examination ("diagnostic window") was undertaken.

Results: In both groups, biometric data and diseases were altogether comparable, and tolerance of respirator treatment was excellent. About 16 h after start of analgosedation, 13 of 14 patients (93%) in the SK/P-group were immediately cooperative. In 2 of 16 patients of the SK/M-group, self extubation occurred, and 9 of 14 remaining patients (64%) were immediately cooperative (p = 0.065). Assessment of control and quality of analgosedation indicated slight advantages in SK/P-patients. SEF90 showed predominant beta-activity in both collectives, which increased in the course of time. Adrenaline, noradrenaline, ADH, ACTH and cortisol were measured at 7 time points. All endocrine stress parameters were consistently above normal range, but decreased during the observation period (p < 0.05). In the SK/M-group, ADH was significantly and noradrenaline initially higher than in controls. Systolic arterial pressure was comparable, whereas heart rate was significantly lower in the SK/P-group (p = 0.001). No relevant changes of endocrine or haemodynamic parameters were observed at neurological examination.

Conclusion: In surgical intensive care patients, analgosedation with SK/P showed some advantages over SK/M with respect to control and quality. The endocrine stress response was reduced by both regimens in course of time. Altogether higher levels of ADH and noradrenaline during SK/M-analgosedation let expect higher cardiocirculatory stability and possible reduction of catecholamine demand. Due to ketamine-typical beta-activity, a reliable assessment of sedation by the pEEG is not possible.