The relationship between sedative infusion requirements and permissive hypercapnia in critically ill, mechanically ventilated patients

Objective: Permissive hypercapnia (PH) may result from mechanical ventilation (MV) strategies that intentionally reduce minute ventilation. Sedative doses required to tolerate PH have not been well characterized. With increased attention to lung-protective ventilation, characterization of sedative requirements with PH and determination of sedative dose changes with PH are needed. Design: Retrospective analysis. Setting., Tertiary care university hospital. Patients: We evaluated 124 patients randomized in a previous study to either propofol or midazolam. PH was employed in ten of 60 patients receiving propofol and 13 at 64 patents receiving midazolam. Interventions. We analyzed dosing of propofol and midazolam in patients undergoing PH through a retrospective analysis of an existing database on MV patients. Total sedative (propofol and midazolam) dose was recorded for the first three days of MV. Linear regression analysis (dependent variable: sedative dose) was used to analyze the following independent variables: PH, age, gender, daily sedative interruption, type of respiratory failure, presence of hepatic and/or renal failure, Acute Physiology and Chronic Health Evaluation II score, morphine dose, and Ramsay sedation score. Measurements and Main Results: Propofol dose was higher in PH patients (42.5 +/- 16.2 vs. 27.0 +/- 15.3; p =.02); Midazolam dose did not differ between PH and non-PH patients (0.05 [0.04, 0.14] vs. 0.05 [0.03, 0.07]; p =.17). By univariate linear regression analysis, propofol dose was significantly dependent on PH, age, type of respiratory failure, morphine dose, and Ramsay score, with PH (regression coefficient, 11.7; 95% confidence interval, 1.2-22.7; p =.03) and age (regression coefficient, -0.3; 95% confidence interval -0.5 to -0.08; p =.005) remaining significant by multivariate linear regression. By univariate linear regression analysis, midazolam dose was dependent on age, morphine dose, and Ramsay score, but not PH; only morphine dose (regression coefficient, 0.44; 95% confidence interval, 0.22-0.67 for a 0.1-unit increase in morphine dose; p <.001) was significant by multivariate linear regression. Conclusions. We conclude that higher doses of propofol but not midazolam are required to sedate patients managed with PH.