Age related inverse dose relation of sedatives and analgesics in the intensive care unit

Sedative and analgesic practices in intensive care units (ICUs) are frequently based on anesthesia regimes but do not take account of the important patient related factors. Pharmacologic properties of sedatives and analgesics change when used as continuous infusions in ICU compared to bolus or short-term infusions during anesthesia. In a prospective observational cohort study, we investigated the association between patient related factors and sedatives/analgesics doses in patients on mechanical ventilation (MV) and their association with cessation of sedation/analgesia. We included patients expected to receive MV for at least 24 hours and excluded those with difficulty in assessing the depth of sedation. We collected data for the first 72 hours or until extubation, whichever occurred first. Multivariate analysis of variance, multivariate regression as well as logistic regression were used. The final cohort (N = 576) was predominantly male (64%) with mean (SD) age 61.7 (15.6) years, weight 63.4 (18.2) Kg, Acute Physiology and Chronic Health Evaluation II score 28.2 (8) and 30% hospital mortality. Increasing age was associated with reduced propofol and fentanyl doses requirements, adjusted to the weight (p<0.001). Factors associated with higher propofol and fentanyl doses were vasopressor use (Relative mean difference (RMD) propofol 1.56 (95% confidence interval (CI) 1.28-1.90); fentanyl 1.48 (1.25-1.76) and central venous line placement (CVL, RMD propofol 1.64 (1.15-2.33); fentanyl 1.41 (1.03-1.91). Male gender was also associated with higher propofol dose (RMD 1.27 (1.06-1.49). Sedation cessation was less likely to occur in restrained patients (Odds Ratio, OR 0.48 (CI 0.30-0.78) or those receiving higher sedative/analgesic doses (OR propofol 0.98 (CI 0.97-0.99); fentanyl 0.99 (CI 0.98-0.997), independent of depth of sedation. In conclusion, increasing age is associated with the use of lower doses of sedative/analgesic in ICU, whereas CVL and vasopressor use were associated with higher doses.