Temporal Trends and Variability in Ketamine Use for Mechanically Ventilated Adults in the United States

Abstract

Rationale: The epidemiology of continuous ketamine use in the management of critically ill adults receiving invasive mechanical ventilation (MV) in the United States is unknown. Objectives: To quantify temporal trends and variation across U.S. hospitals in continuous ketamine use. Methods: We performed a retrospective cohort study of adults (age $ 18 yr) receiving MV who were discharged (alive or dead) from U.S. hospitals contributing data to the Premier Healthcare Database between January 2008 and September 2018. We used mixed-effects multivariable logistic regression modeling (fixed effects: patient and hospital characteristics; random effect: discharge hospital) to evaluate the associations of discharge quarter and discharge hospital with continuous ketamine use (defined as a charge for intravenous ketamine on $2 consecutive calendar days). Results: We identified 2,059,599 adults receiving MV across 842 hospitals; of these, 7,927 (0.4%) received continuous ketamine. Ketamine use increased over time from 0.07% of all patients in quarter 1 of 2008 to 1.1% of all patients in quarter 3 of 2018. After adjustment, the odds of receiving continuous ketamine were consistently increased starting in quarter 4 of 2011 (odds ratio, 1.83 [95% confidence interval, 1.09–3.06] vs. quarter 1 of 2008; P = 0.023), with more than 10-fold increased odds starting in quarter 2 of 2017. Among 842 hospitals, 486 (57.7%) used continuous ketamine on at least one cohort patient during the study period. Across these hospitals ever using ketamine, median use was 0.2% (interquartile range, 0.08–0.5%), with 5 hospitals using continuous ketamine in .5% of patients. The adjusted median odds ratio for discharge hospital was 3.72 (95% confidence interval, 3.37–4.13), which was higher than the odds ratio for any patient or hospital covariable other than discharge quarter. Conclusions: In U.S. hospitals, use of continuous infusion ketamine increased markedly over time in critically ill patients receiving MV, with substantial variability among hospitals. Given the unique properties of ketamine as a sedative, further research is needed to assess its safety and utility in critically ill populations.