Posttraumatic stress disorder (PTSD) refers to a set of characteristic symptoms that occurs after an individual experiences an unusually threatening or catastrophic event: repeated recurrence of traumatic experiences, persistent increased alertness, and avoidance of situations similar to or related to stimuli that may persist for years or decades in trauma-exposed survivors (1–3). As a result, this mental state is highly debilitating and interferes with the patient's daily life and social activities (4, 5). In recent years, due to frequent traffic accidents, natural disasters, wars, terrorist violence and other events, the incidence of PTSD has been as high as 10–22% (6, 7). It has caused a large amount of harm and placed a large economic burden on patients, families and society (8). However, until now, prevention and treatment options for PTSD have been limited (9).

Patients who experience physical trauma in traumatic events such as car accidents, earthquakes and falls often need emergency surgical treatment or intensive care at an early stage. Studies have identified the prevalence of PTSD in intensive care unit (ICU) survivors to be more than twice that in the general population (10). Approximately 20% of patients develop PTSD after surgery or hospitalization (11). These trauma patients are inevitably treated with anesthetic sedatives that act on the central nervous system, propofol being the most commonly used (12). Once PTSD develops, it is difficult to cure (13). An important reason for this is that conditioned fear memory is abnormally strengthened and does not easily fade away (14, 15). One animal study suggested that early application of propofol has a significantly strengthens fear memory (16). A clinical retrospective analysis reported that early use of propofol in ICU patients who experienced car accident trauma was a risk factor for PTSD (17). However, there is no prospective clinical study on the effect of the use of different general anesthetics on PTSD in emergency trauma patients.

The purpose of this study was to investigate the effects of propofol and sevoflurane, two commonly used general anesthetics, on the incidence of postoperative PTSD in emergency trauma patients to lay a theoretical foundation for finding a more suitable general anesthetic for emergency trauma patients.

Epidemiological studies have shown that the prevalence of PTSD in the general U.S. population is 6–8%, and it can be as high as 13–30% in the military (17, 19). More than 230 million patients worldwide undergo surgery each year, and 20% of patients develop PTSD after surgery or hospitalization (11, 20). In this study, among 281 patients who underwent emergency trauma surgery, 50 (17.8%) developed PTSD 1 month after surgery. The incidence of PTSD in the propofol anesthesia group was significantly higher than that in the sevoflurane anesthesia group. The above results show that the incidence of PTSD in emergency trauma patients is not low and that the occurrence of PTSD is affected by early anesthesia treatment.

The pathogenesis of PTSD is complex, and its exact neurobiological mechanism is still unclear (21). Recurrent traumatic experiences, one of the core symptoms of PTSD, have been found to be associated with abnormal enhancement of fear memory (22, 23). Anesthetics are commonly thought to have an amnestic effect (24, 25), but the most recent studies found not only that propofol was relatively ineffective at inhibiting activation of the amygdala-dependent fear system but also that it had an unusual strengthening effect on emotional memories (26, 27). In an animal experiment, it was found that propofol anesthesia could significantly enhance fear memory in experimental animals within 1 h after receiving the conditioned fear stimulus. However, after 1 h, propofol had no significant effect on fear memory, and it was thought that propofol might enhance memory traces in the early consolidation stage of fear memory (16). To this end, this study independently analyzed the correlation between the time to anesthesia and the CAPS-5 score 1 month after propofol and sevoflurane anesthesia. The results showed that the time to anesthesia was negatively correlated with the CAPS-5 score in the propofol group, while there was not a significant negative correlation between the time to anesthesia and the CAPS-5 score in the sevoflurane group. This finding is consistent with animal experiments, suggesting that earlier application of propofol in the early stage of trauma may enhance the degree of traumatic memory reinforcement and thus promote the occurrence of PTSD.

PTSD may be associated with a variety of factors, such as sex, pain, trauma severity, and smoking (28, 29). To identify additional related risk factors, logistic regression analysis was performed on all participants to evaluate the risk factors related to PTSD in emergency trauma patients. Sex, age, operation time, trauma severity and other factors were not significantly correlated with the incidence of PTSD, but the use of propofol was significantly correlated with the incidence of PTSD. These results provide further evidence that propofol use is associated with an increased risk of PTSD.

Nevertheless, this study had several limitations that deserve mention. First, the 6.3% of patients lost by the 1-month follow-up may have resulted in statistical limitations of the PTSD incidence at the 1-month follow-up. Second, surgery itself may have an effect on PTSD. However, animal studies have suggested that surgery itself had no effect on fear memories in PTSD (30). Third, the population in this study was relatively narrow due to the use of strict inclusion and exclusion criteria. Patients with psychiatric or neurological disorders, such as depression or insomnia, were excluded to decrease the likelihood that the disease itself would interfere with the evaluation of PTSD (31, 32). Four, some studies suggested that PTSD was bound up with chronic pain (33). The lack of data on chronic postsurgical pain may be a limitation in this research. Finally, this study evaluated emergency department trauma patients after only 1 month, and a systematic review of traumatic brain injury showed changes in the prevalence of PTSD after 3, 6, 12, and 24 months (34). Our follow-up studies will extend the duration of follow-up.

In conclusion, early use of propofol general anesthesia in emergency surgery for trauma patients has a certain risk of PTSD. Compared with propofol anesthesia, sevoflurane anesthesia may have certain value in reducing postoperative PTSD in trauma patients undergoing early emergency surgery. Therefore, anesthesia should be carefully selected for patients with trauma requiring emergency surgery as soon as possible, and further research on this issue is needed in the future.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.

The studies involving human participants were reviewed and approved by the Ethics Committee of Suzhou Xiangcheng People's Hospital. The patients/participants provided their written informed consent to participate in this study.

JZ formulated the design of the studies. JZ, YL, and LF performed the experiments and analysis of the studies and drafted the manuscript. DH, CG, SH, RW, LW, RY, and BL performed the experiments and collected data. YY and YZ conceived the study, completed its design and coordination, and secured funding for the project. All authors contributed to the article and approved the submitted version.

This study was supported by the Research and Training Program for the Clinical Backbone in Xuzhou (2020GG014) and Science and Technology Development Plan Project of Suzhou (SYSD2019062).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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