Showing papers by "Russell L. Gruen published in 2023"

Prehospital Tranexamic Acid for Severe Trauma.

Abstract: BACKGROUND Whether prehospital administration of tranexamic acid increases the likelihood of survival with a favorable functional outcome among patients with major trauma and suspected trauma-induced coagulopathy who are being treated in advanced trauma systems is uncertain. METHODS We randomly assigned adults with major trauma who were at risk for trauma-induced coagulopathy to receive tranexamic acid (administered intravenously as a bolus dose of 1 g before hospital admission, followed by a 1-g infusion over a period of 8 hours after arrival at the hospital) or matched placebo. The primary outcome was survival with a favorable functional outcome at 6 months after injury, as assessed with the use of the Glasgow Outcome Scale-Extended (GOS-E). Levels on the GOS-E range from 1 (death) to 8 ("upper good recovery" [no injury-related problems]). We defined survival with a favorable functional outcome as a GOS-E level of 5 ("lower moderate disability") or higher. Secondary outcomes included death from any cause within 28 days and within 6 months after injury. RESULTS A total of 1310 patients were recruited by 15 emergency medical services in Australia, New Zealand, and Germany. Of these patients, 661 were assigned to receive tranexamic acid, and 646 were assigned to receive placebo; the trial-group assignment was unknown for 3 patients. Survival with a favorable functional outcome at 6 months occurred in 307 of 572 patients (53.7%) in the tranexamic acid group and in 299 of 559 (53.5%) in the placebo group (risk ratio, 1.00; 95% confidence interval [CI], 0.90 to 1.12; P = 0.95). At 28 days after injury, 113 of 653 patients (17.3%) in the tranexamic acid group and 139 of 637 (21.8%) in the placebo group had died (risk ratio, 0.79; 95% CI, 0.63 to 0.99). By 6 months, 123 of 648 patients (19.0%) in the tranexamic acid group and 144 of 629 (22.9%) in the placebo group had died (risk ratio, 0.83; 95% CI, 0.67 to 1.03). The number of serious adverse events, including vascular occlusive events, did not differ meaningfully between the groups. CONCLUSIONS Among adults with major trauma and suspected trauma-induced coagulopathy who were being treated in advanced trauma systems, prehospital administration of tranexamic acid followed by an infusion over 8 hours did not result in a greater number of patients surviving with a favorable functional outcome at 6 months than placebo. (Funded by the Australian National Health and Medical Research Council and others; PATCH-Trauma ClinicalTrials.gov number, NCT02187120.).

Pre-hospital freeze-dried plasma for critical bleeding after trauma: A pilot randomized controlled trial.

Abstract: OBJECTIVES Transfusion of a high ratio of plasma to packed red blood cells (PRBC), to treat or prevent acute traumatic coagulopathy, has been associated with survival after major trauma. However, the effect of pre-hospital plasma on patient outcomes has been inconsistent. The aim of this pilot trial was to assess the feasibility of transfusing freeze-dried plasma with red blood cells (RBC) using a randomized controlled design in an Australian aeromedical pre-hospital setting. METHODS Patients attended by Helicopter Emergency Medical Service (HEMS) paramedics with suspected critical bleeding after trauma managed with pre-hospital RBC were randomized to receive two units of freeze-dried plasma (Lyoplas N-w) or standard care (no plasma). The primary outcome was the proportion of eligible patients enrolled and provided the intervention. Secondary outcomes included preliminary data on effectiveness, including mortality censored at 24 hours and at hospital discharge, and adverse events. RESULTS During the study period of 01 June to 31 October 2022, there were 25 eligible patients, of whom 20 (80%) were enrolled in the trial and 19 (76%) received the allocated intervention. Median time from randomization to hospital arrival was 92.5 mins (IQR 68-101.5). Mortality may have been lower in the freeze-dried plasma group at 24h (RR 0.24; 95%CI: 0.03 - 1.73) and at hospital discharge (RR 0.73; 95%CI: 0.24 - 2.27). No serious adverse events related to the trial interventions were reported. CONCLUSIONS This first reported experience of freeze-dried plasma use in Australia suggests pre-hospital administration is feasible. Given longer prehospital times typically associated with HEMS attendance, there is potential clinical benefit from this intervention and rationale for a definitive trial.

Systematic reviews and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: mortality, morbidity, and organ failure.

Abstract: BackgroundMortality, morbidity, and organ failure are important and common serious harms after surgery. However, there are many candidate measures to describe these outcome domains. Definitions of these measures are highly variable, and validity is often unclear. As part of the International Standardised Endpoints in Perioperative Medicine (StEP) initiative, this study aimed to derive a set of standardised and valid measures of mortality, morbidity, and organ failure for use in perioperative clinical trials.MethodsThree domains of endpoints (mortality, morbidity, and organ failure) were explored through systematic literature review and a three-stage Delphi consensus process using methods consistently applied across the StEP initiative. Reliability, feasibility, and patient-centredness were assessed in round 3 of the consensus process.ResultsA high level of consensus was achieved for two mortality time points, 30-day and 1-yr mortality, and these two measures are recommended. No organ failure endpoints achieved threshold criteria for consensus recommendation. The Clavien–Dindo classification of complications achieved threshold criteria for consensus in round 2 of the Delphi process but did not achieve the threshold criteria in round 3 where it scored equivalently to the Post Operative Morbidity Survey. Clavien–Dindo therefore received conditional endorsement as the most widely used measure. No composite measures of organ failure achieved an acceptable level of consensus.ConclusionsBoth 30-day and 1-yr mortality measures are recommended. No measure is recommended for organ failure. One measure (Clavien–Dindo) is conditionally endorsed for postoperative morbidity, but our findings suggest that no single endpoint offers a reliable and valid measure to describe perioperative morbidity that is not dependent on the quality of deli-vered care. Further refinement of current measures, or development of novel measures, of postoperative morbidity might improve consensus in this area.

Cell death and barrier disruption by clinically used iodine concentrations

Abstract: Clinically used concentrations of povidone-iodine (PVP-I) are toxic to eukaryotic cells by attacking the lipid bilayer and tight junctions with fast kinetics and urge the reappraisal of PVP-I use. Povidone-iodine (PVP-I) inactivates a broad range of pathogens. Despite its widespread use over decades, the safety of PVP-I remains controversial. Its extended use in the current SARS-CoV-2 virus pandemic urges the need to clarify safety features of PVP-I on a cellular level. Our investigation in epithelial, mesothelial, endothelial, and innate immune cells revealed that the toxicity of PVP-I is caused by diatomic iodine (I2), which is rapidly released from PVP-I to fuel organic halogenation with fast first-order kinetics. Eukaryotic toxicity manifests at below clinically used concentrations with a threshold of 0.1% PVP-I (wt/vol), equalling 1 mM of total available I2. Above this threshold, membrane disruption, loss of mitochondrial membrane potential, and abolition of oxidative phosphorylation induce a rapid form of cell death we propose to term iodoptosis. Furthermore, PVP-I attacks lipid rafts, leading to the failure of tight junctions and thereby compromising the barrier functions of surface-lining cells. Thus, the therapeutic window of PVP-I is considerably narrower than commonly believed. Our findings urge the reappraisal of PVP-I in clinical practice to avert unwarranted toxicity whilst safeguarding its benefits.