The Effectiveness of Dexmedetomidine as a Prophylactic Treatment for Emergence Delirium Among Combat Veterans With High Anxiety: A Randomized Placebo-Controlled Trial.

INTRODUCTION: Emergence delirium (ED) is characterized by agitation, confusion, and violent physical and verbal behavior associated with awakening from general anesthesia. Combat exposure among U.S. military veterans has been identified as a risk factor for ED. Preoperative baseline anxiety was shown to be a predictor of ED, and combat veterans are known to be at high risk for anxiety as well as depression and PTSD. Dexmedetomidine is an alpha-2 receptor agonist proven to mitigate ED in several patient populations. Perioperative use of dexmedetomidine demonstrated promising benefits in pediatric ED but has not been evaluated in combat veterans. MATERIALS AND METHODS: This study was a multi-site, prospective, randomized controlled investigation of 369 patients with a history of military combat exposure who were scheduled for elective surgery with a general anesthetic as the primary means of anesthesia. The trial was funded by the Tri-Service Nursing Research Program Grant HU0001-14-TS05 (N14-PO3) and approved by the Institutional Review Boards at the Naval Medical Center San Diego, Womack Army Medical Center, Walter Reed National Military Medical Center, and the Uniformed Services University of the Health Sciences, Bethesda, MD. All subjects were administered the State-Trait Anxiety Inventory (STAI) to evaluate baseline anxiety. Those enrolled subjects with a low anxiety level (STAI < 39) (n = 215) were placed in the observational arm of the study. Those with a high anxiety level (STAI ≥ 39) were placed in the experimental arm (n = 153) and were further randomized to treatment with intraoperative dexmedetomidine infusion (1 µg/kg bolus at induction, followed by a 0.6 µg/kg/h infusion continued until emergence) (n = 75) or a placebo intraoperative infusion (n = 75). Following the delivery of the prescribed anesthetic, all subjects were observed for signs of ED using the Pediatric Anesthesia Emergence Delirium (PAED) Scale. The patient and data recorder remained blinded to the randomization results. RESULTS: The central tendencies of demographics and clinical characteristics are reported. PAED among those randomized to dexmedetomidine (median 7, interquartile interval (IQI) 5.2-9.2) tended to be less (P < .0001) than that of those randomized to control (median 12, IQI 10-13). Dexmedetomidine was found to be the most important predictor of PAED (35% relative importance), followed by Patient Health Questionnaire (14%), STAI-Trait (9%), and PTSD Checklist-Military Version (8%); the overall rankings are featured. Randomization to receipt of dexmedetomidine was associated with a 3.7-unit reduction (95% CI 2.5-4.9) in PAED (P < .001) in a linear model controlling for several variables, and the directionality of the effect persisted upon regularization in a penalized linear model. CONCLUSIONS: Dexmedetomidine was effective at reducing PAED among combat veterans who were experiencing symptoms of pre-operative anxiety (i.e., STAI-State ≥39). Although psychological morbidity is not unique to the military population, combat veterans carry some of the highest rates of anxiety, PTSD and depression compared to the general population. Dexmedetomidine can be safety employed by anesthesia providers to reduce symptoms of ED in the perioperative period. The double-blind randomized, controlled study design strengthens our analyses; however, this study did not control for the type of surgical procedure or the duration of anesthetic. Furthermore, we only enrolled patients with combat exposure experiencing symptoms of anxiety and did not investigate the role of dexmedetomidine in combat veterans with less anxiety. Further study of the relationship between psychological comorbidities, ED, and dexmedetomidine is warranted.

Adapting Mindfulness Training for Military Service Members With Chronic Pain.

INTRODUCTION: Rates of chronic pain in military personnel are disproportionately high. Chronic pain is often associated with mental health and substance use disorders as comorbid conditions, making treatment of chronic pain complex. Mindfulness-based interventions (MBIs) are a promising behavioral approach to managing chronic pain and psychosocial sequelae. The unique nature of the military context may require adaptations to original MBIs for successful delivery in active-duty military populations. This study adapted the mindfulness-based stress reduction (MBSR) program to create a mindfulness training program that was relevant to active-duty Army personnel experiencing chronic pain. This article delineates the adaptation process employed to modify the MBSR program to the military context and discusses the resulting training program. MATERIALS AND METHODS: The adaptation process consisted of three iterative stages: 1) Drafting the preliminary intervention protocol with recommendations from stakeholders, including military healthcare providers; 2) Refining the preliminary protocol after pretesting the sessions with research team members and a military Veteran advisory committee; and 3) Delivering the preliminary protocol to one cohort of active-duty Soldiers with chronic pain, collecting feedback, and further refining the intervention protocol. RESULTS: Military-related adaptations to MBSR addressed three areas: military culture, language and terminology, and practical and logistical factors relevant to implementation in the military setting. This adaptation process resulted in a live, online program with six, weekly, sessions. Feedback from a military Veteran advisory committee resulted in modifications, including increasing military-relevant examples; preliminary testing with the target population resulted in additional modifications, including shortening the sessions to 75 min and structuring discussions more efficiently. CONCLUSIONS: The adaptation process was successful in generating an engaging mindfulness training program that was highly relevant to the military context. Obtaining input from stakeholders, such as military healthcare providers and active-duty soldiers, and iterative feedback and modification, were key to the process. Moreover, the program was designed to maintain the integrity and core elements of MBIs while adapting to military culture. A future randomized controlled trial design will be used to evaluate the effectiveness of the intervention in improving chronic pain in military personnel. This program is responsive to the military's call for nonpharmacologic treatments for chronic pain that are easily accessible. If effective, the mindfulness program has the potential for widespread dissemination to complement standard care for Service Members experiencing chronic pain.

Effect of Stellate Ganglion Block Treatment on Posttraumatic Stress Disorder Symptoms: A Randomized Clinical Trial.

Importance: This is the first multisite, randomized clinical trial of stellate ganglion block (SGB) outcomes on posttraumatic stress disorder (PTSD) symptoms. Objective: To determine whether paired SGB treatments at 0 and 2 weeks would result in improvement in mean Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total symptom severity scores from baseline to 8 weeks. Design, Setting, and Participants: This multisite, blinded, sham-procedure, randomized clinical trial used a 2:1 SGB:sham ratio and was conducted from May 2016 through March 2018 in 3 US Army Interdisciplinary Pain Management Centers. Only physicians performing the procedures and the procedure nurses were aware of the intervention (but not the participants or assessors); their interactions with the participants were scripted and limited to the 2 interventions. Active-duty service members on stable psychotropic medication dosages who had a PTSD Checklist-Civilian Version (PCL-C) score of 32 or more at screening were included. Key exclusion criteria included a prior SGB treatment, selected psychiatric disorders or substance use disorders, moderate or severe traumatic brain injury, or suicidal ideation in the prior 2 months. Interventions: Paired right-sided SGB or sham procedures at weeks 0 and 2. Main Outcomes and Measures: Improvement of 10 or more points on mean CAPS-5 total symptom severity scores from baseline to 8 weeks, adjusted for site and baseline total symptom severity scores (planned a priori). Results: Of 190 screened individuals, 113 (59.5%; 100 male and 13 female participants; mean [SD] age, 37.3 [6.7] years) were eligible and randomized (74 to SGB and 39 to sham treatment), and 108 (95.6% of 113) completed the study. Baseline characteristics were similar in the SGB and sham treatment groups, with mean (SD) CAPS-5 scores of 37.6 (11.2) and 39.8 (14.4), respectively (on a scale of 0-80); 91 (80.0%) met CAPS-5 PTSD criteria. In an intent-to-treat analysis, adjusted mean total symptom severity score change was -12.6 points (95% CI, -15.5 to -9.7 points) for the group receiving SGB treatments, compared with -6.1 points (95% CI, -9.8 to -2.3 points) for those receiving sham treatment (P = .01). Conclusions and Relevance: In this trial of active-duty service members with PTSD symptoms (at a clinical threshold and subthreshold), 2 SGB treatments 2 weeks apart were effective in reducing CAPS-5 total symptom severity scores over 8 weeks. The mild-moderate baseline level of PTSD symptom severity and short follow-up time limit the generalizability of these findings, but the study suggests that SGB merits further trials as a PTSD treatment adjunct. Trial Registration: ClinicalTrials.gov identifier: NCT03077919.

A randomized, single-blind, prospective trial of auricular 'battlefield' acupuncture for the reduction of postoperative tonsillectomy pain in adults.

AIM: The purpose of this randomized, single-blind trial was to evaluate the efficacy of battlefield acupuncture in reducing postoperative pain and opioid consumption after adult tonsillectomy. METHODS: Adult participants undergoing a tonsillectomy were randomized to either receive auricular 'battlefield' acupuncture or not. Groups were compared using the Wilcox rank sum test, Fisher's exact test and a generalized estimating equations model for post-discharge pain scores. RESULTS: Statistically significant difference was not noted for morphine equivalent opioid use, nor was there any difference noted in the pain scores between the control group and treatment group. CONCLUSION: Acupuncture is cheap, safe and effective in many settings. Peri-operative battlefield auricular acupuncture did not reduce postoperative pain or opioid consumption in this study.

Literature Review of Research on Chronic Pain and Yoga in Military Populations.

Background: Although yoga is increasingly being provided to active duty soldiers and veterans, studies with military populations are limited and effects on chronic pain are largely unknown. We reviewed the existing body of literature and provide recommendations for future research. Methods: We conducted a literature review of electronic databases (PubMed, PsychINFO, Web of Science, Science Citation Index Expanded, Social Sciences Citation Index, Conference Proceedings Citation Index-Science, and Conference Proceedings Citation Index-Social Science & Humanities). The studies were reviewed for characteristics such as mean age of participants, sample size, yoga type, and study design. Only peer-reviewed studies were included in the review. Results: The search yielded only six studies that examined pain as an outcome of yoga for military populations. With one exception, studies were with veteran populations. Only one study was conducted with Operation Enduring Freedom (OEF) or Operation Iraqi Freedom (OIF) veterans. One study was a randomized controlled trial (RCT). Four of the five studies remaining used pre/post design, while the last study used a post-only design. Conclusions: Studies on the use of yoga to treat chronic pain in military populations are in their infancy. Methodological weaknesses include small sample sizes, a lack of studies with key groups (active duty, OEF/IEF veterans), and use of single group uncontrolled designs (pre/post; post only) for all but one study. Future research is needed to address these methodological limitations and build on this small body of literature.

An observational feasibility study to assess the safety and effectiveness of intranasal fentanyl for radiofrequency ablations of the lumbar facet joints.

PURPOSE: The purpose of the present observational, feasibility study is to assess the preliminary safety and effectiveness of intranasal fentanyl for lumbar facet radiofrequency ablation procedures. PATIENTS AND METHODS: This cohort observational study included 23 adult patients. Systolic and diastolic blood pressures, heart rate, oxygen saturation percent, Pasero Opioid-Induced Sedation Scale score, and the Defense and Veterans Pain Rating Scale pain score were assessed prior to the procedure and intranasal fentanyl (100 µg) administration and every 15 minutes after administration, up to 60 minutes post administration. Follow-up of patient satisfaction with pain control and treatment was assessed 24 hours after discharge. The primary outcome was safety as evidenced by adverse events. Secondary outcomes included the above-mentioned vital signs and pain ratings. RESULTS: No adverse events occurred in the present study and all participants maintained an acceptable level of awareness throughout the assessment period. One-way repeated measures analyses of covariance tests with Bonferroni-adjusted means indicated that oxygen saturation, blood pressure, and heart rate changed from baseline, whereas pain scores were lower at post-administration levels compared with baseline. Finally, the majority of participants reported being satisfied with pain control and treatment. CONCLUSION: Preliminary evidence indicates that intranasal fentanyl is safe and effective for lumbar facet radiofrequency ablation procedures. Future rigorous randomized control trials are needed to confirm the present results and to examine the effects of intranasal fentanyl on intraoperative and postoperative opioid use.

A Preliminary Examination of the Comparative Efficacy of Intravenous vs Oral Acetaminophen in the Treatment of Perioperative Pain.

OBJECTIVE: The management of postoperative pain is a major health care issue. While the cost of intravenous acetaminophen (IVA) is significantly greater than its oral acetaminophen (OA) counterpart, less is known regarding comparative effectiveness of these routes. The purpose of this study was to determine whether perioperative IVA is equivalent in reducing postoperative pain compared with perioperative OA for laparoscopic cholecystectomy (LapChole). DESIGN: Double-blinded, prospective, randomized placebo-controlled trial. SETTING: Womack Army Medical Center, Fort Bragg, North Carolina. SUBJECTS: Adults (age > 18 years) active duty military, veterans, and beneficiaries receiving a laparoscopic cholecystectomy. METHODS: This study was conducted at Womack Army Medical Center (WAMC), Fort Bragg, North Carolina, between January 2013 and June 2015. Sixty-seven subjects with symptomatic cholelithiasis were randomly assigned to receive two doses (1,000 mg each) of either IVA or OA. A numerical rating scale (NRS) score of pain was obtained preoperatively and every six hours for 24 hours postoperation. The primary objective was to assess whether treatment groups had significantly different 24-hour postoperative sum of pain intensity differences (SPID24) using an analysis of covariance test. RESULTS: Sixty subjects completed the study and were included in the analysis. Treatment groups did not differ in SPID24, even when controlling for age, gender, and preoperative pain levels (F(1,55) = 0.39, P = 0.54, partial η2 = 0.007), nor did 24-hour opioid consumption when controlling for age, gender, and operation time (F(1, 46) = 0.47, P = 0.50, partial η2 = 0.01). Furthermore, treatment groups were equally as likely to report average postoperative NRS scores of 4 or higher (ß = 0.24, Exp(B) = 1.28, P = 0.68). CONCLUSIONS: The results show no evidence of differences between IVA or OA in pain or opioid consumption among a sample of patients undergoing LapChole. Due to low sample size, these descriptive findings warrant larger studies, which may have a significant economic impact.

Impending paradoxical embolism presenting as a pulmonary embolism, transient ischemic attack, and myocardial infarction.

A 25-year-old man presented with complaints of nonpleuritic, substernal chest pain, dyspnea, and decreasing exercise tolerance. His vital signs were normal, with the exception of an oxygen saturation level of 93% while breathing room air. During his assessment, he developed transient left facial droop, left arm and leg weakness, and an ataxic gait, which lasted 15 min then resolved spontaneously. Cardiac enzyme levels were elevated, and an ECG revealed T-wave inversion in leads III, aVF, V1, and V2 with evolving ST-segment elevation in leads V3 through V5. The findings of a CT scan and MRI of the head were negative; a Doppler ultrasound of the right lower extremity revealed a thrombus extending from the common femoral vein to the popliteal vein. Cardiac catheterization revealed no evidence of epicardial coronary artery disease. CT pulmonary angiography revealed bilateral pulmonary emboli. Transesophageal echocardiography (TEE) showed a 4-cm, dumbbell-shaped mass lodged in a patent foramen ovale, confirming the diagnosis of an impending paradoxical embolism. The patient was started on therapy with unfractionated heparin, and his thrombus resolved spontaneously by hospital day 5. An impending paradoxical embolism is rare but should be suspected in anyone presenting with evidence of both venous and arterial emboli. The therapeutic options include anticoagulation, thrombolysis, and surgical embolectomy. We would propose that initial treatment with anticoagulation therapy and following with serial TEEs may be appropriate therapy in an otherwise stable patient, with surgical embolectomy or thrombolysis reserved for the treatment of thrombi that do not resolve with anticoagulation therapy or for patients with clinical deterioration.