Massive transfusion protocol reactivation as a novel marker of physician team under-triage after injury.

BACKGROUND: Large trauma centers have protocols for the assessment of injury and triaging of care with attempts to over-triage to ensure adequate care for all patients. We noted that a significant number of patients undergo a second massive transfusion protocol (MTP) activation in the first 24 h of care and conducted a retrospective cohort study of patients involved over a 3-year period. METHODS: Transfusion service records of MTP activations 2019-2021 were linked to Trauma Registry records and divided into cohorts receiving a single versus a reactivation of the MTP. Time of activation and amounts of blood products issued were linked to demographic, injury severity, and outcome data. Categorical and continuous data were compared between cohorts with chi-squared, Fisher's, and Wilcoxan tests as appropriate, and multivariable regression models were used to seek interactions (p < .05). RESULTS: MTP activation was recorded for 1884 acute trauma patients over our 3-year study period, 142 of whom (7.5%) had reactivation. Factors associated with reactivation included older age (46 vs. 40 years), higher injury severity score (ISS, 27 vs. 22), leg injuries, and presentation during morning shift change (5-7 a.m., 3.3% vs. 7.7%). Patients undergoing MTP reactivation used more RBCs (5 U vs. 2 U) and had more ICU days (3 vs. 2). CONCLUSIONS: Older patients and those presenting during shift change are at risk for failure to recognize their complex injury patterns and under-triage for trauma care. The fidelity and granularity of transfusion service records can provide unique opportunities for quality assessment and improvement in trauma care.

Characteristics of victims of trauma requiring invasive mechanical ventilation with a short stay in critical care.

BACKGROUND: Many patients who are admitted to the intensive care unit (ICU) have needs which rapidly resolve and are discharged alive within 24 h. We sought to characterize the outcomes of critically ill trauma victims at our institution with a short stay in the ICU. METHODS: We conducted a retrospective cohort study of all critically ill adult trauma victims presenting to our ED between January 1st, 2011 and December 31st, 2019. We included patients who were endotracheally intubated in either the prehospital setting or the ED and were admitted either to the operating room (OR), angiography suite, or ICU. Our primary outcome was the proportion of patients who were discharged alive from the ICU within 24 h. RESULTS: We included 3869 patients meeting the criteria above who were alive at 24 h. This population was 78% male with a median age of 40 and 76% of patients suffered from blunt trauma. The median injury severity score (ISS) of the group was 21 [inter-quartile range (IQR) 11-30]. In-hospital mortality amongst the group was 12%. 17% of the group were discharged alive from the ICU within 24 h. Thirty-four percent of the group had an ISS ≤ 15. Of the group which left the ICU alive within 24 h, six patients (0.9%) died in the hospital, 2 % of patients were re-admitted to an ICU, and 0.6% of patients required re-intubation. CONCLUSIONS: We found that 17% of patients who were intubated in the prehospital setting or emergency department and subsequently hospitalized were discharged alive from the ICU within 24 h.

A Description of Mechanically Ventilated Patients Admitted From the Emergency Department With a Short Critical Care Stay.

BACKGROUND: Patients admitted to an intensive care unit (ICU) requiring invasive mechanical ventilation who are discharged alive from the ICU within 24 h are poorly characterized in the literature. OBJECTIVE: Our aim was to characterize a cohort of intubated emergency department (ED) patients who are extubated and discharged from the ICU within 24 h. METHODS: We conducted a retrospective, observational cohort study at a single level I trauma center from January 2017 to December 2019. We included adults who were admitted to an ICU from the ED requiring invasive mechanical ventilation. Our primary outcome was the proportion of patients who were discharged from the ICU alive within 24 h. RESULTS: Of 13,374 ED patients admitted to an ICU during the study period, 2871 patients were intubated and ventilated in the prehospital or ED settings. Of these, 14% were discharged alive from the ICU within 24 h of admission. Only 21% of these patients were intubated in the ED. We identified the following two distinct subpopulations comprising 62% of this short-stay group: patients with a primary discharge diagnosis of intoxication (47%) and minimally injured trauma patients (53%), with 4% of patients in both subgroups. CONCLUSIONS: A total of 14% of patients receiving intubation with mechanical ventilation in the prehospital environment or in the ED were discharged alive from the ICU within 24 h. We identified two distinct subgroups of patients with a short stay in intensive care who may be candidates for ED extubation, including patients with intoxication and minimally injured trauma patients.

Blood product availability in the Washington state trauma system.

BACKGROUND: Early transfusion can prolong life in injured patients awaiting definitive hemorrhage control. We conducted a community resources assessment of blood product availability at hospitals within the Washington State (WA) Regional Trauma System, with the expectation that a minority of Level IV and V centers would have blood products routinely available for use in resuscitation. METHODS: We designed a questionnaire soliciting information on routinely available unit quantities of red blood cells (RBC), plasma, platelets, cryoprecipitate, and/or whole blood and submitted this questionnaire electronically to the 82 WA designated trauma centers (Levels I-V). Non-responders were contacted directly by telephone. The study was conducted in September and October 2021. US 2020 census data were used to correlate results with local population densities. RESULTS: First-round contact netted responses from 57 (70%) centers; the remaining centers provided information via telephone, for a 100% final response. Packed RBC were available in 79 of the 82 centers (96%; range 6-220 units); plasma, 62 centers (76%, range 1-100 units); platelets, 40 centers (49%, range 1-8 units); cryoprecipitate, 45 centers (55%, range 1-20 units). Whole blood was only available at the Level I center. Three Level V centers, located in 2 of the 8 WA state trauma regions, reported no routine blood availability. The two trauma regions affected represent 12% of the state's population and more than a third of its geographic area. CONCLUSIONS: Within the WA regional trauma system, blood products are wide, if unevenly, available. Large urban/rural disparities in availability exist that should be explored.

Nonoperative Management in Blunt Splenic Trauma: Can Shock Index Predict Failure?

INTRODUCTION: Predicting failure of nonoperative management (NOM) in splenic trauma remains elusive. Shock index (SI) is an indicator of physiologic burden in an injury but is not used as a prediction tool. The purpose of this study was to determine if elevated SI would be predictive of failure of NOM in patients with a blunt splenic injury. METHODS: Adult patients admitted to a level-1 trauma center from January 2011 to April 2017 for NOM of splenic injury were reviewed. Patients were excluded if they underwent a procedure (angiography or surgery) prior to admission. The primary outcome was requiring intervention after an initial trial of noninterventional management (NIM). An SI > 0.9 at admission was considered a high risk. Univariate and multivariate analyses were used to identify predicators of the failure of NOM. Findings were subsequently verified on a validation cohort of patients. RESULTS: Five hundred and eighty-five patients met inclusion criteria; 7.4% failed NIM. On an univariate analysis, findings of pseudoaneurysm or extra-arterial contrast on computed tomography did not differentiate successful NIM versus failure (8.1% versus 14.0%, P = 0.18). Age, the American Association for the Surgery of Trauma injury grade, and elevated SI were included in multivariate modeling. Grade of injury (OR 3.49, P = 0.001), age (OR 1.02, P = 0.009), and high SI (OR 3.49, P = 0.001) were each independently significant for NIM failure. The risk-adjusted odds of failure were significantly higher in patients with a high risk SI (OR 2.35, P < 0.001). Validation of these findings was confirmed for high SI on a subsequent 406 patients with a c-statistic of 0.71 (95% CI 0.62-0.80). CONCLUSIONS: Elevated SI is an independent risk factor for failure of NIM in those with splenic injury. SI along with age and computed tomography findings may aid in predicting the failure of NIM. Trauma providers should incorporate SI into decision-making tools for splenic injury management.

Outcomes of ß-Hemolytic Streptococcal Necrotizing Skin and Soft-tissue Infections and the Impact of Clindamycin Resistance.

BACKGROUND: ß-Hemolytic streptococci are frequently implicated in necrotizing soft-tissue infections (NSTIs). Clindamycin administration may improve outcomes in patients with serious streptococcal infections. However, clindamycin resistance is growing worldwide, and resistance patterns in NSTIs and their impact on outcomes are unknown. METHODS: Between 2015 and 2018, patients with NSTI at a quaternary referral center were followed up for the outcomes of death, limb loss, and streptococcal toxic shock syndrome. Surgical wound cultures and resistance data were obtained within 48 hours of admission as part of routine care. Risk ratios for the association between these outcomes and the presence of ß-hemolytic streptococci or clindamycin-resistant ß-hemolytic streptococci were calculated using log-binomial regression, controlling for age, transfer status, and injection drug use-related etiology. RESULTS: Of 445 NSTIs identified, 85% had surgical wound cultures within 48 hours of admission. ß-Hemolytic streptococci grew in 31%, and clindamycin resistance was observed in 31% of cultures. The presence of ß-hemolytic streptococci was associated with greater risk of amputation (risk ratio, 1.80; 95% confidence interval, 1.07-3.01), as was the presence of clindamycin resistance among ß-hemolytic streptococci infections (1.86; 1.10-3.16). CONCLUSIONS: ß-Hemolytic streptococci are highly prevalent in NSTIs, and in our population clindamycin resistance was more common than previously described. Greater risk of limb loss among patients with ß-hemolytic streptococci-particularly clindamycin-resistant strains-may portend a more locally aggressive disease process or may represent preexisting patient characteristics that predispose to both infection and limb loss. Regardless, these findings may inform antibiotic selection and surgical management to maximize the potential for limb salvage.

A Novel Immune Modulator for Patients With Necrotizing Soft Tissue Infections (NSTI): Results of a Multicenter, Phase 3 Randomized Controlled Trial of Reltecimod (AB 103).

BACKGROUND AND OBJECTIVE: Reltecimod, a CD 28 T-lymphocyte receptor mimetic, inhibits T-cell stimulation by an array of bacterial pathogens. A previous phase 2 trial demonstrated improved resolution of organ dysfunction after NSTI. We hypothesized that early administration of reltecimod would improve outcome in severe NSTI. METHODS: Randomized, double-blind, placebo-controlled trial of single dose reltecimod (0.5 mg/kg) administered within 6 hours of NSTI diagnosis at 65 of 93 study sites. Inclusion: surgical confirmation of NSTI and organ dysfunction [modified Sequential Organ Failure Assessment Score (mSOFA) score ≥3]. Primary analysis was modified Intent-to-Treat (mITT), responder analysis using a previously validated composite endpoint, necrotizing infection clinical composite endpoint, defined as: alive at day 28, ≤3 debridements, no amputation beyond first operation, and day 14 mSOFA ≤1 with ≥3 point reduction (organ dysfunction resolution). A prespecified, per protocol (PP) analysis excluded 17 patients with major protocol violations before unblinding. RESULTS: Two hundred ninety patients were enrolled, mITT (Reltecimod 142, Placebo 148): mean age 55 ±â€Š15 years, 60% male, 42.4% diabetic, 28.6% perineal infection, screening mSOFA mean 5.5 ±â€Š2.4. Twenty-eight-day mortality was 15% in both groups. mITT necrotizing infection clinical composite endpoint success was 48.6% reltecimod versus 39.9% placebo, P = 0.135 and PP was 54.3% reltecimod versus 40.3% placebo, P = 0.021. Resolution of organ dysfunction was 65.1% reltecimod versus 52.6% placebo, P = 0.041, mITT and 70.9% versus 53.4%, P = 0.005, PP. CONCLUSION: Early administration of reltecimod in severe NSTI resulted in a significant improvement in the primary composite endpoint in the PP population but not in the mITT population. Reltecimod was associated with improved resolution of organ dysfunction and hospital discharge status.

Cervical spine evaluation in pediatric trauma: A cost-effectiveness analysis.

OBJECTIVE: The emergent evaluation of children with suspected traumatic cervical spine injuries (CSI) remains a challenge. Pediatric clinical pathways have been developed to stratify the risk of CSI and guide computed tomography (CT) utilization. The cost-effectiveness of their application has not been evaluated. Our objective was to examine the cost-effectiveness of three common strategies for the evaluation of children with suspected CSI after blunt injury. METHODS: We developed a decision analytic model comparing these strategies to estimate clinical outcomes and costs for a hypothetical population of 0-17 year old patients with blunt neck trauma. Strategies included: 1) clinical pathway to stratify risk using NEXUS criteria and determine need for diagnostic testing; 2) screening radiographs as a first diagnostic; and 3) immediate CT scanning for all patients. We measured effectiveness with quality-adjusted life years (QALYs), and costs with 2018 U.S. dollars. Costs and effectiveness were discounted at 3% per year. RESULTS: The use of the clinical pathway results in a gain of 0.04 QALYs and a cost saving of $2800 compared with immediate CT scanning of all patients. Use of the clinical pathway was less costly and more effective than immediate CT scan as long as the sensitivity of the clinical prediction rule was greater than 87% and when the sensitivity of x-ray was greater than 84%. CONCLUSION: A strategy using a clinical pathway to first stratify risk before further diagnostic testing was less costly and more effective than either performing CT scanning or screening cervical radiographs on all patients.

Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury.

Importance: Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI. Objective: To determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI. Design, Setting, and Participants: Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher. Interventions: Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309). Main Outcomes and Measures: The primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events. Results: Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, -0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% [95% CI, -7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 [95% CI, -2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% [95% CI, -12.8% to 2.1%]; P = .16). Conclusions and Relevance: Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended. Trial Registration: ClinicalTrials.gov Identifier: NCT01990768.

Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

Importance: Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. Objective: To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. Design, Setting, and Participants: This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Interventions: Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). Main Outcomes and Measures: The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Results: Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Conclusions and Relevance: Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults. Trial Registration: ClinicalTrials.gov: NCT04332991.

Do Autopsies Still Matter? The Influence of Autopsy Data on Final Injury Severity Score Calculations.

BACKGROUND: Despite a proven record of identifying injuries missed during clinical evaluation, the effect of autopsy on injury severity score (ISS) calculation is unknown. We hypothesized that autopsy data would alter final ISS and improve the accuracy of outcome data analyses. MATERIALS AND METHODS: All trauma deaths from January 2010 through June 2014 were reviewed. Trauma registrars calculated Abbreviated Injury Scale and ISS from clinical documentation alone. The most detailed available autopsy report then was reviewed, and AIS/ISS recalculated. Predictors of ISS change were identified using multivariate logistic regression. RESULTS: Seven hundred thirty-nine deaths occurred, of which 682 (92.3%) underwent autopsy (31% view-only, 3% with preliminary report, and 66% with full report). Patients undergoing full autopsy had a lower median age (39 versus 74 years, P < 0.01), a higher rate of penetrating injury (41.7% versus 0%, P < 0.01), and a higher emergency department mortality rate (30.8% versus 0%, P < 0.01) than those receiving view-only autopsy. Incorporating autopsy findings increased mean ISS (21.3 to 29.6, P < 0.001) and the percentage of patients with ISS ≥ 25 (49.9% to 69.2%, P < 0.001). Multivariate analysis identified length of stay, death in the emergency department, full rather than view-only autopsy, and presenting heart rate as variables associated with ISS increase. CONCLUSIONS: Autopsy data significantly increased ISS values for trauma deaths. This effect was greatest in patients who died early in their course. Targeting this group, rather than all trauma patients, for full autopsy may improve risk-adjustment accuracy while minimizing costs.

Decreased Risk of Delirium With Use of Regional Analgesia in Geriatric Trauma Patients With Multiple Rib Fractures.

OBJECTIVE: The aim of this study was to examine the risk of delirium in geriatric trauma patients with rib fractures treated with systemic opioids compared with those treated with regional analgesia (RA). SUMMARY OF BACKGROUND DATA: Delirium is a modifiable complication associated with increased morbidity and mortality. RA may reduce the need for opioid medications, which are associated with delirium in older adults. METHODS: Cohort study of patients ≥65 years admitted to a regional trauma center from 2011 to 2016. Inclusion factors were ≥ 3 rib fractures, blunt trauma mechanism, and admission to intensive care unit (ICU). Exclusion criteria included head AIS ≥3, spine AIS ≥3, dementia, and death within 24 hours. The primary outcome was delirium positive ICU days, defined using the CAM-ICU assessment. Delirium incident rate ratios (IRRs) and 95% confidence intervals (95% CIs) were estimated using generalized linear mixed models with Poisson distribution and robust standard errors. RESULTS: Of the 144 patients included in the study, 27 (19%) received Acute Pain Service consultation and RA and 117 (81%) received opioid-based systemic analgesia. Patients with RA had more severe chest injury than those without. The risk of delirium decreased by 24% per day per patient with use of RA (IRR 0.76, 95% CI 0.61 to 0.96). Individual opioid use, as measured in daily morphine equivalents (MEDs), was significantly reduced after initiation of RA (mean difference -7.62, 95% CI -14.4 to -0.81). CONCLUSION: Although use of RA techniques in geriatric trauma patients with multiple rib fractures was associated with higher MED, opioid use decreased after RA initiation and Acute Pain Service consultation, and the risk of delirium was lower.

Duration of Respiratory Failure After Trauma Is Not Associated With Increased Long-Term Mortality.

OBJECTIVES: Although 1-year survival in medically critically ill patients with prolonged mechanical ventilation is less than 50%, the relationship between respiratory failure after trauma and 1-year mortality is unknown. We hypothesize that respiratory failure duration in trauma patients is associated with decreased 1-year survival. DESIGN: Retrospective cohort of trauma patients. SETTING: Single center, level 1 trauma center. PATIENTS: Trauma patients admitted from 2011 to 2014; respiratory failure is defined as mechanical ventilation greater than or equal to 48 hours, excluded head Abbreviated Injury Score greater than or equal to 4. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mortality was calculated from the Washington state death registry. Cohort was divided into short (≤ 14 d) and long (> 14 d) ventilation groups. We compared survival with a Cox proportional hazard model and generated a receiver operator characteristic to describe the respiratory failure and mortality relationship. Data are presented as medians with interquartile ranges and hazard ratios with 95% CIs. We identified 1,503 patients with respiratory failure; median age was 51 years (33-65 yr) and Injury Severity Score was 19 (11-29). Median respiratory failure duration was 3 days (2-6 d) with 10% of patients in the long respiratory failure group. Cohort mortality at 1 year was 16%, and there was no difference in mortality between short and long duration of respiratory failure. Predictions for 1-year mortality based on respiratory failure duration demonstrated an area under the receiver operator characteristic curve of 0.57. We determined that respiratory failure patients greater than or equal to 75 years had an increased hazard of death at 1 year, hazard ratio, 6.7 (4.9-9.1), but that within age cohorts, respiratory failure duration did not influence 1-year mortality. CONCLUSIONS: Duration of mechanical ventilation in the critically injured is not associated with 1-year mortality. Duration of ventilation following injury should not be used to predict long-term survival.

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU.

OBJECTIVE: To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU. DESIGN: Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups gathered face-to-face at annual Society of Critical Care Medicine congresses; virtual connections included those unable to attend. A formal conflict of interest policy was developed a priori and enforced throughout the process. Teleconferences and electronic discussions among subgroups and whole panel were part of the guidelines' development. A general content review was completed face-to-face by all panel members in January 2017. METHODS: Content experts, methodologists, and ICU survivors were represented in each of the five sections of the guidelines: Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption). Each section created Population, Intervention, Comparison, and Outcome, and nonactionable, descriptive questions based on perceived clinical relevance. The guideline group then voted their ranking, and patients prioritized their importance. For each Population, Intervention, Comparison, and Outcome question, sections searched the best available evidence, determined its quality, and formulated recommendations as "strong," "conditional," or "good" practice statements based on Grading of Recommendations Assessment, Development and Evaluation principles. In addition, evidence gaps and clinical caveats were explicitly identified. RESULTS: The Pain, Agitation/Sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) panel issued 37 recommendations (three strong and 34 conditional), two good practice statements, and 32 ungraded, nonactionable statements. Three questions from the patient-centered prioritized question list remained without recommendation. CONCLUSIONS: We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

Ketamine versus hydromorphone patient-controlled analgesia for acute pain in trauma patients.

BACKGROUND: It is unknown whether ketamine administered via patient-controlled analgesia (PCA) provides adequate analgesia while reducing opioid consumption in the traumatically injured patient. Differences in opioid consumption, pain scores, and adverse effects between ketamine and hydromorphone PCA were studied. MATERIALS AND METHODS: This is an investigator-initiated, single-center, double-blinded, randomized, pilot trial conducted from 2014 to 2016 at a level 1 trauma center. Nonintubated trauma patients in intensive care, who were receiving PCA, were randomized to ketamine or hydromorphone PCA plus opioid analgesics for breakthrough pain. RESULTS: Twenty subjects were randomized. There was no difference in median daily breakthrough opioid use (10 [0.63-19.38] mg versus 10 [4.38-22.5] mg, P = 0.55). Subjects in the ketamine group had lower median cumulative opioid use on therapy day 1 than the hydromorphone group (4.6 [2.5-15] mg versus 41.8 [31.8-50] mg, P < 0.001), as well as in the first 48 h (10 [3.3-15] mg versus 48.5 [32.1-67.5] mg, P < 0.001) and first 72 h (10 [4.2-15] mg versus 42.5 [31.7-65.2] mg, P < 0.001) of therapy. Daily oxygen supplementation requirements were lower in the ketamine group (0.5 [0-1.5] L/min versus 2 [0.5-3] L/min, P = 0.020). Hallucinations occurred more frequently in the ketamine group (40% versus 0%, P = 0.090). CONCLUSIONS: Ketamine PCA led to lower cumulative opioid consumption and lower oxygen supplementation requirements, though hallucinations occurred more frequently with use of ketamine. Additional studies are needed to investigate the tolerability of ketamine as an alternative to traditional opioid-based PCA.

Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial.

IMPORTANCE: Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. OBJECTIVE: To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. INTERVENTIONS: Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). MAIN OUTCOMES AND MEASURES: Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. RESULTS: No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% [95% CI, -9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7% [95% CI, -10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% [95% CI, -10.4% to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications. CONCLUSIONS AND RELEVANCE: Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01545232.

Early Fluid Is Less Fluid: Comparing Early Versus Late ICU Resuscitation in Severely Injured Trauma Patients.

OBJECTIVES: The temporal trends of crystalloid resuscitation in severely injured trauma patients after ICU admission are not well characterized. We hypothesized early crystalloid resuscitation was associated with less volume and better outcomes than delaying crystalloid. DESIGN: Retrospective, observational. SETTING: High-volume level 1 academic trauma center. PATIENTS: Adult trauma patients admitted to the ICU with emergency department serum lactate greater than or equal to 4 mmol/dL, elevated lactate (≥ 2 mmol/L) at ICU admission, and normal lactate by 48 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the 333 subjects, we analyzed patient and injury characteristics and the first 48 hours of ICU course. Receipt of greater than or equal to 500 mL/hr of crystalloid in the first 6 hours of ICU admission was used to distinguish early vs. late resuscitation. Outcomes included ICU length of stay (LOS), ventilator days, and acute kidney injury (AKI). Unadjusted and multivariable regression methods were used to compare early resuscitation vs. late resuscitation. Compared with the early resuscitation group, the late resuscitation group received more volume by 48 hours (5.5 vs. 4.1 L; p ≤ 0.001), had longer ICU LOS (9 vs. 5 d; p ≤ 0.001), more ventilator days (5 vs. 2 d; p ≤ 0.001), and higher occurrence rate of AKI (38% vs. 11%; p ≤ 0.001). On multivariable regression, late resuscitation remained associated with longer ICU LOS and ventilator days and higher odds of AKI. CONCLUSIONS: Delaying resuscitation is associated with both higher volumes of crystalloid by 48 hours and worse outcomes compared with early resuscitation. Judicious crystalloid given early in ICU admission could improve outcomes in the severely injured.

Predicting high-intensity resuscitation needs in injured patients in the post-hemostasis phase of care following intervention.

BACKGROUND: Best resuscitation practices in the posthemostasis phase of care are poorly defined; this phase of care is characterized by a range of physiologic derangements and multiple therapeutic modalities used to address them. Using a cohort of injured patients who required an immediate intervention in the operating room or angiography suite following arrival to the emergency department, we sought to define high-intensity resuscitation (HIR) in this posthemostasis phase of care; we hypothesized that those who would require HIR could be identified, using only data available at intensive care unit (ICU) admission. METHODS: Clinical data were extracted for consecutive injured patients (2016-2019) admitted to the ICU following an immediate procedure in the operating room or angiography suite. High-intensity resuscitation thresholds were defined as the top decile of blood product (≥3 units) and/or crystalloid (≥4 L) use in the initial 12 hours of ICU care and/or vasoactive medication use between ICU hours 2 and 12. The primary outcome, HIR, was a composite of any of these modalities. Predictive modeling of HIR was performed using logistic regression with predictor variables selected using Least Absolute Shrinkage and Selection Operator (LASSO) estimation. Model was trained using 70% of the cohort and tested on the remaining 30%; model predictive ability was evaluated using area under receiver operator curves. RESULTS: Six hundred five patients were included. Patients were 79% male, young (median age, 39 years), severely injured (median Injury Severity Score, 26), and an approximately 3:2 ratio of blunt to penetrating mechanisms of injury. A total of 215 (36%) required HIR. Predictors selected by LASSO included: shock index, lactate, base deficit, hematocrit, and INR. The area under receiver operator curve for the LASSO-derived HIR prediction model was 0.82. CONCLUSION: Intensive care unit admission data can identify subsequent HIR in the posthemostasis phase of care. Use of this model may facilitate triage, nursing ratio determination, and resource allocation. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

A core outcome set for acute necrotizing pancreatitis: An Eastern Association for the Surgery of Trauma modified Delphi method consensus study.

BACKGROUND: The management of acute necrotizing pancreatitis (ANP) has changed dramatically over the past 20 years including the use of less invasive techniques, the timing of interventions, nutritional management, and antimicrobial management. This study sought to create a core outcome set (COS) to help shape future research by establishing a minimal set of essential outcomes that will facilitate future comparisons and pooling of data while minimizing reporting bias. METHODS: A modified Delphi process was performed through involvement of ANP content experts. Each expert proposed a list of outcomes for consideration, and the panel anonymously scored the outcomes on a 9-point Likert scale. Core outcome consensus defined a priori as >70% of scores receiving 7 to 9 points and <15% of scores receiving 1 to 3 points. Feedback and aggregate data were shared between rounds with interclass correlation trends used to determine the end of the study. RESULTS: A total of 19 experts agreed to participate in the study with 16 (84%) participating through study completion. Forty-three outcomes were initially considered with 16 reaching consensuses after four rounds of the modified Delphi process. The final COS included outcomes related to mortality, organ failure, complications, interventions/management, and social factors. CONCLUSION: Through an iterative consensus process, content experts agreed on a COS for the management of ANP. This will help shape future research to generate data suitable for pooling and other statistical analyses that may guide clinical practice. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level V.