Compensatory reserve and pulse character: Enhanced potential to predict urgency for transfusion and other life-saving interventions after traumatic injury.

BACKGROUND: Field triage of trauma patients requires timely assessment of physiologic status to determine resuscitative needs. Vital signs and rudimentary assessments such as pulse character (PC) are used by first responders to guide decision making. The compensatory reserve measurement (CRM) has demonstrated utility as an easily interpretable method for assessing patient status. We hypothesized that the ability to identify injured patients requiring transfusion and other life-saving interventions (LSI) using a measurement of pulse character could be enhanced by the addition of the CRM. METHODS: We performed a prospective observational study on 300 trauma patients admitted to a level I trauma center. CRM was recorded continuously after device placement on arrival. Patient demographics, field and trauma resuscitation unit vital signs, therapeutic interventions, and outcomes were collected. A field SBP <100 mmHg was utilized as a surrogate for abnormal PC as previously validated. A patient with a CRM threshold value of <60% was considered clinically compromised with a risk of onset of decompensated shock. Data were analyzed to assess the capacity of CRM and pulse character separately or in combination to predict LSI defined as need for transfusion, intubation, tube thoracostomy, or operative/ angiographic hemorrhage control. RESULTS: An improvement in the predictive capability for LSI, transfusion, or a composite outcome was demonstrated by the combination of CRM and PC compared to either measure alone. CONCLUSIONS: Combining PC assessment with CRM has the potential to enhance the recognition of injured patients requiring life-saving intervention thus improving sensitivity of decision support for prehospital providers.

Compensatory reserve detects subclinical shock with more expeditious prediction for need of life-saving interventions compared to systolic blood pressure and blood lactate.

INTRODUCTION: We conducted a prospective observational study on 205 trauma patients at a level I trauma facility to test the hypothesis that a compensatory reserve measurement (CRM) would identify higher risk for progression to shock and/or need a life-saving interventions (LSIs) earlier than systolic blood pressure (SBP) and blood lactate (LAC). METHODS: A composite outcome metric included blood transfusion, procedural LSI, and mortality. Discrete measures assessed as abnormal (ab) were SBP <90 mmHg, CRM <60%, and LAC >2.0. A graded categorization of shock was defined as: no shock (normal [n] SBP [n-SBP], n-CRM, n-LAC); sub-clinical shock (ab-CRM, n-SBP, n-LAC); occult shock (n-SBP, ab-CRM, ab-LAC); or overt shock (ab-SBP, ab-CRM, ab-LAC). RESULTS: Three patients displayed overt shock, 53 displayed sub-clinical shock, and 149 displayed no shock. After incorporating lactate into the analysis, 86 patients demonstrated no shock, 25 were classified as sub-clinical shock, 91 were classified as occult shock, and 3 were characterized as overt shock. Each shock subcategory revealed a graded increase requiring LSI and transfusion. Initial CRM was associated with progression to shock (odds ratio = 0.97; p < .001) at an earlier time than SBP or LAC. CONCLUSIONS: Initial CRM uncovers a clinically relevant subset of patients who are not detected by SBP and LAC. Our results suggest CRM could be used to more expeditiously identify injured patients likely to deteriorate to shock, with requirements for blood transfusion or procedural LSI.

The gut microbiome distinguishes mortality in trauma patients upon admission to the emergency department.

BACKGROUND: Traumatic injury can lead to a compromised intestinal epithelial barrier, decreased gut perfusion, and inflammation. While recent studies indicate that the gut microbiome (GM) is altered early following traumatic injury, the impact of GM changes on clinical outcomes remains unknown. Our objective of this follow-up study was to determine if the GM is associated with clinical outcomes in critically injured patients. METHODS: We conducted a prospective, observational study in adult patients (N = 67) sustaining severe injury admitted to a level I trauma center. Fecal specimens were collected on admission to the emergency department, and microbial DNA from all samples was analyzed using the Quantitative Insights Into Microbial Ecology pipeline and compared against the Greengenes database. α-Diversity and ß-diversity were estimated using the observed species metrics and analyzed with t tests and permutational analysis of variance for overall significance, with post hoc pairwise analyses. RESULTS: Our patient population consisted of 63% males with a mean age of 44 years. Seventy-eight percent of the patients suffered blunt trauma with 22% undergoing penetrating injuries. The mean body mass index was 26.9 kg/m. Significant differences in admission ß-diversity were noted by hospital length of stay, intensive care unit hospital length of stay, number of days on the ventilator, infections, and acute respiratory distress syndrome (p < 0.05). ß-Diversity on admission differed in patients who died compared with patients who lived (mean time to death, 8 days). There were also significantly less operational taxonomic units in samples from patients who died versus those who survived. A number of species were enriched in the GM of injured patients who died, which included some traditionally probiotic species such as Akkermansia muciniphilia, Oxalobacter formigenes, and Eubacterium biforme (p < 0.05). CONCLUSION: Gut microbiome diversity on admission in severely injured patients is predictive of a variety of clinically important outcomes. While our study does not address causality, the GM of trauma patients may provide valuable diagnostic and therapeutic targets for the care of injured patients. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.

A prospective study in severely injured patients reveals an altered gut microbiome is associated with transfusion volume.

BACKGROUND: Traumatic injury can lead to a compromised intestinal epithelial barrier and inflammation. While alterations in the gut microbiome of critically injured patients may influence clinical outcomes, the impact of trauma on gut microbial composition is unknown. Our objective was to determine if the gut microbiome is altered in severely injured patients and begin to characterize changes in the gut microbiome due to time and therapeutic intervention. METHODS: We conducted a prospective, observational study in adult patients (n = 72) sustaining severe injury admitted to a Level I Trauma Center. Healthy volunteers (n = 13) were also examined. Fecal specimens were collected on admission to the emergency department and at 3, 7, 10, and 13 days (±2 days) following injury. Microbial DNA was isolated for 16s rRNA sequencing, and α and ß diversities were estimated, according to taxonomic classification against the Greengenes database. RESULTS: The gut microbiome of trauma patients was altered on admission (i.e., within 30 minutes following injury) compared to healthy volunteers. Patients with an unchanged gut microbiome on admission were transfused more RBCs than those with an altered gut microbiome (p < 0.001). Although the gut microbiome started to return to a ß-diversity profile similar to that of healthy volunteers over time, it remained different from healthy controls. Alternatively, α diversity initially increased postinjury, but subsequently decreased during the hospitalization. Injured patients on admission had a decreased abundance of traditionally beneficial microbial phyla (e.g., Firmicutes) with a concomitant decrease in opportunistic phyla (e.g., Proteobacteria) compared to healthy controls (p < 0.05). Large amounts of blood products and RBCs were both associated with higher α diversity (p < 0.001) and a ß diversity clustering closer to healthy controls. CONCLUSION: The human gut microbiome changes early after trauma and may be aided by early massive transfusion. Ultimately, the gut microbiome of trauma patients may provide valuable diagnostic and therapeutic insight for the improvement of outcomes postinjury. LEVEL OF EVIDENCE: Prognostic and Epidemiological, level III.

Compensatory Reserve Index: Performance of A Novel Monitoring Technology to Identify the Bleeding Trauma Patient.

INTRODUCTION: Hemorrhage is one of the most substantial causes of death after traumatic injury. Standard measures, including systolic blood pressure (SBP), are poor surrogate indicators of physiologic compromise until compensatory mechanisms have been overwhelmed. Compensatory Reserve Index (CRI) is a novel monitoring technology with the ability to assess physiologic reserve. We hypothesized CRI would be a better predictor of physiologic compromise secondary to hemorrhage than traditional vital signs. METHODS: A prospective observational study of 89 subjects meeting trauma center activation criteria at a single level I trauma center was conducted from October 2015 to February 2016. Data collected included demographics, SBP, heart rate, and requirement for hemorrhage-associated, life-saving intervention (LSI) (i.e., operation or angiography for hemorrhage, local or tourniquet control of external bleeding, and transfusion >2 units PRBC). Receiver-operator characteristic (ROC) curves were formulated and appropriate thresholds were calculated to compare relative value of the metrics for predictive modeling. RESULTS: For predicting hemorrhage-related LSI, CRI demonstrated a sensitivity of 83% and a negative predictive value (NPV) of 91% as compared with SBP with a sensitivity to detect hemorrhage of 26% (P < 0.05) and an NPV of 78%. ROC curves generated from admission CRI and SBP measures demonstrated values of 0.83 and 0.62, respectively. CRI identified significant hemorrhage requiring potentially life-saving therapy more reliably than SBP (P < 0.05). CONCLUSION: The CRI device demonstrated superior capacity over systolic blood pressure in predicting the need for posttraumatic hemorrhage intervention in the acute resuscitation phase after injury.

Comparison of compensatory reserve and arterial lactate as markers of shock and resuscitation.

BACKGROUND: During traumatic hemorrhage, the ability to identify shock and intervene before decompensation is paramount to survival. Lactate is extremely sensitive to shock, and its clearance has been demonstrated a useful gauge of shock and resuscitation status. Though lactate can be measured in the field, logistical constraints render it impractical in certain environments. The compensatory reserve represents a new clinical measurement reflecting the remaining capacity to compensate for hypoperfusion. We hypothesized the compensatory reserve index (CRI) would be an effective surrogate marker of shock and resuscitation compared to lactate. METHODS: The CRI device was placed on consecutive patients meeting trauma center activation criteria and remained on the patient until discharge, admission, or transport to operating suite. All subjects had a lactate level measured as part of their routine admission metabolic analysis. Time-corresponding CRI and lactate values were matched in regards to initial and subsequent lactate levels. Mean time from lactate sample collection to data availability in the electronic medical record was calculated. Predictive capacity of CRI and lactate in predicting hemorrhage was determined by receiver-operator characteristic curve analysis. Correlation analysis was performed to determine if any association existed between changing CRI and lactate values. RESULTS: Receiver-operator characteristic (ROC) curves were generated and area under the curve was 0.8052 and 0.8246 for CRI and lactate, respectively. There was no significant difference in each parameter's ability to predict hemorrhage (p = 0.8015). The mean duration from lactate sample collection to clinical availability was 44 minutes whereas CRI values were available immediately. Analysis of the concomitant change in serial CRI and lactate levels revealed a Spearman's correlation coefficient of -0.73 (p < 0.01). CONCLUSION: CRI performed with equivalent predictive capacity to lactate with respect to identifying initial perfusion status associated with hemorrhage and subsequent resuscitation. LEVEL OF EVIDENCE: Diagnostic, Level II.

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.

Impact of the age of transfused red blood cells in the trauma population: a feasibility study.

UNLABELLED: Following injury, transfusion of red blood cells (RBCs) of increased storage duration has been associated with an increased morbidity and mortality. Prospective trials focusing on the impact of the storage age of RBCs in severely bleeding trauma patients have failed to accrue patients. This has been attributed to an inability to maintain a large inventory of fresh RBCs, and the difficulties in obtaining consent in severely bleeding trauma patients. To address these issues, we performed a prospective, observational pilot study to evaluate the feasibility of conducting a trial focusing on RBC age in patients following injury. METHODS: Patients with bleeding due to trauma were transfused RBCs ≤10 day old if they were ABO blood Type O (Group O) or were transfused the oldest RBCs in inventory if they were Type A, B or AB (Group A/B/AB). Clinicians were unaware of the specific age of the RBCs. RESULTS: 63 patients were analyzed (Group O, n=19; Group A/B/AB, n=44). Half of all patients had severe injuries ISS (median 22). The median admission base deficit was -5 mEq/L, and median total 24h use of RBC and FFP was 1.2 L. The age of RBCs transfused to Group O was significantly lower than for Group A/B/AB [median (IQR) A/B/AB=18.4 (11.4-25.4) days, and Group O=6 (4.2-7.8) days; p<0.001]. CONCLUSIONS: It appears feasible to conduct a RBC age trial in trauma patients using ABO blood type to construct comparative groups. Adequate RBC age separation between cohorts and reduced RBC age in the "young" group of patients who received units ≤10 days old was achieved.

Characterizing vasopressin and other vasoactive mediators released during resuscitation of trauma patients.

BACKGROUND: We sought to perform the first characterization of vasopressin and other vasoactive mediators released during resuscitation of hypotensive trauma patients. METHODS: This institutional review board-approved study was conducted under waiver of consent. Adults with clinical evidence of acute traumatic injury and systolic blood pressure less than or equal to 90 mm Hg within 1 hour of arrival were evaluated at our Level I trauma center. Two hundred three patients were screened with 50 enrolled from February 2010 to February 2011. Demographic information was also collected. Blood samples were obtained at 0, 30, 60, 90, 120, and 240 minutes after arrival, and assays were performed for vasopressin, angiotensin II, epinephrine, and cortisol. We assessed the significance of variation in these vasoactive mediators with injury and transfusion of more than 600 mL, with adjustment for time using repeated-measures linear models in log units. RESULTS: We found that vasopressin (p = 0.005) and epinephrine (p = 0.01) increased significantly with injury, while angiotensin (p = 0.60) and cortisol (p = 0.46) did not and that vasopressin (p < 0.001) and epinephrine (p = 0.004) increased significantly in patients requiring transfusion of more than 600 mL but angiotensin II (p = 0.11) and cortisol (p = 0.90) did not. Relatively low levels of vasopressin (<30 pg/mL) were observed at least once during the first 2 hours in 88% of trauma patients, and abnormally low epinephrine levels (<100 pg/mL) were observed at least once during the first 2 hours in 18% of trauma patients. CONCLUSION: This is the first clinical trial to serially evaluate vasopressin and other vasoactive mediators following trauma during the resuscitation phase. Vasopressin, in particular, and epinephrine seem to be the key mediators produced in the human response to severe injury. A deficiency of vasopressin may contribute to intractable shock after trauma. LEVEL OF EVIDENCE: Prognostic/epidemiologic study, level III.