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.
After decades of research in drug development, PDE4Is are a welcomed addition to the COPD therapeutic armamentarium. In its current clinical role, the salubrious clinical effects of PDE4I in reducing exacerbations and stabilizing the frequent exacerbator phenotype have to be cautiously balanced with numerous adverse effects. Developing drugs may provide similar or better clinical benefits while minimizing adverse effects by changing the mode of drug delivery to inhaled formulations, combining dual PDE isoenzyme inhibitors (PDE1/4I and PDE3/4I) and by forming hybrid molecules with other bronchodilators (muscarinic receptor antagonist/PDE4I and β2-agonist/PDE4I).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.