Blood Resuscitation Research Articles

Whole Blood, Fixed Ratio, or Goal-Directed Blood Component Therapy for the Initial Resuscitation of Severely Hemorrhaging Trauma Patients: A Narrative Review.

This narrative review explores the pathophysiology, geographic variation, and historical developments underlying the selection of fixed ratio versus whole blood resuscitation for hemorrhaging trauma patients. We also detail a physiologically driven and goal-directed alternative to fixed ratio and whole blood, whereby viscoelastic testing guides the administration of blood components and factor concentrates to the severely bleeding trauma patient. The major studies of each resuscitation method are highlighted, and upcoming comparative trials are detailed.

Back to the Future: Whole Blood Resuscitation of the Severely Injured Trauma Patient.

ABSTRACTFollowing advances in blood typing and storage, whole blood transfusion became available for the treatment of casualties during World War I. While substantially utilized during World War II and the Korean War, whole blood transfusion declined during the Vietnam War as civilian centers transitioned to blood component therapies. Little evidence supported this shift, and recent conflicts in Iraq and Afghanistan have renewed interest in military and civilian applications of whole blood transfusion. Within the past two decades, civilian trauma centers have begun to study transfusion protocols based upon cold-stored, low anti-A/B titer type O whole blood for the treatment of severely injured civilian trauma patients. Early data suggests equivalent or improved resuscitation and hemostatic markers with whole blood transfusion when compared to balanced blood component therapy. Additional studies are taking place to define the optimal way to utilize low-titer type O whole blood in both prehospital and trauma center resuscitation of bleeding patients.

Prehospital Whole Blood Resuscitation Reduces Fluid Requirement While Maintaining Critical Physiology in a Model of Penetrating Traumatic Brain Injury and Hemorrhage: Implications on Resource-Limited Combat Casualty Care.

Prehospital resuscitation using whole blood (WB) is the standard of care for hemorrhagic shock (HS) but there is no consensus recommendation for resuscitation in the presence of traumatic brain injury (TBI) due to a lack of sufficient evidence. In order to evaluate the optimal resuscitation strategies for TBI+HS, Sprague-Dawley rats were randomized into four groups based on resuscitation fluid and prehospital mean arterial pressure (MAP) threshold (n = 9-10/group): Lactated Ringer's (LR)-60 mm Hg (LR60), LR-70 mm Hg (LR70), WB-60 mm Hg (WB60), WB-70 mm Hg (WB70). All groups received a frontal penetrating ballistic-like brain injury followed by a 35-min period of HS. During the prehospital phase, rats received an initial bolus of resuscitation fluid (WB or LR) followed by LR as needed to maintain MAP above the designated threshold for 90 min. During the in-hospital phase, rats received definitive resuscitation with shed WB. Physiological parameters were recorded continuously and cerebral edema was measured at 3 and 24 h postinjury. The WB60 group demonstrated a significantly lower prehospital fluid requirement compared WB70, LR60, and LR70 (P < 0.05). Compared to the respective LR groups, both the WB60 and WB70 groups also demonstrated improved MAP, cerebral perfusion pressure, brain tissue oxygen tension, and cerebral edema. The edema benefits were observed at 3 h, but not 24 h postinjury, and were localized to the injury site. Together, these results provide evidence that prehospital WB resuscitation and lower MAP resuscitation thresholds can reduce the prehospital fluid requirement while still maintaining critical cerebral physiology in a model of HS and concomitant TBI.

Multifaceted Benefit of Whole Blood Versus Lactated Ringer's Resuscitation After Traumatic Brain Injury and Hemorrhagic Shock in Mice.

Despite increasing use in hemorrhagic shock (HS), whole blood (WB) resuscitation for polytrauma with traumatic brain injury (TBI) is largely unexplored. Current TBI guidelines recommend crystalloid for prehospital resuscitation. Although WB outperforms lactated Ringer's (LR) in increasing mean arterial pressure (MAP) in TBI + HS models, effects on brain tissue oxygenation (PbtO2), and optimal MAP remain undefined. C57BL/6 mice (n = 72) underwent controlled cortical impact followed by HS (MAP = 25-27mmHg). Ipsilateral hippocampal PbtO2 (n = 40) was measured by microelectrode. Mice were assigned to four groups (n = 18/group) for "prehospital" resuscitation (90min) with LR or autologous WB, and target MAPs of 60 or 70mmHg (LR60, WB60, LR70, WB70). Additional LR (10ml/kg) was bolused every 5min for MAP below target. LR requirements in WB60 (7.2 ± 5.0mL/kg) and WB70 (28.3 ± 9.6mL/kg) were markedly lower than in LR60 (132.8 ± 5.8mL/kg) or LR70 (152.2 ± 4.8mL/kg; all p < 0.001). WB70 MAP (72.5 ± 2.9mmHg) was higher than LR70 (59.8 ± 4.0mmHg, p < 0.001). WB60 MAP (68.7 ± 4.6mmHg) was higher than LR60 (53.5 ± 3.2mmHg, p < 0.001). PbtO2 was higher in WB60 (43.8 ± 11.6mmHg) vs either LR60 (25.9 ± 13.0mmHg, p = 0.04) or LR70 (24.1 ± 8.1mmHg, p = 0.001). PbtO2 in WB70 (40.7 ± 8.8mmHg) was higher than in LR70 (p = 0.007). Despite higher MAP in WB70 vs WB60 (p = .002), PbtO2 was similar. WB resuscitation after TBI + HS results in robust improvements in brain oxygenation while minimizing fluid volume when compared to standard LR resuscitation. WB resuscitation may allow for a lower prehospital MAP without compromising brain oxygenation when compared to LR resuscitation. Further studies evaluating the effects of these physiologic benefits on outcome after TBI with HS are warranted, to eventually inform clinical trials.

Low titer group O whole blood resuscitation: Military experience from the point of injury.

In the far forward combat environment, the use of whole blood is recommended for the treatment of hemorrhagic shock after injury. In 2016, US military special operations teams began receiving low titer group O whole blood (LTOWB) for use at the point of injury (POI). This is a case series of the initial 15 patients who received LTOWB on the battlefield. Patients were identified in the Department of Defense Trauma Registry, and charts were abstracted for age, sex, nationality, mechanism of injury, injuries and physiologic criteria that triggered the transfusion, treatments at the POI, blood products received at the POI and the damage-control procedures done by the first surgical team, next level of care, initial interventions by the second surgical team, Injury Severity Score, and 30-day survival. Descriptive statistics were used to characterize the clinical data when appropriate. Of the 15 casualties, the mean age was 28, 50% were US military, and 63% were gunshot wounds. Thirteen patients survived to discharge, one died of wounds after arrival at the initial resuscitative surgical care, and two died prehospital. The mean Injury Severity Score was 21.31 (SD, 18.93). Eleven (68%) of the causalities received additional blood products during evacuation/role 2 and/or role 3. Vital signs were available for 10 patients from the prehospital setting and 9 patients upon arrival at the first surgical capable facility. The mean systolic blood pressure was 80.5 prehospital and 117 mm Hg (p = 0.0002) at the first surgical facility. The mean heart rate was 105 beats per minute prehospital and 87.4 beats per minute (p = 0.075) at the first surgical facility. The mean hospital stay was 24 days. The use of cold-stored LTOWB at POI is feasible during combat operations. Further data are needed to validate and inform best practice for POI transfusion. Therapeutic study, level V.

Nationwide analysis of whole blood hemostatic resuscitation in civilian trauma.

Renewed interest in whole blood (WB) resuscitation in civilians has emerged following its military use. There is a paucity of data on its role in civilians where balanced component therapy (CT) resuscitation is the standard of care. The aim of this study was to assess nationwide outcomes of using WB as an adjunct to CT versus CT alone in resuscitating civilian trauma patients. We analyzed the (2015-2016) Trauma Quality Improvement Program. We included adult (age, ≥18 years) trauma patients presenting with hemorrhagic shock and requiring at least 1 U of packed red blood cells (pRBCs) within 4 hours. Patients were stratified into WB-CT versus CT only. Primary outcomes were 24-hour and in-hospital mortality. Secondary outcomes were hospital length of stay and major complications. Hierarchical logistic regression was performed to account for clustering effect within hospitals and adjusting for patient- and hospital-level potential confounding factors. A total of 8,494 patients were identified, of which 280 received WB-CT (WB, 1 [1-1]; pRBC, 16 [10-23]; FFP, 9 [6-16]; platelets, 3 [2-5]) and 8,214 received CT only (pRBC, 15 [10-24]; FFP, 10 [6-16]; platelets, 2 [1-4]). Mean ± SD age was 34 ± 16 years, 79% were male, Injury Severity Score was 33 (24-43), and 63% had penetrating injuries. Patients who received WB-CT had a lower 24-hour mortality (17% vs. 25%; p = 0.002), in-hospital mortality (29% vs. 40%; p < 0.001), major complications (29% vs. 41%; p < 0.001), and a shorter length of stay (9 [7-12] vs. 15 [10-21]; p = 0.011). On regression analysis, WB was independently associated with reduced 24-hour mortality (odds ratio [OR], 0.78 [0.59-0.89]; p = 0.006), in-hospital mortality (OR, 0.88 [0.81-0.90]; p = 0.011), and major complications (OR, 0.92 [0.87-0.96]; p = 0.013). The use of WB as an adjunct to CT is associated with improved outcomes in resuscitation of severely injured civilian trauma patients. Further studies are required to evaluate the role of adding WB to massive transfusion protocols. Therapeutic, level IV.

Resuscitative endovascular balloon occlusion of the aorta for thoracic trauma in the setting of platelet dysfunction: A translational swine study.

In patients with noncompressible torso hemorrhage, antiplatelet medications may lead to worse outcomes. Resuscitative endovascular balloon occlusion of the aorta (REBOA) may potentially stabilize these patients, but currently, major thoracic bleeding is a contraindication. The goal of this study was to determine if REBOA use for shock with major thoracic bleeding has worse outcomes in the setting of platelet dysfunction (PD). Forty-one male Yorkshire swine (60-80 kg) underwent a 30% hemorrhage and then were randomized to three thoracic injuries, with and without zone 1 REBOA occlusion: pulmonary parenchymal injury (PI), thoracic venous injury (VI), or subclavian artery injury (AI). All animals were given aspirin to produce PD. Following hemorrhage, thoracic injuries were induced (T0) and allowed to bleed freely. Resuscitative endovascular balloon occlusion of the aorta groups had zone 1 occlusion, with deflation at T30. All groups received whole blood resuscitation at T30 and were euthanized at T90. Survival, total blood loss, hemodynamics, and arterial blood gas parameters were analyzed. The PD-VI-REBOA group had 87.5% survival where PD-VI survival was 28.6%. No difference in survival was seen in the PI or AI groups. The PD-VI-REBOA group had total blood loss of 575.0 ± 339.1 mL, which was less than the PD-VI group (1,086.0 ± 532.1 mL). There was no difference in total thoracic blood loss in the PI and AI groups with the addition of REBOA. All groups showed an equivalent decrease in HCO3 and base excess and increase in lactate at the end of the 30-minute prehospital phase. In this study, zone 1 REBOA improved survival and decreased blood loss with major VI, where no differences were seen in parenchymal and subclavian artery injuries. For thoracic bleeding without surgical capability, outcomes may be improved with REBOA, and these findings challenge current guidelines stating the contraindication of REBOA use in this setting.

An Inhibitor of the Sodium-Hydrogen Exchanger-1 (NHE-1), Amiloride, Reduced Zinc Accumulation and Hippocampal Neuronal Death after Ischemia.

Acidosis in the brain plays an important role in neuronal injury and is a common feature of several neurological diseases. It has been reported that the sodium–hydrogen exchanger-1 (NHE-1) is a key mediator of acidosis-induced neuronal injury. It modulates the concentration of intra- and extra-cellular sodium and hydrogen ions. During the ischemic state, excessive sodium ions enter neurons and inappropriately activate the sodium–calcium exchanger (NCX). Zinc can also enter neurons through voltage-gated calcium channels and NCX. Here, we tested the hypothesis that zinc enters the intracellular space through NCX and the subsequent zinc accumulation induces neuronal cell death after global cerebral ischemia (GCI). Thus, we conducted the present study to confirm whether inhibition of NHE-1 by amiloride attenuates zinc accumulation and subsequent hippocampus neuronal death following GCI. Mice were subjected to GCI by bilateral common carotid artery (BCCA) occlusion for 30 min, followed by restoration of blood flow and resuscitation. Amiloride (10 mg/kg, intraperitoneally (i.p.)) was immediately injected, which reduced zinc accumulation and neuronal death after GCI. Therefore, the present study demonstrates that amiloride attenuates GCI-induced neuronal injury, likely via the prevention of intracellular zinc accumulation. Consequently, we suggest that amiloride may have a high therapeutic potential for the prevention of GCI-induced neuronal death.

The compensatory reserve: potential for accurate individualized goal-directed whole blood resuscitation.

Hemorrhagic shock can be mitigated by timely and accurate resuscitation designed to restore adequate delivery of oxygen (DO2 ). Current doctrine of using systolic blood pressure (SBP) as a guide for resuscitation can be associated with increased morbidity. The compensatory reserve measurement (CRM) is a novel vital sign based on the recognition that the sum of all mechanisms that contribute to the compensatory response to hemorrhage reside in features of the arterial pulse waveform. CRM can be assessed continuously and non-invasively in real time. Compared to standard vital signs, CRM provides an early, as well as more sensitive and specific, indicator of patient hemorrhagic status since the activation of compensatory mechanisms occurs immediately at the onset of blood loss. Recent data obtained from our laboratory experiments on non-human primates have demonstrated that CRM is linearly related to DO2 during controlled progressive hemorrhage and subsequent whole blood resuscitation. We used this relationship to determine that the time of hemodynamic decompensation (i.e., CRM = 0%) is defined by a critical DO2 at approximately 5.3 mL O2 ∙kg-1 ∙min-1 . We also demonstrated that a target CRM of 35% during whole blood resuscitation only required replacement of 40% of the total blood volume loss to adequately sustain a DO2 more than 50% (i.e., 8.1 mL O2 ∙kg-1 ∙min-1 ) above critical DO2 (i.e., threshold for decompensated shock) while maintaining hypotensive resuscitation (i.e., SBP at ~90 mmHg). Consistent with our hypothesis, specific values of CRM can be used to accurately maintain DO2 thresholds above critical DO2 , avoiding the onset of hemorrhagic shock with whole blood resuscitation.

Whole blood transfusion versus component therapy in trauma resuscitation: a systematic review and meta-analysis.

BackgroundPatients with hemorrhagic shock from trauma often require balanced blood product transfusion with red blood cells, plasma, and platelets. Resuscitation with whole blood resuscitation is becoming a common practice. We performed a systematic review and meta‐analysis of studies comparing whole blood transfusion with balanced component therapy in patients suffering from traumatic hemorrhagic shock.MethodsWe searched MEDLINE Ovid, EMBASE, and the Cochrane Library for human studies comparing whole blood with component blood therapy published from January 2007 to June 2019. We included studies from both civilian and military settings and that reported 24‐hour, in‐hospital, or 30‐day mortality. We followed the Preferred Reporting Items in Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, assessing study quality, publication bias, and heterogeneity. We used meta‐analytic models to determine the associations (odds ratio [OR] with 95% confidence interval [CI]) between whole blood transfusion and (1) 24‐hour mortality, and (2) in‐hospital or 30‐day mortality.ResultsA total of 1759 identified studies, 12 (reporting on n = 8431 patients) met inclusion criteria. There was heterogeneity in the design, setting, interventions, and outcomes of the studies. On meta‐analysis, whole blood transfusion was not associated with 24‐hour mortality (OR = 0.83; 95% CI = 0.56–1.24) or in‐hospital/30‐day mortality (OR = 0.79; 95% CI = 0.48–1.31).ConclusionIn this systematic review and meta‐analysis, compared with conventional component transfusion, whole blood was not associated with 24‐hour or in‐hospital mortality. However, there were important limitations with and heterogeneity among the primary studies. Additional study is needed to determine the effectiveness of whole blood.

The Mechanisms of Glutamine- and Fish Oil-Supplemented Resuscitation Fluids on Alleviating Oxidative Stress of the Lung and Liver in Rats with Trauma-Hemorrhagic Shock

Abstract Objectives Oxidative stress has been demonstrated to be the cause of cellular and organ damage in patients with trauma hemorrhagic shock and reperfusion (THR). Our previous study showed that resuscitation fluids supplemented with glutamine and fish oil, the antioxidants with anti-inflammatory activities, may alleviate systemic inflammatory response and oxidative stress in the THR rats. The aim of this study was to further investigate the mechanisms of these supplements on alleviating THR-induced damage in the lung and liver, i.e., the 2 vulnerable organs in THR. Methods Male Wistar rats were suffered with 5 cm midline laparotomy and 2 catheterizations in the left carotid artery and right jugular vein individually for blood drawn to a mean arterial pressure 30 to 35 mmHg for 60 minutes and for resuscitation of shed blood and lactate Ringer's solution with or without L-alanyl-L-glutamine (13.5 mmole/kg/day) and/or fish oil (0.5 g/kg/day) within 10 minutes. The different resuscitation fluids were continuous infused (∼1.4 ml/h) for 42 hr. Normal healthy rats and intubation sham-operated rats were included as controls. Results In the lung, the THR-increased lipid peroxidation and toll-like receptor 4 (TLR4) were significantly decreased by glutamine with or without fish oil (one-way ANOVA, P &amp;lt; 0.05). Fish oil was the main factor to decrease myeloperoxidase and activated caspase 3 in the lung of the THR rats (two-way ANOVA, P &amp;lt; 0.05). In the liver, the THR-increased lipid peroxidation and TLR4 and the THR-decreased catalase activity were improved by glutamine and/or fish oil. In addition, fish oil was the main factor to decrease inducible and endothelial nitric oxide synthase (NOS) and to increase IkB and phosphorylated NF-kB and glutamine was the main factor to decrease activated caspase 3 in the liver of the THR rats. Conclusions These results suggest that fish oil may alleviate neutrophil infiltration and NOS activation and fish oil and glutamine may elevate catalase activity and alleviate apoptosis to attenuate the THR-induced damage in the lung and liver. Funding Sources MOST 102-2320-B-030-005-MY3.

Association of Taurine with In-Hospital Mortality in Patients after Out-of-Hospital Cardiac Arrest: Results from the Prospective, Observational COMMUNICATE Study.

Background: Studies have suggested that taurine may have neuro- and cardio-protective functions, but there is little research looking at taurine levels in patients after out-of-hospital cardiac arrest (OHCA). Our aim was to evaluate the association of taurine with mortality and neurological deficits in a well-defined cohort of OHCA patients. Methods: We prospectively measured serum taurine concentration in OHCA patients upon admission to the intensive care unit (ICU) of the University Hospital Basel (Switzerland). We analyzed the association of taurine levels and in-hospital mortality (primary endpoint). We further evaluated neurological outcomes assessed by the cerebral performance category scale. We calculated logistic regression analyses and report odds ratios (OR) and 95% confidence intervals (CI). We calculated different predefined multivariable regression models including demographic variables, comorbidities, initial vital signs, initial blood markers and resuscitation measures. We assessed discrimination by means of area under the receiver operating curve (ROC). Results: Of 240 included patients, 130 (54.2%) survived until hospital discharge and 110 (45.8%) had a favorable neurological outcome. Taurine levels were significantly associated with higher in-hospital mortality (adjusted OR 4.12 (95%CI 1.22 to 13.91), p = 0.02). In addition, a significant association between taurine concentration and a poor neurological outcome was observed (adjusted OR of 3.71 (95%CI 1.13 to 12.25), p = 0.03). Area under the curve (AUC) suggested only low discrimination for both endpoints (0.57 and 0.57, respectively). Conclusion: Admission taurine levels are associated with mortality and neurological outcomes in OHCA patients and may help in the risk assessment of this vulnerable population. Further studies are needed to assess whether therapeutic modulation of taurine may improve clinical outcomes after cardiac arrest.

Resuscitative endovascular balloon occlusion of the aorta for thoracic trauma: A translational swine study.

Forty-eight male Yorkshire swine (60-80 kg) underwent 30% hemorrhage and were randomized to three thoracic injuries, with and without zone 1 REBOA occlusion: pulmonary parenchymal injury, thoracic venous injury, or subclavian artery injury. Following hemorrhage, thoracic injuries were induced (time of major thoracic injury) and allowed to bleed freely. The REBOA groups had zone 1 occlusion after the thoracic injury, with deflation at the end of prehospital. All groups had whole blood resuscitation at the end of prehospital and were euthanized at end of the hospital care phase. Survival, total blood loss, mean arterial pressure, end-tidal CO2, and arterial blood gas parameters were analyzed. Statistical significance was determined by t tests and two-way repeated-measures analysis of variance. The use of REBOA improved the hemodynamics in all three injury patterns, with no differences observed in the outcomes of short-term survival and thoracic blood loss between the REBOA and non-REBOA groups. All groups showed equivalent changes in markers of shock (pH, HCO3, and base excess) prior to resuscitation. In this animal study of hemorrhage and major thoracic bleeding, the addition of zone 1 REBOA did not significantly affect short-term survival or blood loss, while providing hemodynamic stabilization. Therefore, in noncompressible thoracic bleeding, without immediate surgical capability, long-term outcomes may be improved with REBOA, and thoracic hemorrhage should not be considered contraindications to REBOA use.

Improved Hemodynamic Stability in Experimental Trauma/Hemorrhagic Shock by Red Blood Cell‐containing Resuscitation Fluids Secondary to Preserved Diastolic Blood Pressure

ObjectiveFluid resuscitation with blood products is standard of care in the current management of trauma/hemorrhagic shock (T/HS). However, the availability of whole blood is rare in civilian prehospital care, and thus blood component therapy and other fluid replacement options are required. This study sought to differentiate and compare the effects of lactated Ringer’s solution (LR), plasma, washed red blood cells (RBC), and whole blood (Control) as resuscitation fluids for hemodynamic restoration after T/HS.MethodsWister male rats (400g) were randomly divided into four groups: LR, Plasma, RBC, and Control, anesthetized with isoflurane and subjected to experimental T/HS. A mid‐line laparotomy incision was made, and blood was slowly withdrawn to maintain a mean arterial blood pressure (MAP) of 35–40 mmHg for 90 minutes. After the 90‐min shock period, intravenous fluids corresponding to the experimental group were started with the goal of achieving a MAP ≥ 65 mmHg, the clinical target for adequate pressure. Animals were monitored for 120 minutes following start of reperfusion. Vital signs were continuously measured, as well as arterial blood gases, lactate, and hemoglobin.ResultsMAP in animals that received RBCs was similar to that of the whole‐blood Control group (70.4 ± 4.0 mmHg vs 83.0 ± 5.8 mmHg, RBC vs Control, NS), and significantly greater than MAPs of Plasma (59.9 ± 4.4 mmHg, p=0.03) and LR (45.6 ± 4.8 mmHg, p&lt;0.001) groups. As systolic blood pressure (SBP) was not significantly different between RBC, Plasma and Control groups, the higher MAP seen in the RBC group compared to Plasma was due to increased diastolic blood pressure (DBP) (55.5 ± 3.1 mmHg vs 38.6 ± 3.2 mmHg, RBC vs Plasma, p=0.01). The RBC and Control groups were able to achieve a higher MAP with decreased volume resuscitation percentage (RBC: 50.7 ± 13.6%; Control: 39.3 ± 5.1%) compared to the Plasma and LR groups (81.1 ± 4.4% and 190.5 ± 10.6%, respectively). Animals given blood products also displayed significantly lower lactate levels compared to those given LR (Control: 2.3 ± 1.2 mM; Plasma: 4.8 ± 0.9 mM, RBC: 4.3 ± 1.3 mM, vs LR: 10.7 ± 3.5 mM, p=0.004 all groups compared to LR). Ending hemoglobin in RBC animals was significantly greater than in other groups (p&lt;0.001 compared to all groups). However, blood gas analysis revealed that the RBC group also had the lowest O2 saturation (88.3 ± 0.5% vs. LR: 93.9 ± 4.7%, Plasma: 94.8 ± 0.6%, WB: 93.5 ± 4.5%), yet PaO2 was comparable between groups.ConclusionIn our model of experimental T/HS, reperfusion fluids carrying red blood cells substantially improved hemodynamic stability by returning the mean arterial blood pressure to survivable values. The efficacy of RBC and whole blood resuscitation may be largely the result of improvements in diastolic blood pressure, suggesting increased contribution from systemic vascular resistance in these groups.Support or Funding InformationDOD W81XWH‐17‐2‐0047

Tracking DO2 with Compensatory Reserve During Whole Blood Resuscitation in Baboons.

Hemorrhagic shock can be mitigated by timely and accurate resuscitation designed to restore adequate delivery of oxygen (DO2) by increasing cardiac output (CO). However, standard care of using systolic blood pressure (SBP) as a guide for resuscitation may be ineffective and can potentially be associated with increased morbidity. We have developed a novel vital sign called the compensatory reserve measurement (CRM) generated from analysis of arterial pulse waveform feature changes that has been validated in experimental and clinical models of hemorrhage. We tested the hypothesis that thresholds of DO2 could be accurately defined by CRM, a noninvasive clinical tool, while avoiding over-resuscitation during whole blood resuscitation following a 25% hemorrhage in nonhuman primates. To accomplish this, adult male baboons (n = 12) were exposed to a progressive controlled hemorrhage while sedated that resulted in an average (± SEM) maximal reduction of 508 ± 18 mL of their estimated circulating blood volume of 2,130 ± 60 mL based on body weight. CRM increased from 6 ± 0.01% at the end of hemorrhage to 70 ± 0.02% at the end of resuscitation. By linear regression, CRM values of 6% (end of hemorrhage), 30%, 60%, and 70% (end of resuscitation) corresponded to calculated DO2 values of 5.9 ± 0.34, 7.5 ± 0.87, 9.3 ± 0.76, and 11.6 ± 1.3 mL O2·kg·min during resuscitation. As such, return of CRM to ∼65% during resuscitation required only ∼400 mL to restore SBP to 128 ± 6 mmHg, whereas total blood volume replacement resulted in over-resuscitation as indicated by a SBP of 140 ± 7 mmHg compared with an average baseline value of 125 ± 5 mmHg. Consistent with our hypothesis, thresholds of calculated DO2 were associated with specific CRM values. A target resuscitation CRM value of ∼65% minimized the requirement for whole blood while avoiding over-resuscitation. Furthermore, 0% CRM provided a noninvasive metric for determining critical DO2 at approximately 5.3 mL O2·kg·min.

Elicitation of prior probability distributions for a proposed Bayesian randomized clinical trial of whole blood for trauma resuscitation

BACKGROUNDWhole blood trauma resuscitation is conceptually appealing and increasingly used but lacks evidence. A randomized controlled trial is needed but challenging to design. A Bayesian approach might be more efficient and more interpretable than a conventional frequentist design. We report the results on an elicitation meeting to create prior probability distributions to help develop such a trial.METHODSIn‐person expert elicitation meeting, based on Sheffield Elicitation Framework methodology. We used an interactive graphical tool to elicit the quantities of interest (24‐hour mortality and certainty required). Two rounds were conducted, with an intervening discussion of deidentified responses. Individual responses were aggregated into probability distributions.RESULTSFifteen experts participated. The pooled belief was that the median 24‐hour mortality of trauma patients with hemorrhagic shock treated with component therapy (the current standard of care) was 19% (95% credible interval [CrI], 6%‐45%), and the median 24‐hour mortality of those treated with whole blood, 16% (95% CrI, 5%‐39%). The pooled prior distribution for the relative risk had a median of 0.84 (95% CrI, 0.26‐3.1), indicating that the expert group had a 64% prior belief that whole blood decreases 24‐hour mortality compared to component therapy.CONCLUSIONSExperts had moderately strong beliefs that whole blood reduces the 24‐hour mortality of trauma patients with hemorrhagic shock. These data will assist with the design and planning of a Bayesian trial of whole blood resuscitation, which will help to answer a key question in contemporary transfusion practice.

The Evolution of Blood Transfusion in the Trauma Patient: Whole Blood Has Come Full Circle.

Whole blood transfusion in the United States dates back to the Civil War, and it was widely used in all major conflicts since World War I. To understand our current civilian transfusion practices and to anticipate future changes in trauma resuscitation, it is important to understand the series of decisions that led trauma surgeons away from whole blood resuscitation and toward component therapy. In this review, we examine the historical basis for blood transfusion in trauma and examine the recent literature and future directions pertaining to blood product resuscitation in hemorrhaging patients.

2015 Dieulafoy Lesion on the Other Side of the Tract

INTRODUCTION: Dieulafoy lesions involve a large-caliber, tortuous artery in the muscularis mucosa that protrudes due to a submucosal defect with fibrinoid necrosis at the base. The submucosal artery is found to have atypical branching and as a result has a diameter of 1-3 mm, which is 10 times that of a normal mucosal capillary. These lesions can be found throughout the gastrointestinal tract, though they are most frequently found in the stomach, ranging between 61 to 82%. However 10% of all gastrointestinal tract Dieulafoy lesions are found in the colon with 42% of these lesions found in the rectum. CASE DESCRIPTION/METHODS: A 79-year-old male with past medical history significant for prostate cancer, hypertension, gout, degenerative joint disease and alcohol abuse disorder presented with bilateral leg weakness and was admitted to the medical service for alcohol dependency and acute kidney injury. On day 12 of hospitalization, he developed melena with a drop in hemoglobin from 12.0 g/dL at the time of admission to 7.7 g/dL. He was then transferred to the critical care unit and underwent esophagogastroduodenoscopy that revealed angioectatic lesions that bled and were treated with argon photocoagulation. On day 15, he developed hematochezia, which further decreased his hemoglobin to 6.9 g/dL. He became hemodynamically unstable, requiring rapid fluid and blood resuscitation. Emergent CT angiography was concerning for vascular malformation in the rectal wall. Colonoscopy was performed and a stream of pulsatile bleeding without an ulcer or varix, consistent with a Dieulafoy lesion, was seen in the rectum. Epinephrine was applied, the lesion was clipped, and hemostasis was achieved. No repeat episodes of gastrointestinal bleeding were reported afterwards. DISCUSSION: Bleeding from Dieulafoy lesions can cause hemodynamic compromise as noted in this patient. Therefore prompt identification and treatment is warranted. Endoscopy serves as a gold standard for identification. Hemostasis has been achieved with many techniques in case reports including: BICAP cauterization; combined sclerotherapy and electrocoagulation; heater-probe coagulation; and epinephrine injection combined with electrocoagulation. Rebleeding rate ranges from 6 to 28%. Systemic reviews and retrospective analysis suggest that mechanical ligation to achieve hemostasis, especially the use of hemoclips, may be superior to other techniques employed.

Effect of early restrictive fluid resuscitation on inflammatory and immune factors in patients with severe pelvic fracture

PurposeTo study the effect of early restrictive fluid resuscitation (EFR) on inflammatory and immune factors in patients with severe pelvic fracture (SPF). MethodsA total of 174 SPF patients in the Department of Orthopaedics, the First Affiliated Hospital of Chengdu Medical College from July 2015 to June 2018 were involved in this study and divided into EFR group (n = 87) and control group (n = 87) using the random number table method. Conventional fluid resuscitation (CFR) was performed in control group, and EFR was performed in EFR group. The incidences of acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS) during rescue, successful rescue rate, blood transfusion volume, fluid input, and resuscitation time were compared between the two groups. The parameters including prothrombin time (PT), hematocrit (HCT), platelet (PLT) and blood lactate (BL) at the 4th hour after fluid resuscitation were recorded. The levels of inflammatory factors (TNF-α, IL-6, CRP) and immune factors (CD3+, CD4+, CD8+, CD4+/CD8+) were compared between the two groups before treatment and 7 days after treatment. The revised acute physiologic and chronic health evaluation system and the sequential organ failure assessment scores were adopted for evaluation before treatment and 7 days after treatment. ResultsThe incidences of ARDS and MODS during rescue in EFR group were significantly lower than those in control group (p=0.015 and 0.010 respectively), and the successful rescue rate in EFR group was significantly higher than that in control group (p = 0.011). The blood transfusion volume, fluid input, resuscitation time in EFR group were significantly lower than those in control group (p = 0.016, 0.002 and 0.001 respectively). At the 4th hour after fluid resuscitation, PT and BL in EFR group were significantly lower than those in control group (p = 0.021 and 0.003 respectively), while HCT and PLT in EFR group were significantly higher than those in control group (p = 0.016 and 0.021 respectively). On day 7 after treatment, TNF-α, IL-6, CRP and CD8+ in EFR group were significantly lower than those in control group (p = 0.003, 0.004, 0.007 and 0.003 respectively), while CD3+, CD4+ and CD4+/CD8+ in EFR group were significantly higher than those in control group (p = 0.004, 0.000, 0.007 respectively). On day 7 after treatment, the revised acute physiologic and chronic health evaluation (APACHE) system and the sequential organ failure assessment (SOFA) scores in EFR group were significantly lower than those in control group. ConclusionEFR can effectively eliminate inflammatory factors, improve immune function, maintain the stability of blood components, reduce the incidences of ARDS and MODS, and elevate the successful rescue rate in patients with SPF.

Closed chest compressions reduce survival in an animal model of haemorrhage-induced traumatic cardiac arrest

Closed chest compressions (CCC) are recommended for medical cardiac arrest, but there is little evidence to support their inclusion for traumatic cardiac arrest (TCA).This laboratory study evaluated CCC following haemorrhage-induced TCA and whether resuscitation with blood improved survival compared to saline.The study was conducted with the authority of UK Animals (Scientific Procedures) Act 1986 (received institutional ethical approval and a Home Office Licence) using 39 terminally anesthetised, instrumented, juvenile Large White pigs. Following baseline measurements, animals underwent captive bolt injury to the right thigh and controlled haemorrhage (30% blood volume). Sixty minutes later there was a further haemorrhage to a MAP of 20 mmHg. The randomised resuscitation protocol was initiated within 5 min: CCC (Group 1); IV whole blood (Group 2); IV 0.9% saline (Group 3); IV whole blood + CCC (Group 4); and IV saline + CCC (Group 5). Fluid was administered as 3 × 10 ml/kg boluses using the Belmont® Rapid Infuser. The LUCAS™ II Chest Compression System delivered CCC. Primary Outcome was attainment of return of spontaneous circulation (ROSC MAP ≥ 50 mmHg) at Study End (fifteen minutes post-resuscitation) and secondary outcomes included haemodynamics.Mortality (MAP≤10 mmHg) was significantly higher in Group 1 compared to Groups 2 and 3 (P < 0.0001). Resuscitation with whole blood was significantly better than saline (P = 0.0069), no animals in Group 3 attained ROSC. The addition of chest compressions to fluid resuscitation resulted in a significantly worse outcome with saline resuscitation (P = 0.0023) but not with whole blood (P = 0.4411). Cardiovascular variables at the end of the Resuscitation Phase and Study End were significantly worse for Group 5 compared to Group 3. Some significant differences were present at the end of the Resuscitation Phase for Group 4 versus Group 2 but these differences were no longer present by Study End.CCC were associated with increased mortality and compromised haemodynamics compared to intravenous fluid resuscitation. Whole blood resuscitation was better than saline.