Ketamine Administration During Hospitalization Is Not Associated With Posttraumatic Stress Disorder Outcomes in Military Combat Casualties: A Matched Cohort Study BACKGROUND: Ketamine is routinely used within the context of combat casualty care. Despite early concerns that ketamine administration may be associated with elevated risk of posttraumatic stress disorder (PTSD), more recent evidence suggests no relationship. Because PTSD occurs with regular frequency in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Service Members (SMs) and combat-related injuries are associated with higher likelihood of PTSD, it is important to investigate the relationship between ketamine exposure during inpatient medical and surgical care and PTSD symptoms in OIF/OEF SMs. METHODS: Medical record data from OIF/OEF SMs medically evacuated from combat (N = 1158) included demographic characteristics, injury severity, body areas injured, and PTSD Checklist (PCL) scores. The primary analysis assessed the association between ketamine versus nonketamine exposure on positive PTSD screen (logistic regression) and PCL scores (linear regression) after using 1:1 propensity score matching to adjust for available potential confounding variables. Because there were 2 primary outcomes, the binary positive PTSD screen (yes/no) and continuous PCL score, the significance level was set at P ≤ .025. In sensitivity analyses, propensity scores were used to match ketamine to nonketamine records in a 1:4 ratio, as well as to conduct inverse probability treatment weighting (IPTW). Regressions examining the relationship between ketamine exposure and outcomes were repeated for unconditional, 1:4 matching, and IPTW models. RESULTS: In the sample, 107 received ketamine and 1051 did not. In the logistic regression, the probability of a positive PTSD screen was not significantly different between ketamine versus nonketamine patients (odds ratio [OR] = 1.28; 95% confidence interval [CI], 0.48–3.47; P = .62). In the linear regression, PCL scores were not significantly different between ketamine versus nonketamine patients (mean difference = 1.98 [95% CI, −0.99 to 4.96]; P = .19). The results were consistent in the unconditional, 1:4 matching, and IPTW models. CONCLUSIONS: No differences in PTSD screening risk or symptom levels between ketamine exposed and nonexposed were found. Given the small sample size, wide CIs of the effects, and additional confounds inherent to retrospective studies, future studies are needed to examine the complex relationships between ketamine and psychological symptoms. Accepted for publication June 5, 2019. Funding: The present study was funded on a cooperative agreement from the US Army Medical Research and Materiel Command through the Uniformed Services University. The authors declare no conflicts of interest. The opinions and assertions herein are those of the authors and do not necessarily reflect official policy or position of the Uniformed Services University, the Department of Defense, or The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc (HJF). Reprints will not be available from the authors. Address correspondence to Krista B. Highland, PhD, Defense and Veterans Center for Integrative Pain Management, Department of Military & Emergency Medicine, F. Edward Hébert School of Medicine, Uniformed Services University, 11300 Rockville Pike, Suite 709, Rockville, MD 20852. Address e-mail to khighland@dvcipm.org. © 2019 International Anesthesia Research Society