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Study objective The transfusion of older packed RBCs may be harmful in critically ill patients. We seek to determine the association between packed RBC age and mortality among trauma patients requiring massive packed RBC transfusion. Methods We analyzed data from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. Subjects in the parent trial included critically injured adult patients admitted to 1 of 12 North American Level I trauma centers who received at least 1 unit of packed RBCs and were predicted to require massive blood transfusion. The primary exposure was volume of packed RBC units transfused during the first 24 hours of hospitalization, stratified by packed RBC age category: 0 to 7 days, 8 to 14 days, 15 to 21 days, and greater than or equal to 22 days. The primary outcome was 24-hour mortality. We evaluated the association between transfused volume of each packed RBC age category and 24-hour survival, using random-effects logistic regression, adjusting for total packed RBC volume, patient age, sex, race, mechanism of injury, Injury Severity Score, Revised Trauma Score, clinical site, and trial treatment group. Results The 678 patients included in the analysis received a total of 8,830 packed RBC units. One hundred patients (14.8%) died within the first 24 hours. On multivariable analysis, the number of packed RBCs greater than or equal to 22 days old was independently associated with increased 24-hour mortality (adjusted odds ratio [OR] 1.05 per packed RBC unit; 95% confidence interval [CI] 1.01 to 1.08): OR 0.97 for 0 to 7 days old (95% CI 0.88 to 1.08), OR 1.04 for 8 to 14 days old (95% CI 0.99 to 1.09), and OR 1.02 for 15 to 21 days old (95% CI 0.98 to 1.06). Results of sensitivity analyses were similar only among patients who received greater than or equal to 10 packed RBC units. Conclusion Increasing quantities of older packed RBCs are associated with increased likelihood of 24-hour mortality in trauma patients receiving massive packed RBC transfusion (≥10 units), but not in those who receive fewer than 10 units.

Endotheliopathy of trauma is characterized by breakdown of the endothelial glycocalyx. Elevated biomarkers of endotheliopathy, such as serum syndecan-1 (Synd-1) ≥ 40 ng/mL, have been associated with increased need for transfusions, complications, and mortality. We hypothesized that severely injured trauma patients who exhibit elevated Synd-1 levels shortly after admission have an increased likelihood of developing sepsis.We analyzed a subset of patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial who survived at least 72 hours after hospital admission, and we determined elevated Synd-1 levels (≥ 40 ng/mL) 4 hours after hospital arrival. Sepsis was defined a priori as meeting systemic inflammatory response criteria and having a known or suspected infection. Univariate analysis was performed to identify variables associated with elevated Synd-1 levels and sepsis. Significant variables at a value of p0.2 in the univariate analysis were chosen by purposeful selection and analyzed in a mixed effects multivariate logistic regression model to account for the 12 different study sites.We included 512 patients. Of these, 402 (79%) had elevated Synd-1 levels, and 180 (35%) developed sepsis. Median Synd-1 levels at 4 hours after admission were 70 ng/dL (interquartile range [IQR] 36 to 157 ng/dL) in patients who did not develop sepsis, and 165 ng/dL [IQR 67 to 336 ng/dL] in those who did (p0.001). Adjusting for treatment arm and site, multivariable analyses revealed that elevated Synd-1 status, Injury Severity Score (ISS), and total blood transfused were significantly associated with an increased likelihood of developing sepsis.Elevated Synd-1 levels 4 hours after admission in severely injured adult trauma patients who survived the initial 72 hours after hospital admission are associated with subsequent sepsis.

Background Positive Focused Assessment with Sonography in Trauma examination and hypotension often indicate urgent surgery. An abdomen/pelvis computed tomography (apCT) may allow less invasive management but the delay may be associated with adverse outcomes. Methods Patients in the Prospective Observational Multicenter Major Trauma Transfusion study with hypotension and a positive Focused Assessment with Sonography in Trauma (HF+) examination who underwent a CT (apCT+) were compared with those who did not. Results Of the 92 HF+ identified, 32 (35%) underwent apCT during initial evaluation and apCT was associated with decreased odds of an emergency operation (odds ratio .11, 95% confidence interval .001 to .116) and increased odds of angiographic intervention (odds ratio 14.3, 95% confidence interval 1.5 to 135). There was no significant difference in 30-day mortality or need for dialysis. Conclusions An apCT in HF+ patients is associated with reduced odds of emergency surgery, but not mortality. Select HF+ patients can safely undergo apCT to obtain clinically useful information.

BACKGROUND: The classic definition of massive transfusion, 10 or more units of red blood cells (RBCs) in 24 hours, has never been demonstrated as a valid surrogate for severe hemorrhage and can introduce survival bias. In addition, the definition fails to capture other products that the clinician may have immediately available, and may use, during the initial resuscitation. Assuming that units of resuscitative fluids reflect patient illness, our objective was to identify a rate of resuscitation intensity (RI) that could serve as an early surrogate of sickness for patients with substantial bleeding after injury. METHODS: Adult patients surviving at least 30 minutes after admission and receiving one or more RBCs within 6 hours of admission from 10 US Level 1 trauma centers were enrolled in the PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. Total fluid units were calculated as the sum of the number of crystalloid units (1 L = 1 U), colloids (0.5 L = 1 U), and blood products (1 RBC = 1 U, 1 plasma = 1 U, 6 pack platelets = 1 U). Univariable and multivariable logistic regressions were used to evaluate associations between RI and 6-hour mortality, adjusting for age, center, penetrating injury, weighted Revised Trauma Score (RTS), and Injury Severity Score (ISS). RESULTS: A total of 1,096 eligible patients received resuscitative fluids within 30 minutes, including 620 transfused with blood products. Despite varying products used, the total fluid RI was similar across all sites (3.2T 2.5 U). Patients who received four or more units of any resuscitative fluid had a 6-hour mortality rate of 14.4% versus 4.5% in patients who received less than 4 U. The adjusted odds ratio of 6-hour mortality for patients receiving 4 U or more within 30 minutes was 2.1 (95% confidence interval, 1.2Y3.5). CONCLUSION: Resuscitation with four or more units of any fluid was significantly associated with 6-hour mortality. This study suggests that early RI regardless of fluid type can be used as a surrogate for sickness and mortality in severely bleeding patients. ( JT rauma Acute Care Surg. 2013;74: S16YS23. Copyright * 2013 by Lippincott Williams & Wilkins) LEVEL OF EVIDENCE: Epidemiologic/prognostic study, level III.

Early predictors of massive transfusion (MT) would prevent undertriage of patients likely to require MT. This study validates triggers using the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study.All enrolled patients in PROMMTT were analyzed. The initial emergency department value for each trigger (international normalized ratio [INR], systolic blood pressure, hemoglobin, base deficit, positive result for Focused Assessment for the Sonography of Trauma examination, heart rate, temperature, and penetrating injury mechanism) was compared for patients receiving MT (≥ 10 U of packed red blood cells in 24 hours) versus no MT. Adjusted odds ratios (ORs) for MT are reported using multiple logistic regression. If all triggers were known, a Massive Transfusion Score (MTS) was created, with 1 point assigned for each met trigger.A total of 1,245 patients were prospectively enrolled with 297 receiving an MT. Data were available for all triggers in 66% of the patients including 67% of the MTs (199 of 297). INR was known in 87% (1,081 of 1,245). All triggers except penetrating injury mechanism and heart rate were valid individual predictors of MT, with INR as the most predictive (adjusted OR, 2.5; 95% confidence interval, 1.7-3.7). For those with all triggers known, a positive INR trigger was seen in 49% receiving MT. Patients with an MTS of less than 2 were unlikely to receive MT (negative predictive value, 89%). If any two triggers were present (MTS ≥ 2), sensitivity for predicting MT was 85%. MT was present in 33% with an MTS of 2 greater compared with 11% of those with MTS of less than 2 (OR, 3.9; 95% confidence interval, 2.6-5.8; p0.0005).Parameters that can be obtained early in the initial emergency department evaluation are valid predictors for determining the likelihood of MT.Diagnostic, level II.

Hypertonic saline (HS) has been investigated as an immune modulator following hemorrhagic shock and sepsis. The polymorphonuclear neutrophil (PMN) response to HS is regulated by the release of ATP, which is converted to adenosine and activates adenosine receptors. Binding to A3 adenosine receptors promotes PMN activation, and inhibition of A3 receptors improves the efficacy of HS resuscitation. A3 receptor expression of PMNs has not been previously evaluated in injured patients. Whole blood was obtained from 10 healthy volunteers and 60 injured patients within 2 h of injury. Inclusion criteria were blunt or penetrating injury with evidence of hypovolemic shock (systolic blood pressure [SBP] ≤90 mmHg and base deficit ≥6 mEq/L or need for blood transfusion) or evidence of severe traumatic brain injury including initial Glasgow Coma Scale score of 8 or less or evidence of traumatic brain injury on head computed tomography scan (head Abbreviated Injury Score ≥3) or intubation in the field or emergency department. A3 receptor expression was assessed by flow cytometry. Polymorphonuclear neutrophils were also exposed to fMLP or HS (20-40 mM) in vitro. Clinical data were collected including admission physiology, injury severity (Injury Severity Score [ISS]), development of multiple organ failure, and survival. In normal volunteers, less than 1% of PMNs expressed A3 receptors on the cell surface. A3 receptor expression was significantly higher in injured patients, and the level of expression correlated with the severity of injury (ISS ≥25: A3 positive PMN 36.6% vs. ISS25: 16.2%; P = 0.019) and degree of hypovolemic shock (SBP ≤90 mmHg: A3 positive PMN 43.8% vs. SBP90 mmHg: 20.6%; P = 0.008). Stimulation with fMLP or HS increased A3 expression in normal volunteers, but only in patients with ISS of less than 25 or without hypovolemic shock. A3 receptor expression on the surface of PMNs is upregulated by injury, and increased expression levels are associated with greater injury severity and hypovolemic shock. Hypertonic saline increases A3 expression of PMNs from healthy volunteers and less severely injured patients.

We reported similar rates of ventilator-associated pneumonia (VAP) previously in trauma patients intubated either in a pre-hospital (PH) venue or the emergency department. A subset of PH intubations with continuous quality assessment was re-examined to identify the intubation factors associated with VAP.The subgroup was derived from an existing data set of consecutive adult trauma patients intubated prior to Level I trauma center admission July 2007-July 2008. Intubation details recorded included bag-valve mask ventilation (BVM) and the presence of material in the airway. The diagnosis of VAP was made preferentially by quantitative bronchoalveolar lavage (BAL) cultures (≥ 10⁴ colony-forming units indicating infection). Baseline data, injury characteristics, and circumstances of intubation of patients with and without VAP were compared by univariable analysis.Detailed data were available for 197 patients; 32 (16.2%) developed VAP, on average 6.0±0.7 days after admission. Baseline characteristics were similar in the groups, but diabetes mellitus was more common in the VAP group (4 [12.5%] vs. 5 [3.0%]; p=0.02). There was a higher rate of blunt injury in the VAP patients (28 [87.5%] vs. 106 [64.2%]; p=0.01) and higher injury severity scores (33.1±2.8 vs. 23.0±1.0; p=0.0002) and chest Abbreviated Injury Scores (2.6±0.3 vs. 1.5±0.1; p=0.002). Lower Glasgow Coma Scale scores (7.9±0.9 vs. 9.9±0.4; p=0.04) and greater use of BVM (18 [56.3%] vs. 56 [34.0%]; p=0.02) were observed in patients who developed VAP. Among aspirations, 10 (31.3%) of patients with emesis developed VAP compared with only 4 (12.5%) with blood in the airway (p=0.003).Aspiration, along with depressed consciousness and greater injury severity, may predispose trauma patients to VAP. Prospective studies should focus on the quality and timing of aspiration relative to intubation to determine if novel interventions can prevent aspiration or decrease the risk of VAP after aspiration.

Pressure ulcers are estimated to be present in more than one-third of patients with spinal cord injury. The rate of recurrence after flap surgery over last 50 years has ranged between 3 and 82 percent, with no trend toward improvement. This study seeks to identify and evaluate patient and operative characteristics associated with flap dehiscence and ulcer recurrence.A retrospective chart review of all patients who underwent pressure ulcer flap coverage between 1993 and 2008 was performed. Thirty-one demographic and operative variables were collected. Multivariate logistic regression with generalized estimating equation was used to evaluate the effect of significant variables. The primary outcome was recurrence of pressure ulcer at the operative site. Secondary outcomes included flap line dehiscence and the need for operative revision.There were 88 recurrences of pressure ulcers after flap surgery (39 percent) of 227 operations performed on 135 patients. Thirty-six flaps (16 percent) had dehiscences necessitating return to the operating room. Hemoglobin A1c less than 6 percent and previous same-site flap failure were associated with both dehiscence and recurrence (odds ratios, 2.15 and 3.84; and odds ratios, 6.51 and 3.27). Younger age and albumin less than 3.5 were associated with early flap failure (odds ratios, 5.95 and 2.45). Ischial wound location correlated with late recurrence (odds ratio, 4.01). Patients with multiple risk factors had operative success rates that approached zero.Confirmation of adequate nutritional status and strict preoperative management of blood glucose may improve operative success rates. The authors propose that operative management should be approached with trepidation, if at all, in young patients with recurrent ischial ulcers.

Emergency airway management is an important component of resuscitation of critically ill patients. Multiple studies demonstrate variable endotracheal intubation (ETI) success by prehospital providers. Data describing how many ETI training experiences are required to achieve high success rates are sparse.To describe the relationship between the number of prehospital ETI experiences and the likelihood of success on subsequent ETI and to specifically look at uncomplicated first-pass ETI in a university-based training program with substantial resources.We conducted a secondary analysis of a prospectively collected cohort of paramedic student prehospital intubation attempts. Data collected on prehospital ETIs included indication, induction agents, number of direct laryngoscopy attempts, and advanced airway procedures performed. We used multivariable generalized estimating equations (GEE) analysis to determine the effect of cumulative ETI experience on first-pass and overall ETI success rates.Over a period of three years, 56 paramedic students attempted 576 prehospital ETIs. The odds of overall ETI success were associated with cumulative ETI experience (odds ratio [OR] 1.097 per encounter, 95% confidence interval [CI] = 1.026-1.173, p = 0.006). The odds of first-pass ETI success were associated with cumulative ETI experience (OR 1.061 per encounter, 95% CI = 1.014-1.109, p = 0.009).In a training program with substantial clinical opportunities and resources, increased ETI success rates were associated with increasing clinical exposure. However, first-pass placement of the ETT with a high success rate requires high numbers of ETI training experiences that may exceed the number available in many training programs.

The role of prehospital endotracheal intubation (ETI) remains controversial, with significant national variability in practice. The purpose of this project was to evaluate ETI management in a system of advanced life support (ALS) providers experienced in ETI and other advanced airway techniques, and describe management and outcomes of patients with a "difficult airway." Data were collected prospectively for all ETIs performed by the fire department over a 4-year period (2001-2005), and included demographics, number of laryngoscopy attempts, airway procedures, complications, and outcomes. Of 80,501 ALS patient contacts, 4091 (5.1%) underwent attempted oral ETI, with a 96.8% success rate in four or fewer attempts. The difficult airway cohort included 130 patients (3.2%), whose airway management consisted of oral ETI after more than four attempts (46%), bag-valve-mask ventilation (33%), cricothyroidotomy (8%), retrograde ETI (5%), and digital ETI (1%). Procedural success rates ranged from 14% (digital ETI) to 91% (cricothyroidotomy). Nine patients (7%) had failed airway management, of whom 5 were found in cardiac arrest. The two most common reasons subjectively reported by ALS providers for airway difficulty were anterior trachea (39%) and small mouth (30%). Overall mortality for the difficult airway cohort was 44%. Prehospital ETI can be performed with a high success rate by experienced ALS providers, but may still require advanced airway techniques in a small subset of patients. Patient anatomy is a primary factor in failed ETI. Among the advanced procedures, cricothyroidotomy had the highest success rate and should not be delayed by other interventions.

An arterial CO2 (Paco2) of 30 mm Hg to 39 mm Hg has been shown to be the ideal target range for early ventilation in trauma patients; however, this requires serial arterial blood gases. The use of end-tidal capnography (EtCO2) has been recommended as a surrogate measure of ventilation in the prehospital arena. This is based on the observation of close EtCO2 Pa(CO2) correlation in healthy patients, yet trauma patients frequently suffer from impaired pulmonary ventilation/perfusion. Thus, we hypothesize that EtCO2 will demonstrate a poor reflection of actual ventilation status after severe injury.Prospective observational study on consecutive intubated trauma patients treated in our emergency department (ED) during 9 months. Arterial blood gas values and concomitant EtCO2 levels were recorded. Regression was used to determine the strength of correlation among all trauma patients and subgroups based on injury severity (Abbreviated Injury Score and Injury Severity Score) and physiologic markers of perfusion status (lactate, shock index, and arterial base deficit).During 9 months, 180 patients were evaluated. The EtCO2 Paco2 correlation was poor at R2 = 0.277. Patients ventilated in the recommended EtCO2 (range, 35 to 40) were likely to be under ventilated (Pa(CO2)40 mm Hg) 80% of the time, and severely under ventilated (Pa(CO2)50 mm Hg) 30% of the time. Correlation was best for patients with isolated traumatic brain injury and worst for those with evidence of poor tissue perfusion.EtCO2 has low correlation with Pa(CO2), and therefore should not be used to guide ventilation in intubated trauma patients in the ED. Better strategies for guiding prehospital and ED ventilation are needed.

Background Damage-control laparotomy has become increasingly common after operative resuscitation of severe hemorrhagic shock after injury. Despite increased use, uncertainty exists about the safety and timing of enteral nutrition. The purpose of this study was to determine the safety and effect of immediate enteral nutrition. Study Design Data were obtained from a multicenter prospective cohort study evaluating clinical outcomes in adults with hemorrhagic shock after injury and were limited to patients with an open abdomen and no hollow viscus injury. The immediate enteral nutrition cohort was defined as initiation of enteral feeds within 36 hours after acute resuscitation completion. Multivariate stepwise logistic regression was used to evaluate factors associated with immediate enteral nutrition. Results One hundred subjects met inclusion criteria; 32 immediate enteral nutrition and 68 nonimmediate enteral nutrition. Nearly all patients underwent fascial closure (93.8% immediate enteral nutrition versus 94.1% nonimmediate enteral nutrition), with an average closure day of 6.47 ± 0.83 with immediate enteral nutrition and 8.55 ± 0.85 with nonimmediate enteral nutrition (p = 0.129). No significant difference in multiorgan dyfunction syndrome, length of ventilator days, ICU days, hospital days, or mortality was seen between groups. The rate of pneumonia was significantly different: 14 (43.8%) in immediate enteral nutrition and 49 (72.1%) in nonimmediate enteral nutrition (p = 0.008). Immediate enteral nutrition remained independently associated with a reduction in pneumonia within our stepwise regression (odds ratio=0.32; 95% CI, 0.13 to 0.79). Conclusions Immediate enteral nutrition after damage control appears safe, with no effect on abdominal closure rate. In addition, the reduction in pneumonia associated with immediate enteral nutrition suggests a tangible benefit. Immediate enteral nutrition should be considered in patients with open abdomens after severe trauma.

Traumatic brain injury has a devastating impact on society, utilizing many resources and disproportionately affecting the young. Recent evidence demonstrates the early care of the brain injured patient impacts patient outcomes. While prevention of systolic hypotension and hypoxia are mainstays of prehospital management of the injured patient ventilatory management performed in the prehospital environment has recently been shown to impact outcomes. Hypocapnea from hyperventilation has been shown in several trials to cause deleterious effects from cerebral vasoconstriction and ischemia. The importance of balancing the prevention of both hypocapnea and hypercapnea has led to the idea of a target ventilation range for arterial carbon dioxide tension, the ideal way to achieve this balance in the prehospital setting remains elusive. This article reviews the background, physiologic effects, impact on outcomes, and implications for prehospital care of prehospital ventilation.

BACKGROUND: Prediction of outcome after injury is fraught with uncertainty and statistically beset by misspecified models. Single-time point regression only gives prediction and inference at one time, of dubious value for continuous prediction of ongoing bleeding. New statistical machine learning techniques such as SuperLearner (SL) exist to make superior prediction at iterative time points while evaluating the changing relative importance of each measured variable on an outcome. This then can provide continuously changing prediction of outcome and evaluation of which clinical variables likely drive a particular outcome. METHODS: PROMMTT data were evaluated using both naive (standard stepwise logistic regression) and SL techniques to develop a time-dependent prediction of future mortality within discrete time intervals. We avoided both underfitting and overfitting using cross validation to select an optimal combination of predictors among candidate predictors/machine learning algorithms. SL was also used to produce interval-specific robust measures of variable importance measures (VIM resulting in an ordered list of variables, by time point) that have the strongest impact on future mortality. RESULTS: Nine hundred eighty patients had complete clinical and outcome data and were included in the analysis. The prediction of ongoing transfusion with SL was superior to the naive approach for all time intervals (correlations of cross-validated predictions with the outcome were 0.819, 0.789, 0.792 for time intervals 30-90, 90-180, 180-360, >360 minutes). The estimated VIM of mortality also changed significantly at each time point. CONCLUSION: The SL technique for prediction of outcome from a complex dynamic multivariate data set is superior at each time interval to standard models. In addition, the SLVIM at each time point provides insight into the time-specific drivers of future outcome, patient trajectory, and targets for clinical intervention. Thus, this automated approach mimics clinical practice, changing form and content through time to optimize the accuracy of the prognosis based on the evolving trajectory of the patient. (Copyright (C) 2013 by Lippincott Williams & Wilkins)

Acute traumatic coagulopathy (ATC) occurs after severe injury and shock and is associated with increased bleeding, morbidity, and mortality. The effects of ATC and hemostatic resuscitation on outcome are not well-explored. The PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study provided a unique opportunity to characterize coagulation and the effects of resuscitation on ATC after severe trauma.Blood samples were collected upon arrival on a subset of PROMMTT patients. Plasma clotting factor levels were prospectively assayed for coagulation factors. These data were analyzed with comprehensive PROMMTT clinical data.There were 1,198 patients with laboratory results, of whom 41.6% were coagulopathic. Using international normalized ratio of 1.3 or greater, 41.6% of patients (448) were coagulopathic, while 20.5% (214) were coagulopathic using partial thromboplastin time of 35 or greater. Coagulopathy was primarily associated with a combination of an Injury Severity Score (ISS) of greater than 15 and a base deficit (BD) of less than -6 (p0.05). Regression modeling for international normalized ratio-based coagulopathy shows that prehospital crystalloid (odds ratio [OR], 1.05), ISS (OR, 1.03), Glasgow Coma Scale (GCS) score (OR, 0.93), heart rate (OR, 1.08), systolic blood pressure (OR, 0.96), BD (OR, 0.92), and temperature (OR, 0.84) were significant predictors of coagulopathy (all p0.03). A subset of 165 patients had blood samples collected and coagulation factor analysis performed. Elevated ISS and BD were associated with elevation of aPC and depletion of factors (all p0.05). Reductions in factors I, II, V, VIII and an increase in aPC drive ATC (all p0.04). Similar results were found for partial thromboplastin time-defined coagulopathy.ATC is associated with the depletion of factors I, II, V, VII, VIII, IX, and X and is driven by the activation of the protein C system. These data provide additional mechanistic understanding of the drivers of coagulation abnormalities after injury. Further understanding of the drivers of ATC and the effects of resuscitation can guide factor-guided resuscitation and correction of coagulopathy after injury.

BACKGROUND: Because randomized clinical trials in trauma outcomes research are expensive and complex, they have rarely been the basis for the clinical care of trauma patients. Most published findings are derived from retrospective and occasionally prospective observational studies that may be particularly susceptible to bias. The sources of bias include some common to other clinical domains, such as heterogeneous patient populations with competing and interdependent short- and long-term outcomes. Other sources of bias are unique to trauma, such as rapidly changing multisystem responses to injury that necessitate highly dynamic treatment regimens such as blood product transfusion. The standard research design and analysis strategies applied in published observational studies are often inadequate to address these biases. METHODS: Drawing on recent experience in the design, data collection, monitoring, and analysis of the 10-site observational PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, 7 common and sometimes overlapping biases are described through examples and resolution strategies. RESULTS: Sources of bias in trauma research include ignoring (1) variation in patients' indications for treatment (indication bias), (2) the dependency of intervention delivery on patient survival (survival bias), (3) time-varying treatment, (4) time-dependent confounding, (5) nonuniform intervention effects over time, (6) nonrandom missing data mechanisms, and (7) imperfectly defined variables. This list is not exhaustive. CONCLUSION: The mitigation strategies to overcome these threats to validity require epidemiologic and statistical vigilance. Minimizing the highlighted types of bias in trauma research will facilitate clinical translation of more accurate and reproducible findings and improve the evidence-base that clinicians apply in their care of injured patients. Language: en

BACKGROUND: Nonphysician advanced life support (ALS) providers often perform tracheal intubation (TI) for cardiac arrest or other life-threatening indications in the prehospital setting, where airway assessment and airway management tools are limited. However, the frequency of difficult TI in obese patients in this setting is unclear. In this study we determined factors associated with TI success, and determined TI difficulty as a function of body mass index (BMI) in a system of ALS providers experienced in TI, to guide future prehospital education efforts. METHODS: A retrospective review was performed of all patients ≥15 years of age who underwent prehospital TI by paramedics in the Seattle Medic One system over a 4-year period, and were transported to the regional level 1 trauma center (Harborview Medical Center). Data were abstracted from a prospectively collected prehospital airway management database and from the hospital medical records, including demographic information, number of TI attempts, TI success or failure, and body weight/height (BMI). Descriptive statistics and multivariable logistic regression were calculated, with the primary end point being difficult TI (defined as ≥4 TI attempts or the need to use an alternative airway management technique). RESULTS: Of 80,501 patient contacts in whom 4114 TIs were attempted during the 4-year study period, 823 met study entry criteria (including a calculable BMI). The overall TI success rate in the study population was 98.5% (811 out of 823), with 6.8% (56 out of 823) meeting the predetermined definition for difficult TI. There was no significant association between difficult TI and patient age, gender, use of succinylcholine, or medical diagnosis (trauma vs. nontrauma). In comparison with the lean patient subgroup (BMI 40 kg/m 2 ) had a significant association with difficult TI (odds ratio 3.68; confidence interval [CI] 1.27-10.59), whereas those with class I/II obesity (BMI ≥30 kg/m 2 and

Allogeneic packed red blood cells (PRBCs) suppress immunity and influence outcomes. The influence of blood on the risk of infection and death may be related to the duration of storage. We sought to determine whether blood storage duration was associated with infection or death in a large cohort of injury victims. We reviewed a cohort of trauma patients transfused at least 1 U of PRBCs within 24 h of admission to a level 1 trauma center. The outcomes of interest were complicated sepsis and mortality. We compared the amount of older blood (14 days storage) given to patients who did or did not develop the outcomes of interest using univariate and multivariate methods. A total of 820 patients were included. Patients who died (n = 117) received more units of older blood than those who lived (5 U [inter quartile range {IQR}, 2-9] vs. 3 U [IQR, 2-6]; P0.001). Patients with complicated sepsis (n = 244) received a greater volume of older blood than those without complicated sepsis (6 U [IQR, 2-10] vs. 3 U [IQR, 1-5]; P0.001). After adjusting for clinical factors, including the total amount of blood transfused, patients receiving greater than or equal to 7 U of older blood had a higher risk of complicated sepsis than patients receiving 1 or fewer units (odds ratio, 1.9; P = 0.03). The risk for complicated sepsis and death in trauma victims who are transfused blood is high. The amount of older blood transfused is associated with complicated sepsis. Although the best strategy to minimize the effects of allogeneic blood is to avoid unnecessary transfusions, it may be particularly important to avoid transfusing multiple units of older blood.

Background: Etomidate is an induction agent used for the rapid sequence intubation (RSI) of trauma patients because of its favorable hemodynamic profile and rapid onset. However, recent studies have shown etomidate to decrease circulating cortisol concentrations, potentially influencing inflammation. We hypothesized that etomidate may alter the occurrence of acute respiratory distress syndrome (ARDS) in injury victims. Methods: We analyzed data collected prospectively from a clinical trial of prehospital hypertonic saline administration. Post hoc, patients were grouped according to whether they did or did not receive etomidate for prehospital airway management. The incidence of ARDS was compared between the two groups by Fisher's exact test. Logistic regression was used to adjust for the effects of other known risk factors for ARDS. Results: Over a 2-year period, 94 study patients underwent RSI, of which 35 received etomidate (37%). There were no significant differences in demographic, physiology, anatomic injury scores, or use of hypertonic saline resuscitation between the groups. After adjusting for physiology, injury severity, and transfusion, etomidate use remained associated with ARDS (aOR = 3.9, 95% CI = 1.24―12.0). Conclusion: Single-dose etomidate for RSI in severely injured trauma patients is associated with increased ARDS and multiple organ dysfunction syndrome, in part, because of an effect of etomidate on the inflammatory response.

The use of prehospital needle thoracostomy (NT) is controversial as it is not without risk. Issues such as inappropriate patient selection, misplacement causing iatrogenic injury, treatment failures in obese patients, and delaying definitive tube thoracostomy in the emergency department contribute to this controversy. The purpose of this study is to evaluate a cohort of patients undergoing NT by paramedics for tension pneumothorax and review the indications for use, complications, and emergency department outcomes of NT.We conducted a retrospective review of patients undergoing NT in the prehospital setting and transported directly to a Level 1 trauma center over a one-year period. Patients were transported by a single ground transport agency staffed by paramedics. All paramedics were trained to follow uniform protocols for treatment procedures. Variables included indications for NT, patient demographics, prehospital vital signs, injury mechanism, chest X-ray, and Emergency Department outcomes.Paramedics responded to 20,330 advanced life support calls, and 39 (0.2%) patients had a NT placed for treatment of tension pneumothorax. Twenty-two (56.4%) patients were in circulatory arrest, with 12 suffering traumatic arrest and 10 patients in nontraumatic PEA arrest. The remaining 17 (43.6%) patients were treated for nonarrest causes.The use of NT appears to be a safe procedure when preformed by paramedics in an urban EMS system. Prehospital NT resulted in four cases of unexpected survival.

Background The leading cause of late mortality after trauma is multiple organ failure syndrome, due to a dysfunctional inflammatory response early after injury. Preclinical studies demonstrate that hypertonicity alters the activation of inflammatory cells, leading to reduction in organ injury. The purpose of this study was to evaluate the effect of hypertonicity on organ injury after blunt trauma. Design Double-blind, randomized controlled trial from October 1, 2003, to August 31, 2005. Setting Prehospital enrollment at a single level I trauma center. Patients Patients older than 17 years with blunt trauma and prehospital hypotension (systolic blood pressure, ≤ 90 mm Hg). Interventions Treatment with 250 mL of 7.5% hypertonic saline and 6% dextran 70 (HSD) vs lactated Ringer solution (LRS). Main Outcome Measures The primary end point was survival without acute respiratory distress syndrome (ARDS) at 28 days. Cox proportional hazards regression was used to adjust for confounding factors. A preplanned subset analysis was performed for patients requiring 10 U or more of packed red blood cells in the first 24 hours. Results A total of 209 patients were enrolled (110 in the HSD group and 99 in the LRS group). The study was stopped for futility after the second interim analysis. Intent-to-treat analysis demonstrated no significant difference in ARDS-free survival (hazard ratio, 1.01; 95% confidence interval, 0.63-1.60). There was improved ARDS-free survival in the subset (19% of the population) requiring 10 U or more of packed red blood cells (hazard ratio, 2.18; 95% confidence interval, 1.09-4.36). Conclusions Although no significant difference in ARDS-free survival was demonstrated overall, there was benefit in the subgroup of patients requiring 10 U or more of packed red blood cells in the first 24 hours. Massive transfusion may be a better predictor of ARDS than prehospital hypotension. The use of HSD may offer maximum benefit in patients at highest risk of ARDS. Trial Registration clinicaltrials.gov Identifier:NCT00113685

Prehospital intubation has been challenged on the grounds that it predisposes to hyperventilation, which is detrimental after traumatic brain injury (TBI), and impairs venous return in patients with hypovolemia. We sought to determine the incidence of hyperventilation among a cohort of trauma patients undergoing prehospital intubation and the impact of ventilation on outcome after severe TBI.Data were prospectively collected for all intubated trauma patients transported directly from the field for a period of 14 months (n = 574). An arrival Pco230 mm Hg was termed severe hypocapnea and considered a marker of hyperventilation. Patients with a Pco245 mm Hg were considered severely hypercapneic. Targeted ventilation was defined as a Pco2 between 30 and 35 mm Hg based on the Brain Trauma Foundation guidelines.The rate of severe hypocapnea was 18% and women were more likely to be hyperventilated (p0.05). Patients with severe hypercapnia had higher Injury Severity Scores and were more likely hypotensive, hypoxic, and acidodic (p0.05). Patients in the targeted ventilation range were less likely to die than were those outside the range even after excluding the severe hypercapnea group (odds ratio, 0.57; 95% confidence interval, 0.33-0.99). This effect was even greater among patients with isolated TBI (odds ratio, 0.31; 95% confidence interval, 0.10-0.96).Targeted prehospital ventilation is associated with lower mortality after severe TBI.

The advent and incorporation of the air bag into motor vehicles has resulted in the mitigation of many head and truncal injuries in motor vehicle collisions. However, air bag deployment is not risk free. We present a case of sodium azide-induced laryngospasm after air bag deployment. An unrestrained male driver was in a moderate-speed motor vehicle collision with air bag deployment. Medics found him awake, gasping for air with stridorous respirations and guarding his neck. The patient had no external signs of trauma and was presumed to have tracheal injury. The patient was greeted by the Anesthesiology service, which intubated him using glidescope-assisted laryngoscopy. The patient was admitted for overnight observation and treatment of alkaline ocular injury and laryngospasm. Although air bags represent an important advance in automobile safety, their use is not without risk. Bruising and tracheal rupture secondary to air bag deployment have been reported in out-of-position occupants. Additionally, alkaline by-products from the combustion of sodium azide in air bags have been implicated in ocular injury and facial burns. Laryngospasm after sodium azide exposure presents another diagnostic challenge for providers. Therefore, it is incumbent to maintain vigilance in the physical examination and diagnosis of occult injuries after air bag deployment.

In an emergency medical system with established rapid-sequence intubation protocols, prehospital (PH) intubation of patients with trauma is not associated with a higher rate of ventilator-associated pneumonia (VAP) than emergency department (ED) intubation.Retrospective observational cohort.Level I trauma center.Adult patients with trauma intubated in a PH or an ED setting from July 1, 2007, through July 31, 2008.Diagnosis of VAP by means of bronchoscopic alveolar lavage or clinical assessment when bronchoscopic alveolar lavage was impossible. Secondary outcomes included time to VAP, length of hospitalization, and in-hospital mortality.Of 572 patients, 412 (72.0%) underwent PH intubation. The ED group was older than the PH group (mean ages, 46.4 vs 39.1 years; P.001) and had a higher incidence of blunt injury (142 [88.8%] vs 322 [78.2%]; P = .002). The mean (SD) lowest recorded ED systolic blood pressure was lower in the ED group (102.8 [1.9] vs 111.4 [1.2] mm Hg; P.001), despite similar mean injury severity scores in both groups (27.2 [0.7] vs 27.0 [1.1]; P = .94). There was no difference in the mean rate of VAP (30 [18.8%] vs 71 [17.2%]; P = .66) or mean time to diagnosis (8.1 [1.2] vs 7.8 [1.0] days; P = .89). Logistic regression analysis identified history of drug abuse, lowest recorded ED systolic blood pressure, and injury severity score as 3 independent factors predictive of VAP.Prehospital intubation of patients with trauma is not associated with higher risk of VAP. Further investigation of intubation factors and the incidence and timing of aspiration is required to identify potentially modifiable factors to prevent VAP.

Background Patients receiving total parenteral nutrition (TPN) are at high risk for bloodstream infections (BSI). The notion that intravenous calories and glucose lead to hyperglycemia, which in turn contributes to BSI risk, is widely held but is unproven. We therefore sought to determine the role that hyperglycemia and parenteral calories play in the development of BSI in hospitalized patients receiving TPN. Methods Two hundred consecutive patients initiated on TPN between June 2004 and August 2005 were prospectively studied. Information was collected on patient age, sex, admission diagnosis, baseline laboratory values, intensive care unit (ICU) status and indication for TPN. Patients in the ICU were managed with strict glycemic control, whereas control on the general ward was more liberal. The maximum blood glucose level over each 8-hour period was recorded, as were parenteral daily intake, enteral daily intake and total daily caloric intake. The primary outcome measure was the incidence of BSI. Additional endpoints were ICU length of stay, hospital length of stay and mortality. Results A total of 78 patients (39%) developed at least one BSI, which were more common in ICU patients than in other hospitalized patients (60/122 patients versus 18/78 patients; P < 0.001). Maximum daily blood glucose concentrations were similar in patients with BSI and in patients without BSI (197 mg/dl versus 196 mg/dl, respectively). Patients with BSI received more calories parenterally than patients without BSI (36 kcal/kg/day versus 31 kcal/kg/day, P = 0.003). Increased maximum parenteral calories, increased average parenteral calories, and treatment in the ICU were strong risk factors for developing BSI. There was no difference in mortality between patients with and without BSI. Conclusion Increased parenteral caloric intake is an independent risk factor for BSI in patients receiving TPN. This association appears unrelated to hyperglycemia. Based upon our observations, we suggest that parenteral caloric intake be prescribed and adjusted judiciously with care taken to account for all intravenous caloric sources and to avoid even short periods of increased intake.