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.

Early empiric antibiotic use in COVID-19 patients: results from the international VIRUS registry.

OBJECTIVES: COVID-19 escalated inappropriate antibiotic use. We determined the distribution of pathogens causing community-acquired co-infections, the rate, and factors associated with early empiric antibiotic (EEAB) treatment among hospitalized COVID-19 patients. METHODS: The Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 Registry including 68,428 patients from 28 countries enrolled between January 2020 and October 2021 were screened. After exclusions, 7830 patients were included in the analysis. Azithromycin and/or other antibiotic treatment given within the first 3 days of hospitalization was investigated. Univariate and multivariate analyses were performed to determine factors associated with EEAB use. RESULTS: The majority (6214, 79.4%) of patients received EEAB, with azithromycin combination being the most frequent (3146, 40.2%). As the pandemic advanced, the proportion of patients receiving EEAB regressed from 84.4% (786/931) in January-March 2020 to 65.2% (30/46) in April-June 2021 (P < 0.001). Beta-lactams, especially ceftriaxone was the most commonly used antibiotic. Staphylococcus aureus was the most commonly isolated pathogen. Multivariate analysis showed geographical location and pandemic timeline as the strongest independent predictors of EEAB use. CONCLUSIONS: EEAB administration decreased as pandemic advanced, which may be the result of intensified antimicrobial stewardship efforts. Our study provides worldwide goals for antimicrobial stewardship programs in the post-COVID-19 era.

Oxygenation and Respiratory System Compliance Associated With Pulmonary Contusion.

BACKGROUND: Blunt pulmonary contusions are associated with severe chest injuries and are independently associated with worse outcomes. Previous preclinical studies suggest that contusion progression precipitates poor pulmonary function; however, there are few current clinical data to corroborate this hypothesis. We examined pulmonary dynamics and oxygenation in subjects with pulmonary contusions to evaluate for impaired respiratory function. METHODS: A chest injury database was reviewed for pulmonary contusions over 5 years at an urban trauma center. This database was expanded to capture mechanical ventilation parameters for the first 7 days on all patients with pulmonary contusion and who were intubated. Daily [Formula: see text]:[Formula: see text], oxygenation indexes (OI), and dynamic compliances were calculated. Pulmonary contusions were stratified by severity. The Fisher exact and chi square tests were performed on categorical variables, and Mann-Whitney U-tests were performed on continuous variables. Significance was assessed at a level of 0.05. RESULTS A TOTAL OF: 1,176 patients presented with pulmonary contusions, of whom, 301 subjects (25.6%) required intubation and had available invasive mechanical ventilation data. Of these, 144 (47.8%) had mild-moderate pulmonary contusion and 157 (52.2%) had severe pulmonary contusion. Overall injury severity score was high, with a median injury severity score of 29 (interquartile range, 22-38). The median duration of mechanical ventilation for mild-moderate pulmonary contusion was 7 d versus 10 d for severe pulmonary contusion (P = .048). All the subjects displayed moderate hypoxemia, which worsened until day 4-5 after intubation. Severe pulmonary contusion was associated with significantly worse early hypoxia on day 1 and day 2 versus mild-moderate pulmonary contusion. Severe pulmonary contusion also had a higher oxygenation index than mild-moderate pulmonary contusion. This trend persisted after adjustment for other factors, including transfusion and fluid administration. CONCLUSIONS: Pulmonary contusions played an important role in the course of subjects who were acutely injured and required mechanical ventilation. Contusions were associated with hypoxemia not fully characterized by [Formula: see text]: [Formula: see text], and severe contusions had durable elevations in the oxygenation index despite confounders.

Assessment of Detectable Serum Tobramycin Concentrations in Patients Receiving Inhaled Tobramycin for Ventilator-Associated Pneumonia.

BACKGROUND: Inhaled tobramycin can be used for empiric or definitive therapy of ventilator-associated pneumonia (VAP) in mechanically ventilated patients. This is believed to minimize systemic exposure and potential adverse drug toxicities including acute kidney injury (AKI). However, detectable serum tobramycin concentrations have been reported after inhaled tobramycin therapy with AKI. METHODS: This retrospective, observational study evaluated mechanically ventilated adult subjects admitted to ICUs at a large, urban academic medical center that received empiric inhaled tobramycin for VAP. Subjects were separated into detectable (ie, ≥ 0.6 mg/L) or undetectable serum tobramycin concentration groups, and characteristics were compared. Independent predictors for detectable serum tobramycin concentration and new onset AKI during or within 48 h of therapy discontinuation were assessed. RESULTS: Fifty-nine inhaled tobramycin courses in 53 subjects were included in the analysis, of which 39 (66.1%) courses administered to 35 (66.0%) subjects had detectable serum tobramycin concentrations. Subjects with detectable serum tobramycin concentrations were older (57.1 y ± 11.4 vs 45.9 ±15.0, P = .004), had higher PEEP (9.2 cm H2O [7.0-11.0] vs 8.0 [5.6-8.9], P = .049), chronic kidney disease stage ≥ 2 (10 [29.4%] vs 0 [0%], P = .009), and higher serum creatinine before inhaled tobramycin therapy (1.26 mg/dL [0.84-2.18] vs 0.76 [0.47-1.28], P = .004). Age (odds ratio 1.09 [95% CI 1.02-1.16], P = .009) and PEEP (odds ratio 1.47 [95% CI 1.08-2.0], P =.01) were independent predictors for detectable serum tobramycin concentration. Thirty-seven subjects had no previous renal disease or injury, of which 9 (24.3%) developed an AKI. Sequential Organ Failure Assessment score (odds ratio 1.72 [95% CI 1.07-2.76], P = .03) was the only independent predictor for AKI. CONCLUSIONS: Detectable serum tobramycin concentrations were frequently observed in critically ill, mechanically ventilated subjects receiving empiric inhaled tobramycin for VAP. Subject age and PEEP were independent predictors for detectable serum tobramycin concentration. Serum monitoring and empiric dose reductions should be considered in older patients and those requiring higher PEEP.

Endocutter Staple Height Auto-Adjusts to Tissue Thickness.

BACKGROUND: Surgeon choice of the appropriate staple height has been cited as a factor in the mechanical integrity of a staple line. However, tissue measured at the industry standard 8 g/mm2 is usually thicker than the formed staple height of the staples that hold it together. This means that the pressure that the staples apply must be greater than 8g/mm2. Additionally, formed staple heights in tissue may be different than formed staple heights of the same cartridge type when fired without tissue. This means that there is likely a compressive limit to the individual staples deployed by the stapling system. The purpose of this study is to establish the degree to which staple heights of endocutter staples auto-adjust to tissue and the compressive limit to tissue that this infers. MATERIALS AND METHODS: Excised gastric remnants from laparoscopic sleeve gastrectomy were measured for tissue thickness at different external pressures. An optimized experimental staple line was then created in parallel to the clinical staple line. The doubly-stapled gastric sliver then underwent computed tomography with solid modeling software to measure staple heights. RESULTS: Staple heights fired in gastric tissue were significantly different than industry labelled and control staple heights. Clinical staple heights were significantly shorter than measured tissue thickness at 8 g/mm2. Staple height more closely approximated tissue thickness under 15 g/mm2 of pressure, rather than the 8 g/mm2 loading pressure used by industry for tissue thickness range labelling. CONCLUSIONS: Staples deployed in human gastric tissue are taller than commercial labelling. The closed staple height corresponds to tissue thickness under 15g/mm2 of pressure, not the labelled staple height. These results demonstrate that staple heights from modern endocutter staplers adjust to tissue, approximating a maximum compressive force just above 15g/mm2.

Variation in Early Management Practices in Moderate-to-Severe ARDS in the United States: The Severe ARDS: Generating Evidence Study.

BACKGROUND: Although specific interventions previously demonstrated benefit in patients with ARDS, use of these interventions is inconsistent, and patient mortality remains high. The impact of variability in center management practices on ARDS mortality rates remains unknown. RESEARCH QUESTION: What is the impact of treatment variability on mortality in patients with moderate to severe ARDS in the United States? STUDY DESIGN AND METHODS: We conducted a multicenter, observational cohort study of mechanically ventilated adults with ARDS and Pao2 to Fio2 ratio of ≤ 150 with positive end-expiratory pressure of ≥ 5 cm H2O, who were admitted to 29 US centers between October 1, 2016, and April 30, 2017. The primary outcome was 28-day in-hospital mortality. Center variation in ventilator management, adjunctive therapy use, and mortality also were assessed. RESULTS: A total of 2,466 patients were enrolled. Median baseline Pao2 to Fio2 ratio was 105 (interquartile range, 78.0-129.0). In-hospital 28-day mortality was 40.7%. Initial adherence to lung protective ventilation (LPV; tidal volume, ≤ 6.5 mL/kg predicted body weight; plateau pressure, or when unavailable, peak inspiratory pressure, ≤ 30 mm H2O) was 31.4% and varied between centers (0%-65%), as did rates of adjunctive therapy use (27.1%-96.4%), methods used (neuromuscular blockade, prone positioning, systemic steroids, pulmonary vasodilators, and extracorporeal support), and mortality (16.7%-73.3%). Center standardized mortality ratios (SMRs), calculated using baseline patient-level characteristics to derive expected mortality rate, ranged from 0.33 to 1.98. Of the treatment-level factors explored, only center adherence to early LPV was correlated with SMR. INTERPRETATION: Substantial center-to-center variability exists in ARDS management, suggesting that further opportunities for improving ARDS outcomes exist. Early adherence to LPV was associated with lower center mortality and may be a surrogate for overall quality of care processes. Future collaboration is needed to identify additional treatment-level factors influencing center-level outcomes. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03021824; URL: www.clinicaltrials.gov.

Impact of antithrombin III and enoxaparin dosage adjustment on prophylactic anti-Xa concentrations in trauma patients at high risk for venous thromboembolism: a randomized pilot trial.

The impact of antithrombin III activity (AT-III) on prophylactic enoxaparin anti-factor Xa concentration (anti-Xa) is unknown in high-risk trauma patients. So too is the optimal anti-Xa-adjusted enoxaparin dosage. This prospective, randomized, pilot study sought to explore the association between AT-III and anti-Xa goal attainment and to preliminarily evaluate two enoxaparin dosage adjustment strategies in patients with subprophylactic anti-Xa. Adult trauma patients with Risk Assessment Profile (RAP) ≥ 5 prescribed enoxaparin 30 mg subcutaneously every 12 h were eligible. AT-III and anti-Xa were drawn 8 h after the third enoxaparin dose and compared between patients with anti-Xa ≥ 0.1 IU/mL (goal; control group) or anti-Xa < 0.1 IU/mL (subprophylactic; intervention group). The primary outcome was difference in baseline AT-III. Subsequently, intervention group patients underwent 1:1 randomization to either enoxaparin 40 mg every 12 h (up to 50 mg every 12 h if repeat anti-Xa < 0.1 IU/mL) (enox12) or enoxaparin 30 mg every 8 h (enox8) with repeat anti-Xa assessments. The proportion of patients achieving goal anti-Xa after dosage adjustment were compared. A total of 103 patients were included. Anti-Xa was subprophylactic in 50.5%. Baseline AT-III (median [IQR]) was 87% [80-98%] in control patients versus 82% [71-96%] in intervention patients (p = 0.092). Goal trough anti-Xa was achieved on first assessment in 38.1% enox12 versus 50% enox8 patients (p = 0.67), 84.6% versus 53.3% on second assessment (p = 0.11), and 100% vs. 54.5% on third trough assessment (p = 0.045). AT-III activity did not differ between high-risk trauma patients with goal and subprophylactic enoxaparin anti-Xa concentrations, although future investigation is warranted. Enoxaparin dose adjustment rather than frequency adjustment may be associated with a higher proportion of patients achieving goal anti-Xa over time.

Healthcare disparities among anticoagulation therapies for severe COVID-19 patients in the multi-site VIRUS registry.

Here we analyze hospitalized andintensive care unit coronavirus disease 2019 (COVID-19) patient outcomes from the international VIRUS registry (https://clinicaltrials.gov/ct2/show/NCT04323787). We find that COVID-19 patients administered unfractionated heparin but not enoxaparin have a higher mortality-rate (390 of 1012 = 39%) compared to patients administered enoxaparin but not unfractionated heparin (270 of 1939 = 14%), presenting a risk ratio of 2.79 (95% confidence interval [CI]: [2.42, 3.16]; p = 4.45e-52). This difference persists even after balancing on a number of covariates including demographics, comorbidities, admission diagnoses, and method of oxygenation, with an increased mortality rate on discharge from the hospital of 37% (268 of 733) for unfractionated heparin versus 22% (154 of 711) for enoxaparin, presenting a risk ratio of 1.69 (95% CI: [1.42, 2.00]; p = 1.5e-8). In these balanced cohorts, a number of complications occurred at an elevated rate for patients administered unfractionated heparin compared to patients administered enoxaparin, including acute kidney injury, acute cardiac injury, septic shock, and anemia. Furthermore, a higher percentage of Black/African American COVID patients (414 of 1294 [32%]) were noted to receive unfractionated heparin compared to White/Caucasian COVID patients (671 of 2644 [25%]), risk ratio 1.26 (95% CI: [1.14, 1.40]; p = 7.5e-5). After balancing upon available clinical covariates, this difference in anticoagulant use remained statistically significant (311 of 1047 [30%] for Black/African American vs. 263 of 1047 [25%] for White/Caucasian, p = .02, risk ratio 1.18; 95% CI: [1.03, 1.36]). While retrospective studies cannot suggest any causality, these findings motivate the need for follow-up prospective research into the observed racial disparity in anticoagulant use and outcomes for severe COVID-19 patients.

A study of the possible factors affecting COVID-19 spread, severity and mortality and the effect of social distancing on these factors: Machine learning forecasting model.

BACKGROUNDS: SARS-CoV-2 is affecting different countries all over the world, with significant variation in infection-rate and death-ratio. We have previously shown a presence of a possible relationship between different variables including the Bacillus Calmette-Guérin (BCG) vaccine, average age, gender, and malaria treatment, and the rate of spread, severity and mortality of COVID-19 disease. This paper focuses on developing machine learning models for this relationship. METHODS: We have used real-datasets collected from the Johns Hopkins University Center for Systems Science and Engineering and the European Centre for Disease Prevention and Control to develop a model from China data as the baseline country. From this model, we predicted and forecasted different countries' daily confirmed-cases and daily death-cases and examined if there was any possible effect of the variables mentioned above. RESULTS: The model was trained based on China data as a baseline model for daily confirmed-cases and daily death-cases. This machine learning application succeeded in modelling and forecasting daily confirmed-cases and daily death-cases. The modelling and forecasting of viral spread resulted in four different regions; these regions were dependent on the malarial treatments, BCG vaccination, weather conditions, and average age. However, the lack of social distancing resulted in variation in the effect of these factors, for example, double-humped spread and mortality cases curves and sudden increases in the spread and mortality cases in different countries. The process of machine learning for time-series prediction and forecasting, especially in the pandemic COVID-19 domain, proved usefulness in modelling and forecasting the end status of the virus spreading based on specific regional and health support variables. CONCLUSION: From the experimental results, we confirm that COVID-19 has a very low spread in the African countries with all the four variables (average young age, hot weather, BCG vaccine and malaria treatment); a very high spread in European countries and the USA with no variable (old people, cold weather, no BCG vaccine and no malaria). The effect of the variables could be on the spread or the severity to the extent that the infected subject might not have symptoms or the case is mild and can be missed as a confirmed-case. Social distancing decreases the effect of these factors.

AARC Clinical Practice Guideline: Management of Adult Patients with Tracheostomy in the Acute Care Setting.

Management of patients with a tracheostomy tube includes many components of care provided by clinicians from various health care disciplines. In recent years, clinicians worldwide have demonstrated a renewed interest in the management of patients with tracheostomy due to the recognition that more effective and efficient management of this patient population is necessary to decrease morbidity and mortality and to optimize the value of the procedure. Commensurate with the goal of enhancing the care of patients with tracheostomy, we conducted a systematic review to facilitate the development of recommendations relevant to the care of adult patients with tracheostomy in the acute care setting. From our systematic review, clinical practice guidelines were developed to address questions regarding the impact of tracheostomy bundles, tracheostomy teams, and protocol-directed care on time to decannulation, length of stay, tracheostomy-related cost, tracheostomy-related adverse events, and other tracheostomy-related outcomes in tracheostomized adult patients in the acute care setting. Using a modification of the RAND/UCLA Appropriateness Method, 3 recommendations were developed to assist clinicians with tracheostomy management of adult patients in the acute care setting: (1) evidence supports the use of tracheostomy bundles that have been evaluated and approved by a team of individuals experienced in tracheostomy management to decrease time to decannulation, tracheostomy-related adverse events, and other tracheostomy-related outcomes, namely, improved tolerance of oral diet; (2) evidence supports the addition of a multidisciplinary tracheostomy team to improve time to decannulation, length of stay, tracheostomy-related adverse events, and other tracheostomy-related outcomes, namely, increased speaking valve use; (3) evidence supports the use of a weaning/decannulation protocol to guide weaning and removal of the tracheostomy tube to improve time to decannulation.

Assessment of a novel stapler performance for laparoscopic sleeve gastrectomy.

BACKGROUND: Optimal stapler selection during laparoscopic sleeve gastrectomy requires careful balance between tissue compression, hemostasis, and mechanical integrity. Junctions along a staple line can further increase the risks of technical or mechanical staple line failures. The aim of this study was to compare two commonly utilized laparoscopic linear gastrointestinal staplers (Ethicon, Medtronic) with a novel linear stapler (Titan) designed to perform a sleeve gastrectomy with a single stapler firing. METHODS: Excised gastric remnants from laparoscopic sleeve gastrectomy were utilized and tissue thickness was measured from fundus to antrum. An optimized experimental staple line was then created. The greater curve remnant was insufflated to determine the staple line burst pressure and location. The doubly stapled (clinical and experimental) gastric specimen underwent staple analysis for junctional location, malformation, and height. RESULTS: The Titan stapler withstood a significantly higher burst pressure than both Ethicon and Medtronic linear cutting staplers. While the Medtronic and Ethicon staplers had a similar percentage of staples in junctions, the Titan stapler has no junctions. In considering the formation of all staples outside of junctions, the Medtronic and Titan staplers had no difference in percentage of malformed staples, while the Ethicon stapler had a significantly higher percentage. Additionally, there were no differences in mismatch between staple height and tissue thickness between experimental groups. CONCLUSIONS: The Titan stapler conveys the mechanical benefits of higher burst pressure with the advantage of single load functionality. This single staple load eliminates staple line junctions without sacrificing the integrity of staple formation.

Bacillus Calmette-Guérin vaccine, antimalarial, age and gender relation to COVID-19 spread and mortality.

COVID-19 is affecting different countries all over the world with great variation in infection rate and death ratio. Some reports suggested a relation between the Bacillus Calmette-Guérin (BCG) vaccine and the malaria treatment to the prevention of SARS-CoV-2 infection. Some reports related infant's lower susceptibility to the COVID-19. Some other reports a higher risk in males compared to females in such COVID-19 pandemic. Also, some other reports claimed the possible use of chloroquine and hydroxychloroquine as prophylactic in such a pandemic. The present commentary is to discuss the possible relation between those factors and SARS-CoV-2 infection.

Acute care research competencies for clinical research professionals.

INTRODUCTION: Acute care research (ACR) is uniquely challenged by the constraints of recruiting participants and conducting research procedures within minutes to hours of an unscheduled critical illness or injury. Existing competencies for clinical research professionals (CRPs) are gaining traction but may have gaps for the acute environment. We sought to expand existing CRP competencies to include the specialized skills needed for ACR settings. METHODS: Qualitative data collected from job shadowing, clinical observations, and interviews were analyzed to assess the educational needs of the acute care clinical research workforce. We identified competencies necessary to succeed as an ACR-CRP, and then applied Bloom's Taxonomy to develop characteristics into learning outcomes that frame both knowledge to be acquired and job performance metrics. RESULTS: There were 28 special interest competencies for ACR-CRPs identified within the eight domains set by the Joint Task Force (JTF) of Clinical Trial Competency. While the eight domains were not prioritized by the JTF, in ACR an emphasis on Communication and Teamwork, Clinical Trials Operations, and Data Management and Informatics was observed. Within each domain, distinct proficiencies and unique personal characteristics essential for success were identified. The competencies suggest that a combination of competency-based training, behavioral-based hiring practices, and continuing professional development will be essential to ACR success. CONCLUSION: The competencies developed for ACR can serve as a training guide for CRPs to be prepared for the challenges of conducting research within this vulnerable population. Hiring, training, and supporting the development of this workforce are foundational to clinical research in this challenging setting.

Optimizing a serum-free/xeno-free culture medium for culturing and promoting the proliferation of human dental pulp stem cells.

BACKGROUND: Dental pulp stem cells (DPSCs) hold great promise for utilization in tissue repair and regenerative medicine. Routinely, culture media used for culturing stem cells are supplemented with animal serum for promoting growth and successful maintenance of stem cells. However, there is a growing demand for optimizing a well-defined culture media that could safely increase the efficacy and reproducibility of the cultured cells. In this study, we aimed at optimizing a serum-free/xeno-free culture medium. METHODS: A cocktail of various supplements intended to enrich DPSCs proliferation in defined concentrations was designed. It consisted of recombinant human basic fibroblast growth factor (hbFGF), insulin transferrin selenium (ITS), ascorbic acid (vitamin C), Beta mercaptoethanol and cholesterol. The effect of this optimized media on the proliferation of DPSCs was assessed by MTT assay and flow cytometric analysis (FACS) of early apoptotic marker annexin V. Expression of stemness-related genes (OCT4, SOX and NANOG) was assessed by qRT-PCR. RESULTS: Proliferation results by MTT illustrated a significant increase in the proliferation rate of DPSCs cultured in the proposed media. FACS analysis of annexin V expression was nil. Expression of OCT4, SOX and NANOG genes was also up-regulated. CONCLUSIONS: The proposed combination of supplements utilized in the proposed culture media successfully increased the proliferation potential of DPSCs in addition to enhancing the stemness properties. Thus, it can be considered a promising and safe substitute to traditional animal derived supplements like fetal bovine serum (FBS).

Risk Factors for the Development of Acute Respiratory Distress Syndrome Following Hemorrhage.

BACKGROUND: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) study evaluated the effects of plasma and platelets on hemostasis and mortality after hemorrhage. The pulmonary consequences of resuscitation strategies that mimic whole blood, remain unknown. METHODS: A secondary analysis of the PROPPR study was performed. Injured patients predicted to receive a massive transfusion were randomized to 1:1:1 versus 1:1:2 plasma-platelet-red blood cell ratios at 12 Level I North American trauma centers. Patients with survival >24 h, an intensive care unit (ICU) stay, and a recorded PaO2/FiO2 (P/F) ratio were included. Acute respiratory distress syndrome (ARDS) was defined as a P/F ratio < 200, with bilateral pulmonary infiltrates, and adjudicated by investigators. RESULTS: Four hundred fifty-four patients were reviewed (230 received 1:1:1, 224 1:1:2). Age, sex, injury mechanism, and regional abbreviated injury scale (AIS) scores did not differ between cohorts. Tidal volume, positive end-expiratory pressure, and lowest P/F ratio did not differ. No significant differences in ARDS rates (14.8% vs. 18.4%), ventilator-free (24 vs. 24) or ICU-free days (17.5 vs. 18), hospital length of stay (22 days vs. 18 days), or 30-day mortality were found (28% vs. 28%). ARDS was associated with blunt injury (OR 3.61 [1.53-8.81] P < 0.01) and increasing chest AIS (OR 1.40 [1.15-1.71] P < 0.01). Each 500 mL of crystalloid infused during hours 0 to 6 was associated with a 9% increase in the rate of ARDS (OR 1.09 [1.04-1.14] P < 0.01). Blood given at 0 to 6 or 7 to 24 h were not risk factors for lung injury. CONCLUSION: Acute crystalloid exposure, but not blood products, is a potentially modifiable risk factor for the prevention of ARDS following hemorrhage.

Incompatible type A plasma transfusion in patients requiring massive transfusion protocol: Outcomes of an Eastern Association for the Surgery of Trauma multicenter study.

With a relative shortage of type AB plasma, many centers have converted to type A plasma for resuscitation of patients whose blood type is unknown. The goal of this study is to determine outcomes for trauma patients who received incompatible plasma transfusions as part of a massive transfusion protocol (MTP). METHODS: As part of an Eastern Association for the Surgery of Trauma multi-institutional trial, registry and blood bank data were collected from eight trauma centers for trauma patients (age, ≥ 15 years) receiving emergency release plasma transfusions as part of MTPs from January 2012 to August 2016. Incompatible type A plasma was defined as transfusion to patient blood type B or type AB. RESULTS: Of the 1,536 patients identified, 92% received compatible plasma transfusions and 8% received incompatible type A plasma. Patient characteristics were similar except for greater penetrating injuries (48% vs 36%; p = 0.01) in the incompatible group. In the incompatible group, patients were transfused more plasma units at 4 hours (median, 9 vs. 5; p < 0.001) and overall for stay (11 vs. 9; p = 0.03). No hemolytic transfusion reactions were reported. Two transfusion-related acute lung injury events were reported in the compatible group. Between incompatible and compatible groups, there was no difference in the rates of acute respiratory distress syndrome (6% vs. 8%; p = 0.589), thromboembolic events (9% vs. 7%; p = 0.464), sepsis (6% vs. 8%; p = 0.589), or acute renal failure (8% vs. 8%, p = 0.860). Mortality at 6 (17% vs. 15%, p = 0.775) and 24 hours (25% vs. 23%, p = 0.544) and at 28 days or discharge (38% vs. 35%, p = 0.486) were similar between groups. Multivariate regression demonstrated that Injury Severity Score, older age and more red blood cell transfusion at 4 hours were independently associated with death at 28 days or discharge; Injury Severity Score and more red blood cell transfusion at 4 hours were predictors for morbidity. Incompatible transfusion was not an independent determinant of mortality or morbidity. CONCLUSION: Transfusion of type A plasma to patients with blood groups B and AB as part of a MTP does not appear to be associated with significant increases in morbidity or mortality. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Impact of Oxygenation Status on the Noninvasive Measurement of Hemoglobin.

BACKGROUND: Noninvasive monitoring of hemoglobin (SpHgb) via pulse oximetry has the potential to alert caregivers to blood loss. Previous studies have demonstrated that changes in oxygenation may impact accuracy. METHODS: Twenty normal volunteers were monitored using SpHgb at sea level, during ascent to 14,000 feet, at 14,000 feet with 100% oxygen delivery, and again at sea level. Each period consisted of 15 minutes of monitoring. SpHgb measurements were compared to a blood sample using Bland Altman analysis. The loss of the SpHgb signal was also recorded. RESULTS: The mean difference in measured hemoglobin (Hgb) between a venous sample and SpHgb was -2.6 ± 0.96 at 14,000 feet. Ascent to 14,000 feet resulted in a predictable fall in SpO2 and was associated with loss of the SpHgb signal for half the period of observation (7.4 minutes). In the other three conditions, SpHgb signal was missing 1 to 12.6% of the time. The nadir SpO2 was not predictive of the loss of SpHgb signal. DISCUSSION: Changes in oxygenation in normal volunteers are associated with short-term SpHgb signal loss (<10 minutes), but no impact on the measured SpHgb.

Transfusion of cryopreserved packed red blood cells is safe and effective after trauma: a prospective randomized trial.

OBJECTIVES: To determine the safety and efficacy of cryopreserved packed red blood cell (CPRBC) transfusion in trauma patients. BACKGROUND: Liquid packed red blood cells (LPRBCs) have an abbreviated shelf-life and worsening storage lesion with age. CPRBCs are frozen 2 to 6 days after donation, stored up to 10 years, and are available for 14 days after thawing and washing. CPRBCs can be utilized in diverse settings, but the effect on clinical outcomes is unknown. METHODS: We performed a prospective, randomized, double-blind study at 5 level 1 trauma centers. Stable trauma patients requiring transfusion were randomized to young LPRBCs (≤14 storage days), old LPRBCs (>14 storage days), or CPRBCs. Tissue oxygenation (StO2), biochemical and inflammatory mediators were measured, and clinical outcomes were determined. RESULTS: Two hundred fifty-six patients with well-matched injury severity and demographics (P > 0.2) were randomized (84 young, 86 old, and 86 CPRBCs). Pretransfusion and final hematocrits were similar (P > 0.68). Patients in all groups received the same number of units postrandomization (2 [1-4]; P > 0.05). There was no difference in the change in tissue oxygenation between groups. CPRBCs contained less α2-macrogobulin, haptoglobin, C-reactive protein, and serum amyloid P (P < 0.001). Organ failure, infection rate, and mortality did not differ between groups (P > 0.2). CONCLUSIONS: Transfusion of CPRBCs is as safe and effective as transfusion of young and old LPRBCs and provides a mechanism to deliver PRBCs in a wide variety of settings.