HEMORRHAGIC / HYPOVOLEMIC SHOCK

Do lactate levels in the emergency department predict outcome in adult trauma patients? A systematic review.

Baxter J, Cranfield KR, Clark G, Harris T, Bloom B, Gray AJ.

J Trauma Acute Care Surg. 2016 Sep;81(3):555-66

BACKGROUND: Serum lactate may be associated with clinical outcomes in trauma, even in the absence of physiological abnormality. Sensitive markers of injury and outcomes are needed to guide triage and management of trauma patients within the Emergency Department. We completed a systematic review to determine if lactate levels in adult trauma patients presenting to the Emergency Department were associated with clinical outcomes including mortality.

METHODS: A systematic literature search was conducted in August 2014, updated in March 2016, using MEDLINE, Embase, and CINAHL. Abstracts and full texts were screened for inclusion by two independent reviewers using predetermined inclusion and exclusion criteria. Data extraction and quality assessment was performed by each reviewer using a standardized form. A total of 998 studies were screened; 28 studies were included and reviewed.

RESULTS: The 28 studies recruited 44,154 adults in eight countries between 1997 and 2016. Twenty-one studies found a significant association between elevated Emergency Department lactate and risk of mortality. Three studies looked at lactate clearance; two showed poor clearance was an additional determinant of mortality, but the other found no association. Ten studies also found an association between elevated lactate and other clinical outcomes. These included injury severity, Intensive Care Unit admission, length of hospital stay, organ failure, respiratory complications, blood loss, blood product requirement, catecholamine support, or emergency operation. Two studies concluded that lactate levels do not affect management.

CONCLUSIONS: This review shows that elevated Emergency Department lactate levels are associated with mortality and may be associated with other clinical outcomes in adult trauma patients. We conclude that lactate is a useful marker of outcome in trauma, in addition to current markers of severity. The potential roles of serial lactate measurement and lactate clearance require further research.

LEVEL OF EVIDENCE: Systematic review, level III.

A retrospective analysis of the respiratory adjusted shock index to determine the presence of occult shock in trauma patients.

Caputo N, Reilly J, Kanter M, West J.

J Trauma Acute Care Surg. 2018 Apr;84(4):674-678

BACKGROUND: The shock index (SI), calculated as hear rate/systolic blood pressure, is a simple hemodynamic marker that may be used to assess for the presence of occult shock in trauma patients. The normal range for a healthy adult patient is 0.5 to 0.7. Recently, studies have demonstrated that tachypnea is the most important predictor of cardiac arrest in hospital wards and is an important indicator of derangements across multiple organ systems. As such, we have sought to determine whether the inclusion of the patient's respiratory rate (RR) to the already existing SI (called the Respiratory Adjusted Shock Index [RASI]), calculated as hear rate/systolic blood pressure*(RR/10), will improve the overall diagnostic accuracy of detecting patients in early occult shock.

METHODS: A retrospective chart review over a 4-year period (2012-2016) at an urban, Level I trauma center was performed. All patients admitted to hospital for trauma were included in the study. Exclusion criteria were patients in traumatic arrest or in overt shock. Charts were reviewed for triage vital signs and point of care lactate drawn within 30 minutes of presentation. A lactate greater than 2 mmol/L was used to determine presence of hypoperfusion. The upper limit of normal for the RASI was calculated by multiplying the upper limit of the SI by 1.9 (RR of 19 divided by 10) and validated internally.

RESULTS: A total of 3,093 patients were included in this study. There was no difference in SI for patients discharged versus patients admitted, 0.6 (95% CI, 0.5-0.7) versus 0.7 (95% CI, 0.5-0.8) and a significant difference between the same groups of patients (discharged vs. admitted) for the RASI, 1.1 (95% CI, 1.04-1.18) versus 1.46 (95% CI, 1.35-1.55), respectively. Area under the curve for SI was 0.58 and for the RASI score was 0.94.

CONCLUSION: The RASI score improves diagnostic accuracy for detecting early occult shock in trauma patients when compared to the SI.

LEVEL OF EVIDENCE: Diagnostic, level II.

Use of intrathoracic pressure regulation therapy in breathing patients for the treatment of hypotension secondary to trauma.

Convertino VA, Parquette BA, Wampler DA, Manifold CA, Lindstrom DA, Boland LL, Burkhart NT, Lurie KG, Lick CJ

Scand J Trauma Resusc Emerg Med. 2017 Oct 30;25(1):105

BACKGROUND: Intrathoracic pressure regulation (IPR) therapy has been shown to increase blood pressure in hypotensive patients. The potential value of this therapy in patients with hypotension secondary to trauma with bleeding is not well understood. We hypothesized that IPR would non-invasively and safely enhance blood pressure in spontaneously breathing patients with trauma-induced hypotension.

METHODS: This prospective observational cohort study assessed vital signs from hypotensive patients with a systolic blood pressure (SBP) ≤90 mmHg secondary to trauma treated with IPR (ResQGARD™, ZOLL Medical) by pre-hospital emergency medical personnel in three large US metropolitan areas. Upon determination of hypotension, facemask-based IPR was initiated as long as bleeding was controlled. Vital signs were recorded before, during, and after IPR. An increased SBP with IPR use was the primary study endpoint. Device tolerance and ease of use were also reported.

RESULTS: A total of 54 patients with hypotension secondary to trauma were treated from 2009 to 2016. The mean ± SD SBP increased from 80.9 ± 12.2 mmHg to 106.6 ± 19.2 mmHg with IPR (p < 0.001) and mean arterial pressures (MAP) increased from 62.2 ± 10.5 mmHg to 81.9 ± 16.6 mmHg (p < 0.001). There were no significant changes in mean heart rate or oxygen saturation. Approximately 75% of patients reported moderate to easy tolerance of the device. There were no safety concerns or reported adverse events.

CONCLUSIONS: These findings support the use of IPR to treat trauma-induced hypotension as long as bleeding has been controlled.

Damage Control Resuscitation Supplemented with Vasopressin in a Severe Polytrauma Model with Traumatic Brain Injury and Uncontrolled Internal Hemorrhage.

Dickson JM, Wang X, St John AE, Lim EB, Stern SA, White NJ.

Mil Med. 2018 Mar 14. Epub ahead of print 

Introduction: Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of traumatic death worldwide and particularly on the battlefield. They are especially challenging when present simultaneously (polytrauma), and clear blood pressure end points during fluid resuscitation are not well described for this situation. The goal of this study is to evaluate for any benefit of increasing blood pressure using a vasopressor on brain blood flow during initial fluid resuscitation in a swine polytrauma model.

Materials and Methods: We used a swine polytrauma model with simultaneous TBI, femur fracture, and HS with uncontrolled noncompressible internal bleeding from an aortic tear injury. Five animals were assigned to each of three experimental groups (hydroxyethyl starch only [HES], HES + 0.4 U/kg vasopressin, and no fluid resuscitation [No Fluids]). Fluids were given as two 10 mL/kg boluses according to tactical field care guidelines. Primary outcomes were mean arterial blood pressure (MAP) and brain blood flow at 60 min. Secondary outcomes were blood flows in the heart, intestine, and kidney; arterial blood lactate level; and survival at 6 hr. Organ blood flow was measured using injection of colored microspheres.

Results: Five animals were tested in each of the three groups. There was a statistically significant increase in MAP with vasopressin compared with other experimental groups, but no significant increase in brain blood flow during the first 60 min of resuscitation. The vasopressin group also exhibited greater total internal hemorrhage volume and rate. There was no difference in survival at 6 hours.

Conclusion: In this experimental swine polytrauma model, increasing blood pressure with vasopressin did not improve brain perfusion, likely due to increased internal hemorrhage. Effective hemostasis should remain the top priority for field treatment of the polytrauma casualty with TBI.

Coagulopathy and Mortality in Combat Casualties: Do the Kidneys Play a Role?

Ferencz SE, Davidson AJ, Howard JT, Janak JC, Sosnov JA, Chung KK, Stewart IJ

Mil Med. 2018 Mar 1;183(suppl_1):34-39 

Background: Acute traumatic coagulopathy (ATC) is a common condition after traumatic injury and is known to be associated with an increase in morbidity and mortality in trauma patients. ATC has been implicated as a causative factor in both early hemorrhage and late organ failure in this population, yet the pathophysiology remains largely unknown. Additionally, acute kidney injury (AKI)  is a common condition among critically injured trauma patients. AKI has been associated with an elevated International Normalized Ratio (INR) and warfarin use, but its development has not been well studied in the setting of ATC. We hypothesized that the presence of ATC influences the development of AKI and may mediate mortality in combat casualties.

Methods: Data were obtained from the Department of Defense Trauma Registry, Medical Data Store and Composite Healthcare System, and the Armed Forces Medical Examiner System. A retrospective review was conducted of US service members injured in Iraq or Afghanistan between February 1, 2002 and February 1, 2011, who required ICU level care and survived evacuation out of theater. Exclusions were made for missing data. Cox proportional hazard regression was performed to determine the effect of ATC (a priori defined as first INR > 1.3) on the development of AKI. Further analysis was conducted to determine the influence of these variables on 30-d mortality, and multiple sensitivity analyses were performed to determine the effect of ATC on both AKI and mortality.

Results: A total of 1,288 patients were identified for analysis. ATC was a risk factor for subsequent AKI after adjustment (HR 1.67, 95% CI 1.28-2.18; p < 0.001). However, ATC was not a risk factor for mortality after adjustment in the full model (HR 1.87, 95% CI 0.95-3.65; p = 0.069). On sensitivity analyses exploring alternate definitions of ATC, an INR of 1.2 remained associated with AKI (HR 1.46, 95% CI 1.13-1.88; p = 0.004) and an INR of 1.5 became significant for mortality (HR 1.76, 95% CI 1.32-2.35; p < 0.001).

Conclusion: ATC is independently associated with the development of AKI. Although ATC is associated with mortality in the unadjusted model, it is not significant after adjustment for AKI. This implies that the kidneys may play a role in the adverse outcomes observed after ATC. Increased awareness and monitoring for coagulopathy and the subsequent development of AKI in combat casualty patients may lead to earlier diagnosis and treatment of these conditions, possibly decreasing morbidity and mortality.

Walter B. Cannon's World War I experience: treatment of traumatic shock then and now.

Ryan KL

Adv Physiol Educ. 2018 Jun 1;42(2):267-276

Walter B. Cannon (1871-1945), perhaps America's preeminent physiologist, volunteered for service with the Army Expeditionary Force (AEF) during World War I. He initially served with Base Hospital No. 5, a unit made up of Harvard clinicians, before moving forward to the front lines to serve at a casualty clearing station run by the British. During his time there, he performed research on wounded soldiers to understand the nature and causes of traumatic shock. Subsequently, Cannon performed animal experimentation on the causes of traumatic shock in the London laboratory of Dr. William Bayliss before being assigned to the AEF Central Medical Laboratory in Dijon, France, where he continued his experimental studies. During this time, he also developed and taught a curriculum on resuscitation of wounded soldiers to medical providers. Although primarily a researcher and teacher, Cannon also performed clinical duties throughout the war, serving with distinction under fire. After the war, Cannon wrote a monograph entitled Traumatic Shock (New York: Appleton, 1923), which encapsulated the knowledge that had been gained during the war, both from direct observation of wounded soldiers, as well as laboratory experimentation on the causes and treatment of traumatic shock. In his monograph, Cannon elucidates a number of principles concerning hemorrhagic shock that were later forgotten, only to be "rediscovered" during the current conflicts in Iraq and Afghanistan. This paper summarizes Cannon's wartime experiences and the knowledge gained concerning traumatic shock during World War I, with a comparison of current combat casualty care practices and knowledge to that which Cannon and his colleagues understood a century ago.

Comparisons of Traditional Metabolic Markers and Compensatory Reserve as Early Predictors of Tolerance to Central Hypovolemia in Humans.

Schiller AM, Howard JT, Lye KR, Magby CG, Convertino VA.

Shock. 2017 Oct 18 Epub ahead of print

Circulatory shock remains a leading cause of death in both military and civilian trauma. Early, accurate and reliable prediction of decompensation is necessary for the most efficient interventions and clinical outcomes. Individual tolerance to reduced central blood volume can serve as a model to assess the sensitivity and specificity of vital sign measurements. The compensatory reserve (CRM) is the measurement of this capacity. Measurements of muscle oxygen saturation (SmO2), blood lactate and end tidal CO2 (EtCO2) have recently gained attention as prognostic tools for early assessment of the status of patients with progressive hemorrhage, but lack the ability to adequately differentiate individual tolerance to hypovolemia. We hypothesized that the CRM would better predict hemodynamic decompensation and provide greater specificity and sensitivity than metabolic measures. To test this hypothesis, we employed lower body negative pressure (LBNP) on healthy human subjects until symptoms of presyncope were evident. Receiver operating characteristic area under the curve (ROC AUC), sensitivity and specificity were used to evaluate the ability of CRM, pO2, pCO2, SmO2, lactate, EtCO2, pH, base excess and hematocrit (Hct) to predict hemodynamic decompensation. The ROC AUC for CRM (0.94) had a superior ability to predict decompensation compared to pO2 (0.85), pCO2 (0.62), SmO2 (0.72), lactate (0.57), EtCO2 (0.74), pH (0.55), base excess (0.59), and Hct (0.67). Similarly, CRM also exhibited the greatest sensitivity and specificity. These findings support the notion that CRM provides superior detection of hemodynamic compensation compared to commonly used clinical metabolic measures.

Prehospital Lactate Predicts Need for Resuscitative Care in Non-hypotensive Trauma Patients.

St John AE, McCoy AM, Moyes AG, Guyette FX, Bulger EM, Sayre MR

West J Emerg Med. 2018 Mar;19(2):224-231

Introduction: The prehospital decision of whether to triage a patient to a trauma center can be difficult. Traditional decision rules are based heavily on vital sign abnormalities, which are insensitive in predicting severe injury. Prehospital lactate (PLac) measurement could better inform the triage decision. PLac's predictive value has previously been demonstrated in hypotensive trauma patients but not in a broader population of normotensive trauma patients transported by an advanced life support (ALS) unit.

Methods: This was a secondary analysis from a prospective cohort study of all trauma patients transported by ALS units over a 14-month period. We included patients who received intravenous access and were transported to a Level I trauma center. Patients with a prehospital systolic blood pressure ≤ 100 mmHg were excluded. We measured PLac's ability to predict the need for resuscitative care (RC) and compared it to that of the shock index (SI). The need for RC was defined as either death in the emergency department (ED), disposition to surgical intervention within six hours of ED arrival, or receipt of five units of blood within six hours. We calculated the risk associated with categories of PLac.

Results: Among 314 normotensive trauma patients, the area under the receiver operator characteristic curve for PLac predicting need for RC was 0.716, which did not differ from that for SI (0.631) (p=0.125). PLac ≥ 2.5 mmol/L had a sensitivity of 74.6% and a specificity of 53.4%. The odds ratio for need for RC associated with a 1-mmol/L increase in PLac was 1.29 (95% confidence interval [CI] [0.40 - 4.12]) for PLac < 2.5 mmol/L; 2.27 (1.10 - 4.68) for PLac from 2.5 to 4.0 mmol/L; and 1.26 (1.05 - 1.50) for PLac ≥ 4 mmol/L.

Conclusion: PLac was predictive of need for RC among normotensive trauma patients. It was no more predictive than SI, but it has certain advantages and disadvantages compared to SI and could still be useful. Prospective validation of existing triage decision rules augmented by PLac should be investigated.

Early identification of patients requiring massive transfusion, embolization or hemostatic surgery for traumatic hemorrhage: A systematic review and meta-analysis.

Tran A, Matar M, Lampron J, Steyerberg E, Taljaard M, Vaillancourt C.

J Trauma Acute Care Surg. 2018 Mar;84(3):505-516

BACKGROUND: Delays in appropriate triage of bleeding trauma patients result in poor outcomes. Clinical gestalt is fallible and objective measures of risk stratification are needed. The objective of this review is to identify and assess prediction models and predictors for the early identification of traumatic hemorrhage patients requiring massive transfusion, surgery, or embolization.

METHODS: We searched electronic databases through to September 31, 2016, for studies describing clinical, laboratory, and imaging predictors available within the first hour of resuscitation for identifying patients requiring major intervention for hemorrhage within the first 24 hours.

RESULTS: We included 84 studies describing any predictor-outcome association, including 47 multivariable models; of these, 26 (55%) were specifically designed for prediction. We identified 35 distinct predictors of which systolic blood pressure, age, heart rate, and mechanism of injury were most frequently studied. Quality of multivariable models was generally poor with only 21 (45%) meeting a commonly recommended sample size threshold of 10 events per predictor. From 21 models meeting this threshold, we identified seven predictors that were examined in at least two models: mechanism of injury, systolic blood pressure, heart rate, hemoglobin, lactate, and focussed abdominal sonography for trauma. Pooled odds ratios were obtained from random-effects meta-analyses.

CONCLUSION: The majority of traumatic hemorrhagic prediction studies are of poor quality, as assessed by the Prognosis Research Strategy recommendations and Critical Appraisal and Data Extraction for Systematic Reviews of Modeling Studies checklist. There exists a need for a well-designed clinical prediction model for early identification of patients requiring intervention. The variables of clinical importance identified in this review are consistent with recent expert guideline recommendations and may serve as candidates for future derivation studies.

Permissive hypotension versus conventional resuscitation strategies in adult trauma patients with hemorrhagic shock: A systematic review and meta-analysis of  randomized controlled trials.

Tran A, Yates J, Lau A, Lampron J, Matar M.

J Trauma Acute Care Surg. 2018 May;84(5):802-808

BACKGROUND: Aggressive fluid resuscitation in trauma promotes deleterious effects such as clot disruption, dilutional coagulopathy and hypothermia. Animal studies suggest that permissive hypotension maintains appropriate organ perfusion, reduces bleeding and improves mortality. This review assesses the efficacy and safety of permissive hypotension in adult trauma patients with hemorrhagic shock.

METHODS: We searched the MEDLINE and EMBASE databases from inception to May 2017 for randomized controlled trials comparing permissive hypotension vs. conventional resuscitation following traumatic injury. We included preoperative and intraoperative resuscitation strategies. The primary outcome was 30-day or in-hospital mortality. Secondary outcomes included blood product utilization, estimated blood loss and in-hospital complications. Pooling was performed with a random-effects model.

RESULTS: We screened 722 abstracts, from which five randomized trials evaluating 1,158 patients were included. Blood pressure targets in the intervention arms varied from systolic BP 50 mm Hg to 70 mm Hg or mean arterial pressure of 50 mm Hg or higher as compared to systolic BP 65 mm Hg to 100 mm Hg or mean arterial pressure of 65 or higher in the control arms. Two studies evaluated only patients with penetrating injury while the remaining three additionally included blunt injuries. Four trials suggested a survival benefit for 30-day or in-hospital mortality with hypotensive resuscitation, although three studies were insufficiently powered to find statistical significance. Studies were of poor to moderate quality due to poor protocol reporting and lack of blinding. The pooled odds ratio was 0.70 (95% confidence interval, 0.53-0.92), suggesting a survival benefit for permissive hypotension. Those patients received fewer blood products and had lesser estimated blood loss.

CONCLUSION: Permissive hypotension may offer a survival benefit over conventional resuscitation for patients with hemorrhagic injury. It may additionally reduce blood loss and blood product utilization. However, the majority of studies were underpowered, thus reflecting a need for high quality, adequately powered trials.

PROSPERO REGISTRATION: Systematic Review, level II.CRD42017070526.

Trauma hemostasis and oxygenation research network position paper on the role of hypotensive resuscitation as part of remote damage control resuscitation.

Woolley T, Thompson P, Kirkman E, et al:

J Trauma Acute Care Surg 2018;Epub ahead of print.

The Trauma Hemostasis and Oxygenation Research (THOR) Network has developed a consensus statement on the role of permissive hypotension in remote damage control resuscitation (RDCR).A summary of the evidence on permissive hypotension follows the THOR Network position on the topic. In RDCR, the burden of time in the care of the patients suffering from noncompressible hemorrhage affects outcomes  .Despite the lack of published evidence, and based on clinical experience and expertise, it is the THOR Network’s opinion that the increase in prehospital time leads to an increased burden of shock, which poses a greater risk to the patient than the risk of rebleeding due to slightly increased blood pressure, especially when blood products are available as part of prehospital resuscitation. The THOR Network’s consensus statement is, “In a Casualty with life-threatening hemorrhage, shock should be reversed as soon as possible using a blood-based HR fluid. Whole blood is preferred to blood components.  As a part of this HR , the initial systolic blood pressure target should be 100mm Hg.  In RDCR, it is vital for higher echelon care providers to receive a casualty with sufficient physiologic reserve to survive definitive surgical hemostasis and aggressive resuscitation. The combined use of blood-based resuscitation and limiting systolic blood pressure is believed to be effective in promoting hemostasis and reversing shock.”

BLOOD / BLOOD PRODUCTS

The effect of blood transfusion on compensatory reserve: A prospective clinical trial.

Benov A, Yaslowitz O, Hakim T, Amir-Keret R, Nadler R, Brand A, Glassberg E,

Yitzhak A, Convertino VA, Paran H.

J Trauma Acute Care Surg. 2017 Jul;83(1 Suppl 1):S71-S76

BACKGROUND: Bleeding activates the body's compensatory mechanisms, causing changes in vital signs to appear late in the course of progressive blood loss. These vital signs are maintained even when up to 30% to 40% of blood volume is lost. Laboratory tests such as hemoglobin, hematocrit, lactate, and base deficit levels do not change during acute phase of bleeding. The compensatory reserve measurement (CRM) represents a new paradigm that measures the total of all physiological compensatory mechanisms, using noninvasive photoplethysmography to read changes in arterial waveforms. This study compared CRM to traditional vital signs and laboratory tests in actively bleeding patients.

METHODS: Study patients had gastrointestinal bleeding and required red blood cell (RBC) transfusion (n = 31). Control group patients had similar demographic and medical backgrounds. They were undergoing minor surgical procedures and not expected to receive RBC transfusion. Vital signs, mean arterial pressure, pulse pressure, hemoglobin and hematocrit levels, and CRM were recorded before and after RBC transfusion or the appropriate time interval for the control group. Receiver operator characteristic curves were plotted and areas under the curves (AUCs) were compared.

RESULTS: CRM increased 10.5% after RBC transfusion, from 0.77 to 0.85 (p < 0.005). Hemoglobin level increased 22.4% after RBC transfusion from 7.3 to 8.7 (p < 0.005). Systolic and diastolic blood pressure, mean arterial pressure, pulse pressure, and heart rate did change significantly. The AUC for CRM as a single measurement for predicting hemorrhage at admission was 0.79, systolic blood pressure was 0.62, for heart rate was 0.60, and pulse pressure was 0.36.

CONCLUSIONS: This study demonstrated that CRM is more sensitive to changes in blood volume than traditional vital signs are and could be used to monitor and assess resuscitation of actively bleeding patients.

LEVEL OF EVIDENCE: Care management, level II.

The evolution of pediatric transfusion practice during combat operations 2001-2013.

Cannon JW, Neff LP, Pidcoke HF, Aden JK, Spinella PC, Johnson MA, Cap AP, Borgman MA

J Trauma Acute Care Surg. 2018 Mar 16. Epub ahead of print

BACKGROUND: Hemostatic resuscitation principles have significantly changed adult trauma resuscitation over the past decade. Practice patterns in pediatric resuscitation likely have changed as well; however, this evolution has not been quantified. We evaluated pediatric resuscitation practices over time within a combat trauma system.

METHODS: The Department of Defense Trauma Registry (DoDTR) was queried from 2001-2013 for pediatric patients (<18 years). Patients with burns, drowning, and missing injury severity score (ISS) were excluded. Volumes of crystalloid, packed red blood cells (PRBC), whole blood (WB), plasma (PLAS), and platelets (PLT) given in the first 24 hours were calculated per kg body weight. Tranexamic acid (TXA) use was also determined. Patients were divided into EARLY (2001-2005) and LATE (2006-2013) cohorts, and subgroups of transfused (TX+) and massively transfused (MT+) patients were created. ICU and hospital length of stay (LOS) and 24-hour and in-hospital mortality were compared.

RESULTS: 4,358 patients met inclusion criteria. Comparing EARLY vs. LATE, injuries from explosions, isolated or predominant head injuries, and ISS all increased. The proportion of TX+ patients also increased significantly (13.6% vs. 37.4%, p<0.001) as did the number of MT+ patients (2.1% vs. 15.5%, p<0.001). Transfusion of high PLAS:RBC and PLT:RBC ratios increased in both the TX+ and MT+ subgroups, although overall PLT and WB use was low. After adjusting for differences between groups, the odds of death was no different EARLY vs. LATE but decreased significantly in the MT+ patients with time as a continuous variable.

CONCLUSION: Transfusion practice in pediatric combat casualty care shifted towards a more hemostatic approach over time. All-cause mortality was low and remained stable overall and even decreased in MT+ patients despite more injuries due to explosions, more head injuries and greater injury severity. However, further study is required to determine the optimal resuscitation practices in critically injured children.

LEVEL OF EVIDENCE: Epidemiologic study, level IV.

"Immediate effects of blood donation on physical and cognitive performance – A randomized controlled double blinded trial".

Eliassen HS, Hervig T, Backlund S, Sivertsen J, Iversen VV, Kristoffersen M, Wengaard E, Gramstad A, Fosse T, Bjerkvig CK, Apelseth T, Doughty H, Strandenes G

J Trauma Acute Care Surg. 2018 Mar 22. Epub ahead of print

BACKGROUND: The success of implementing Damage Control Resuscitation principles pre-hospital has been at the expense of several logistic burdens including the requirements for resupply, and the question of donor safety during the development of whole blood programs. Previous studies have reported effects on physical performance after blood donation, however none have investigated the effects of blood donation on cognitive performance.

METHOD: We describe a prospective double blinded, randomized controlled study comprised of a battery of tests: three cognitive tests, and VO2max testing on a cycle ergometer. Testing was performed 7 days before blinded donation (Baseline day), immediately after donation (Day 0), and 7 days (Day 7) after donation. The inclusion criteria included being active blood donors at the Haukeland University Hospital blood bank where eligibility requirements were met on the testing days and providing informed consent. Participants were randomized to either the experimental (n=26) or control group (n=31). Control group participants underwent a 'mock donation" in which a phlebotomy needle was placed but blood was not withdrawn.

RESULTS: In the experimental group, mean VO2max declined 6% from 41.35 +/-1.7 /(min.kg) at baseline to 39.0 +/-1.6 /(min.kg) on Day 0, and increased to 40.51 +/-1.5 /(min.kg) on Day 7. Comparable values in the control group were 42.1 +/-1.8 /(min.kg) at baseline, 41.6 +/-1.8 /(min.kg) on Day 1 (1% decline from basline), and 41.8 +/-1.8 /(min.kg) on Day 7.Comparing scores of all three cognitive tests on Day 0 and Day 7 showed no significant differences, p>0.05.

CONCLUSION: Our main findings are that executive cognitive and physical performance were well-maintained after whole blood donation in healthy blood donors. The findings inform post-donation guidance on when donors may be required to return to duty.

 

Massive transfusions for critical bleeding: is everything old new again?

Flint AWJ, McQuilten ZK, Wood EM

Transfus Med. 2018 Apr;28(2):140-149

Massive transfusion or major haemorrhage protocols have been widely adopted in the treatment of critically bleeding patients. Following evidence that higher ratios of transfused plasma and platelets to red blood cells may offer survival benefits in military trauma patients, these ratios are now commonly incorporated into massive transfusion protocols. They more closely resemble the effects of whole blood transfusion, which in the second half of last century was largely replaced by individual blood component transfusion based on laboratory-guided indicators. However, high-quality evidence to guide transfusion support for critically bleeding patients across the range of bleeding contexts is lacking, including for both trauma and non-trauma patients. More data on major haemorrhage support and clinical outcomes are needed to inform guidelines and practice.

Blood transfusion management in the severely bleeding military patient.

Gurney JM, Spinella PC

Curr Opin Anaesthesiol. 2018 Apr;31(2):207-214

PURPOSE OF REVIEW: Hemorrhage remains the primary cause of preventable death on the battlefield and in civilian trauma. Hemorrhage control is multifactorial and starts with point-of-injury care. Surgical hemorrhage control and time from injury to surgery is paramount; however, interventions in the prehospital environment and perioperative period affect outcomes. The purpose of this review is to understand concepts and strategies for successful management of the bleeding military patient. Understanding the life-threatening nature of coagulopathy of trauma and implementing strategies aimed at full spectrum hemorrhage management from point of injury to postoperative care will result in improved outcomes in patients with life-threatening bleeding.

RECENT FINDINGS: Timely and appropriate therapies impact survival. Blood product resuscitation for life-threatening hemorrhage should either be with whole blood or a component therapy strategy that recapitulates the functionality of whole blood. The US military has transfused over 10 000 units of whole blood since the beginning of the wars in Iraq and Afghanistan. The well recognized therapeutic benefits of whole blood have pushed this therapy far forward into prehospital care in both US and international military forces. Multiple hemostatic adjuncts are available that are likely beneficial to the bleeding military patient; and other products and techniques are under active investigation.

SUMMARY: Lessons learned in the treatment of combat casualties will likely continue to have positive impact and influence and the management of hemorrhage in the civilian trauma setting.

Pre-hospital Low Titer Cold Stored Whole Blood: Philosophy for Ubiquitous Utilization of O Positive Product for Emergency Use in Hemorrhage due to Injury.

McGinity AC, Zhu CS, Greebon L, Xenakis E, Waltman E, Epley E, Cobb D, Jonas R, Nicholson SE, Eastridge BJ, Stewart RM, Jenkins DH

J Trauma Acute Care Surg. 2018 Mar 16 Epub ahead of print

The mortality from hemorrhage in trauma patients remains high. Early balanced resuscitation improves survival. These truths, balanced with the availability of local resources and our goals for positive regional impact, were the foundation for the development of our pre-hospital whole blood initiative-using low titer cold stored O RhD positive whole blood (LTOWB). The main concern with use of RhD positive blood is the potential development of isoimmunization in RhD negative patients. We used our retrospective massive transfusion protocol (MTP) data to analyze the anticipated risk of this change in practice. In 30 months, out of 124 total MTP patients, only one female of childbearing age that received an MTP was RhD negative. With the risk of isoimmunization very low and the benefit of increased resources for the early administration of balanced resuscitation high, we determined that utilization of LTOWB would be safe and best serve our community.

Red Tides: Mass casualty and whole blood at sea Red Tides.

Miller BT, Lin AH, Clark SC, Cap AP, Dubose JJ

J Trauma Acute Care Surg. 2018 Feb 13 Epub ahead of print

BACKGROUND: The U.S. Navy's casualty-receiving ships provide remote damage control resuscitation (RDCR) platforms to treat injured combatants deployed afloat and ashore. We report a significant mass casualty incident aboard the USS Bataan, and the most warm fresh whole blood (WFWB) transfused at sea for traumatic hemorrhagic shock since the Vietnam War.

METHODS: Casualty-receiving ships have robust medical capabilities, including a frozen blood bank with packed red blood cells (pRBC) and fresh frozen plasma (FFP). The blood supply can be augmented with WFWB collected from a "walking blood bank" (WBB).

RESULTS: Following a helicopter crash, six patients were transported by MV-22 Osprey to the USS Bataan. Patient 1 had a pelvic fracture, was managed with a pelvic binder, and received 4 units of pRBC, 2 units of FFP, and 6 units of WFWB. Patient 2, with a comminuted tibia and fibula fracture, underwent lower extremity four-compartment fasciotomy, and received 4 units of WFWB. Patient 3 underwent several procedures, including left anterior thoracotomy, aortic cross-clamping, exploratory laparotomy, small bowel resection, and tracheostomy. He received 8 units of pRBC, 8 units of FFP, and 28 units of WFWB. Patients 4 and 5 had suspected spine injuries and were managed non-operatively. Patient 6, with open tibia and fibula fractures, underwent lower extremity four-compartment fasciotomy with tibia external fixation and received 1 unit of WFWB. All patients survived aeromedical evacuation to a Role 4 medical facility and subsequent transfer to local hospitals.

DISCUSSION: Maritime military mass casualty incidents are challenging, but the U.S. Navy's casualty-receiving ships are ready to perform RDCR at sea. Activation of the ship's WBB to transfuse WFWB is essential for hemostatic resuscitations afloat.

LEVEL OF EVIDENCE: V STUDY TYPE: Case series.

Use of French lyophilized plasma transfusion in severe trauma patients is associated with an early plasma transfusion and early transfusion ratio improvement.

Nguyen C, Bordes J, Cungi PJ, Esnault P, Cardinale M, Mathais Q, Cotte J, Beaume S, Sailliol A, Prunet B, Meaudre E.

J Trauma Acute Care Surg. 2018 May;84(5):780-785

BACKGROUND: Early transfusion of high ratio of fresh frozen plasma (FFP) and red blood cells (RBC) is associated with mortality reduction. However, time to reach high ratio is limited by the need to thaw the FFP. French lyophilized plasma (FLYP) used by French army and available in military teaching hospital does not need to be thawed and is immediately available. We hypothesize that the use of FLYP may reduce time to reach a plasma/RBC ratio of 1:1.

METHODS: A retrospective study performed in a Level 1 trauma center between January 2012 and December 2015. Severe trauma patients who received 2 U of RBC in the emergency room were included and assigned to two groups according to first plasma transfused: FLYP group and FFP group.

RESULTS: Forty-three severe trauma patients in the FLYP group and 29 in the FFP group were included. The time until first plasma transfusion was shorter in the FLYP group than in the FFP group, respectively 15 min (10-25) versus 95 min (70-145) (p < 0.0001). Time until a 1:1 ratio was shorter in the FLYP group than in the FFP group. There were significantly fewer cases of massive transfusion in the FLYP group than in the FFP group with respectively 7% vs. 45% (p < 0.0001).

CONCLUSION: The use of FLYP provided significantly faster plasma transfusions than the use of FFP as well as a plasma and RBC ratio superior to 1:2 that was reached more rapidly in severe trauma patients. These results may explain the less frequent need for massive transfusion in the patients who received FLYP. These positive results should be confirmed by a prospective and randomized evaluation.

LEVEL OF EVIDENCE: Therapeutic, level IV.

Multicenter study of crystalloid boluses and transfusion in pediatric trauma-when to go to blood?

Polites SF, Nygaard RM, Reddy PN, Zielinski MD, Richardson CJ, Elsbernd TA, Petrun BM, Weinberg SL, Murphy S, Potter DD, Klinkner DB, Moir CR.

J Trauma Acute Care Surg. 2018 Mar 12

BACKGROUND: The 9th edition of ATLS recommends up to three crystalloid boluses in pediatric trauma patients with consideration of transfusion after the second bolus however this approach is debated. We aimed to determine if requirement of more than one fluid bolus predicts the need for transfusion.

METHODS: 2010-2016 highest tier activation patients <15 years of age from two ACS Level I pediatric trauma centers were identified from prospectively maintained trauma databases. Those with a shock index (heart rate/systolic blood pressure) >0.9 were included. Crystalloid boluses (20±10 cc/kg) and transfusions administered prehospital and within 12 hours of hospital arrival were determined. Univariate and multivariable analyses were conducted to determine association between crystalloid volume and transfusion.

RESULTS: Among 208 patients, the mean age was 5±4 years (60% male), 91% sustained blunt injuries, and median (IQR) ISS was 11 (6,25). 29% received one bolus, 17% received two, and 10% received at least three. Transfusion of any blood product occurred in 50 (24%) patients; mean (range) RBC was 23 (0-89) cc/kg, plasma 8 (0-69), and platelets 1 (0,18). The likelihood of transfusion increased logarithmically from 11% to 43% for those requiring ≥2 boluses (Figure 1). This relationship persisted on multivariable analysis that adjusted for institution, age, and shock index with good discrimination (AUROC 0.84). Shock index was also strongly associated with transfusion.

CONCLUSION: Almost half of pediatric trauma patients with elevated shock index require transfusion following two crystalloid boluses and the odds of requiring a transfusion plateau at this point in resuscitation. This supports consideration of blood with the second bolus in conjunction with shock index though prospective studies are needed to confirm this and its impact on outcomes.

LEVEL OF EVIDENCE: III: Therapeutic.

Military Prehospital Use of Low Titer Group O Whole Blood.

Warner N, Zheng J, Nix G, Fisher AD, Johnson JC, Williams JE, Northern DM, Hellums JS.

J Spec Oper Med. Spring 2018;18(1):15-18.

The military's use of whole-blood transfusions is not new but has recently received new emphasis by the Tactical Combat Casualty Care Committee. US Army units are implementing a systematic approach to obtain and use whole blood on the battlefield. This case report reviews the care of the first patient to receive low titer group O whole blood (LTOWB) transfusion, using a new protocol.

FLUID RESUSCITATION

The Association of Prehospital Intravenous Fluids and Mortality in Patients with Penetrating Trauma.

Bores SA, Pajerowski W, Carr BG, Holena D, Meisel ZF, Mechem CC, Band RA

J Emerg Med. 2018 Apr;54(4):487-499

BACKGROUND: The optimal approach to prehospital care of trauma patients is controversial, and thought to require balancing advanced field interventions with rapid transport to definitive care.

OBJECTIVE: We sought principally to examine any association between the amount of prehospital IV fluid (IVF) administered and mortality.

METHODS: We conducted a retrospective cohort analysis of trauma registry data patients who sustained penetrating trauma between January 2008 and February 2011, as identified in the Pennsylvania Trauma Systems Foundation registry with corresponding prehospital records from the Philadelphia Fire Department. Analyses were conducted with logistic regression models and instrumental variable analysis, adjusted for injury severity using scene vital signs before the intervention was delivered.

RESULTS: There were 1966 patients identified. Overall mortality was 22.60%. Approximately two-thirds received fluids and one-third did not. Both cohorts had similar Trauma and Injury Severity Score-predicted mortality. Mortality was similar in those who received IVF (23.43%) and those who did not (21.30%) (p = 0.212). Patients who received IVF had longer mean scene times (10.82 min) than those who did not (9.18 min) (p < 0.0001), although call times were similar in those who received IVF (24.14 min) and those who did not (23.83 min) (p = 0.637). Adjusted analysis of 1722 patients demonstrated no benefit or harm associated with prehospital fluid (odds ratio [OR] 0.905, 95% confidence interval [CI] 0.47-1.75). Instrumental variable analysis utilizing variations in use of IVF across different Emergency Medical Services (EMS) units also found no association between the unit's percentage of patients that were provided fluids and mortality (OR 1.02, 95% CI 0.96-1.08).

CONCLUSIONS: We found no significant difference in mortality or EMS call time between patients who did or did not receive prehospital IVF after penetrating trauma.

Preoperative fluid restriction for trauma patients with hemorrhagic shock decreases ventilator days.

Matsuyama S, Miki R, Kittaka H, Nakayama H, Kikuta S, Ishihara S, Nakayama S

Acute Med Surg. 2018 Feb 12;5(2):154-159

Aim: In recent years, with the concept of damage control resuscitation, hemostasis and preoperative fluid restriction have been carried out, but there is controversy regarding the effectiveness of fluid restriction.

Methods: From April 2007 to March 2013, 101 trauma patients presented with hemorrhagic shock (systolic blood pressure ≤90 mmHg) at the prehospital or emergency department and were admitted to Hyogo Emergency Medical Center (Hyogo, Japan). They underwent emergency hemostasis by surgery and transcatheter arterial embolization. We compared two groups in a historical cohort study, the aggressive fluid resuscitation (AR) group, which included 59 cases treated in the period April 2007-March 2010, and the fluid restriction (FR) group, which included 42 cases treated in the period April 2010-March 2013.

Results: There was no difference between both groups in patient background (heart rate, 110 b.p.m.; systolic blood pressure, 70 mmHg). The Injury Severity Score was 34 (AR) versus 38 (FR) (not significant). Preoperative infusion volume of crystalloid significantly decreased, from 2310 mL (AR) to 1025 mL (FR) (P ≤ 0.01). There was no difference in mortality (36% [AR] versus 41% [FR]). Ventilator days significantly decreased, from 8.5 days (AR) to 5.5 days (FR) (P = 0.02).

Conclusions: Preoperative fluid restriction for trauma patients with hemorrhagic shock did not improve mortality, but it decreased ventilator days by reducing the perioperative plus water balance and it might contribute to perioperative intensive care.

Balanced Crystalloids versus Saline in Critically Ill Adults.

Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD, May AK, Weavind L, Casey JD, Siew ED, Shaw AD, Bernard GR, Rice TW; SMART Investigators and the Pragmatic Critical Care Research Group.

Collaborators: Brown RM, Noto MJ, Lindsell CJ, Domenico HJ, Costello WT, Gibson J, Holcombe EW, Pretorius M, McCall AS, Atchison L, Dunlap DF, Felbinger M, Hamblin SE, Knostman M, Rumbaugh KA, Sullivan M, Valenzuela JY, Young JB, Mulherin DP, Hargrove FR, Strawbridge S.

N Engl J Med. 2018 Mar 1;378(9):829-839

BACKGROUND: Both balanced crystalloids and saline are used for intravenous fluid administration in critically ill adults, but it is not known which results in better clinical outcomes.

METHODS: In a pragmatic, cluster-randomized, multiple-crossover trial conducted in five intensive care units at an academic center, we assigned 15,802 adults to receive saline (0.9% sodium chloride) or balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A) according to the randomization of the unit to which they were admitted. The primary outcome was a major adverse kidney event within 30 days - a composite of death from any cause, new renal-replacement therapy, or persistent renal dysfunction (defined as an elevation of the creatinine level to  ≥200% of baseline) - all censored at hospital discharge or 30 days, whichever occurred first.

RESULTS: Among the 7942 patients in the balanced-crystalloids group, 1139 (14.3%) had a major adverse kidney event, as compared with 1211 of 7860 patients (15.4%) in the saline group (marginal odds ratio, 0.91; 95% confidence interval [CI], 0.84 to 0.99; conditional odds ratio, 0.90; 95% CI, 0.82 to 0.99; P=0.04). In-hospital mortality at 30 days was 10.3% in the balanced-crystalloids group and 11.1% in the saline group (P=0.06). The incidence of new renal-replacement therapy was 2.5% and 2.9%, respectively (P=0.08), and the incidence of persistent renal dysfunction was 6.4% and 6.6%, respectively (P=0.60).

CONCLUSIONS: Among critically ill adults, the use of balanced crystalloids for intravenous fluid administration resulted in a lower rate of the composite outcome of death from any cause, new renal-replacement therapy, or persistent renal dysfunction than the use of saline. (Funded by the Vanderbilt Institute for Clinical and Translational Research and others; SMART-MED and SMART-SURG ClinicalTrials.gov numbers, NCT02444988 and NCT02547779 .).