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.

Publication outcomes among intensive care trainees.

There is a paucity of literature describing the research productivity among trainees in intensive care medicine. We sought to examine the occurrence and determinants of successful publication outcomes associated with intensive care training. The study cohort consisted of all individuals admitted to fellowship of the College of Intensive Care Medicine of Australia and New Zealand (CICM) from 2012 to 2019. The primary outcome measure of this study was manuscripts indexed on PubMed within one year after and four years prior to admittance to CICM fellowship. Four hundred and eighty-five fellows were identified of whom 216 (45%) had at least one publication; 129 (27%) had one, 34 (7%) had two, 21 (4%) had three and 32 (7%) had four or more publications. Overall 138 (28%) fellows had at least one publication that was likely associated with their mandatory CICM training project for which they were first (n = 110; 80%) and/or corresponding (n = 72; 52%) author in the majority of cases. Overall 107 different senior/mentor authors were identified, with 13 individuals supporting more than one publication. Although gender and location at the time of fellowship award were not associated, location of receipt of medical degree, shorter time period between medical school graduation and fellowship award, more recent year of award, and completion of medical degree/fellowship in the same geographical region were associated with project publication. A minority of CICM fellows have PubMed-indexed publications related to their training. Further efforts are warranted to better define the determinants of successful project publication to optimise future opportunities.

Cannabis use disorders and outcome of admission to intensive care: A retrospective multi-centre cohort study.

PURPOSE: To identify factors associated with cannabinoid use among patients admitted to ICU and its impact on survival. METHODS: A cohort of adult patients admitted to four public Australian ICUs was assembled. Individuals with mental and behavioural disorders related to cannabinoids were identified using ICD10-AM codes. RESULTS: Of a cohort of 34,680 admissions among 28,689 adults, 292 (0.8%) had an associated diagnosis related to cannabinoids, of which 66% were classified as harmful use, 26% as dependence syndrome/withdrawal state, 4% as psychosis/delirium, and 4% as acute intoxication. Patients with cannabinoid-use disorders were more likely to be male (73%), tended to be younger (36 vs 62 years), with fewer comorbidities and lesser severity of disease. ICU LOS was longer for those with cannabinoid-use disorders (2 vs 1 days; p < 0.0001). Patients with cannabinoid-use disorders had lower 90-day case-fatality (6% vs. 10%; p = 0.034), however no significant effect on mortality was present after adjustment for severity of illness, age, and chronic comorbidities (p = 1.0). CONCLUSION: Cannabinoid-use disorders were present in 0.8% of ICU admissions in our region and were associated with increased ICU length of stay. Further studies are needed to examine cannabinoids as contributors to and modifiers of critical illness.

Fingolimod does not prevent syndecan-4 shedding from the endothelial glycocalyx in a cultured human umbilical vein endothelial cell model of vascular injury.

BACKGROUND: Shedding of the endothelial glycocalyx (EG) is associated with poor outcomes in a range of conditions including sepsis. Fresh frozen plasma (FFP) restores the damaged EG to baseline thickness, however the mechanism for this effect is unknown, and some components of FFP have adverse effects unrelated to the EG. There is some limited evidence that sphingosine-1-phosphate (S1P) within FFP restores the EG by activating the endothelial cell S1P receptor 1 (S1PR1). However, there are disadvantages to using S1P clinically as an EG restorative therapy. A potential alternative is the S1PR agonist fingolimod (FTY720). The aim of this study was to assess whether FTY720 prevents EG shedding in injured cultured human umbilical vein endothelial cells. METHODS: Shedding of the EG was induced in cultured human umbilical vein endothelial cells (HUVECs) by exposure to adrenaline, TNF-α and H2O2. The cells were then assigned to one of six conditions for 4 h: uninjured and untreated, injured and untreated, injured and treated with FTY720 with and without the S1PR1 inhibitor W146, and injured and treated with 25% FFP with and without W146. Syndecan-4, a component of the EG, was measured in cell supernatants, and syndecan-4 and thrombomodulin mRNA expression was quantitated in cell lysates. RESULTS: The injury resulted in a 2.1-fold increase in syndecan-4 (p < 0.001), consistent with EG shedding. Syndecan-4 and thrombomodulin mRNA expression was increased (p < 0.001) and decreased (p < 0.05), respectively, by the injury. Syndecan-4 shedding was not affected by treatment with FTY720, whereas FFP attenuated syndecan-4 shedding back to baseline levels in the injured cells and this was unaffected by W146. Neither treatment affected syndecan-4 or thrombomodulin mRNA expression. CONCLUSIONS: FTY720 did not prevent syndecan-4 shedding from the EG in the HUVEC model of endothelial injury, suggesting that activation of S1PR does not prevent EG damage. FFP prevented syndecan-4 shedding from the EG via a mechanism that was independent of S1PR1 and upregulation of SDC-4 production. Further studies to examine whether FTY720 or another S1PR agonist might have EG-protective effects under different conditions are warranted, as are investigations seeking the mechanism of EG protection conferred by FFP in this experimental model.

Resuscitation Fluid Choices to Preserve the Endothelial Glycocalyx.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2019 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

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.

Comprehensive review of platelet storage methods for use in the treatment of active hemorrhage.

This review considers the various methods currently in use, or under investigation, for the storage of platelets intended for use in the treatment of active hemorrhage. The current standard practice of storing platelets at room temperature (RT) (20°C-24°C) optimizes circulating time, but at the expense of hemostatic function and logistical considerations. A number of alternatives are under investigation. Novel storage media additives appear to attenuate the deleterious changes that affect RT stored platelets. Cold storage was originally abandoned due to the poor circulating time of platelets stored at 4°C, but such platelets may actually be more hemostatically effective, with a number of other advantages, compared to RT stored platelets. Periodically re-warming cold stored platelets (temperature cycling, TC) may combine the hemostatic efficacy of cold stored platelets with the longer circulating times of RT storage. Alternatives to liquid storage include cryopreservation (freezing) or lyophilization (freeze-drying). The former has had some limited clinical use and larger clinical trials are underway, while the latter is still in the preclinical stage with promising in vitro and in vivo results. The importance of platelet transfusion in the management of active hemorrhage is now well accepted, so it is timely that platelet storage methods are reviewed with consideration of not only their circulating time, but also their hemostatic efficacy.