Authors: Herzog N et al.
Anesthesia & Analgesia 142(3): 483–486, March 2026, 10.1213/ANE.0000000000007666
This systematic review examined whether anesthetic drugs used during emergency trauma surgery under general anesthesia influence later development of posttraumatic stress disorder (PTSD). The authors searched MEDLINE, Embase, Cochrane Library, CINAHL, and Google Scholar through May 2024 and included randomized trials plus observational studies. Because the available studies were few, clinically heterogeneous, and methodologically weak, the authors performed a narrative synthesis rather than a meta-analysis.
Five studies involving 1,257 trauma patients were included. The evidence base was narrow. About 51% of patients had burn injuries, 51% were US military personnel, and many important trauma populations were underrepresented or excluded. In the randomized trials, patients with shock, spinal cord injury, ASA IV or V status, traumatic brain injury, psychiatric history, neurologic disease, or sensory deficits were excluded. This limits generalizability because many of the highest-risk trauma patients were not actually studied.
The most concerning signal in the review involved propofol. In one randomized trial of 300 trauma patients undergoing emergency surgery, propofol maintenance was associated with a higher 1-month PTSD incidence than sevoflurane maintenance, 23.2% versus 12.2%, along with a higher CAPS-5 score. Logistic regression in that study also found a significant association between propofol use and PTSD occurrence. The authors therefore suggest that propofol may contribute to PTSD development, although that conclusion currently rests mainly on one trial rather than a large body of replicated evidence.
Dexmedetomidine showed a potentially protective effect. In one randomized study, patients who received intraoperative dexmedetomidine plus nightly administration during the first 3 postoperative days had a lower 1-month PTSD incidence than placebo, 14.1% versus 24.0%. CAPS-5 scores were also modestly lower. This suggests dexmedetomidine may reduce early PTSD symptoms or incidence in selected trauma patients, though broader confirmation is still needed.
The data for ketamine were mixed. Two retrospective studies in burned US service members produced conflicting findings. One found no significant difference in PTSD prevalence with perioperative ketamine, while the other showed a lower PTSD prevalence in the ketamine group. Because both studies were retrospective and the ketamine dose was not clearly specified, the review concludes only that ketamine may be neutral or possibly beneficial, but the evidence is not strong enough to define its effect with confidence.
Midazolam did not show a significant association with PTSD reduction in the single retrospective study included. No meaningful conclusion could be made for other agents, and the authors specifically note that etomidate has not been studied in this context despite its common use in trauma anesthesia.
Overall, the review’s main message is that the literature remains sparse, heterogeneous, and at substantial risk of bias. The authors believe concerns are reasonable regarding propofol because of the observed association with increased PTSD onset, while dexmedetomidine appears promising as a possible protective adjunct. However, the total evidence base is too limited to establish a definitive trauma anesthesia strategy for PTSD prevention.
What You Should Know
This review is clinically interesting because it connects anesthetic choice with later psychiatric outcomes, not just intraoperative physiology. For trauma anesthesiologists, that is an important shift in thinking.
The strongest practical takeaway is caution, not a mandate. Propofol cannot be said to cause PTSD based on current evidence, but this review raises enough concern that the question deserves serious attention.
Dexmedetomidine is the most promising candidate for PTSD risk reduction in this literature. Still, the favorable signal comes from limited data and needs replication before practice standards should change.
Ketamine remains unresolved. Given its frequent use in trauma and its mechanistic relevance to memory and stress pathways, this is an especially important area for future randomized trials.
The biggest weakness in the current evidence is patient selection. Many of the trauma patients most likely to develop PTSD, especially those with traumatic brain injury or more severe injury patterns, were excluded. That means the findings may not fully apply to the real-world trauma population.
Key Points
The review included 5 studies with 1,257 trauma patients.
Propofol was associated in one randomized trial with higher 1-month PTSD incidence than sevoflurane.
Dexmedetomidine was associated in one randomized trial with lower 1-month PTSD incidence and lower CAPS-5 scores versus placebo.
Ketamine data were mixed and inconclusive.
Midazolam showed no significant PTSD benefit in the one included study.
The available literature is limited, heterogeneous, and largely at serious or critical risk of bias.
Thank you to Anesthesia & Analgesia for allowing us to summarize this article.