Critical Administration Threshold Research Articles

Predicting the critical administration threshold in bleeding trauma patients.

Delays in promptly recognizing and appropriately managing hemorrhagic injuries contribute to preventable trauma related deaths nationwide. We sought to identify patient variables available at the time of emergency department arrival associated with meeting the critical administration threshold. We conducted a trauma registry review from September 2016 to March 2020 of trauma team activations at The Ottawa Hospital, a Level 1 Trauma Center. Our primary outcome was the frequency of meeting the critical administration threshold. Secondary outcomes included time to critical administration threshold, 24-h all-cause mortality, and 30-day all-cause mortality. Multivariate logistic regression identified factors independently associated with meeting the critical administration threshold. We assessed 762 patients, of which 78 (10.2%) met the critical administration threshold. The median time to critical administration threshold was 28.9min. Mortality at 24h occurred in 58 (7.6%) patients. Four variables available upon patient arrival predicted the critical administration threshold, including systolic blood pressure ≤ 90mmHg (OR 6.6; 95% CI 3.7-12.0), Glasgow Coma Scale ≤ 8 (OR 5.9; 95% CI 3.2-10.6), heart rate ≥ 100 beats/minute (OR 4.4; 95% CI 2.4-8.1), and respiratory rate ≥ 20 breaths/min (OR 2.2; 95% CI 1.2-4.0). We identified four clinical variables readily available to physicians upon patient arrival associated with meeting the critical administration threshold: systolic blood pressure ≤ 90mmHg, Glasgow Coma Scale ≤ 8, heart rate ≥ 100 beats/minute, and respiratory rate ≥ 20 breaths/min. Patients presenting with any of these clinical parameters should prompt physicians to consider ordering blood products immediately.

A machine learning-based Coagulation Risk Index predicts acute traumatic coagulopathy in bleeding trauma patients.

Acute traumatic coagulopathy (ATC) is a well-described phenomenon known to begin shortly after injury. This has profound implications for resuscitation from hemorrhagic shock, as ATC is associated with increased risk for massive transfusion (MT) and mortality. We describe a large-data machine learning-based Coagulation Risk Index (CRI) to test the early prediction of ATC in bleeding trauma patients. Coagulation Risk Index was developed using continuous vital signs (VSs) available during the first 15 minutes after admission at a single trauma center over 4 years. Data to compute the CRI were derived from continuous features of photoplethymographic and electrocardiographic waveforms, oximetry values, and blood pressure trends. Two groups of patients at risk for ATC were evaluated: critical administration threshold and patients who received an MT. Acute traumatic coagulopathy was evaluated in separate models and defined as an international normalized ratio (INR) >1.2 and >1.5 upon arrival. The CRI was developed using 2 years of cases for training and 2 years for testing. The accuracy of the models is described by area under the receiver operator curve with 95% confidence intervals. A total of 17,567 patients were available for analysis with continuous VS data, 52.8% sustained blunt injury, 30.2% were female, and the mean age was 44.6 years. The ability of CRI to predict ATC in critical administration threshold patients was excellent. The true positive and true negative rates were 95.6% and 88.3%, and 94.9% and 89.2% for INR >1.2 and INR >1.5, respectively. The CRI also demonstrated excellent accuracy in patients receiving MT; true positive and true negative rates were 92.8% and 91.3%, and 100% and 88.1% for INR >1.2 and INR >1.5, respectively. Using continuous VSs and large-data machine learning capabilities, the CRI accurately predicts early ATC in bleeding patients. Clinical application may guide early hemostatic resuscitation. Extension of this technology into the prehospital setting could provide earlier treatment of ATC. Retrospective, Prognostic Study; Level III.

Life-threatening hemorrhage as defined by the critical administration threshold in nontraumatic critical bleeding: A descriptive observational study.

Evaluations of critical bleeding and massive transfusion have focused on traumatic hemorrhage. However, most critical bleeding in hospitalized patients occurs outside trauma. The purpose of this study was to provide an in-depth description examining the critical administration threshold (CAT; ≥3 units red blood cells (RBCs) in a 1-h period) occurrences in nontraumatic hemorrhage. This will assist in establishing the framework for future investigations in nontraumatic hemorrhage. This is an observational cohort study of adults experiencing critical bleeding defined as being CAT+ during hospitalization from 2016 to 2021 at a single academic institution. A CAT episode started with administration of the first qualifying RBC unit and ended at the time of completion of the last allogeneic unit prior to a ≥4-h gap without subsequent transfusion. The primary goal was to describe demographic, clinical and transfusion characteristics of participants with nontraumatic critical bleeding. 2433 patients suffered critical bleeding, most often occurring in the operating room (71.1%) followed by the intensive care unit (20.8%). 57% occurred on the initial day of hospitalization, with a median duration of 138 (36, 303) minutes. The median number of RBCs transfused during the episode was 5 (4, 8), with median total allogeneic units of 9 (4, 9). Hospital mortality was 19.2%. The most common cause of death was multi-organ failure (50.3%), however death within 24 h was due to exsanguination (72.7%). The critical administration threshold may be employed to identify critical bleeding in non-trauma settings of life-threatening hemorrhage, with a mortality rate of approximately 20%.

Evaluating the Shock Index, Revised Assessment of Bleeding and Transfusion (RABT), Assessment of Blood Consumption (ABC) and novel PTTrauma score to predict critical transfusion threshold (CAT) in penetrating thoracic trauma

The shock index (SI) has been associated with predicting transfusion needs in trauma patients. However, its utility in penetrating thoracic trauma (PTTrauma) for predicting the Critical Administration Threshold (CAT) has not been well-studied. This study aimed to evaluate the prognostic value of SI in predicting CAT in PTTrauma patients and compare its performance with the Assessment of Blood Consumption (ABC) and Revised Assessment of Bleeding and Transfusion (RABT) scores. We conducted a prognostic type 2, single-center retrospective observational cohort study on patients with PTTrauma and an Injury Severity Score (ISS) > 9. The primary exposure was SI at admission, and the primary outcome was CAT. Logistic regression and decision curve analysis were used to assess the predictive performance of SI and the PTTrauma score, a novel model incorporating clinical variables. Of the 620 participants, 53 (8.5%) had more than one CAT. An SI > 0.9 was associated with CAT (adjusted OR 4.89, 95% CI 1.64–14.60). The PTTrauma score outperformed SI, ABC, and RABT scores in predicting CAT (AUC 0.867, 95% CI 0.826–0.908). SI is a valuable predictor of CAT in PTTrauma patients. The novel PTTrauma score demonstrates superior performance compared to existing scores, highlighting the importance of developing targeted predictive models for specific injury patterns. These findings can guide clinical decision-making and resource allocation in the management of PTTrauma.

Early Prediction of Massive Transfusion for Patients With Traumatic Hemorrhage: Development of a Multivariable Machine Learning Model.

Develop a novel machine learning (ML) model to rapidly identify trauma patients with severe hemorrhage at risk of early mortality. The critical administration threshold (CAT, 3 or more units of red blood cells in a 60-minute period) indicates severe hemorrhage and predicts mortality, whereas early identification of such patients improves survival. Patients from the PRospective, Observational, Multicenter, Major Trauma Transfusion and Pragmatic, Randomized Optimal Platelet, and Plasma Ratio studies were identified as either CAT+ or CAT-. Candidate variables were separated into 4 tiers based on the anticipated time of availability during the patient's assessment. ML models were created with the stepwise addition of variables and compared with the baseline performance of the assessment of blood consumption (ABC) score for CAT+ prediction using a cross-validated training set and a hold-out validation test set. Of 1245 PRospective, Observational, Multicenter, Major Trauma Transfusion and 680 Pragmatic, Randomized Optimal Platelet and Plasma Ratio study patients, 1312 were included in this analysis, including 862 CAT+ and 450 CAT-. A CatBoost gradient-boosted decision tree model performed best. Using only variables available prehospital or on initial assessment (Tier 1), the ML model performed superior to the ABC score in predicting CAT+ patients [area under the receiver-operator curve (AUC = 0.71 vs 0.62)]. Model discrimination increased with the addition of Tier 2 (AUC = 0.75), Tier 3 (AUC = 0.77), and Tier 4 (AUC = 0.81) variables. A dynamic ML model reliably identified CAT+ trauma patients with data available within minutes of trauma center arrival, and the quality of the prediction improved as more patient-level data became available. Such an approach can optimize the accuracy and timeliness of massive transfusion protocol activation.

Evaluation of the association of factor XIII at hospital arrival and outcomes in a cohort of severely injured patients

BackgroundSevere traumatic bleeding depletes coagulation factor XIII (FXIII) and fibrinogen. However, the role of FXIII level in bleeding-related outcomes is unknown. ObjectivesTo evaluate the association between FXIII levels at hospital arrival and critical administration threshold (≥3 red blood cell units in 1 hour within the first 24 hours), bleeding-related outcomes, death, and baseline characteristics. MethodsA retrospective cohort study was conducted in severely injured adult patients (Injury Severity Score of ≥22 or ≥2 red blood cell units transfused in 24 hours) admitted to a level 1 trauma center. Clinical and laboratory data were collected. Baseline FXIII antigen levels were measured in banked patient plasma. Multivariable logistic and linear regression models were used to estimate the association between FXIII levels, outcomes, and baseline characteristics. ResultsThree hundred sixty-four of 1730 subjects admitted during a 2-year period were analyzed. Median age was 44 years (IQR, 27-62 years), and median Injury Severity Score was 29 (IQR, 22-34). FXIII levels were not associated with critical administration threshold (odds ratio [OR], 1.06; 95% CI, 0.97-1.17) or death (OR, 0.98; 95% CI, 0.90-1.07). FXIII was associated with major bleeding (OR, 1.10; 95% CI, 1.02-1.2) and massive transfusion (OR, 1.25; 95% CI, 1.08-1.44). Lower baseline FXIII levels were associated with arrival from a referring hospital (FXIII level, −0.07 U/mL; 95% CI, −0.11 to −0.03), hemoglobin (FXIII level, −0.05 U/mL; 95% CI, −0.07 to −0.03), fibrinogen level (FXIII level, −0.05 U/mL; 95% CI, −0.08 to −0.02), and platelet count (FXIII level, −0.02 U/mL; 95% CI, −0.04 to −0.008). ConclusionsBaseline FXIII levels in severely injured patients were inconsistently associated with bleeding-related outcomes and mortality. However, their association with major bleeding warrants further investigation of the role of FXIII in massively transfused patients with trauma.

Whole Blood Massive Transfusion Score is the Most Sensitive Predictor of Mortality among Patients Requiring Emergent Trauma Laparotomy and Massive Resuscitation

Introduction: The whole blood massive transfusion score (WB MT = 3*RBC+WB) was developed to account for the use of whole blood (WB) in trauma resuscitations. A positive WB MT (WB MT ≥7) has shown to better predict mortality among patients requiring activation of massive transfusion (MTP). We sought to evaluate the ability of WB MT to predict mortality in patients with activation of MTP requiring emergent trauma laparotomy (ETL). Methods: A retrospective cohort study of all trauma patients with both ETL and activation of MTP from 11/2019-12/2021. ETL was defined as laparotomy from the trauma bay within 90 minutes of arrival. WB MT was compared with other markers of resuscitation volume [classic massive transfusion (cMT), critical administration threshold (CAT), and resuscitation intensity (RI)] on the basis of diagnostic ability to identify 24-hour and hospital mortality. Results: There were 227 patients included with 24-hour and hospital mortality rates of 18% (n = 40) and 22% (n = 51), respectively. Those with 24-hour mortality were significantly more likely to receive WB MT (100 vs 60%, p < 0.001), cMT (68 vs 13%, p < 0.001), and CAT (90 vs 42%, p < 0.001) compared with survivors. WB MT was the most sensitive predictor of 24-hour and hospital mortality compared with all other markers of massive resuscitation. Conclusion: WB MT was the most sensitive marker of mortality in patients with ETL requiring activation of MTP. Patients with 24-hour survival were significantly more likely to receive WB only MTP while those that died were significantly more likely to received mixed blood products.

Recognizing life-threatening bleeding in pediatric trauma: A standard for when to activate massive transfusion protocol.

Traumatic hemorrhage is the most common cause of preventable death in civilian and military trauma. Early identification of pediatric life-threatening hemorrhage is challenging. There is no accepted clinical critical administration threshold (CAT) in children for activating massive transfusion protocols. Children 0 to 17 years old who received any transfusion in the first 24 hours after injury between 2010 and 2019 were included. The type, volume, and time of administration for each product were recorded. The greatest volume of weight-adjusted products transfused within 1 hour was calculated. The cut point for the number of products that maximized sensitivity and specificity to predict in-hospital mortality, need for urgent surgery, and second life-threatening bleeding episode was determined using Youden's index. A binary variable (CAT+) was generated using this threshold for inclusion in a multivariable logistic regression model. In total, 287 patients were included. The median (interquartile range) age was 6 (2-14) years, 60% were males, 83% sustained blunt trauma, and the median (interquartile range) Injury Severity Score was 26 (17-35). The optimal cutoff to define CAT+ was >20 mL/kg of product; this optimized test characteristics for mortality (sensitivity, 70%; specificity, 77%), need for urgent hemorrhage control procedure (sensitivity, 65%; specificity, 74%). and second bleeding episode (sensitivity, 77%; specificity, 74%). There were 93 children (32%) who were CAT+. On multivariate regression, being CAT+ was associated with 3.4 increased odds of mortality (95% confidence interval, 1.67-6.89; p = 0.001) after controlling for age, hypotension, Injury Severity Score, and Glasgow Coma Scale. For every unit of product administered, there was a 10% increased risk of mortality (odds ratio, 1.1; p < 0.001). Transfusion of more than 20 mL/kg of any blood product within an hour should be used as a threshold for activating massive transfusion protocols in children. Children who meet this CAT are at high risk of mortality and need for interventions; this population may benefit from targeted, timely, and aggressive hemostatic resuscitation. Therapeutic/Care Management; Level III.

A new definition for massive transfusion in the modern era of whole blood resuscitation.

Multiple thresholds are defined to identify patients at risk of death from hemorrhage, including massive transfusion (MT), critical administration threshold (CAT), and resuscitation intensity (RI). All fail to account for the use of whole blood (WB). We hypothesized that a definition including WB transfusion would better predict early mortality following trauma. This is a retrospective review of all trauma patients with activation of the MT protocol from December 2018 to February 2020. Combinations of WB, RBCs, and fresh frozen plasma (FFP) units transfused during the initial hour of resuscitation were compared using receiver operating characteristic and area under the receiver curve (AUC) for 3- and 6-h mortality. WB massive transfusion (WB MT) score was defined as the sum of each unit RBC plus three times each unit of WB transfused within the first hour of resuscitation. There were 235 patients eligible for analysis with 60 resuscitated using ≥1 unit of WB. Overall, 27 and 29 patients died in the first 3 and 6h, respectively. WB MT ≥7 had the greatest 3-h and 6-h mortality AUC values (0.78 and 0.79, respectively) when compared to MT, CAT, RI4+, and other attempted definitions using units of WB, RBC, and FFP. Compared to WB MT-, WB MT+ patients died at significantly higher rates at 3h (28.9% vs. 3.1%, p < .001), 24 h (35.5% vs. 5.7%, p < .001), and 28 days (42.1% vs. 11.9%, p < .001). WB MT is the first measure of massive resuscitation to incorporate WB and better identifies early mortality than other definitions.

Euglobulin clot lysis time reveals a high frequency of fibrinolytic activation in trauma

Activation of the fibrinolytic system plays a central role in the host response to trauma. There is significant heterogeneity in the degree of fibrinolysis activation at baseline that is usually assessed by whole blood thromboelastography (TEG). Few studies have focused on plasma markers of fibrinolysis that could add novel insights into the frequency and mechanisms of fibrinolytic activation in trauma. Global fibrinolysis in plasma was assessed using a modified euglobulin clot lysis time (ECLT) assay in 171 major trauma patients and compared to commonly assessed analytes of fibrinolysis. The median ECLT in trauma patients was significantly shorter at 8.5 h (IQR, 1.3–19.5) compared to 19.9 h (9.8–22.6) in healthy controls (p < 0.0001). ECLT values ≤2.5th percentile of the reference range were present in 83 (48.5%) of trauma patients, suggesting increased fibrinolytic activation. Shortened ECLT values were associated with elevated plasmin-antiplasmin (PAP) complexes and free tissue plasminogen activator (tPA) levels in plasma. Sixteen (9.2%) individuals met the primary outcome for massive transfusion, here defined as the critical administration threshold (CAT) of 3 units of packed red cells in any 60-minute period within the first 24 h. In a univariate screen, plasma biomarkers associated with CAT included D-dimer (p < 0.001), PAP (p < 0.05), free tPA (p < 0.05) and ECLT (p < 0.05). We conclude that fibrinolytic activation, measured by ECLT, is present in a high proportion of trauma patients at presentation. The shortened ECLT is partially driven by high tPA levels and is associated with high levels of circulating PAP complexes. Further studies are needed to determine whether ECLT is an independent predictor of trauma outcomes.

Evidence for use of damage control surgery and damage control interventions in civilian trauma patients: a systematic review

BackgroundAlthough damage control (DC) surgery is widely assumed to reduce mortality in critically injured patients, survivors often suffer substantial morbidity, suggesting that it should only be used when indicated. The purpose of this systematic review was to determine which indications for DC have evidence that they are reliable and/or valid (and therefore in which clinical situations evidence supports use of DC or that DC improves outcomes).MethodsWe searched 11 databases (1950–April 1, 2019) for studies that enrolled exclusively civilian trauma patients and reported data on the reliability (consistency of surgical decisions in a given clinical scenario) or content (surgeons would perform DC in that clinical scenario or the indication predicted use of DC in practice), construct (were associated with poor outcomes), or criterion (were associated with improved outcomes when DC was conducted instead of definitive surgery) validity for suggested indications for DC surgery or DC interventions.ResultsAmong 34,979 citations identified, we included 36 cohort studies and three cross-sectional surveys in the systematic review. Of the 59 unique indications for DC identified, 10 had evidence of content validity [e.g., a major abdominal vascular injury or a packed red blood cell (PRBC) volume exceeding the critical administration threshold], nine had evidence of construct validity (e.g., unstable patients with combined abdominal vascular and pancreas gunshot injuries or an iliac vessel injury and intraoperative acidosis), and six had evidence of criterion validity (e.g., penetrating trauma patients requiring > 10 U PRBCs with an abdominal vascular and multiple abdominal visceral injuries or intraoperative hypothermia, acidosis, or coagulopathy). No studies evaluated the reliability of indications.ConclusionsFew indications for DC surgery or DC interventions have evidence supporting that they are reliable and/or valid. DC should be used with respect for the uncertainty regarding its effectiveness, and only in circumstances where definitive surgery cannot be entertained.

Thrombin Generation Kinetics are Predictive of Rapid Transfusion in Trauma Patients Meeting Critical Administration Threshold.

We hypothesize that a patient (pt) with accelerated thrombin generation, time to peak height (ttPeak), will have a greater odds of meeting critical administration threshold (CAT) criteria (> 3 packed red blood cell [pRBC] transfusions [Tx] per 60 min interval), within the first 24 h after injury, independent of international normalized ratio (INR). In a prospective cohort study, trauma patients were enrolled over a 4.5-year period and serial blood samples collected at various time points. We retrospectively stratified pts into three categories: CAT+, CAT- but receiving some pRBC Tx, receiving no Tx within the first 24 h. Blood collected prior to Tx was analyzed for thrombin generation parameters and prothrombin time (PT)/INR. A total of 484 trauma pts were analyzed: injury severity score = 13 [7,22], age = 48 [28, 64] years, and 73% male. Fifty pts met criteria for CAT+, 64 pts CAT-, and 370 received no Tx. Risk factors for meeting CAT+: decreased arrival systolic blood pressure (OR 2.82 [2.17, 3.67]), increased INR (OR 2.09, [1.66, 2.62]) and decreased time to peak OR 2.27 [1.74, 2.95]). These variables remained independently associated with increased risk of requiring Tx in a multivariable logistic model, after adjusting for sex and trauma type. Pts in hemorrhagic shock, who meet CAT+ criteria, are characterized by accelerated thrombin generation. In our multivariable analysis, both ttPeak and PT/INR have a complementary role in predicting those injured patients who will require a high rate of Tx.

Massive transfusion and the response to prehospital plasma: It is all in how you define it.

A recent analysis derived from the Prehospital Air Medical Plasma trial data set demonstrated no significant independent plasma survival benefit in those who required massive transfusion (≥10 units of red cells in 24 hours). The definition of massive transfusion has evolved over time to minimize bias and predict those at highest risk of death. We sought to characterize the definition of massive transfusion, their associated mortality risks and the survival benefit associated with prehospital plasma. A secondary analysis was performed using data from a recent prehospital plasma trial. Patients transferred directly from the scene were characterized. We defined historic massive transfusion using ≥10 units red cells in 24 hours and critical administration threshold (CAT) as ≥3 units per hour in the first hour (CAT1hr) or in any of the first 4 hours (CAT4hr) from arrival. The primary outcome was 30-day mortality. Kaplan-Meier analysis and Cox hazard regression were used to characterize the survival benefit of prehospital plasma. There were a total of 390 enrolled patients who were transferred from the scene and represent the study cohort. Overall, 126 patients were positive for the CAT1hr metric, 183 patients were positive for the CAT4hr metric and 84 patients were positive for historic massive transfusion metric. The overall study mortality rate for those patients who met each transfusion definition was 13.1%, 17.4% and 10.0%, respectively. The CAT4hr metric had the lowest potential for survival bias. Kaplan-Meier survival analysis demonstrated a prehospital plasma survival benefit in the patients who were CAT4hr positive. The current analysis demonstrates the superior utility of the CAT4hr definition with optimization of survival bias while conserving mortality risk prediction. This transfusion definition was associated with a prehospital plasma survival benefit and may be the most appropriate definition of massive transfusion for pragmatic studies which focus on hemorrhagic shock. Epidemiologic, Level II.

Ratios of Plasma and Platelets to Red Blood Cells in Surgical Patients With Acute Intraoperative Hemorrhage.

The relationships between the ratios of transfused allogeneic blood products and clinical outcomes in patients with acute intraoperative hemorrhage are poorly defined. To better define these ratios, we undertook a single-center, observational cohort study of all surgical patients (≥18 years) who received rapid transfusion defined by a critical administration threshold of 3 or more units of red blood cells (RBCs) intraoperatively within 1 hour between January 1, 2011 and December 31, 2015. Multivariable regression analyses were used to assess relationships between ratios of plasma to RBCs and platelets to RBCs at 3, 12, and 24 hours and clinical outcomes. The primary outcome was hospital mortality, with secondary outcomes of intensive care unit and hospital-free days. The study included 2385 patients, of whom 14.9% had a plasma-to-RBC ratio of 1.0+, and 47.6% had a platelet-to-RBC ratio of 1.0+. Higher plasma-to-RBC and platelet-to-RBC ratios were observed for patients who underwent cardiac, transplant, and vascular surgery and in patients with greater derangements in hemostatic laboratory values. Ratios did not differ by patient age or severity of illness. Higher ratios were not associated with improved clinical outcomes. Mortality differed by platelet-to-RBC but not plasma-to-RBC ratio, with the highest mortality observed with a platelet-to-RBC ratio of 0.1-0.9 at 24 hours (odds ratio, 3.34 [1.62-6.88]) versus no platelets (P= .001). Higher plasma-to-RBC ratios were associated with decreased hospital-free days, although differences in clinical outcomes were not significant after exclusion of patients receiving only RBCs without component therapies. Transfusion ratios in surgical patients with critical intraoperative hemorrhage were largely related to surgical and hemostatic features rather than baseline patient characteristics. Higher ratios were not associated with improved outcomes.

Pulse Pressure as an Early Warning of Hemorrhage in Trauma Patients

Hypotension based on low systolic blood pressure (SBP) is a well-documented indicator of ongoing blood loss. However, the utility of pulse pressure (PP) for detection of hemorrhage has not been well studied. The purpose of this study was to determine whether a narrowed PP in nonhypotensive patients is an independent predictor of critical administration threshold (CAT+) hemorrhage requiring surgical or endovascular control. We performed a retrospective single-center study (January 2010 to October 2014), including trauma patients ≥16 years old with SBP ≥ 90 mmHg upon emergency department (ED) admission. We identified patients who were both CAT+ and required either surgical or interventional radiology for definitive hemorrhage control as the active hemorrhage (AH) group. Analyses were then performed to elucidate the association between PP and hemorrhage. Of the total 18,015 patients identified, 283 (1.6%) met the criteria for clinically significant hemorrhage. Mean PP was significantly lower in the AH group compared with the non-AH group (39 ± 18 mmHg vs 53 ± 19 mmHg, p < 0.0001). Multivariate analysis revealed that narrowed initial ED PP is an independent predictor of AH (adjusted odds ratio [AOR] 0.975) along with age (AOR 1.01), penetrating mechanism (AOR 9.476), field SBP (AOR 0.985), ED heart rate (AOR 1.024), and Injury Severity Score (AOR 1.126). Cutoff analysis of PP values identified a significantly higher risk of AH at a PP cutoff of 55 mmHg (AOR 3.44, p= 0.005, AUC 0.955) in patients 61 years or older vs 40 mmHg (AOR 2.73, p < 0.0001, AUC 0.940) for patients 16 to 60 years old. The predicted probability of AH increases as PP narrows. In patients who are nonhypotensive, a narrowed PP is an independent early predictor of active hemorrhage requiring blood product transfusion and intervention for hemorrhage control.

Prognostic Accuracy of Massive Transfusion, Critical Administration Threshold, and Resuscitation Intensity in Assessing Mortality in Traumatic Patients with Severe Hemorrhage: a Meta-Analysis.

BackgroundThe aim of this study was to assess the prognostic value of massive transfusion (MT), critical administration threshold (CAT), and resuscitation intensity (RI) for the mortality of trauma patients with severe hemorrhage.MethodsSeventeen relevant articles were obtained by searching the PubMed databases through February 15, 2019. The estimated mortality rates and injury severity scores were obtained through a meta-analysis. In addition, diagnostic test accuracy (DTA) reviews were conducted to obtain the sensitivity, specificity, diagnostic odds ratio, and the summary receiver operating characteristic curve.ResultsAt 24 hours, the estimated mortality rates were 0.194, 0.126, and 0.168 in assessments using MT, CAT, and RI, respectively. In addition, the pooled sensitivity of CAT (0.89; 95% confidence interval [CI], 0.82–0.94) was significantly higher than that of MT (0.63; 95% CI, 0.57–0.68) and RI (0.69; 95% CI, 0.63–0.75). Overall, the pooled specificity of MT and CAT was 0.82 (95% CI, 0.80–0.83) and 0.85 (95% CI, 0.83–0.88), respectively, while the pooled sensitivity was 0.49 (95% CI, 0.44–0.54) and 0.50 (95% CI, 0.38–0.62), respectively.ConclusionCAT may be a more sensitive predictor for 24-hour mortality than other predictors. Furthermore, RI also appears to be a useful predictor for 24-hour mortality. Both MT and CAT showed high specificity for overall mortality.

Accuracy of massive transfusion as a surrogate for significant traumatic bleeding in health administrative datasets

Background: Due to the challenge of identifying need for intervention in bleeding patients, there is a growing interest in prediction modeling. Massive transfusion (MT; 10 or more packed red cells in 24 h) is the most commonly studieddependent variable, serving as a surrogate for severe bleeding and its prediction guides the need for intervention. The critical administration threshold (CAT; 3 packed red cells in 1 h) has been proposed as an alternative. In this study, we aim to compare the classification accuracy of these two surrogates for hemorrhage-related outcomes in health administrative datasets.Methods: We performed a secondary analysis of major trauma patients from the prospectively collected Ottawa Trauma Registry, from September 2014 to September 2017. We conducted a logistic regression analysis utilizing need for hemostasis or hemorrhagic death as dependent variables. We compared classification accuracy in terms of sensitivity, specificity, positive predictive value, negative predictive value and AUC. CAT + and MT + status is not mutually exclusive.Results: We studied 890 major trauma patients, including 145 CAT + and 48 MT + patients. CAT + demonstrated a superior association for the composite outcome of 24-hour hemorrhage-related mortality and need for hemostasis (AUC 0.815 vs. 0.644, p < 0.0001). This performance was driven by a substantial difference in sensitivity, noted to be 70.0% (95% CI 62.1–77.9%) for CAT + but only 30.0% (95% CI 22.1–37.9%) for MT+. CAT + and MT + demonstrated specificities of 92.9% (95% CI 91.1–94.7%) and 98.9% (98.1–99.6%) respectively.Conclusion: This study illustrates the concepts of survivorship and competing risk bias for massive transfusion. Utilizing a composite outcome of need for hemostasis and early hemorrhagic death, we demonstrate that CAT + is more accurate for identifying significantly bleeding patients.

External validation of a smartphone app model to predict the need for massive transfusion using five different definitions

Previously, a model to predict massive transfusion protocol (MTP) (activation) was derived using a single-institution data set. The PRospective, Observational, Multicenter, Major Trauma Transfusion database was used to externally validate this model's ability to predict both MTP activation and massive transfusion (MT) administration using multiple MT definitions. The app model was used to calculate the predicted probability of MTP activation or MT delivery. The five definitions of MT used were: (1) 10 units packed red blood cells (PRBCs) in 24 hours, (2) Resuscitation Intensity score ≥ 4, (3) critical administration threshold, (4) 4 units PRBCs in 4 hours; and (5) 6 units PRBCs in 6 hours. Receiver operating curves were plotted to compare the predicted probability of MT with observed outcomes. Of 1,245 patients in the data set, 297 (24%) met definition 1, 570 (47%) met definition 2, 364 (33%) met definition 3, 599 met definition 4 (49.1%), and 395 met definition 5 (32.4%). Regardless of the outcome (MTP activation or MT administration), the predictive ability of the app model was consistent: when predicting activation of the MTP, the area under the curve for the model was 0.694 and when predicting MT administration, the area under the curve ranged from 0.695 to 0.711. Regardless of the definition of MT used, the app model demonstrates moderate ability to predict the need for MT in an external, homogenous population. Importantly, the app allows the model to be iteratively recalibrated ("machine learning") and thus could improve its predictive capability as additional data are accrued. Diagnostic test study/Prognostic study, level III.

Quality management of a massive transfusion protocol.

Massive transfusion is a response to massive uncontrolled hemorrhage. To be effective, it must be timely and address the patient's needs for blood volume, oxygen transport, and hemostasis. A review was performed on all activations of the massive transfusion protocol (MTP) in a hospital with large emergency medicine, trauma, and vascular surgery programs. Indications, transfused amounts, and outcomes were determined for each MTP event to determine appropriateness of MTP use. Results are presented as descriptive statistics, categorical associations, and simple linear trend relationships. The MTP was activated 309 times in 2016. Of these episodes, 237 were for trauma, 29 for gastrointestinal bleeding, 16 for ruptured abdominal aortic aneurisms, and 25 for a variety of other causes. Trauma-related MTP activations had a mean injury severity score of 32. Blood use averaged 6.6 units of red blood cells (RBCs), 6.5 units of plasma, and 1.2 units of apheresis platelets. Fourteen activations ended without the administration of any blood products, and 45 (14%) did not meet the critical administration threshold of three components. Only 60 (19%) activations met the historic definition of massive with at least 10 units of RBCs administered. Mortality was 15% for the trauma-related activations. Massive transfusion protocol activations were frequent and conducted with high fidelity to the 1:1:1 unit ratio standard. Making blood components available quickly was associated with low rates of total component usage and low mortality for trauma patients and was not associated with overuse.

End-tidal CO2 on admission is associated with hemorrhagic shock and predicts the need for massive transfusion as defined by the critical administration threshold: A pilot study

BackgroundCritical administration threshold (≥3 units of packed red blood cells/h or CAT+) has been proposed as a new definition for massive transfusion (MT) that includes volume and rate of blood transfusion. CAT+ has been shown to eliminate survivor bias and be a better predictor of mortality than the traditional MT (>10 units/24h). End-tidal CO2 (ET CO2) negatively correlates with lactate and is an early predictor of shock in trauma patients. We conducted a pilot study to test the hypothesis that low ET CO2 on admission predicts CAT+. MethodsET CO2 via capnography and serum lactate were prospectively collected on admission for 131 patients requiring trauma team activation. Demographic data were obtained from patient charts. Excluded were patients with isolated head injuries, traumatic arrests, or pre-hospital intubations. CAT± status was determined for each hour up to 6h from admission as described; likewise, MT± status was determined up to 24h from admission. ResultsAfter exclusion criteria, 67 patients were analyzed. Mean age was 41.2 (SD 18.5). Thirty-three patients had a blunt mechanism of injury (49%), median ISS was 9 (interquartile range 4–19), and there were 6 deaths (9%). ET CO2 and lactate were negatively correlated by Spearman rank-based correlation (rho=−0.41, p=0.0006). Twenty-one (31%) and 8 (12%) patients were CAT+ and traditional MT+, respectively. There were a significantly greater proportion of patients with ISS>15, ET CO2 <35, or who died found to be CAT+. A binomial logistic regression model adjusting for age, SBP <90, HR, and ISS >15 revealed ET CO2 < 35 to be independently predictive of CAT+ (OR 9.24, 95% CI 1.51-56.57, p=0.016). ConclusionsThis pilot study demonstrated that low ET CO2 had strong association with standard indicators for shock and was predictive of patients meeting CAT+ criteria in the first 6h after admission. Further study to verify these results and to elucidate CAT criteria’s association with mortality will require a larger sample size.