Hypobaria During Aeromedical Evacuation and Systemic Inflammation after Porcine Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI)-related morbidity is caused largely by secondary injury resulting from hypoxia, excessive sympathetic drive, and uncontrolled inflammation. Aeromedical evacuation (AE) is utilized by the military for transport of wounded soldiers to higher levels of care. We hypothesized that the hypobaric, hypoxic conditions of AE may exacerbate uncontrolled inflammation following TBI that could contribute to more severe TBI-related secondary injury. STUDY DESIGN: Thirty-six female pigs were used to test TBI vs. TBI sham, hypoxia vs. normoxia, and hypobaria vs. ground conditions. TBI was induced by controlled cortical injury, hypobaric conditions of 12,000 feet were established in an altitude chamber, and hypoxic exposure was titrated to 85% SpO2 while at altitude. Serum cytokines, UCH-L1 and TBI biomarkers were analyzed via ELISA. Gross analysis and staining of cortex and hippocampus tissue was completed for glial fibrillary acidic protein (GFAP) and phosphorylated tau (p-tau). RESULTS: Serum IL-1b, IL-6, and TNFα were significantly elevated following TBI in pigs exposed to altitude-induced hypobaria/hypoxia, as well as hypobaria alone, compared to ground level/normoxia. No difference in TBI biomarkers following TBI or hypobaric, hypoxic exposure was noted. No difference in brain tissue GFAP or p-tau when comparing the most different conditions of sham TBI+ground/normoxia to the TBI+hypobaria/hypoxia group was noted. CONCLUSION: The hypobaric environment of AE induces systemic inflammation following TBI. Severe inflammation may play a role in exacerbating secondary injury associated with TBI and contribute to worse neurocognitive outcomes. Measures should be taken to minimize barometric and oxygenation changes during AE following TBI.

Impact of Rank, Provider Specialty, and Unit Sustainment Training Frequency on Military Critical Care Air Transport Team Readiness.

BACKGROUND: The Critical Care Air Transport (CCAT) Advanced Course utilizes fully immersive high-fidelity simulations to assess personnel readiness for deployment. This study aims to determine whether simple well-defined demographic identifiers can be used to predict CCAT students' performance at CCAT Advanced. MATERIALS AND METHODS: CCAT Advanced student survey data and course status (pass/fail) between March 2006 and April 2020 were analyzed. The data included students' Air Force Specialty Code (AFSC), military status (active duty and reserve/guard), CCAT deployment experience (yes/no), prior CCAT Advanced training (yes/no), medical specialty, rank, and unit sustainment training frequency (never, frequency less often than monthly, and frequency at least monthly). Following descriptive analysis and comparative tests, multivariable regression was used to identify the predictors of passing the CCAT Advanced course for each provider type. RESULTS: A total of 2,576 student surveys were analyzed: 694 (27%) physicians (MDs), 1,051 (40%) registered nurses (RNs), and 842 (33%) respiratory therapists (RTs). The overall passing rates were 92.2%, 90.3%, and 85.4% for the MDs, RNs, and RTs, respectively. The students were composed of 579 (22.5%) reserve/guard personnel, 636 (24.7%) with CCAT deployment experience, and 616 (23.9%) with prior CCAT Advanced training. Regression analysis identified groups with lower odds of passing; these included (1) RNs who promoted from Captain to Major (post-hoc analysis, P = .03), (2) RTs with rank Senior Airman, as compared to Master Sergeants (post-hoc analysis, P = .04), and (3) MDs with a nontraditional AFSC (P = .0004). Predictors of passing included MDs and RNs with CCAT deployment experience, odds ratio 2.97 (P = .02) and 2.65 (P = .002), respectively; and RTs who engaged in unit CCAT sustainment at least monthly (P = .02). The identifiers prior CCAT Advanced training or reserve/guard military status did not confer a passing advantage. CONCLUSION: Our main result is that simple readily available metrics available to unit commanders can identify those members at risk for poor performance at CCAT Advanced readiness training; these include RNs with rank Major or above, RTs with rank Senior Airman, and RTs who engage in unit sustainment training less often than monthly. Finally, MD specialties which are nontraditional for CCAT have significantly lower CCAT Advanced passing rates, reserve/guard students did not outperform active duty students, there was no difference in the performance between different RN specialties, and for MD and RN students' previous deployment experience was a strong predictor of passing.

Just Say NO: Inhaled Nitric Oxide Effect on Respiratory Parameters Following Traumatic Brain Injury in Humans and a Porcine Model.

INTRODUCTION: The mechanism of post-traumatic brain injury (TBI) hypoxemia involves ventilation/perfusion mismatch and loss of pulmonary hypoxic vasoconstriction. Inhaled nitric oxide (iNO) has been studied as an adjunct treatment to avoid the use of high positive end-expiratory pressure and inspired oxygen in treatment-refractory hypoxia. We hypothesized that iNO treatment following TBI would improve systemic and cerebral oxygenation via improved matching of pulmonary perfusion and ventilation. METHODS: Thirteen human patients with isolated TBI were enrolled and randomized to receive either placebo or iNO with measured outcomes including pulmonary parameters, blood gas data, and intracranial pressure (ICP) /perfusion. To complement this study, a porcine model of TBI (including 10 swine) was utilized with measured outcomes of brain tissue blood flow and oxygenation, ventilator parameters, and blood gas data both after administration and following drug removal and clearance. RESULTS: There were no clinically significant changes in pulmonary parameters in either the human or porcine arm following administration of iNO when compared to either the placebo group (human arm) or the internal control (porcine arm). Analysis of pooled human data demonstrated the preservation of alveolar recruitment in TBI patients. There were no clinically significant changes in human ICP or cerebral perfusion pressure following iNO administration compared to controls. CONCLUSIONS: iNO had no significant effect on clinically relevant pulmonary parameters or ICPs following TBI in both human patients and a porcine model. The pressure-based recruitment of the human lungs following TBI was preserved. Further investigation will be needed to determine the degree of utility of iNO in the setting of hypoxia after polytrauma.

Validation of Preload Assessment Technologies at Altitude in a Porcine Model of Hemorrhage.

INTRODUCTION: Dynamic preload assessment measures including pulse pressure variation (PPV), stroke volume variation (SVV), pleth variability index (PVI), and hypotension prediction index (HPI) have been utilized clinically to guide fluid management decisions in critically ill patients. These values aid in the balance of correcting hypotension while avoiding over-resuscitation leading to respiratory failure and increased mortality. However, these measures have not been previously validated at altitude or in those with temporary abdominal closure (TAC). METHODS: Forty-eight female swine (39 ± 2 kg) were separated into eight groups (n = 6) including all combinations of flight versus ground, hemorrhage versus no hemorrhage, and TAC versus no TAC. Flight animals underwent simulated aeromedical evacuation via an altitude chamber at 8000 ft. Hemorrhagic shock was induced via stepwise hemorrhage removing 10% blood volume in 15-min increments to a total blood loss of 40% or a mean arterial pressure of 35 mmHg. Animals were then stepwise transfused with citrated shed blood with 10% volume every 15 min back to full blood volume. PPV, SVV, PVI, and HPI were monitored every 15 min throughout the simulated aeromedical evacuation or ground control. Blood samples were collected and analyzed for serum levels of serum IL-1ß, IL-6, IL-8, and TNF-α. RESULTS: Hemorrhage groups demonstrated significant increases in PPV, SVV, PVI, and HPI at each step compared to nonhemorrhage groups. Flight increased PPV (P = 0.004) and SVV (P = 0.003) in hemorrhaged animals. TAC at ground level increased PPV (P < 0.0001), SVV (P = 0.0003), and PVI (P < 0.0001). When TAC was present during flight, PPV (P = 0.004), SVV (P = 0.003), and PVI (P < 0.0001) values were decreased suggesting a dependent effect between altitude and TAC. There were no significant differences in serum IL-1ß, IL-6, IL-8, or TNF-α concentration between injury groups. CONCLUSIONS: Based on our study, PPV and SVV are increased during flight and in the presence of TAC. Pleth variability index is slightly increased with TAC at ground level. Hypotension prediction index demonstrated no significant changes regardless of altitude or TAC status, however this measure was less reliable once the resuscitation phase was initiated. Pleth variability index may be the most useful predictor of preload during aeromedical evacuation as it is a noninvasive modality.

Quality of Integration of Air Force Trauma Surgeons Within the Center for Sustainment of Trauma and Readiness Skills, Cincinnati: A Pilot Study.

INTRODUCTION: While previous studies have analyzed military surgeon experience within military-civilian partnerships (MCPs), there has never been an assessment of how well military providers are integrated within an MCP. The Center for Sustainment of Trauma and Readiness Skills, Cincinnati supports the Critical Care Air Transport Advanced Course and maintains the clinical skills of its staff by embedding them within the University of Cincinnati Medical Center. We hypothesized that military trauma surgeons are well integrated within University of Cincinnati Medical Center and that they are exposed to a similar range of complex surgical pathophysiology as their civilian partners. MATERIALS AND METHODS: After Institutional Review Board approval, Current Procedural Terminology (CPT) codes were abstracted from billing data for trauma surgeons covering University of Cincinnati Hospitals in 2019. The number of trauma resuscitations and patient acuity metrics were abstracted from the Trauma Registry and surgeon Knowledge, Skills, and Abilities clinical activity (KSA-CA) scores were calculated using their CPT codes. Finally, surgeon case distributions were studied by sorting their CPT codes into 23 categories based on procedure type and anatomic location. Appropriate, chi-squared or Mann-Whitney U-tests were used to compare these metrics between the military and civilian surgeon groups and the metrics were normalized by the group's full-time equivalent (FTE) to adjust for varying weeks on service between groups. RESULTS: Data were available for two active duty military and nine civilian staff. The FTEs were significantly lower in the military group: military 0.583-0.583 (median 0.583) vs. civilian 0.625-1.165 (median 1.0), P = 0.04. Per median FTE and surgeon number, both groups performed a similar number of trauma resuscitations (civilian 214 ± 54 vs. military 280 ± 13, P = 0.146) and KSA-CA points (civilian 55,629 ± 25,104 vs. military 36,286 ± 11,267; P = 0.582). Although the civilian surgeons had a higher proportion of hernia repairs (P < 0.001) and laparoscopic procedures (P = 0.006), the CPT code categories most relevant to combat surgery (those relating to solid organ, hollow viscus, cardiac, thoracic, abdominal, and tissue debridement procedures) were similar between the surgeon groups. Finally, patient acuity metrics were similar between groups. CONCLUSION: This is the first assessment of U.S. Air Force trauma surgeon integration relative to their civilian partners within an MCP. Normalized by FTE, there was no difference between the two groups' trauma experience to include patient acuity metrics and KSA-CA scores. The proportion of CPT codes that was most relevant to expeditionary surgery was similar between the military and civilian partners, thus optimizing the surgical experience for the military trauma surgeons within University of Cincinnati Medical Center. The methods used within this pilot study can be generalized to any American College of Surgeons verified Trauma Center MCP, as standard databases were used.

Effectiveness of Negative Pressure Wound Therapy During Aeromedical Evacuation Following Soft Tissue Injury and Infection.

INTRODUCTION: Negative pressure wound therapy (NPWT) is utilized early after soft tissue injury to promote tissue granulation and wound contraction. Early post-injury transfers via aeromedical evacuation (AE) to definitive care centers may actually induce wound bacterial proliferation. However, the effectiveness of NPWT or instillation NPWT in limiting bacterial proliferation during post-injury AE has not been studied. We hypothesized that instillation NPWT during simulated AE would decrease bacterial colonization within simple and complex soft tissue wounds. METHODS: The porcine models were anesthetized before any experiments. For the simple tissue wound model, two 4-cm dorsal wounds were created in 34.9 ± 0.6 kg pigs and were inoculated with Acinetobacter baumannii (AB) or Staphylococcus aureus 24 hours before a 4-hour simulated AE or ground control. During AE, animals were randomized to one of the five groups: wet-to-dry (WTD) dressing, NPWT, instillation NPWT with normal saline (NS-NPWT), instillation NPWT with Normosol-R® (NM-NPWT), and RX-4-NPWT with the RX-4 system. For the complex musculoskeletal wound, hind-limb wounds in the skin, subcutaneous tissue, peroneus tertius muscle, and tibia were created and inoculated with AB 24 hours before simulated AE with WTD or RX-4-NPWT dressings. Blood samples were collected at baseline, pre-flight, and 72 hours post-flight for inflammatory cytokines interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor alpha. Wound biopsies were obtained at 24 hours and 72 hours post-flight, and the bacteria were quantified. Vital signs were measured continuously during simulated AE and at each wound reassessment. RESULTS: No significant differences in hemodynamics or serum cytokines were noted between ground or simulated flight groups or over time in either wound model. Simulated AE alone did not affect bacterial proliferation compared to ground controls. The simple tissue wound arm demonstrated a significant decrease in Staphylococcus aureus and AB colony-forming units at 72 hours after simulated AE using RX-4-NPWT. NS-NPWT during AE more effectively prevented bacterial proliferation than the WTD dressing. There was no difference in colony-forming units among the various treatment groups at the ground level. CONCLUSION: The hypoxic, hypobaric environment of AE did not independently affect the bacterial growth after simple tissue wound or complex musculoskeletal wound. RX-4-NPWT provided the most effective bacterial reduction following simulated AE, followed by NS-NPWT. Future research will be necessary to determine ideal instillation fluids, negative pressure settings, and dressing change frequency before and during AE.

The Ability of Military Critical Care Air Transport Members to Visually Estimate Percent Systolic Pressure Variation.

INTRODUCTION: Inappropriate fluid management during patient transport may lead to casualty morbidity. Percent systolic pressure variation (%SPV) is one of several technologies that perform a dynamic assessment of fluid responsiveness (FT-DYN). Trained anesthesia providers can visually estimate and use %SPV to limit the incidence of erroneous volume management decisions to 1-4%. However, the accuracy of visually estimated %SPV by other specialties is unknown. The aim of this article is to determine the accuracy of estimated %SPV and the incidence of erroneous volume management decisions for Critical Care Air Transport (CCAT) team members before and after training to visually estimate and utilize %SPV. MATERIAL AND METHODS: In one sitting, CCAT team providers received didactics defining %SPV and indicators of fluid responsiveness and treatment with %SPV ≤7 and ≥14.5 defining a fluid nonresponsive and responsive patient, respectively; they were then shown ten 45-second training arterial waveforms on a simulated Propaq M portable monitor's screen. Study subjects were asked to visually estimate %SPV for each arterial waveform and queried whether they would treat with a fluid bolus. After each training simulation, they were told the true %SPV. Seven days post-training, the subjects were shown a different set of ten 45-second testing simulations and asked to estimate %SPV and choose to treat, or not. Nonparametric limits of agreement for differences between true and estimated %SPV were analyzed using Bland-Altman graphs. In addition, three errors were defined: (1) %SPV visual estimate errors that would label a volume responsive patient as nonresponsive, or vice versa; (2) incorrect treatment decisions based on estimated %SPV (algorithm application errors); and (3) incorrect treatment decisions based on true %SPV (clinically significant treatment errors). For the training and testing simulations, these error rates were compared between, and within, provider groups. RESULTS: Sixty-one physicians (MDs), 64 registered nurses (RNs), and 53 respiratory technicians (RTs) participated in the study. For testing simulations, the incidence and 95% CI for %SPV estimate errors with sufficient magnitude to result in a treatment error were 1.4% (0.5%, 3.2%), 1.6% (0.6%, 3.4%), and 4.1% (2.2%, 6.9%) for MDs, RNs, and RTs, respectively. However, clinically significant treatment errors were statistically more common for all provider types, occurring at a rate of 7%, 10%, and 23% (all P < .05). Finally, students did not show clinically relevant reductions in their errors between training and testing simulations. CONCLUSIONS: Although most practitioners correctly visually estimated %SPV and all students completed the training in interpreting and applying %SPV, all groups persisted in making clinically significant treatment errors with moderate to high frequency. This suggests that the treatment errors were more often driven by misapplying FT-DYN algorithms rather than by inaccurate visual estimation of %SPV. Furthermore, these errors were not responsive to training, suggesting that a decision-making cognitive aid may improve CCAT teams' ability to apply FT-DYN technologies.

Descriptive Analysis of Intratheater Critical Care Air Transport Team Patient Movements During Troop Drawdown: Afghanistan (2017-2019).

BACKGROUND: The majority of critical care air transport (CCAT) flights are regulated, meaning that a theater-validating flight surgeon has confirmed that the patient is medically cleared for flight and that evacuation is appropriate. If the conditions on the ground do not allow for this process, the flight is unregulated. Published data are limited regarding CCAT unregulated missions to include the period of troop drawdown at the end of the Afghanistan conflict. The objective of our study was to characterize the unregulated missions within Afghanistan during troop drawdown and compare them to regulated missions during the same timeframe. STUDY DESIGN: We performed a retrospective review of all CCAT medical records of patients transported via CCAT within Afghanistan between January 2017 and December 2019. We abstracted data from the records, including mission characteristics, patient demographics, injury descriptors, preflight military treatment facility procedures, CCAT procedures, in-flight CCAT treatments, in-flight events, and equipment issues. Following descriptive and comparative analysis, a Cochran-Armitage test was performed to evaluate the statistical significance of the trend in categorical data over time. Multivariable regression was used to assess the association between vasopressors and preflight massive transfusions, preflight surgical procedures, injury patterns, and age. RESULTS: We reviewed 147 records of patients transported via CCAT: 68 patients were transported in a regulated fashion and 79 on an unregulated flight. The number of patients evacuated increased year-over-year (n = 22 in 2017, n = 57 in 2018, and n = 68 in 2019, P < .001), and the percentage of missions that were unregulated grew geometrically (14%, n = 3 in 2017; 37%, n = 21 in 2018; and 81%, n = 55 in 2019, P < .001). During the time studied, CCAT teams were being used more to decompress forward surgical teams (FST) and, therefore, they were transporting patients just hours following initial damage control surgery in an unregulated fashion. In 2 instances, CCAT decompressed an FST following a mass casualty, during which aeromedical evacuation (AE) crews assisted with patient care. For the regulated missions, the treatments that were statistically more common were intravenous fluids, propofol, norepinephrine, any vasopressors, and bicarbonate. During unregulated missions, the statistically more common treatments were ketamine, fentanyl, and 3% saline. Additional analysis of the mechanically ventilated patient subgroup revealed that vasopressors were used twice as often on regulated (38%) vs. unregulated (13%) flights. Multivariable regression analysis demonstrated that traumatic brain injury (TBI) was the only significant predictor of in-flight vasopressor use (odds ratio = 3.53, confidence interval [1.22, 10.22], P = .02). CONCLUSION: During the troop drawdown in Afghanistan, the number of unregulated missions increased geometrically because the medical footprint was decreasing. During unregulated missions, CCAT providers used ketamine more frequently, consistent with Tactical Combat Casualty Care guidelines. In addition, TBI was the only predictor of vasopressor use and may reflect an attempt to adhere to unmonitored TBI clinical guidelines. Interoperability between CCAT and AE teams is critical to meet mass casualty needs in unregulated mission environments and highlights a need for joint training. It remains imperative to evaluate changes in mission requirements to inform en route combat casualty care training.

Postinjury Treatment to Mitigate the Effects of Aeromedical Evacuation After Traumatic Brain Injury in a Porcine Model.

INTRODUCTION: Early aeromedical evacuation after traumatic brain injury (TBI) has been associated with worse neurologic outcomes in murine studies and military populations. The goal of this study was to determine if commonly utilized medications, including allopurinol, propranolol, or tranexamic acid (TXA), could mitigate the secondary traumatic brain injury experienced during the hypobaric and hypoxic environment of aeromedical evacuation. METHODS: Porcine TBI was induced via controlled cortical injury. Twenty nonsurvival pigs were separated into four groups (n = 5 each): TBI+25 mL normal saline (NS), TBI+4 mg propranolol, TBI+100 mg allopurinol, and TBI+1g TXA. The pigs then underwent simulated AE to an altitude of 8000 ft for 4 h with an SpO2 of 82-85% and were sacrificed 4 h later. Hemodynamics, serum cytokines, and hippocampal p-tau accumulation were assessed. An additional survival cohort was partially completed with TBI/NS (n = 5), TBI/propranolol (n = 2) and TBI/allopurinol groups (n = 2) survived to postinjury day 7. RESULTS: There were no significant differences in hemodynamics, tissue oxygenation, cerebral blood flow, or physiologic markers between treatment groups and saline controls. Transient differences in IL-1b and IL-6 were noted but did not persist. Neurological Severity Score (NSS) was significantly lower in the TBI + allopurinol group on POD one compared to NS and propranolol groups. P-tau accumulation was decreased in the nonsurvival animals treated with allopurinol and TXA compared to the TBI/NS group. CONCLUSIONS: Allopurinol, propranolol, and TXA, following TBI, do not induce adverse changes in systemic or cerebral hemodynamics during or after a simulated postinjury flight. While transient changes were noted in systemic cytokines and p-tau accumulation, further investigation will be needed to determine any persistent neurological effects of injury, flight, and pharmacologic treatment.

Relevance of Deployment Experience and Clinical Practice Characteristics on Military Critical Care Air Transport Team Readiness: A Study of Simulation Construct Validity.

INTRODUCTION: The Critical Care Air Transport Team (CCATT) Advanced course utilizes fully immersive high-fidelity simulations to train CCATT personnel and assess their readiness for deployment. This study aims to (1) determine whether these simulations correctly discriminate between students with previous deployment experience ("experienced") and no deployment experience ("novices") and (2) examine the effects of students' clinical practice environment on their performance during training simulations. MATERIALS AND METHODS: Critical Care Air Transport Team Advanced student survey data and course status (pass/no pass) between March 2006 and April 2020 were analyzed. The data included students' specialty, previous exposure to the CCATT Advanced course, previous CCATT deployment experience, years in clinical practice (<5, 5-15, and >15 years), and daily practice of critical care (yes/no), as well as a description of the students' hospital to include the total number of hospital (<100, 100-200, 201-400, and >400) and intensive care unit (0, 1-10, 11-20, and >20) beds. Following descriptive analysis and comparative tests, multivariable regression was used to identify the predictors of passing the CCATT Advanced course. RESULTS: A total of 2,723 surveys were analyzed: 841 (31%) were physicians (MDs), 1,035 (38%) were registered nurses, and 847 (31%) were respiratory therapists (RTs); 641 (24%) of the students were repeating the course for sustainment training and 664 (24%) had previous deployment experience. Grouped by student specialty, the MDs', registered nurses', and RTs' pass rates were 92.7%, 90.6%, and 85.6%, respectively. Multivariable regression results demonstrated that deployment experience was a robust predictor of passing. In addition, the >15 years in practice group had a 47% decrease in the odds of passing as compared to the 5 to 15 years in practice group. Finally, using MDs as the reference, the RTs had a 61% decrease in their odds of passing. The daily practice of critical care provided a borderline but nonsignificant passing advantage, whereas previous CCATT course exposure had no effect. CONCLUSION: Our primary result was that the CCATT Advanced simulations that are used to evaluate whether the students are mission ready successfully differentiated "novice" from "experienced" students; this is consistent with valid simulation constructs. Finally, novice CCATT students do not sustain their readiness skills during the period between mandated refresher training.

Hemodynamic events during en route critical care for patients with traumatic brain injury.

BACKGROUND: Exposure to stressors of flight may increase risk of secondary insults among critically injured combat casualties wounded with traumatic brain injury (TBI). The primary objective of this study was to describe the prevalence of hemodynamic events by phase of transport among patients with TBI transported by Critical Care Air Transport Teams (CCATT). METHODS: We performed a secondary analysis of a retrospective cohort of 477 adults with moderate to severe TBI, who required transport by CCATT to Germany from multiple hospitals in the Middle East between January 2007 and May 2014. We abstracted clinical data from handwritten CCATT medical records. Hemodynamic events included systolic blood pressure <100 mm Hg and cerebral perfusion pressure <60 mm Hg. We calculated the proportion of patients experiencing hemodynamic events for each phase of flight. RESULTS: We analyzed 404 subjects after exclusions for catastrophic brain injury (n = 39) and missing timestamps (n = 34). Subjects had high Injury Severity Scores (median, 29; interquartile range [IQR], 21-35) and a median flight time of 423 minutes (IQR, 392.5-442.5 minutes). The median of documented in-flight vital signs was 8 measurements (IQR, 6.5-8 measurements). Documented systolic blood pressure in-flight events occurred in 3% of subjects during ascent, 7.9% during early flight, 7.7% during late flight, and 2.2% during descent, with an overall in-flight prevalence of 13.9%. Among patients with intracranial pressure monitoring (n = 120), documented cerebral perfusion pressure events occurred in 5% of subjects during ascent, 23% during early flight, 17% during late flight, and 5.8% during descent, with an overall in-flight prevalence of 30.8%. CONCLUSION: Documented hemodynamic events occurred during each phase of flight in severely injured combat casualties wounded with TBI, and episodic documentation likely underestimated the actual in-flight frequency of secondary insults. LEVEL OF EVIDENCE: Prognostic and epidemiological; Level IV.

Association of Hypocalcemia With Mortality of Combat Casualties With Brain Injury and Polytrauma Transported by Critical Care Air Transport Teams.

INTRODUCTION: Hypocalcemia at hospital presentation is associated with increased mortality in trauma patients with hemorrhagic shock. The 2019 updates to the Joint Trauma System Damage Control Resuscitation (DCR) Clinical Practice Guideline recommend calcium supplementation for ionized calcium (iCa) measurements <1.2 mmol/L. Ionized calcium goals for en route critical care (ERCC) following DCR are less defined, and the impact of in-flight hypocalcemia events among critically injured combat wounded is unknown. This study aimed to describe the association between hypocalcemia and mortality for combat-wounded with brain injury and polytrauma requiring transport by Critical Care Air Transport Teams (CCATT). METHODS: We performed a secondary analysis of a retrospective cohort of patients with moderate-to-severe traumatic brain injury transported by CCATT out of combat theater between January 2007 and May 2014. Additional inclusion criteria included polytrauma and at least one documented in-flight iCa measurement. We categorized exposures based on the minimum in-flight iCa measurement as severe hypocalcemia (iCa <0.9 mmol/L), hypocalcemia (iCa 0.9-1.11 mmol/L), and never hypocalcemic (iCa ≥1.12 mmol/L). The primary outcome measure was mortality. We calculated descriptive statistics and performed multivariate logistic regression to assess the association between hypocalcemia and mortality. RESULTS: We analyzed 190 subjects, with a median age of 24 years (interquartile range [IQR] 21 to 29 years) and 97.7% male gender. Explosive injuries (82.1%) and gunshot wounds (6.3%) were the most common mechanisms of injury. The median injury severity score was 34 (IQR 27 to 43). During the flight, 11.6% of patients had severe hypocalcemia, and 39.5% had hypocalcemia. Among patients with any hypocalcemia measurement in-flight (n = 97), 41.2% had hypocalcemia on pre-flight iCa, 28.9% received blood products in-flight, and 23.7% received in-flight calcium supplementation. Only 32.4% of patients with hypocalcemia or severe hypocalcemia in the setting of vasopressor administration received in-flight calcium supplementation. There was no significant difference in mortality between severe hypocalcemia (9.1%), hypocalcemia (5.3%), and never hypocalcemic (3.2%) patients even after controlling for pre-flight variables. CONCLUSION: In-flight hypocalcemia events were common among critically ill combat-wounded polytrauma patients transported by CCATT but were not associated with differences in mortality. Future training should emphasize the need for calcium correction among ERCC patients requiring vasopressors. Future studies with larger sample sizes of patients receiving ERCC are needed to assess the association between in-flight calcium supplementation with clinical outcomes.

En Route Critical Care Evacuations From Rarely Utilized Partner Medical Treatment Facilities: A Case Series With Lessons Learned.

Retaining lessons learned from Critical Care Air Transport (CCAT) missions is essential given the recent decrease in operational currency among CCAT personnel. The objective of this case series was to identify and analyze logistical lessons learned from recent critical care transports involving foreign medical treatment facilities with sufficient detail for the CCAT community to incorporate these lessons into future readiness and sustainment training. The provider from each mission submitted a mission narrative with lessons learned. A qualitative analysis of lessons learned described themes from the lessons, as well as similarities and differences from included missions. Three missions were reviewed and four distinct mission stages were identified: (1) pre-mission, (2) at U.S. aircraft, (3) away from U.S. aircraft, and (4) post-mission. Pre-mission lessons learned included the need for professional civilian attire for deployed CCAT teams and the limited availability of pre-mission clinical information. Lessons learned at the aircraft included the following: the need for flexible mission timelines, coordinate and pre-plan transitions with foreign medical teams when possible, and plan for difficult environmental conditions if flight line transfer is required. Lessons learned away from the aircraft included communication challenges between CCAT and the aircraft, contingency planning for narcotic transports, and equipment interoperability issues. Post-mission lessons learned included the need for written communication to disseminate information to the CCAT community. This case series described logistical challenges that present during transport missions involving foreign hospitals. This published series will enable dissemination to the en route care community for possible incorporation into future training.

Intercostal liposomal bupivacaine injection for rib fractures: A prospective randomized controlled trial.

BACKGROUND: Blunt chest wall injury accounts for 15% of trauma admissions. Previous studies have shown that the number of rib fractures predicts inpatient opioid requirements, raising concerns for pharmacologic consequences, including hypotension, delirium, and opioid dependence. We hypothesized that intercostal injection of liposomal bupivacaine would reduce analgesia needs and improve spirometry metrics in trauma patients with rib fractures. METHODS: A prospective, double-blinded, randomized placebo-control study was conducted at a Level I trauma center as a Food and Drug Administration investigational new drug study. Enrollment criteria included patients 18 years or older admitted to the intensive care unit with blunt chest wall trauma who could not achieve greater than 50% goal inspiratory capacity. Patients were randomized to liposomal bupivacaine or saline injections in up to six intercostal spaces. Primary outcome was to examine pain scores and breakthrough pain medications for 96-hour duration. The secondary endpoint was to evaluate the effects of analgesia on pulmonary physiology. RESULTS: One hundred patients were enrolled, 50 per cohort, with similar demographics (Injury Severity Score, 17.9 bupivacaine 17.6 control) and comorbidities. Enrolled patients had a mean age of 60.5 years, and 47% were female. Rib fracture number, distribution, and targets for injection were similar between groups. While both groups displayed a decrease in opioid use over time, there was no change in mean daily pain scores. The bupivacaine group achieved higher incentive spirometry volumes over Days 1 and 2 (1095 mL, 1063 mL bupivacaine vs. 900 mL, 866 mL control). Hospital and intensive care unit lengths of stay were similar and there were no differences in postinjection pneumonia, use of epidural catheters or adverse events bet ween groups. CONCLUSION: While intercostal liposomal bupivacaine injection is a safe method for rib fracture-related analgesia, it was not effective in reducing pain scores, opioid requirements, or hospital length of stay. Bupivacaine injection transiently improved incentive spirometry volumes, but without a reduction in the development of pneumonia. LEVEL OF EVIDENCE: Therapeutic/care management, Level II.

Blood product resuscitation mitigates the effects of aeromedical evacuation after polytrauma.

BACKGROUND: The combined injury of traumatic brain injury and hemorrhagic shock has been shown to worsen coagulopathy and systemic inflammation, thereby increasing posttraumatic morbidity and mortality. Aeromedical evacuation to definitive care may exacerbate postinjury morbidity because of the inherent hypobaric hypoxic environment. We hypothesized that blood product resuscitation may mitigate the adverse physiologic effects of postinjury flight. METHODS: An established porcine model of controlled cortical injury was used to induce traumatic brain injury. Intracerebral monitors were placed to record intracranial pressure, brain tissue oxygenation, and cerebral perfusion. Each of the 42 pigs was hemorrhaged to a goal mean arterial pressure of 40 ± 5 mm Hg for 1 hour. Pigs were grouped according to resuscitation strategy used-Lactated Ringer's (LR) or shed whole blood (WB)-then placed in an altitude chamber for 2 hours at ground, 8,000 ft, or 22,000 ft, and then observed for 4 hours. Hourly blood samples were analyzed for proinflammatory cytokines and lactate. Internal jugular vein blood flow was monitored continuously for microbubble formation with altitude changes. RESULTS: Cerebral perfusion, tissue oxygenation, and intracranial pressure were unchanged among the six study groups. Venous microbubbles were not observed even with differing altitude or resuscitation strategy. Serum lactate levels from hour 2 of flight to the end of observation were significantly elevated in 22,000 + LR compared with 8,000 + LR and 22,000 + WB. Serum IL-6 levels were significantly elevated in 22,000 + LR compared with 22,000 + WB, 8,000 + LR and ground+LR at hour 1 of observation. Serum tumor necrosis factor-α was significantly elevated at hour 2 of flight in 8,000 + LR versus ground+LR, and in 22,000 + LR vs. 22,000 + WB at hour 1 of observation. Serum IL-1ß was significantly elevated hour 1 of flight between 8,000 + LR and ground+LR. CONCLUSION: Crystalloid resuscitation during aeromedical transport may cause a prolonged lactic acidosis and proinflammatory response that can predispose multiple-injury patients to secondary cellular injury. This physiologic insult may be prevented by using blood product resuscitation strategies.

Joint Trauma System Clinical Practice Guideline: Acute Coronary Syndrome (ACS). 14 May 2021.

Deployed medical providers at all roles of care must be prepared to recognize and manage acute coronary syndrome (ACS). Under optimal conditions, treatment is initiated with medical therapy and may be followed by prompt coronary angiography and revascularization. Emergent percutaneous coronary intervention (PCI) is not available in most deployed locations, however, and the time for such intervention is often dependent on long-range evacuation. This CPG provides guidance on best management for ACS patients in the deployed and resource-constrained environment.

Intranasal Ketamine as an Adjunct to Fentanyl for the Prehospital Treatment of Acute Traumatic Pain: Design and Rationale of a Randomized Controlled Trial.

Objective: Acute pain management is fundamental in prehospital trauma care. Early pain control may decrease the risk of developing post-traumatic stress disorder (PTSD) and chronic pain. Fentanyl and ketamine are frequently used off-label, but there is a paucity of comparative data to guide decision-making about treatment of prehospital severe, acute pain. This trial will determine whether the addition of single dose of intranasal ketamine to fentanyl is more effective for the treatment of acute traumatic pain than administration of fentanyl alone.Methods: This two-part study consists of prehospital and 90-day follow-up components (NCT02866071). The prehospital trial is a blinded, randomized, controlled trial of adult men (age 18-65 years) rating pain ≥7/10 after an acute traumatic injury of any type. Women will be excluded due to inability to confirm pregnancy status and unknown fetal risk. Paramedics will screen patients receiving standard of care fentanyl and, after obtaining standard informed consent, administer 50 mg intranasal ketamine or matching volume saline as placebo. Upon emergency department (ED) arrival, research associates will serially assess pain, concomitant treatments, and adverse side effects. Enrolled subjects will be approached for consent to participate in the 90-day follow-up study to determine rates of PTSD and chronic pain development. The primary outcome of the prehospital study is reduction in pain on the Verbal Numerical Rating Scale between baseline and 30-minutes after study drug administration. The proportion achieving a reduction of ≥2-points will be compared between study arms using a Chi-square test. Secondary outcomes of the prehospital trial include reduction in reported pain at the time of ED arrival and at 30 minutes intervals for up to three hours of ED care, the incidence of adverse events, and additional opiate requirements prior to ED arrival and within the first three hours of ED care. The outcomes in the follow-up study are satisfaction with life and development of PTSD or chronic pain at 90 days after injury. An intention-to-treat approach will be used.Conclusion: These studies will test the hypotheses that ketamine plus fentanyl, when compared to fentanyl alone, effectively manages pain, decreases opiate requirements, and decreases PTSD at 90 days.

Intermittent gastric feeds lower insulin requirements without worsening dysglycemia: A pilot randomized crossover trial.

INTRODUCTION: We hypothesized that critically ill medical patients would require less insulin when fed intermittently. METHODS: First, 26 patients were randomized to receive intermittent or continuous gastric feeds. Once at goal nutrition, data were collected for the first 4-hr data collection period. Next, the enteral feed type was switched, goal nutrition was repeated, and a second 4-h data collection period was completed. The primary endpoint was the total amount of insulin infused; secondary endpoints were glucose concentration mean, maximum, minimum, and standard deviation, as well as episodes of hypoglycemia. RESULTS: Sixteen of the 26 patients successfully completed the protocol. One patient experienced a large, rapid, and sustained decline in insulin requirement from liver failure, creating a bias of lesser insulin in the intermittent arm; this patient was removed from the analysis. For the remaining 15 patients, the average total amount of insulin infused was 1.4 U/patient/h less following intermittent feeds: P =0.027, 95% confidence interval (0.02, 11.17), and effect size 0.6. Secondary endpoints were statistically similar. CONCLUSIONS: Critically ill medical patients who require an insulin infusion have a reduced insulin requirement when fed intermittently, whereas dysglycemia metrics are not adversely affected. A larger clinical study is required to confirm these findings.

Clinical and laboratory predictors of blood loss in young swine: a model for pediatric hemorrhage.

BACKGROUND: The pediatric patient's response to hemorrhage as a function of young age is not well understood. As a result, there is no consensus on optimal resuscitation strategies for hemorrhagic shock in pediatric patients, or on the identification of clinical triggers to prompt implementation. The study objective was to develop a model of pediatric hemorrhage using young pigs to simulate school-aged children, and determine clinical and laboratory indicators for significant hemorrhage. MATERIALS AND METHODS: 29 non-splenectomized female pigs, aged 3 months, weighing 30-40 kg, were randomized into groups with varying degrees of hemorrhage. Bleeding occurred intermittently over 5 h while the animals were anesthetized but spontaneously breathing. Various physiologic and biochemical markers were used to monitor the piglets during hemorrhage. RESULTS: Swine experiencing up to 50% hemorrhage survived without exception throughout the course of hemorrhage. 80% (4/5) of the animals in the 60% hemorrhage group survived. Need for respiratory support was universal when blood loss reached 50% of estimated blood volume. Blood pressure was not useful in classifying the degree of shock. Heart rate was helpful in differentiating between the extremes of blood loss examined. Arterial pCO2, pH, lactate, HCO3 and creatinine levels, as well as urine output, changed significantly with increasing blood loss. CONCLUSIONS: Young swine are resilient against hemorrhage, although hemorrhage of 50% or greater universally require respiratory support. In this animal model, with the exception of heart rate, vital signs were minimally helpful in identification of shock. However, change in select laboratory values from baseline was significant with increasing blood loss. LEVEL OF EVIDENCE: This was a level II prospective comparative study.

Simulation and qualitative analysis of glucose variability, mean glucose, and hypoglycemia after subcutaneous insulin therapy for stress hyperglycemia.

BACKGROUND: The critically ill can have persistent dysglycemia during the "subacute" recovery phase of their illness because of altered gene expression; it is also not uncommon for these patients to receive continuous enteral nutrition during this time. The optimal short-acting subcutaneous insulin therapy that should be used in this clinical scenario, however, is unknown. Our aim was to conduct a qualitative numerical study of the glucose-insulin dynamics within this patient population to answer the above question. This analysis may help clinicians design a relevant clinical trial. METHODS: Eight virtual patients with stress hyperglycemia were simulated by means of a mathematical model. Each virtual patient had a different combination of insulin resistance and insulin deficiency that defined their unique stress hyperglycemia state; the rate of gluconeogenesis was also doubled. The patients received 25 injections of subcutaneous regular or Lispro insulin (0-6 U) with 3 rates of continuous nutrition. The main outcome measurements were the change in mean glucose concentration, the change in glucose variability, and hypoglycemic episodes. These end points were interpreted by how the ultradian oscillations of glucose concentration were affected by each insulin preparation. RESULTS: Subcutaneous regular insulin lowered both mean glucose concentrations and glucose variability in a linear fashion. No hypoglycemic episodes were noted. Although subcutaneous Lispro insulin lowered mean glucose concentrations, glucose variability increased in a nonlinear fashion. In patients with high insulin resistance and nutrition at goal, "rebound hyperglycemia" was noted after the insulin analog was rapidly metabolized. When the nutritional source was removed, hypoglycemia tended to occur at higher Lispro insulin doses. Finally, patients with severe insulin resistance seemed the most sensitive to insulin concentration changes. CONCLUSIONS: Subcutaneous regular insulin consistently lowered mean glucose concentrations and glucose variability; its linear dose-response curve rendered the preparation better suited for a sliding-scale protocol. The longer duration of action of subcutaneous regular insulin resulted in better glycemic-control metrics for patients who were continuously postprandial. Clinical trials are needed to examine whether these numerical results represent the glucose-insulin dynamics that occur in intensive care units; if present, their clinical effects should be evaluated.