Dataset Information

Resuscitation with whole blood or blood components improves survival and lessens the pathophysiological burden of trauma and haemorrhagic shock in a pre-clinical porcine model.

ABSTRACT:

Purpose

In military trauma, disaster medicine, and casualties injured in remote locations, times to advanced medical and surgical treatment are often prolonged, potentially reducing survival and increasing morbidity. Since resuscitation with blood/blood components improves survival over short pre-surgical times, this study aimed to evaluate the quality of resuscitation afforded by blood/blood products or crystalloid resuscitation over extended 'pre-hospital' timelines in a porcine model of militarily relevant traumatic haemorrhagic shock.

Methods

This study underwent local ethical review and was done under the authority of Animals (Scientific Procedures) Act 1986. Forty-five terminally anaesthetised pigs received a soft tissue injury to the right thigh, haemorrhage (30% blood volume and a Grade IV liver injury) and fluid resuscitation initiated 30 min later [Group 1 (no fluid); 2 (0.9% saline); 3 (1:1 packed red blood cells:plasma); 4 (fresh whole blood); or 5 (plasma)]. Fluid (3 ml/kg bolus) was administered during the resuscitation period (maximum duration 450 min) when the systolic blood pressure fell below 80 mmHg. Surviving animals were culled with an overdose of anaesthetic.

Results

Survival time was significantly shorter for Group 1 compared to the other groups (P < 0.05). Despite the same triggers for resuscitation when compared to blood/blood components, saline was associated with a shorter survival time (P = 0.145), greater pathophysiological burden and significantly greater resuscitation fluid volume (P < 0.0001).

Conclusion

When times to advanced medical care are prolonged, resuscitation with blood/blood components is recommended over saline due to the superior quality and stability of resuscitation achieved, which are likely to lead to improved patient outcomes.

SUBMITTER: Watts SA

PROVIDER: S-EPMC9925484 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Resuscitation with whole blood or blood components improves survival and lessens the pathophysiological burden of trauma and haemorrhagic shock in a pre-clinical porcine model.

Watts Sarah Ann SA Smith Jason Edward JE Woolley Thomas T Rickard Rory Frederick RF Gwyther Robert R Kirkman Emrys E

European journal of trauma and emergency surgery : official publication of the European Trauma Society 20220727 1

<h4>Purpose</h4>In military trauma, disaster medicine, and casualties injured in remote locations, times to advanced medical and surgical treatment are often prolonged, potentially reducing survival and increasing morbidity. Since resuscitation with blood/blood components improves survival over short pre-surgical times, this study aimed to evaluate the quality of resuscitation afforded by blood/blood products or crystalloid resuscitation over extended 'pre-hospital' timelines in a porcine model ...[more]

PMID: 35900383

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Project description:BackgroundTime to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red blood cells (PRBC) and lyophilised plasma (LyoPlas) was superior to use of 0·9% sodium chloride for improving tissue perfusion and reducing mortality in trauma-related haemorrhagic shock.MethodsResuscitation with pre-hospital blood products (RePHILL) is a multicentre, allocation concealed, open-label, parallel group, randomised, controlled, phase 3 trial done in four civilian prehospital critical care services in the UK. Adults (age ≥16 years) with trauma-related haemorrhagic shock and hypotension (defined as systolic blood pressure <90 mm Hg or absence of palpable radial pulse) were assessed for eligibility by prehospital critial care teams. Eligible participants were randomly assigned to receive either up to two units each of PRBC and LyoPlas or up to 1 L of 0·9% sodium chloride administered through the intravenous or intraosseous route. Sealed treatment packs which were identical in external appearance, containing PRBC-LyoPlas or 0·9% sodium chloride were prepared by blood banks and issued to participating sites according to a randomisation schedule prepared by the co-ordinating centre (1:1 ratio, stratified by site). The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. This study is completed and registered with ISRCTN.com, ISRCTN62326938.FindingsFrom Nov 29, 2016 to Jan 2, 2021, prehospital critical care teams randomly assigned 432 participants to PRBC-LyoPlas (n=209) or to 0·9% sodium chloride (n=223). Trial recruitment was stopped before it achieved the intended sample size of 490 participants due to disruption caused by the COVID-19 pandemic. The median follow-up was 9 days (IQR 1 to 34) for participants in the PRBC-LyoPlas group and 7 days (0 to 31) for people in the 0·9% sodium chloride group. Participants were mostly white (62%) and male (82%), had a median age of 38 years (IQR 26 to 58), and were mostly involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, IQR 25 to 50). Before randomisation, participants had received on average 430 mL crystalloid fluids and tranexamic acid (90%). The composite primary outcome occurred in 128 (64%) of 199 participants randomly assigned to PRBC-LyoPlas and 136 (65%) of 210 randomly assigned to 0·9% sodium chloride (adjusted risk difference -0·025% [95% CI -9·0 to 9·0], p=0·996). The rates of transfusion-related complications in the first 24 h after ED arrival were similar across treatment groups (PRBC-LyoPlas 11 [7%] of 148 compared with 0·9% sodium chloride nine [7%] of 137, adjusted relative risk 1·05 [95% CI 0·46-2·42]). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in 0·9% sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the 0·9% sodium chloride group (abnormal liver function test). There were no treatment-related deaths.InterpretationThe trial did not show that prehospital PRBC-LyoPlas resuscitation was superior to 0·9% sodium chloride for adult patients with trauma related haemorrhagic shock. Further research is required to identify the characteristics of patients who might benefit from prehospital transfusion and to identify the optimal outcomes for transfusion trials in major trauma. The decision to commit to routine prehospital transfusion will require careful consideration by all stakeholders.FundingNational Institute for Health Research Efficacy and Mechanism Evaluation.

Project description:BackgroundAssessment of tissue hypoxia at the bedside has yet to be translated into daily clinical practice in septic shock patients. Perfusion markers are surrogates of deeper physiological phenomena. Lactate-to-pyruvate ratio (LPR) and the ratio between veno-arterial PCO2 difference and Ca-vO2 (ΔPCO2/Ca-vO2) have been proposed as markers of tissue hypoxia, but they have not been compared in the clinical scenario. We studied acute septic shock patients under resuscitation. We wanted to evaluate the relationship of these hypoxia markers with clinical and biochemical markers of hypoperfusion during septic shock resuscitation.MethodsSecondary analysis of a randomized controlled trial. Septic shock patients were randomized to fluid resuscitation directed to normalization of capillary refill time (CRT) versus normalization or significant lowering of lactate. Multimodal assessment of perfusion was performed at 0, 2, 6 and 24 hours, and included macrohemodynamic and metabolic perfusion variables, CRT, regional flow and hypoxia markers. Patients who attained their pre-specified endpoint at 2-hours were compared to those who did not.ResultsForty-two patients were recruited, median APACHE-II score was 23 [15-31] and 28-day mortality 23%. LPR and ΔPCO2/Ca-vO2 ratio did not correlate during early resuscitation (0-2 h) and the whole study period (24-hours). ΔPCO2/Ca-vO2 ratio derangements were more prevalent than LPR ones, either in the whole cohort (52% vs. 23%), and in association with other perfusion abnormalities. In patients who reached their resuscitation endpoints, the proportion of patients with altered ΔPCO2/Ca-vO2 ratio decreased significantly (66% to 33%, P=0.045), while LPR did not (14% vs. 25%, P=0.34).ConclusionsHypoxia markers did not exhibit correlation during resuscitation in septic shock patients. They probably interrogate different pathophysiological processes and mechanisms of dysoxia during early septic shock. Future studies should better elucidate the interaction and clinical role of hypoxia markers during septic shock resuscitation.

Project description:BackgroundFast and effective treatment of hemorrhagic shock is one of the most important preclinical trauma care tasks e.g., in combat casualties in avoiding severe end-organ damage or death. In scenarios without immediate availability of blood products, alternate regimens of fluid resuscitation represent the only possibility of maintaining sufficient circulation and regaining adequate end-organ oxygen supply. However, the fluid choice alone may affect the extent of the bleeding by interfering with coagulation pathways. This study investigates the impact of hydroxyethyl starch (HES), gelatine-polysuccinate (GP) and balanced electrolyte solution (BES) as commonly used agents for fluid resuscitation on coagulation using a porcine hemorrhagic shock model.MethodsFollowing approval by the State and Institutional Animal Care Committee, life-threatening hemorrhagic shock was induced via arterial blood withdrawal in 24 anesthetized pigs. Isovolumetric fluid resuscitation with either HES, GP or BES (n = 3 × 8) was performed to compensate for the blood loss. Over four hours, hemodynamics, laboratory parameters and rotational thromboelastometry-derived coagulation were analyzed. As secondary endpoint the porcine values were compared to human blood.ResultsAll the agents used for fluid resuscitation significantly affected coagulation. We measured a restriction of laboratory parameters, clot development and clot firmness, particularly in HES- and GP-treated animals. Hemoglobin content dropped in all groups but showed a more pronounced decline in colloid-treated pigs. This effect was not maintained over the four-hour monitoring period.ConclusionHES, GP, and BEL sufficiently stabilized the macrocirculation, but significantly affected coagulation. These effects were most pronounced after colloid and particularly HES administration. Despite suitability for rapid hemodynamic stabilization, colloids have to be chosen with caution, because their molecular properties may affect coagulation directly and as a consequence of pronounced hemodilution. Our comparison of porcine and human coagulation showed increased coagulation activity in pig blood.

Project description:BackgroundPlasma is integral to haemostatic resuscitation after injury, but the timing of administration remains controversial. Anticipating approval of lyophilised plasma by the US Food and Drug Administration, the US Department of Defense funded trials of prehospital plasma resuscitation. We investigated use of prehospital plasma during rapid ground rescue of patients with haemorrhagic shock before arrival at an urban level 1 trauma centre.MethodsThe Control of Major Bleeding After Trauma Trial was a pragmatic, randomised, single-centre trial done at the Denver Health Medical Center (DHMC), which houses the paramedic division for Denver city. Consecutive trauma patients in haemorrhagic shock (defined as systolic blood pressure [SBP] ≤70 mm Hg or 71-90 mm Hg plus heart rate ≥108 beats per min) were assessed for eligibility at the scene of the injury by trained paramedics. Eligible patients were randomly assigned to receive plasma or normal saline (control). Randomisation was achieved by preloading all ambulances with sealed coolers at the start of each shift. Coolers were randomly assigned to groups 1:1 in blocks of 20 according to a schedule generated by the research coordinators. If the coolers contained two units of frozen plasma, they were defrosted in the ambulance and the infusion started. If the coolers contained a dummy load of frozen water, this indicated allocation to the control group and saline was infused. The primary endpoint was mortality within 28 days of injury. Analyses were done in the as-treated population and by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01838863.FindingsFrom April 1, 2014, to March 31, 2017, paramedics randomly assigned 144 patients to study groups. The as-treated analysis included 125 eligible patients, 65 received plasma and 60 received saline. Median age was 33 years (IQR 25-47) and median New Injury Severity Score was 27 (10-38). 70 (56%) patients required blood transfusions within 6 h of injury. The groups were similar at baseline and had similar transport times (plasma group median 19 min [IQR 16-23] vs control 16 min [14-22]). The groups did not differ in mortality at 28 days (15% in the plasma group vs 10% in the control group, p=0·37). In the intention-to-treat analysis, we saw no significant differences between the groups in safety outcomes and adverse events. Due to the consistent lack of differences in the analyses, the study was stopped for futility after 144 of 150 planned enrolments.InterpretationDuring rapid ground rescue to an urban level 1 trauma centre, use of prehospital plasma was not associated with survival benefit. Blood products might be beneficial in settings with longer transport times, but the financial burden would not be justified in an urban environment with short distances to mature trauma centres.FundingUS Department of Defense.

Project description:ObjectivesHeart rate (HR) is one of the physiological variables in the early assessment of trauma-related haemorrhagic shock, according to Advanced Trauma Life Support (ATLS). However, its efficiency as predictor of mortality is contradicted by several studies. Furthermore, the linear association between HR and the severity of shock and blood loss presented by ATLS is doubtful. This systematic review aims to update current knowledge on the role of HR in the initial haemodynamic assessment of patients who had a trauma.DesignThis study is a systematic review and meta-regression that follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.Data sourcesEMBASE, MEDLINE, CENTRAL and Web of Science databases were systematically searched through on 1 September 2020.Eligibility criteriaPapers providing early HR and mortality data on bleeding patients who had a trauma were included. Patient cohorts were considered haemorrhagic if the inclusion criteria of the studies contained transfusion and/or positive focused assessment with sonography for trauma and/or postinjury haemodynamical instability and/or abdominal gunshot injury. Studies on burns, traumatic spinal or brain injuries were excluded. Papers published before January 2010 were not considered.Data extraction and synthesisData extraction and risk of bias were assessed by two independent investigators. The association between HR and mortality of patients who had a trauma was assessed using meta-regression analysis. As subgroup analysis, meta-regression was performed on patients who received blood products.ResultsFrom a total of 2017 papers, 19 studies met our eligibility criteria. Our primary meta-regression did not find a significant relation (p=0.847) between HR and mortality in patients who had a trauma with haemorrhage. Our subgroup analysis included 10 studies, and it could not reveal a linear association between HR and mortality rate.ConclusionsIn accordance with the literature demonstrating the multiphasic response of HR to bleeding, our study presents the lack of linear association between postinjury HR and mortality. Modifying the pattern of HR derangements in the ATLS shock classification may result in a more precise teaching tool for young clinicians.

Project description:BackgroundClosed-loop resuscitation can improve personalization of care, decrease workload and bring expert knowledge in isolated areas. We have developed a new device to control the administration of fluid or simultaneous co-administration of fluid and norepinephrine using arterial pressure.MethodWe evaluated the performance of our prototype in a rodent model of haemorrhagic shock. After haemorrhagic shock, rats were randomized to five experimental groups: three were resuscitated with fluid and two with co-administration of fluid and norepinephrine. Among groups resuscitated with fluid, one was resuscitated by a physician and two were resuscitated according to two different closed-loop algorithms. Among groups resuscitated with fluid and norepinephrine, one was resuscitated by a physician and the other one by the closed-loop device. The precision of arterial pressure during the resuscitation period was assessed using rising time, time passed in the target area and performance error calculations.ResultsGroups resuscitated with fluid had similar performances and passed as much time in the target area of 80-90 mmHg as the manual group [manual: 76.8% (67.9-78.2), closed-loop: 64.6% (45.7-72.9) and 80.9% (59.1-85.3)]. Rats resuscitated with fluid and norepinephrine using closed-loop passed similar time in target area than manual group [closed-loop: 74.4% (58.4-84.5) vs. manual: 60.1% (46.1-72.4)] but had shorter rising time to reach target area [160 s (106-187) vs. 434 s (254-1081)] than those resuscitated by a physician. Rats resuscitated with co-administration of fluid and norepinephrine required less fluid and had less hemodilution than rats resuscitated with fluid alone. Lactate decrease was similar between groups resuscitated with fluid alone and fluid with norepinephrine.ConclusionsThis study assessed extensively the performances of several algorithms for closed-loop resuscitation of haemorrhagic shock with fluid alone and with co-administration of fluid and norepinephrine. The performance of the closed-loop algorithms tested was similar to physician-guided treatment with considerable saving of work for the caregiver. Arterial pressure closed-loop guided algorithms can be extended to combined administration of fluid and norepinephrine.

Project description:BackgroundModern resuscitation strategies following haemorrhagic shock are influenced by global haemodynamic parameters such as blood pressure and cardiac output. Microcirculatory dysfunction in this context may persist even after restoration of satisfactory global parameters. Additional monitoring of the microcirculatory function may therefore be warranted in order to facilitate goal-directed therapy at a tissue oxygenation level. Although such a phenomenon is recognised in the case of sepsis, clinical evidence regarding the behaviour of the microcirculation following the delivery of resuscitation fluids after haemorrhagic shock is sparse. A summation of the current state of pre-clinical evidence is justified in order to direct avenues for future clinical research.Methods/designSystematic review methodology will be utilised in order to identify relevant studies, assess for bias, and extract data for analysis. Medical databases will be searched to find pre-clinical studies that monitor the microcirculatory function following haemorrhagic shock and subsequent fluid resuscitation. Different fluid types (e.g. blood products, crystalloid, and colloid fluids) will be compared. The search strategy will combine terms for the animal model, resuscitation fluid, and microcirculatory parameters. Randomised and non-randomised experiments, as well as case series, will be eligible for inclusion. Specific quality assessment tools for pre-clinical research will be used depending on study design. A combination of narrative and meta-analysis techniques will be used for the synthesis of data.DiscussionThe choice of type, sequence, and quantity of resuscitation fluid following haemorrhagic shock is controversial, and the optimal strategy for restoration of microcirculatory function is yet unknown. A detailed examination of pre-clinical data regarding the microcirculation is timely and will enable a focussed approach to clinical research for the improvement of resuscitation following haemorrhagic shock.Systematic review registrationCollaborative Approach to Meta Analysis and Review of Animal Data from Experimental Studies ( CAMARADES).

Dataset Information

Resuscitation with whole blood or blood components improves survival and lessens the pathophysiological burden of trauma and haemorrhagic shock in a pre-clinical porcine model.

Purpose

Methods

Results

Conclusion

Publications

Resuscitation with whole blood or blood components improves survival and lessens the pathophysiological burden of trauma and haemorrhagic shock in a pre-clinical porcine model.

Similar Datasets

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