Type-specific whole blood still has a role in the era of low titer O universal donor transfusion for severe trauma hemorrhage.

ABSTRACT: Whole blood can be ABO-type specific (TSWB) or Low-Titer O universal donor (LTOWB). Having previously used LTOWB, the US Armed Forces Blood Program began using TSWB in 1965 as a method of increasing the donor pool. In contrast to military practice, the AABB (Association for the Advancement of Blood and Biotherapies), from its first guidelines in 1958 until 2018, permitted only TSWB. Attempting to reduce time to transfusion, the US military reintroduced LTOWB in the deployed environment in 2015; this practice was endorsed by the AABB in 2018 and is progressively being implemented by military and civilian providers worldwide. LTOWB is the only practical solution prehospital. However, there are several reasons to retain the option of TSWB in hospitals with a laboratory. These include 1. as-yet ill-defined risks of immunological complications from ABO-incompatible plasma (even when this has low titres of anti A and B); 2. risks of high volumes of LTOWB including published historical advice (based on clinical experience) not to transfuse type-specific blood for 2-3 weeks following a substantial LTOWB transfusion; 3. uncertainty as to the optimal definition of "low titre"; and 4. expanding the potential donor pool by allowing type-specific transfusion. Several large randomised controlled trials currently underway are comparing LTOWB to component therapy, but none address the question of LTOWB vs. TSWB. There is sufficient data to suggest the additional risks of transfusing LTOWB to non-group O recipients should be avoided by using TSWB as soon as possible. Combined with the advantage of maintaining an adequate supply of blood products in times of high demand, this suggests retaining TSWB within the civilian and military blood supply system is desirable. TSWB should be preferred when patient blood group is confirmed in facilities with a hematology laboratory, with LTOWB reserved for patients whose blood group is unknown.

Delayed Tracheoesophageal Fistula and Refractory Respiratory Failure Caused by Inhalation Burns and Emergency Venovenous ECMO to Facilitate Its Management: A Case Report.

Acquired tracheoesophageal fistulae are uncommon in burn patients but can occur as a complication of inhalation injury. We report a case of a 30-yr-old male patient presenting after suffering from inhalation and 25% total body surface area burns. On postburns day 14, he developed a massive tracheoesophageal fistula causing refractory acute respiratory failure. Veno-venous extracorporeal membrane (VV ECMO) oxygenation was initiated without systemic anticoagulation via bi-femoral cannulation under transthoracic echocardiography guidance. He underwent successful 5-hr apnoeic ventilation-assisted surgical repair of the fistula via a right posterolateral thoracotomy. ECMO was discontinued after 36 hr, and he was discharged to the ward after 33 d in the intensive care unit. Inhalation burn injury can cause a delayed life-threatening tracheoesophageal fistula. Surgical repair can be successfully performed for this condition. VV- ECMO can be used to facilitate prolonged apnoeic surgery and to manage refractory respiratory failure due to this condition.

Perspective: the top 11 priorities to improve trauma outcomes, from system to patient level.

BACKGROUND: The Haemorrhage, Airway, Breathing, Circulation, Disability, Exposure/Environmental control approach to individual patient management in trauma is well established and embedded in numerous training courses worldwide. Further improvements in trauma outcomes are likely to result from a combination of system-level interventions in prevention and quality improvement, and from a sophisticated approach to clinical innovation. TOP ELEVEN TRAUMA PRIORITIES: Based on a narrative review of remaining preventable mortality and morbidity in trauma, the top eleven priorities for those working throughout the spectrum of trauma care, from policy-makers to clinicians, should be: (1) investment in effective trauma prevention (likely to be the most cost-effective intervention); (2) prioritisation of resources, quality improvement and innovation in prehospital care (where the most preventable mortality remains); (3) building a high-performance trauma team; (4) applying evidence-based clinical interventions that stop bleeding, open & protect the airway, and optimise breathing most effectively; (5) maintaining enough circulating blood volume and ensuring adequate cardiac function; (6) recognising the role of the intensive care unit in modern damage control surgery; (7) prioritising good intensive care unit intercurrent care, especially prophylaxis for thromboembolic disease; (8) conducting a thorough tertiary survey, noting that on average the intensive care unit is where approximately 15% of injuries are detected; (9) facilitating early extubation; (10) investing in formal quantitative and qualitative quality assurance and improvement; and (11) improving clinical trial design. CONCLUSION: Dramatic reductions in population trauma mortality and injury case fatality rate over recent decades have demonstrated the value of a comprehensive approach to trauma quality and process improvement. Continued attention to these principles, targeting areas with highest remaining preventable mortality while also prioritising functional outcomes, should remain the focus of both clinician and policy-makers.

A pilot randomized clinical trial of cryopreserved versus liquid-stored platelet transfusion for bleeding in cardiac surgery: The cryopreserved versus liquid platelet-New Zealand pilot trial.

BACKGROUND AND OBJECTIVES: Platelets for transfusion have a shelf-life of 7 days, limiting availability and leading to wastage. Cryopreservation at -80°C extends shelf-life to at least 1 year, but safety and effectiveness are uncertain. MATERIALS AND METHODS: This single centre blinded pilot trial enrolled adult cardiac surgery patients who were at high risk of platelet transfusion. If treating clinicians determined platelet transfusion was required, up to three units of either cryopreserved or liquid-stored platelets intraoperatively or during intensive care unit admission were administered. The primary outcome was protocol safety and feasibility. RESULTS: Over 13 months, 89 patients were randomized, 23 (25.8%) of whom received a platelet transfusion. There were no differences in median blood loss up to 48 h between study groups, or in the quantities of study platelets or other blood components transfused. The median platelet concentration on the day after surgery was lower in the cryopreserved platelet group (122 × 103 /µl vs. 157 × 103 /µl, median difference 39.5 ×103 /µl, p = 0.03). There were no differences in any of the recorded safety outcomes, and no adverse events were reported on any patient. Multivariable adjustment for imbalances in baseline patient characteristics did not find study group to be a predictor of 24-h blood loss, red cell transfusion or a composite bleeding outcome. CONCLUSION: This pilot randomized controlled trial demonstrated the feasibility of the protocol and adds to accumulating data supporting the safety of this intervention. Given the clear advantage of prolonged shelf-life, particularly for regional hospitals in New Zealand, a definitive non-inferiority phase III trial is warranted.

Cryopreserved platelets compared with liquid-stored platelets for the treatment of surgical bleeding: protocol for two multicentre randomised controlled blinded non-inferiority trials (the CLIP-II and CLIPNZ-II trials).

INTRODUCTION: Cryopreservation at -80°C in dimethylsulphoxide extends platelet shelf-life from 7 days to 2 years. Only limited comparative trial data supports the safety and effectiveness of cryopreserved platelets as a treatment for surgical bleeding. Cryopreserved platelets are not currently registered for civilian use in most countries. METHODS AND ANALYSIS: CLIP-II and CLIPNZ-II are harmonised, blinded, multicentre, randomised, controlled clinical non-inferiority trials comparing bleeding, transfusion, safety and cost outcomes associated with cryopreserved platelets versus conventional liquid platelets as treatment for bleeding in cardiac surgery. CLIP-II is planning to enrol patients in 12 tertiary hospitals in Australia; CLIPNZ-II will recruit in five tertiary hospitals in New Zealand. The trials use near-identical protocols aside from details of cryopreserved platelet preparation. Patients identified preoperatively as being at high risk of requiring a platelet transfusion receive up to three units of study platelets if their treating doctor considers platelet transfusion is indicated. The primary endpoint is blood loss through the surgical drains in the 24 hours following intensive care unit (ICU) admission after surgery. Other endpoints are blood loss at other time points, potential complications, adverse reactions, transfusion and fluid requirement, requirement for procoagulant treatments, time to commencement of postoperative anticoagulants, delay between platelet order and commencement of infusion, need for reoperation, laboratory and point-of-care clotting indices, cost, length of mechanical ventilation, ICU and hospital stay, and mortality. Transfusing 202 (CLIP-II) or 228 (CLIPNZ-II) patients with study platelets will provide 90% power to exclude the possibility of greater than 20% inferiority in the primary endpoint. If cryopreserved platelets are not inferior to liquid-stored platelets, the advantages of longer shelf-life would justify rapid change in clinical practice. Cost-effectiveness analyses will be incorporated into each study such that, should clinical non-inferiority compared with standard care be demonstrated, the hospitals in each country that would benefit most from changing to a cryopreserved platelet blood bank will be known. ETHICS AND DISSEMINATION: CLIP-II was approved by the Austin Health Human Research Ethics Committee (HREC/54406/Austin-2019) and by the Australian Red Cross Lifeblood Ethics Committee (2019#23). CLIPNZ-II was approved by the New Zealand Southern Health and Disability Ethics Committee (21/STH/66). Eligible patients are approached for informed consent at least 1 day prior to surgery. There is no provision for consent provided by a substitute decision-maker. The results of the two trials will be submitted separately for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBERS: NCT03991481 and ACTRN12621000271808.

Synthetic blood and blood products for combat casualty care and beyond.

ABSTRACT: Synthetic biology adopts an engineering design approach to create innovative treatments that are reliable, scalable, and customizable to individual patients. Interest in substitutes for allogenic blood components, primarily red blood cells and platelets, increased in the 1980s because of concerns over infectious disease transmission. However, only now, with emerging synthetic approaches, are such substitutes showing genuine promise. Affordable alternatives to donated blood would be of enormous benefit worldwide. Several approaches to replacing the oxygen-carrying function of red cells are under advanced investigation. Hemoglobin-based oxygen carriers incorporate modifications to reduce the renal toxicity and nitric oxide scavenging of free hemoglobin. While use of earlier-generation hemoglobin-based oxygen carriers may be limited to circumstances in which blood transfusion is not an option, recent advances in chemical modification of hemoglobin may eventually overcome such problems. Another approach encases hemoglobin molecules in biocompatible synthetic nanoparticles. An alternative is the ex vivo production of red cells in bioreactors, with or without genetic manipulation, that offers the potential of a universal donor product. Various strategies to manufacture synthetic platelets are also underway, ranging from simple phospholipid liposomes encapsulating adenosine diphosphate and decorated with fibrinogen fragments, to more complex capsules with multiple receptor peptide sequences. Ex vivo production of platelets in bioreactors is also possible including, for example, platelets derived from induced pluripotent stem cells that are differentiated into a megakaryocytic lineage. Prior to clinical use, trials assessing synthetic blood components must evaluate meaningful safety and effectiveness outcomes in relatively large numbers of critically ill patients. Overcoming these challenges may be as much a hurdle as product design. This article reviews the state of the science of the synthetic biology approach to developing blood component substitutes.

Staff perceptions of military chemical-biological-radiological-nuclear (CBRN) air-purifying masks during a simulated clinical task in the context of SARS-CoV-2.

Air-purifying full-face masks, such as military chemical-biological-radiological-nuclear masks, might offer superior protection against severe acute respiratory syndrome coronavirus 2 compared to disposable polypropylene P2 or N95 masks. In addition, disposable masks are in short supply, while military chemical-biological-radiological-nuclear masks can be disinfected then reused. It is unknown whether such masks might be appropriate for civilians with minimal training in their use. Accordingly, we compared the Australian Defence Force in-service chemical-biological-radiological-nuclear Low Burden Mask (AirBoss Defense, Newmarket, Canada) with polypropylene N95 masks and non-occlusive glasses worn during simulated tasks performed by civilian clinicians in an Australian tertiary referral hospital intensive care unit. After brief training in the use of the Low Burden Mask, participants undertook a simulated cardiac arrest scenario. Previous training with polypropylene N95 masks had been provided. Evaluation of 10 characteristics of each mask type were recorded, and time to mask application was assessed. Thirty-three participants tested the Low Burden Mask, and 28 evaluated polypropylene N95 masks and glasses. The Low Burden Mask was donned more quickly: mean time 7.0 (standard deviation 2.1) versus 18.3 (standard deviation 6.7) seconds; P = 0.0076. The Low Burden Mask was rated significantly higher in eight of the 10 assessed criteria, including ease of donning, comfort (initially and over a prolonged period), fogging, seal, safety while removing, confidence in protection, and overall. Visibility and communication ability were rated equally highly for both systems. We conclude that this air-purifying full-face mask is acceptable to clinicians in a civilian intensive care unit. It enhances staff confidence, reduces waste, and is likely to be a lower logistical burden during a prolonged pandemic. Formal testing of effectiveness is warranted.

Caravan explosions: a case series of burns patients at the Royal Brisbane and Women's Hospital.

BACKGROUND: Caravan explosions due to gas cylinder explosions or gas leaks are responsible for a small but significantly injured group of burns patients. Those involved in explosions are sometimes assumed to be at risk of primary blast wave injury; however, the likelihood of such injuries is unclear. The aim of this research was to seek evidence of primary blast injury in groups defined by clinicians as having sustained burns in explosive and non-explosive events. METHODS: This is a single-centre case series of patients with caravan-related burns from 2009 to 2019, identified using the burns data registry at the Royal Brisbane and Women's Hospital. Patients were divided into two groups based on the mechanism of injury, with injuries sustained from either a gas bottle explosion (group 1) or from gas ignition (group 2). RESULTS: Twenty-one patients were identified over the 10-year period. The explosion group suffered more extensive burns, with a median % total body surface area of 31% (23.5-43.5) and 9.5% (5-20) in group 1 and group 2, respectively (P = 0.01). There was a numerically longer median hospital and intensive care unit length of stay in group 1. In multivariable analysis, there were no statistically significant predictors of intensive care unit or hospital length of stay. None of the patients appeared to have suffered any of the expected effects of primary blast wave injury. CONCLUSION: Gas bottle explosions in caravans uncommonly, if ever, result in a blast wave of sufficient energy to cause primary blast injury.

Octreotide for resuscitation of cardiac arrest due to carcinoid crisis precipitated by novel peptide receptor radionuclide therapy (PRRT): A case report.

Peptide receptor radionuclide therapy (PRRT) is an effective treatment for metastatic carcinoid tumours but can precipitate a carcinoid crisis through release of stored bioamines. Cardiac arrest is an uncommon manifestation of carcinoid crisis and has never been reported as a complication of PRRT. We report a case of a 58-year old female who suffered from cardiac arrest following PRRT for metastatic carcinoid tumour. She was successfully resuscitated using intravenous octreotide following 22 min of failure to resuscitate with a standard advanced cardiac life support protocol. Following resuscitation, severe carcinoid heart disease was diagnosed, and the patient subsequently underwent successful surgical valve replacement. Although there is no trial evidence, considering pharmacological rationale and successful outcome in this case, we suggest early administration of intravenous octreotide during resuscitation of patients suffering cardiac arrest post PRRT for carcinoid disease and recommend preventive strategies.

Preoperative identification of cardiac surgery patients at risk of receiving a platelet transfusion: The Australian Cardiac Surgery Platelet Transfusion (ACSePT) risk prediction tool.

Platelet (PLT) transfusions are limited and costly resources. Accurately predicting clinical demand while limiting product wastage remains difficult. A PLT transfusion prediction score was developed for use in cardiac surgery patients who commonly require PLT transfusions. STUDY DESIGN AND METHODS: Using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons National Cardiac Surgery Database, significant predictors for PLT transfusion were identified by multivariate logistic regression. Using a development data set containing 2005 to 2016 data, the Australian Cardiac Surgery Platelet Transfusion (ACSePT) risk prediction tool was developed by assigning weights to each significant predictor that corresponded to a probability of PLT transfusion. The predicted probability for each score was compared to actual PLT transfusion occurrence in a validation (2017) data set. RESULTS: The development data set contained 38 independent variables and 91 521 observations. The validation data set contained 12 529 observations. The optimal model contained 23 variables significant at P < .001 and an area under the receiver operating characteristic (ROC) curve of 0.69 (95% confidence interval [CI], 0.68-0.69). ACSePT contained nine variables and had an area under the ROC curve of 0.66 (95% CI, 0.65-0.66) and overall predicted probability of PLT transfusion of 19.8% for the validation data set compared to an observed risk of 20.3%. CONCLUSION: The ACSePT risk prediction tool is the first scoring system to predict a cardiac surgery patient's risk of receiving a PLT transfusion. It can be used to identify patients at higher risk of receiving PLT transfusions for inclusion in clinical trials and by PLT inventory managers to predict PLT demand.

Multidisciplinary quality improvement programme for older patients admitted to a vascular surgery ward.

BACKGROUND: Older vascular surgical patients are at high risk of hospital-associated complications and prolonged stays. AIMS: To implement a multidisciplinary co-management model for older vascular patients and evaluate impact on length of stay (LOS), delirium incidence, functional decline, medical complications and discharge destination. METHODS: Prospective pre-post evaluation of a quality improvement intervention, enrolling pre-intervention (August 2012-January 2013) and post-intervention cohort (September 2013-March 2014). Participants were consenting patients aged 65 years and over admitted to the vascular surgical ward of a metropolitan teaching hospital for at least 3 days. Intervention was physician-led co-management plus a multidisciplinary improvement programme targeting delirium and functional decline. Primary outcomes were LOS, delirium and functional decline. Secondary outcomes were medical complications and discharge destination. Process measures included documented consultation patterns. Administrative data were also compared for all patients aged 65 and older for 12 months pre- and post-intervention. RESULTS: We enrolled 112 participants pre-intervention and 123 participants post-intervention. LOS was reduced post-intervention (geometric mean 7.6 days vs 9.3 days; ratio of geometric means 0.82 (95% confidence interval CI0.68-1.00), P = 0.04). There was a trend to less delirium (18 (14.6%) vs 24 (21.4%), P = 0.17) and functional decline (18 (14.6%) vs 27 (24.3%), P = 0.06), with greatest reductions in the urgently admitted subgroup. Administrative data showed reduced median LOS (5.2 days vs 6 days, P = 0.03) and greater discharge home (72% vs 50%, P < 0.01). CONCLUSIONS: Physician-led co-management plus a multidisciplinary improvement programme may reduce LOS and improve functional outcomes in older vascular surgical patients.

Short- and long-term outcomes of neutropenic cancer patients in intensive care according to requirement for invasive ventilation.

BACKGROUND: Neutropenic fever is a frequently encountered complication when caring for cancer patients and can lead to intensive care admission, with high mortality rates in those patients who require invasive mechanical ventilation (IMV). Although hospital survival in this population has improved, long-term outcomes of critically ill neutropenic cancer patients have not been well defined. AIMS: To evaluate short- and long-term outcomes of neutropenic cancer patients admitted to intensive care, according to requirement for invasive ventilation. Additionally, we aimed to determine predictors of poor clinical outcomes in this group. METHODS: A retrospective cohort study of neutropenic cancer patients admitted to our intensive care unit (ICU) from 2008 to 2016. RESULTS: We included 192 cancer patients of whom 100 (52.1%) required IMV. Overall ICU mortality was 29.7% and 12-month post-ICU mortality was 61.5%. Patients requiring IMV had significantly higher short- and long-term mortality (P < 0.001). Multivariate analysis determined three variables to be predictors of mortality at ICU discharge in the whole cohort: IMV (OR 13.52), renal replacement therapy (RRT, OR 2.37) and higher APACHE II scores (OR 1.1 for each unit increase). These variables were identical in the subgroup requiring invasive ventilation, with RRT (OR 2.76) and APACHE II scores (OR 1.1 for each unit increase) predicting short-term mortality. CONCLUSION: Neutropenic cancer patients admitted to ICU have lower short-term mortality than previously reported in cohort studies, however their mortality rises significantly following discharge from ICU. Those patients who require IMV are at significantly increased risk of both short- and long-term mortality.

A randomized, controlled pilot clinical trial of cryopreserved platelets for perioperative surgical bleeding: the CLIP-I trial (Editorial, p. 2759).

BACKGROUND: Cryopreservation extends platelet (PLT) shelf life from 5 to 7 days to 2 to 4 years. However, only 73 patients have been transfused cryopreserved PLTs in published randomized controlled trials (RCTs), making safety data insufficient for regulatory approval. STUDY DESIGN AND METHODS: The Cryopreserved vs. Liquid Platelet (CLIP) study was a double-blind, pilot, multicenter RCT involving high-risk cardiothoracic surgical patients in four Australian hospitals. The objective was to test, as the primary outcome, the feasibility and safety of the protocol. Patients were allocated to study group by permuted block randomization, with patients and clinicians blinded by use of an opaque shroud placed over each study PLT unit. Up to 3 units of cryopreserved or liquid-stored PLTs were administered per patient. No other aspect of patient care was affected. Adverse events were actively sought. RESULTS: A total of 121 patients were randomized, of whom 23 received cryopreserved PLTs and 18 received liquid-stored PLTs. There were no differences in blood loss (median, 715 mL vs. 805 mL at 24 hr; difference between groups 90 mL [95% CI, -343.8 to 163.8 mL], p = 0.41), but the Bleeding Academic Research Consortium criterion for significant postoperative hemorrhage in cardiac surgery composite bleeding endpoint occurred in nearly twice as many patients in the liquid-stored group (55.6% vs. 30.4%, p = 0.10). Red blood cell transfusion requirements were a median of 3 units in the cryopreserved group versus 4 units with liquid-stored PLTs (difference between groups, 1 unit [95% CI, -3.1 to 1.1 units]; p = 0.23). Patients in the cryopreserved group were more likely to be transfused fresh-frozen plasma (78.3% vs. 27.8%, p = 0.002) and received more study PLT units (median, 2 units vs. 1 unit; difference between groups, 1 unit [95% CI, -0.03 to 2.0 units]; p = 0.012). There were no between-group differences in potential harms including deep venous thrombosis, myocardial infarction, respiratory function, infection, and renal function. No patient had died at 28 days, and postoperative length of stay was similar in each group. CONCLUSION: In this pilot RCT, compared to liquid-stored PLTs, cryopreserved PLTs were associated with no evidence of harm. A definitive study testing safety and hemostatic effectiveness is warranted.

Association of time to craniectomy with survival in patients with severe combat-related brain injury.

OBJECTIVEIn combat and austere environments, evacuation to a location with neurosurgery capability is challenging. A planning target in terms of time to neurosurgery is paramount to inform prepositioning of neurosurgical and transport resources to support a population at risk. This study sought to examine the association of wait time to craniectomy with mortality in patients with severe combat-related brain injury who received decompressive craniectomy.METHODSPatients with combat-related brain injury sustained between 2005 and 2015 who underwent craniectomy at deployed surgical facilities were identified from the Department of Defense Trauma Registry and Joint Trauma System Role 2 Registry. Eligible patients survived transport to a hospital capable of diagnosing the need for craniectomy and performing surgery. Statistical analyses included unadjusted comparisons of postoperative mortality by elapsed time from injury to start of craniectomy, and Cox proportional hazards modeling adjusting for potential confounders. Time from injury to craniectomy was divided into quintiles, and explored in Cox models as a binary variable comparing early versus delayed craniectomy with cutoffs determined by the maximum value of each quintile (quintile 1 vs 2-5, quintiles 1-2 vs 3-5, etc.). Covariates included location of the facility at which the craniectomy was performed (limited-resource role 2 facility vs neurosurgically capable role 3 facility), use of head CT scan, US military status, age, head Abbreviated Injury Scale score, Injury Severity Score, and injury year. To reduce immortal time bias, time from injury to hospital arrival was included as a covariate, entry into the survival analysis cohort was defined as hospital arrival time, and early versus delayed craniectomy was modeled as a time-dependent covariate. Follow-up for survival ended at death, hospital discharge, or hospital day 16, whichever occurred first.RESULTSOf 486 patients identified as having undergone craniectomy, 213 (44%) had complete date/time values. Unadjusted postoperative mortality was 23% for quintile 1 (n = 43, time from injury to start of craniectomy 30-152 minutes); 7% for quintile 2 (n = 42, 154-210 minutes); 7% for quintile 3 (n = 43, 212-320 minutes); 19% for quintile 4 (n = 42, 325-639 minutes); and 14% for quintile 5 (n = 43, 665-3885 minutes). In Cox models adjusted for potential confounders and immortal time bias, postoperative mortality was significantly lower when time to craniectomy was within 5.33 hours of injury (quintiles 1-3) relative to longer delays (quintiles 4-5), with an adjusted hazard ratio of 0.28, 95% CI 0.10-0.76 (p = 0.012).CONCLUSIONSPostoperative mortality was significantly lower when craniectomy was initiated within 5.33 hours of injury. Further research to optimize craniectomy timing and mitigate delays is needed. Functional outcomes should also be evaluated.

Trauma Hemostasis and Oxygenation Research Network position paper on the role of hypotensive resuscitation as part of remote damage control resuscitation.

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 100 mm 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".

Activation of the protein C pathway and endothelial glycocalyx shedding is associated with coagulopathy in an ovine model of trauma and hemorrhage.

INTRODUCTION: Acute traumatic coagulopathy (ATC) is an endogenous coagulopathy that develops following tissue injury and shock. The pathogenesis of ATC remains poorly understood, with platelet dysfunction, activation of the protein C pathway, and endothelial glycocalyx shedding all hypothesized to contribute to onset. The primary aim of this study was to develop an ovine model of traumatic coagulopathy, with a secondary aim of assessing proposed pathophysiological mechanisms within this model. METHODS: Twelve adult Samm-Border Leicester cross ewes were anesthetized, instrumented, and divided into three groups. The moderate trauma group (n = 4) underwent 20% blood volume hemorrhage, bilateral tibial fractures, and pulmonary contusions. The severe trauma group (n = 4) underwent the same injuries, an additional hamstring crush injury, and 30% blood volume hemorrhage. The remaining animals (n = 4) were uninjured controls. Blood samples were collected at baseline and regularly after injury for evaluation of routine hematology, arterial blood gases, coagulation and platelet function, and factor V, factor VIII, plasminogen activator inhibitor 1, syndecan 1, and hyaluranon levels. RESULTS: At 4 hours after injury, a mean increase in international normalized ratio of 20.50% ± 12.16% was evident in the severe trauma group and 22.50% ± 1.00% in the moderate trauma group. An increase in activated partial thromboplastin time was evident in both groups, with a mean of 34.25 ± 1.71 seconds evident at 2 hours in the severe trauma animals and 34.75 ± 2.50 seconds evident at 4 hours in the moderate trauma animals. This was accompanied by a reduction in ROTEM EXTEM A10 in the severe trauma group to 40.75 ± 8.42 mm at 3 hours after injury. Arterial lactate and indices of coagulation function were significantly correlated (R = -0.86, p < 0.0001). Coagulopathy was also correlated with activation of the protein C pathway and endothelial glycocalyx shedding. While a significant reduction in platelet count was evident in the severe trauma group at 30 minutes after injury (p = 0.018), there was no evidence of altered platelet function on induced aggregation testing. Significant fibrinolysis was not evident. CONCLUSIONS: Animals in the severe trauma group developed coagulation changes consistent with current definitions of ATC. The degree of coagulopathy was correlated with the degree of shock, quantified by arterial lactate. Activation of the protein C pathway and endothelial glycocalyx shedding were correlated with the development of coagulopathy; however, altered platelet function was not evident in this model.

Frailty and Geriatric Syndromes in Vascular Surgical Ward Patients.

BACKGROUND: Preoperative frailty is an important predictor of poor outcomes but the relationship between frailty and geriatric syndromes is less clear. The aims of this study were to describe the prevalence of frailty and incidence of geriatric syndromes in a cohort of older vascular surgical ward patients, and investigate the association of frailty and other key risk factors with the occurrence of one or more geriatric syndromes (delirium, functional decline, falls, and/or pressure ulcers) and two hospital outcomes (acute length of stay and discharge destination). METHODS: This prospective cohort study was conducted in a vascular surgical ward in a tertiary teaching hospital in Brisbane, Australia. Consecutive patients aged ≥65 years, admitted for ≥72 hr, were eligible for inclusion. Frailty was defined as one or more of functional dependency, cognitive impairment, or nutritional impairment at admission. Delirium was identified using the Confusion Assessment Method and a validated chart extraction tool. Functional decline from admission to discharge was identified from daily nursing documentation of activities of daily living. Falls were identified according to documentation in the medical record cross-checked with the incident reporting system. Pressure ulcers, acute length of stay, and discharge destination were identified by documentation in the medical record. Risk factors associated with geriatric syndromes, acute length of stay, and discharge destination were assessed using multivariable logistic regression models. RESULTS: Of 110 participants, 43 (39%) patients were frail and geriatric syndromes occurred in 40 (36%). Functional decline occurred in 25% of participants, followed by delirium (20%), pressure ulcers (12%), and falls (4%). In multivariable logistic analysis, frailty [odds ratio (OR) 6.7, 95% confidence interval (CI) 2.0-22.1, P = 0.002], nonelective admission (OR 7.2, 95% CI 2.2-25.3, P = 0.002), higher physiological severity (OR 5.5, 95% CI 1.1-26.8, P = 0.03), and operative severity (OR 4.6, 95% CI 1.2-17.7, P = 0.03) increased the likelihood of any geriatric syndrome. Frailty was an important predictor of longer length of stay (OR 2.6, 95% CI 1.0-6.8, P = 0.06) and discharge destination (OR 4.2, 95% CI 1.2-13.8, P = 0.02). Nonelective admission significantly increased the likelihood of discharge to a higher level of care (OR 5.3, 95% CI 1.3-21.6, P = 0.02). CONCLUSIONS: Frailty and geriatric syndromes were common in elderly vascular surgical ward patients. Frail patients and nonelective admissions were more likely to develop geriatric syndromes, have a longer length of stay, and be discharged to a higher level of care.

Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial.

IMPORTANCE: Acute kidney injury (AKI) is characterized by severe loss of glomerular filtration rate (GFR) and is associated with a prolonged intensive care unit (ICU) stay and increased risk of death. No interventions have yet been shown to prevent AKI or preserve GFR in critically ill patients. Evidence from mammalian physiology and small clinical trials suggests higher amino acid intake may protect the kidney from ischemic insults and thus may preserve GFR during critical illness. OBJECTIVE: To determine whether amino acid therapy, achieved through daily intravenous (IV) supplementation with standard amino acids, preserves kidney function in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, phase II, randomized clinical trial conducted between December 2010 and February 2013 in the ICUs of 16 community and tertiary hospitals in Australia and New Zealand. Participants were adult critically ill patients expected to remain in the study ICU for longer than 2 days. INTERVENTIONS: Random allocation to receive a daily supplement of up to 100 g of IV amino acids or standard care. MAIN OUTCOMES AND MEASURES: Duration of renal dysfunction (primary outcome); estimated GFR (eGFR) derived from creatinine; eGFR derived from cystatin C; urinary output; renal replacement therapy (RRT) use; fluid balance and other measures of renal function. RESULTS: 474 patients were enrolled and randomized (235 to standard care, 239 to IV amino acid therapy). At time of enrollment, patients allocated to receive amino acid therapy had higher APACHE II scores (20.2 ± 6.8 vs. 21.7 ± 7.6, P = 0.02) and more patients had pre-existing renal dysfunction (29/235 vs. 44/239, P = 0.07). Duration of renal dysfunction after enrollment did not differ between groups (mean difference 0.21 AKI days per 10 patient ICU days, 95 % CI -0.27 to 1.04, P = 0.45). Amino acid therapy significantly improved eGFR (treatment group × time interaction, P = 0.004), with an early peak difference of 7.7 mL/min/1.73 m(2) (95 % CI 1.0-14.5 mL/min/1.73 m(2), P = 0.02) on study day 4. Daily urine output was also significantly increased (+300 mL/day, 95 % CI 145-455 mL, P = 0.0002). There was a trend towards increased RRT use in patients receiving amino acid therapy (13/235 vs. 25/239, P = 0.062); however, this trend was not present after controlling for baseline imbalance (P = 0.21). CONCLUSION AND RELEVANCE: Treatment with a daily IV supplement of standard amino acids did not alter our primary outcome, duration of renal dysfunction. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12609001015235.

In vitro comparison of cryopreserved and liquid platelets: potential clinical implications.

BACKGROUND: Platelet (PLT) concentrates can be cryopreserved in dimethyl sulfoxide (DMSO) and stored at -80°C for 2 years. These storage conditions improve availability in both rural and military environments. Previous phenotypic and in vitro studies of cryopreserved PLTs are limited by comparison to fresh liquid-stored PLTs, rather than PLTs stored over their clinically relevant shelf life. Further, nothing is known of the effect of reconstituting cryopreserved PLTs in plasma stored at a variety of clinically relevant temperatures. STUDY DESIGN AND METHODS: Apheresis PLTs were either stored at room temperature for 5 days or cryopreserved at -80°C with 5% DMSO. Cryopreserved PLTs were thawed at 37°C and reconstituted in plasma (stored at different temperatures) and compared to fresh and expired liquid-stored PLTs. In vitro assays were performed to assess glycoprotein expression, PLT activity, microparticle content, and function. RESULTS: Compared to liquid PLTs over storage, cryopreserved PLTs had reduced expression of the key glycoprotein receptors GPIbα and GPIIb. However, the proportion of PLTs expressing activation markers CD62P and CD63 was similar between cryopreserved and liquid-stored PLTs at expiry. Cryopreserved PLT components contained significantly higher numbers of phosphatidylserine- and tissue factor-positive microparticles than liquid-stored PLTs, and these microparticles reduced the time to clot formation and increased thrombin generation. CONCLUSION: There are distinct differences between cryopreserved and liquid-stored PLTs. Cryopreserved PLTs also have an enhanced hemostatic activity. Knowledge of these in vitro differences will be essential to understanding the outcomes of a clinical trial comparing cryopreserved PLTs and liquid PLTs stored for various durations.