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Psychological Sequelae of Surgery in a Prospective Cohort of Patients from Three Intraoperative Awareness Prevention Trials

Whitlock, Elizabeth L. MD, MSc*; Rodebaugh, Thomas L. PhD; Hassett, Afton L. PsyD; Shanks, Amy M. MS; Kolarik, Ellen MS; Houghtby, Janet MS; West, Hannah M.*; Burnside, Beth A. BA§; Shumaker, Erik PhD; Villafranca, Alex MSc; Edwards, W. Alex MD§; Levinson, Cheri A. MA; Langer, Julia K. MA; Fernandez, Katya C. MA; El-Gabalawy, Renee MA#; Zhou, Elizabeth Y. MD§; Sareen, Jitender MD, FRCPC#; Jacobsohn, Eric MBChB, MHPE, FRCPC; Mashour, George A. MD, PhD; Avidan, Michael S. MBBCh, FCASA**

doi: 10.1213/ANE.0000000000000498
Patient Safety: Research Report

BACKGROUND: Elective surgery can have long-term psychological sequelae, especially for patients who experience intraoperative awareness. However, risk factors, other than awareness, for symptoms of posttraumatic stress disorder (PTSD) after surgery are poorly defined, and practical screening methods have not been applied to a broad population of surgical patients.

METHODS: The Psychological Sequelae of Surgery study was a prospective cohort study of patients previously enrolled in the United States and Canada in 3 trials for the prevention of intraoperative awareness. The 68 patients who experienced definite or possible awareness were matched with 418 patients who denied awareness based on age, sex, surgery type, and awareness risk. Participants completed the PTSD Checklist-Specific (PCL-S) and/or a modified Mini-International Neuropsychiatric Interview telephone assessment to identify symptoms of PTSD and symptom complexes consistent with a PTSD diagnosis. We then used structural equation modeling to produce a composite PTSD score and examined potential risk factors.

RESULTS: One hundred forty patients were unreachable; of those contacted, 303 (88%) participated a median of 2 years postoperatively. Forty-four of the 219 patients (20.1%) who completed the PCL-S exceeded the civilian screening cutoff score for PTSD symptoms resulting from their surgery (15 of 35 [43%] with awareness and 29 of 184 [16%] without). Nineteen patients (8.7%; 5 of 35 [14%] with awareness and 14 of 184 [7.6%] without) both exceeded the cutoff and endorsed a breadth of symptoms consistent with the Diagnostic and Statistical Manual Fourth Edition diagnosis of PTSD attributable to their surgery. Factors independently associated with PTSD symptoms were poor social support, previous PTSD symptoms, previous mental health treatment, dissociation related to surgery, perceiving that one’s life was threatened during surgery, and intraoperative awareness (all P ≤ 0.017). Perioperative dissociation was identified as a potential mediator for perioperative PTSD symptoms.

CONCLUSIONS: Events in the perioperative period can precipitate psychological symptoms consistent with subsyndromal and syndromal PTSD. We not only confirmed the high rate of postoperative PTSD in awareness patients but also identified a significant rate in matched nonawareness controls. Screening surgical patients, especially those with potentially mediating risk factors such as intraoperative awareness or perioperative dissociation, for postoperative PTSD symptoms with the PCL-S is practical and could promote early referral, evaluation, and treatment.

Published ahead of print November 7, 2014.Supplemental Digital Content is available in the text.

From the *Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri; Department of Psychology, Washington University in St. Louis, St. Louis, Missouri; Department of Anesthesiology, University of Michigan Medical School, Ann Arbor, Michigan; §Department of Anesthesiology, Washington University in St. Louis, St. Louis, Missouri; Department of Anesthesia and Perioperative Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; #Department of Psychology and Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; and **Department of Anesthesiology and Surgery, Washington University in St. Louis, St. Louis, Missouri.

Elizabeth L. Whitlock, MD, MSc, is currently affiliated with Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California.

Hannah M. West is currently affiliated with Truman State University, Kirksville, Missouri.

Erik Shumaker, PhD, is currently affiliated with VA Boston Healthcare System, Boston, Massachusetts.

W. Alex Edwards, MD, is currently affiliated with Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco, California.

Elizabeth Y Zhou, MD, is currently affiliated with Department of Anesthesia and Critical Care, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Accepted for publication August 31, 2014.

Published ahead of print November 7, 2014.

Funding: ELW was a predoctoral research scholar under grant number UL1 RR024992 and subaward number TL1 RR024995 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH). The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. The B-Unaware trial was supported by a grant from the Barnes-Jewish Hospital Foundation, St. Louis, Missouri, to MSA (grant no. 6043-02). The BAG-RECALL trial was supported by a grant from the Foundation for Anesthesia Education and Research, Rochester, Minnesota, and the American Society of Anesthesiologists, Park Ridge, Illinois, to MSA (grant no. CFM-08/15/2007). The Michigan Awareness Control Study was supported by the Cerebral Function Monitoring grant (to GAM) from the Foundation for Anesthesia Education and Research, Rochester, Minnesota, and the American Society of Anesthesiologists, Park Ridge, Illinois, and grant no. KL2 RR024987-01 (to GAM) from the National Institutes of Health, Bethesda, Maryland. JS receives funding from the Manitoba Health Research Council Chair award.

The authors declare no conflicts of interest.

Drs. George A. Mashour and Michael S. Avidan contributed equally to this manuscript.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Reprints will not be available from the authors.

Address correspondence to Michael S. Avidan, MBBCh, FCASA, Washington University School of Medicine, Department of Anesthesiology, 660 S. Euclid Ave., Campus Box 8054, St. Louis, MO 63110. Address e-mail to avidanm@anest.wustl.edu.

More than 200 million major surgical procedures are performed each year worldwide, the majority with general anesthesia.1 Prospective studies using structured interviews have found that between 0.1% and 0.4% of all general anesthetics are complicated by unintended intraoperative awareness with explicit recall, hereafter referred to as awareness.2 Patients reporting awareness may experience ongoing psychological sequelae on a spectrum from subsyndromal to syndromal posttraumatic stress disorder (PTSD); small studies have suggested that between 0% and 71% develop PTSD.3–10 However, intraoperative awareness is likely to be only 1 of many perioperative experiences associated with posttraumatic stress spectrum disorder.11 Certain patient factors, such as depressive symptoms and pain,12 as well as perioperative factors including intensive care unit (ICU) admission,13 mechanical ventilation,14 and in-hospital cardiac arrest,15 have been described as risk factors for health care–associated PTSD.

Many studies of health care–associated PTSD symptoms have used face-to-face interview techniques that, although valid, cannot feasibly be implemented for routine screening.4–7,9,10 Well-validated PTSD screening instruments have not been broadly applied to an elective surgical population. We previously conducted 3 large prospective trials of interventions to prevent awareness, enrolling >29,000 patients at 4 institutions.16–18 The assessment of psychological sequelae and/or PTSD was a prespecified secondary aim in all 3 trials and is the focus of the present Psychological Sequelae of Surgery (Psych SOS) study. The objectives of the Psych SOS study were (1) to apply practical screening instruments to detect symptoms of PTSD (e.g., subsyndromal PTSD) and symptom complexes consistent with a diagnosis of postoperative PTSD, and (2) to identify factors, such as intraoperative awareness, that are associated with increased risk of postoperative PTSD symptoms.

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METHODS

This multicenter study was approved by the Human Studies Committees at Washington University in St. Louis, MO, the University of Manitoba in Winnipeg (Canada), and the University of Michigan in Ann Arbor, MI. Verbal informed consent was obtained for each telephone interview; return of a completed study form implied consent for the written portion of the study.

The requirement for written informed consent was waived by the IRB. The study was not registered before patient enrollment. The parent studies (B-Unaware, BIS or Anesthetic Gas to Reduce Explicit Recall trial [BAG-RECALL], and Michigan Awareness Control Study [MACS]) were registered at clinicaltrials.gov as NCT00281489, NCT00682825, and NCT00689091, respectively. Evaluation of psychological sequelae was a secondary outcome of interest of these studies.

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Study Design

Psych SOS was designed as a matched double-cohort study. Patients who experienced definite or possible awareness were matched 1:4 with control patients who denied awareness from the same institution and trial. Other matching factors were sex, age (in study population quartiles: 18–50, 51–60, 61–70, and 71 years and older), ICU care after surgery, and surgical procedure (if possible) or service. Screening tools were used to identify patients with postoperative PTSD complex symptoms (Supplemental Digital Content 1,.

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Telephone Interview

The MINI was developed as a broad screening tool for many psychiatric diagnoses, according to the criteria described in the DSM-IV21 (Supplemental Digital Content 1, http://links.lww.com/AA/B22). A psychologist who was an expert in anxiety disorders expanded the questions in the PTSD section of the MINI by (a) including assessments for each symptom and (b) including severity scales for those symptoms for which it was possible to assess symptom severity. This brought a degree of dimensionality to the mMINI similar to that found in the PCL-S, which is appropriate when considering PTSD symptoms along a spectrum from mild to severe. We supplemented the MINI with an assessment of social support based on the Multidimensional Perceived Social Support Scale,23 questions about mental health history, and the depression items from the 21-item version of the Depression Anxiety and Stress Scales.24 We also inquired about past PTSD symptoms attributed to the index surgery that had resolved before the interview, and past experiences with PTSD symptoms due to other events. Finally, 2 items to evaluate perioperative experiences of dissociation, that is, a feeling that one is numbed, dazed, or dreaming during real events, were inserted. The telephone interview script is reproduced in Supplemental Digital Content 3, http://links.lww.com/AA/B24.

Interviewers from all 3 institutions received a standardized training regimen and were blinded to awareness status.

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Statistical Analysis

Descriptive and univariate statistics were performed using SPSS Statistics versions 19 and 20 (IBM Corporation, Somers, NY). Modeling of risk factors for the PTSD symptom complex using mMINI and PCL-S data was conducted using structural equation modeling with the software package Mplus (Version 7; Muthén & Muthén, Los Angeles, CA). For each participant, we estimated a composite PTSD factor corresponding to PTSD symptom severity using available information from the mMINI, PCL-S, or both. Self-report and interview responses to PTSD symptoms in the B, C, and D clusters (Supplemental Digital Content 1, http://links.lww.com/AA/B22) were treated as ordered categorical variables and used to estimate the composite PTSD factor; missing data were estimated using available information.25 We then regressed the PTSD factor on predictors to determine what variables predicted PTSD symptom severity. This approach avoids the statistical and scientific problems associated with the use of a single measure of a construct, falsely dichotomizing dimensional scores,26 and inappropriately discarding cases with partially missing data. Indirect effects were assessed using bias-corrected bootstrapping with 5000 draws.27 A P value <0.05 was considered to indicate statistical significance.

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RESULTS

Patients

We attempted to recruit all 68 patients from the 3 institutions with definite or possible intraoperative awareness and an additional 418 who denied awareness. After exclusion of those who were deceased or unreachable, and those who refused participation, 49 patients with awareness and 254 without participated and contributed to the study (Fig. 1) by completing the mMINI (n = 84), the PCL-S (n = 23), or both (n = 196). Because of the iterative process of matching within the nonawareness cohort, more nonawareness patients were recruited than the planned 1:4 match. Nonawareness patients who completed 1 or both surveys were not excluded from analysis if it became apparent later that the awareness patient with whom they had been matched would not be participating in Psych SOS.

Figure 1

Figure 1

Those who participated were not significantly different from those who did not, in terms of sex, whether or not they reported awareness, their study intervention, age at surgery, and the type of surgery they received. However, patients who participated were significantly more likely to have reported distress during their initial awareness experience (Table 1).28 Those who participated also had a significantly shorter time between their surgery and entry into the Psych SOS study, were more likely to have had an ICU stay, and were less likely to have been judged at high risk for awareness (Table 1).

Table 1

Table 1

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Assessment for Psychological Sequelae and the PTSD Symptom Complex Using the PCL-S

Of all patients who completed the PCL-S, 20.1% exceeded the civilian PCL-S cutoff score for the presence of significant PTSD symptoms attributed to their surgery and hospitalization. Twenty-nine of 184 patients (15.8%) who did not experience awareness and 15 of 35 (42.9%) who experienced definite or possible awareness screened positive (unadjusted absolute risk increase = 27.1%; 95% confidence interval, 11.1%–44.0%). Patients with a PCL-S total severity score >30 were more likely to have reported definite or possible awareness (Table 2). Nineteen patients (8.7%; 14 of 184 who denied awareness and 5 of 35 with definite or possible awareness) had both a total severity score >30 and reported symptoms on the PCL-S or during the mMINI interview from the B, C, and D clusters consistent with presumptive DSM-IV criterion-based diagnosis of PTSD related to their surgery.

Table 2

Table 2

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Modeling Risk Factors for the PTSD Symptom Complex Using Composite Scores

Validity Testing for Confirmatory Factor Analysis

We first tested whether all the PTSD items regarding the B, C, and D clusters could be used to estimate a single PTSD factor by using a confirmatory factor analysis. A single factor fit the model well according to standard definitions, both locally and globally,29 indicating that both the self-report and interview essentially measure a single construct. Supporting this interpretation, when scaled scores were created from the same items, the interview and self-report severity scores correlated well (r = 0.77, P < 0.001).

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Impact of Intraoperative Awareness and Other Hypothesized Risk Factors on PTSD Symptom Complex Severity Factor

Evaluation of independent relationships among the PTSD factor, awareness, and the additional predictors described in Table 3 excluded 25 participants who did not complete the interview and thus had incomplete data for 1 or more predictor. A sensitivity analysis excluding those predictors, so all participants could be included, yielded substantively identical results.

Table 3

Table 3

The significant independent predictors of the PTSD factor were dissociation related to surgery, perceiving that one’s life was threatened during surgery, history of PTSD before surgery, low current social support, and a history of mental health treatment (Table 3). Awareness continued to be a significant predictor of PTSD complex symptom severity with all other variables in the model. Age, sex, ICU care, and whether the patient underwent cardiac surgery were not independent predictors of PTSD symptoms attributed to the surgery itself in this sample.

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Indirect Effects

Tests for indirect effects provide a surrogate for a causal chain of events. There was a significant indirect effect for awareness on PTSD through dissociation (P < 0.01).a Furthermore, multiple regression demonstrated patients reporting awareness were more likely to uniquely endorse depersonalization and derealization (P = 0.04), as opposed to feeling numbed or dazed (P = 0.21), even after accounting for the overlap between the 2 dissociation items.

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DISCUSSION

Using practical screening tools, this study identified a striking percentage of postoperative patients with significant PTSD symptoms attributed to surgery and, through indirect analysis, we demonstrated that the experience of dissociation in the perioperative period may be a mediating step to the development of PTSD symptoms after surgery (as has been shown for other trauma-related precipitants of PTSD).30 Although the cohort studied included patients with awareness who might be expected to be at risk for psychological sequelae, a large number of matched nonawareness controls also reported psychological symptoms attributed to surgery.

The presence of PTSD is regarded as dichotomous in terms of strict diagnostic criteria, but PTSD symptoms have a spectrum of severity, with even subsyndromal PTSD having major implications for functionality and quality of life of patients.31–35 The screening and analytic approaches used in Psych SOS allowed for the fact that all participants in the study had the potential for some level of PTSD symptoms (whether very low, average, or very high) attributable to their surgery that could be predicted within the model. The novel and practical approach to screening for postoperative PTSD in the current study yielded findings that are consistent with previous studies of patients reporting intraoperative awareness (Table 4)3–10 and confirmed that awareness substantially increases the risk of PTSD symptoms. The findings are also consistent with a previous study identifying postoperative PTSD in 3 of 25 patients (12%) from a matched surgical cohort not experiencing awareness,5 and in 14 of 73 consecutive patients after elective lumbar spine arthrodesis, for whom awareness status was not assessed.36

Table 4

Table 4

It is impractical to perform detailed psychological assessment of every patient who undergoes surgery. However, targeted screening could identify those at highest risk for subsequent referral to assessment or support services. In this study, we demonstrated 6 major risk factors for the PTSD symptom complex attributed to surgery (i.e., poor social support, history of PTSD symptoms, previous mental health treatment, dissociation related to surgery, perceiving that one’s life was threatened during surgery, and intraoperative awareness), that substantially overlap with known risk factors for PTSD after psychological trauma. These (and potentially other validated) risk factors could be applied to patients who have undergone surgery to identify a target population for further screening, progressing to formal assessment and intervention as needed (Fig. 2). A similar step-wise care pathway has been shown to improve PTSD symptoms and remission rates in traumatic injury survivors.37

Figure 2

Figure 2

The incidence of PTSD-related symptom complexes in Psych SOS was substantially higher than that would be expected from a random sample of adults in the community. Using DSM-IV criteria, the National Comorbidity Survey Replication suggested that the lifetime prevalence of PTSD in United States adults is about 6.8%.38 The 12-month PTSD prevalence for adults was estimated at 3.5%.39 In contrast, 8.7% of the surgical patients in the cohort studied in Psych SOS (or 7.6% of those who did not report intraoperative awareness) had symptoms consistent with PTSD in response to a single event, surgery. PTSD symptoms and diagnoses, unlike other psychiatric diagnoses, are established in reference to a specific (traumatic) event, which in the case of Psych SOS was the index surgery. Indeed, a number of surgery-specific factors were independent predictors of PTSD symptomatology in the Psych SOS study. These data suggest that a surgery confers approximately the same risk of persistent PTSD symptoms as being mugged or witnessing a killing or serious injury.40 Although this risk appears surprisingly high, a recent study screened >500 stroke or transient ischemic attack survivors with the PCL-S and demonstrated that 18% of these patients had probable syndromal PTSD attributed to the event a mean of 2 years later.41

There are important limitations to consider when interpreting these results. First, we did not compare our screening methods against a “gold standard,” typically a face-to-face interview with a clinician experienced in the diagnosis of PTSD using DSM-IV criteria. Second, because no outcome data were assessed, we cannot be certain about inferences regarding the clinical importance of the PTSD symptoms we identified. However, as discussed, even subsyndromal levels of PTSD symptoms significantly impair function. Future work is needed to define the quality-of-life implications for persistent psychological distress many years after surgery. Third, the prevalence of PTSD symptoms in this study may not be generalizable to all surgical patients as this was a sample of surgical patients enriched for patients reporting intraoperative awareness and that was subject to the inclusion criteria of the parent studies. Furthermore, the awareness of patients who participated in this study had a higher incidence of initial emotional distress than nonparticipants and thus might be expected to have a higher incidence of psychological sequelae attributed to awareness.8 In addition, we were unable to compare patient-reported perioperative distress in control participants versus nonparticipants. Differential willingness of patients to participate in this study depending on perioperative (awareness or nonawareness) distress may have been a source of bias in our findings for which we were unable to adjust; 11% of those contacted declined to participate. Finally, no PCL-S score cutoff (above which a patient is considered to have a symptom complex consistent with PTSD) has been described for this population of postoperative patients 1 to 6 years after their index surgery. Therefore, further work to refine cutoff scores, taking the time elapsed since surgery into consideration, will be needed to optimize the screening. PTSD symptoms tend to wane with time, with median duration of about 60 months, although long-term longitudinal follow-up demonstrates symptoms fail to remit in approximately one-third of patients,42 and the distribution of PCL-S total severity scores if performed shortly after surgery may be different from the distribution we describe here. Variability in time-to-assessment may also underlie some of the differences in incidence rates reported in other peer-reviewed studies of PTSD after awareness (Table 3). Interestingly, 2 small studies of similar design to the present work found markedly different PTSD rates depending on time since the awareness event: a median of 5.3 years after surgery, 71% of the awareness patients studied had PTSD,5 compared with no patients a median of 17.2 years after surgery.10

One in 5 of our study population screened positive for PTSD complex symptoms; 8.7% of the study population, including 7.6% of patients who did not experience awareness, reported lasting psychological symptoms attributed to surgery of the breadth and severity consistent with DSM-IV criteria for PTSD. This study provides evidence that there is a large population of surgical patients potentially at risk for postoperative PTSD. Our findings suggest that both perioperative physicians and general practitioners should be aware that persistent PTSD symptoms occur fairly frequently as a complication of surgery. However, this must be confirmed by further studies assessing reliability of the PCL-S screening tool and comparison with gold standard diagnostic techniques in the surgical population. Furthermore, surgical patients judged to be at risk for PTSD, based on perioperative screening, may benefit from a broad, multidisciplinary approach toward preoperative prevention and/or postoperative screening and treatment, as at-risk patients have in other settings.36,43 The data presented here provide a framework for risk identification and practical screening that could be broadly implemented in an effort to identify and appropriately refer these patients for formal psychiatric assessment and early intervention.

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DISCLOSURES

Name: Elizabeth L. Whitlock, MD, MSc.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Elizabeth L. Whitlock has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.

Name: Thomas L. Rodebaugh, PhD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Thomas L. Rodebaugh has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.

Name: Afton L. Hassett, PsyD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Afton L. Hassett approved the final manuscript.

Name: Amy M. Shanks, MS.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Amy M. Shanks approved the final manuscript.

Name: Ellen Kolarik, MS.

Contribution: This author helped conduct the study, analyze the data, and write the manuscript.

Attestation: Ellen Kolarik approved the final manuscript.

Name: Janet Houghtby, MS.

Contribution: This author helped conduct the study, analyze the data, and write the manuscript.

Attestation: Janet Houghtby approved the final manuscript.

Name: Hannah M. West.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Hannah M. West approved the final manuscript.

Name: Beth A. Burnside, BA.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Beth A. Burnside approved the final manuscript.

Name: Erik Shumaker, PhD.

Contribution: This author helped conduct the study, analyze the data, and write the manuscript.

Attestation: Erik Shumaker approved the final manuscript.

Name: Alex Villafranca, MSc.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Alex Villafranca approved the final manuscript.

Name: W. Alex Edwards, MD.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Attestation: W. Alex Edwards approved the final manuscript.

Name: Cheri A. Levinson, MA.

Contribution: This author helped conduct the study, analyze the data, and write the manuscript.

Attestation: Cheri A. Levinson approved the final manuscript.

Name: Julia K. Langer, MA.

Contribution: This author helped conduct the study, analyze the data, and write the manuscript.

Attestation: Julia K. Langer approved the final manuscript.

Name: Katya C. Fernandez, MA.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Katya C. Fernandez approved the final manuscript.

Name: Renee El-Gabalawy, MA.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Renee El-Gabalawy approved the final manuscript.

Name: Elizabeth Y. Zhou, MD.

Contribution: This author helped conduct the study and write the manuscript.

Attestation: Elizabeth Y. Zhou approved the final manuscript.

Name: Jitender Sareen, MD, FRCPC.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Attestation: Jitender Sareen approved the final manuscript.

Name: Eric Jacobsohn, MBChB, MHPE, FRCPC.

Contribution: This author helped design the study, analyze the data, and write the manuscript.

Attestation: Eric Jacobsohn approved the final manuscript.

Name: George A. Mashour, MD, PhD.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: George A. Mashour reviewed the analysis of the data and approved the final manuscript.

Name: Michael S. Avidan, MBBCh, FCASA.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Attestation: Michael S. Avidan reviewed the analysis of the data and approved the final manuscript.

This manuscript was handled by: Sorin J. Brull, MD, FCARCSI (Hon.).

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FOOTNOTE

a The MPlus bias-corrected bootstrapped point estimate with 99% 2-sided confidence interval for the indirect effect of awareness (on PTSD) via dissociation is 0.211 (0.036–0.470). The “P < 0.01” is reported based on the 99% confidence interval not including 0. These estimates do not have a clinical meaning (e.g., they cannot be translated into a standardized coefficient).
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