Continuous Infusion Ketamine for Adjunctive Analgosedation in Mechanically Ventilated, Critically Ill Patients

Abstract

Objective: Ketamine is an N-methyl-D-aspartate antagonist with emerging evidence assessing its use as a continuous infusion agent to provide concomitant analgesia and sedation. The role of ketamine as adjunctive therapy in mechanically ventilated patients is unclear. This study sought to investigate the impact of adjunctive continuous infusion ketamine on concomitant analgesic and sedative dosing while providing goal comfort in mechanically ventilated patients.

Methods: This retrospective two-center intrapatient comparison study included mechanically ventilated adult ICU patients who received continuous infusion ketamine with at least one other analgesic or sedative infusion. The primary outcome assessed percent relative change in concomitant analgesic-sedative doses 24 hours after ketamine initiation. Secondary outcomes included percent of Richmond Agitation and Sedation Score (RASS) assessments at goal, adverse effects, and delirium incidence. Exploratory evaluation of independent factors associated with ketamine responders (50% or more relative reduction in analgesic-sedative dosing requirements at 24 hrs) and nonresponders (less than 50% relative reduction) was performed using multivariate logistic regression.

Results: Overall, 104 patients were included. A total of 160 concomitant analgesic-sedative infusions were used in combination with ketamine, most commonly fentanyl (98 [61.3%]) and propofol (46 [28.8%]). A 20% (interquartile range [IQR] -63.6 to 0.0, p<0.001) relative reduction in total analgesic-sedative infusion pharmacotherapy was achieved at 24 hours after ketamine initiation. Analgesic and sedative infusion doses decreased at 24 hours (fentanyl: pre, 175 μg/hr [IQR 100-200 μg/hr] vs post, 125 μg/hr [IQR 50-200 μg/hr], p<0.001; propofol: pre, 42.5 μg/kg/min [IQR 20.0-60.0 μg/kg/min] vs post, 20.0 μg/kg/min [IQR 3.8-31.3 μg/kg/min], p<0.001). Median percent time within goal RASS improved after ketamine initiation (pre, 7.1% [0-40%] vs post, 25% [0-66.7%], p=0.005). No differences were observed in secondary outcomes between responders and nonresponders, except a longer non-ICU hospital length of stay in responders. Independent factors associated with ketamine response included a lower body mass index, higher starting dose of ketamine, lower severity of illness, and need for multiple concomitant analgesic-sedative infusions before initiation of ketamine.

Conclusions: Adjunctive continuous infusion ketamine promotes analgesic and sedative dose-sparing effects in mechanically ventilated patients while improving time spent within goal sedation range. Further prospective research is warranted.

Keywords: adjunctive; analgesia; analgosedation; critical care; ketamine; mechanical ventilation; pain; pharmacotherapy; sedation.