This retrospective cohort study (n=274) investigated whether PTSD prevalence amongst wounded French war veterans was linked to ketamine administration during anesthesia, but found no evidence to support such a relationship.
Abstract
“Introduction: The objective of this study was to explore whether ketamine prevents or exacerbates acute or post‐traumatic stress disorders in military trauma patients. We conducted a retrospective study of a database from the French Military Health Service, including all soldiers surviving a war injury in Afghanistan (2010–2012).
Methods: The diagnosis of post‐traumatic stress disorder was made by a psychiatrist and patients were analysed according to the presence or absence of this condition. Analysis included the following covariables: age; sex; acute stress disorder; blast injury; associated fatality; brain injury; traumatic amputation; Glasgow coma scale; injury severity score; administered drugs; number of surgical procedures; physical, neurosensory or aesthetic sequelae; and the development chronic pain. Covariables related to post‐traumatic and acute stress disorders with a p ≤ 0.10 were included in a multivariable logistic regression model.
Results: The data from 450 soldiers were identified; 399 survived, of which 274 were analysed. Among these, 98 (36%) suffered from post‐traumatic stress disorder and 89 (32%) had received ketamine. Fifty‐four patients (55%) in the post‐traumatic stress disorder group received ketamine vs. 35 (20%) in the no PTSD group (p < 0.001). The 89 injured soldiers who received ketamine had a median (IQR [range]) injury severity score of 5 (3–13 [1–26]) vs. 3 (2–4 [1–6] in the 185 patients who did not (p < 0.001). At multivariable analysis, only acute stress disorder and total number of surgical procedures were independently associated with the development of post‐traumatic stress disorder.
Discussion: In this retrospective study, ketamine administration was not a risk factor for the development of post‐traumatic stress disorder in the military trauma setting.”
Authors: G. Mion, J. Le Masson, C. Granier & C. Hoffmann
Summary
Introduction
Ketamine has unquestionable advantages for pre-hospital anaesthesia, but it is not clear whether ketamine administration could increase or decrease psychological stress associated with traumatic events and thereby affect the subsequent development of acute stress disorder and post-traumatic stress disorder.
We investigated the influence of ketamine administration on the incidence of PTSD and ASD in a cohort of combat-injured soldiers. We found no association between ketamine administration and ASD.
Methods
This study covered the French military intervention in Afghanistan from 2010 to 2012 and included all soldiers wounded by firearms, explosives or in a military transport accident.
The FMHS is particularly involved with the identification, prevention, treatment and reparation of psychological trauma in wounded soldiers. The soldier completes a PTSD checklist and a personal clinical interview.
Analysis of the scientific literature allowed selection of relevant covariables among the 780 basic items: ASD, explosion, associated fatality, injury severity score, head injury, initial Glasgow coma scale, traumatic amputation, administered drugs, and chronic pain.
All individuals in whom a psychiatrist had made a diagnosis of PTSD were included in the PTSD group, and all other patients were analysed in the no PTSD group. A multivariable logistic regression analysis was performed to detect independent links between covariates and the development of PTSD.
Results
450 patients were reviewed, 274 were analysed (two women, 0.7%), 89 received ketamine, 98 were diagnosed with PTSD and 49 with ASD, and the most severely injured soldiers received ketamine.
Age, GCS, blast injury and associated fatality were not significantly related to PTSD. Soldiers with PTSD were more severely wounded, had more surgical procedures and received more morphine, ketamine and midazolam.
54 out of 89 patients who received ketamine developed PTSD, whereas it was only 24% among the 185 patients who did not. The mean doses of ketamine administered were similar between the 32 patients in the PTSD group and the 18 patients in the no PTSD group.
Covariates linked to the development of PTSD were introduced into a logistic regression model. The number of surgical procedures and development of ASD were the only independent associations with PTSD development.
Forty-one among 98 patients with PTSD experienced an ASD, compared to only 8 among 176 patients without PTSD. An ASD predicted subsequent PTSD with 42% sensitivity and 95% specificity.
Discussion
In this study of 274 war-wounded soldiers, ketamine administration was not associated with the occurrence of ASD or subsequent PTSD.
Ketamine may aggravate, prevent or have no effect on the subsequent development of PTSD depending on the dosage and the number of administrations.
In 1999, involvement of hyperglutamatergic states in the context of traumatic stress had been suspected; ketamine may elicit dissociative symptoms, but it also possesses an antidepressant activity, and has thus been proposed as a fast antidepressant for treatment-resistant depression.
Ketamine has been shown to protect burned soldiers from PTSD, and to be superior to midazolam for reducing PTSD symptoms. It may do this by restoring the correct balance between detrimental and protective inputs from the amygdala to the medial prefrontal cortex.
In a study of soldiers who had suffered a traumatic event, the incidence of PTSD was 35.8%, which is 10% higher than in a study by McGee et al. . However, the diagnosis of PTSD was made by a psychiatrist rather than a checklist and took place later in relation to the traumatic event.
Our study has some limitations, such as its retrospective design and the small number of precise ketamine doses. However, it is similar in size to other published work and may be adequately powered for the primary end-point.
Ketamine use has increased over the last 15 years. Our study suggests that it does not have a detrimental effect on the development of PTSD.