Sedation of patients in intensive care units by midazolam (MDZ): clinical and biological evaluation

Aim

To assess if the clinical scoring of sedation (Ramsay scale), the administered dose of MDZ, the serum levels of MDZ from the beginning to the end of sedation are related to clinical parameters (body area), biological data (creatinine clearance, liver enzymes, protidemia), and pharmacokinetic parameters (elimination half-life T_1/2).

Patients and methods

The study was conducted with 31 patients (70 ± 10 year-old: IGS II = 41 ± 14). The objective was to reach a score of sedation of 2 up to 4. Sedation of patients was initiated with an intravenous bolus of MDZ (B = 0.1 mg/kg) and maintained with MDZ at the rate (H₁ = 0.08 mg/kg/h). If needed, the dose of MDZ was gradually increased: H₂ = 1/2B+ 1, 5H₁; H₃ = 1/2B+ 2H₁ (if H3 was insufficient, sufentanil was added (0.17 μg/kg/h and 0.34 μg/kg/h)). Waking up of patients was monitored by the beginning of respiratory weaning. Liver enzymes, protidemia and creatinine clearance are evaluated even day and 24 h after the end of sedation. The serum levels of MDZ and its metabolites were measured by HPLC and RRA every 8 h during the first day; then every 24 h, before and after each change of posology and finally every 4 h after the end of sedation for 24 h. The correlations between the different parameters monitored were evaluated by a Pearson's test.

Results

No correlation between time to awakening (22 ± 21 h) and duration of sedation (96 ± 57 h) or clinical parameters or biological data was observed. In a similar way, score of sedation, posology and serum levels of MDZ were not correlated. The pharmaco-kinetic parameters of MDZ were: T1/2 = 11.77 ± 4.8 h, clearance = 8.6 ± 4 l/h, Vd = 149 ± 981, concentration at steady state = 1008.7 ± 395 ng/ml. The unique parameter modulating the time to awakening was T1/2 of benzodiazepinique total activity (T1/2 = 12 ± 4.96 h) with 7 patients.

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Conclusion

The clinical evaluation of sedation is sufficient to adjust the dose of MDZ required for sedation and efficient awake in intensive care units.