Effect of intravenous fluid volume on biomarkers of endothelial glycocalyx shedding and inflammation during initial resuscitation of sepsis.

PURPOSE: To investigate the effect of IV fluid resuscitation on endothelial glycocalyx (EG) shedding and activation of the vascular endothelium and inflammation. MATERIALS AND METHODS: A planned biomarker sub-study of the REFRESH trial in which emergency department (ED) patients) with suspected sepsis and hypotension were randomised to a restricted fluid/early vasopressor regimen or IV fluid resuscitation with later vasopressors if required (usual care). Blood samples were collected at randomisation (T0) and at 3 h (T3), 6 h (T6)- and 24 h (T24) for measurement of a range of biomarkers if EG shedding, endothelial cell activation and inflammation. RESULTS: Blood samples were obtained in 95 of 99 enrolled patients (46 usual care, 49 restricted fluid). Differences in the change in biomarker over time between the groups were observed for Hyaluronan (2.2-fold from T3 to T24, p = 0.03), SYN-4 (1.5-fold from T3 to T24, P = 0.01) and IL-6 (2.5-fold from T0 to T3, p = 0.03). No difference over time was observed between groups for the other biomarkers. CONCLUSIONS: A consistent signal across a range of biomarkers of EG shedding or of endothelial activation or inflammation was not demonstrated. This could be explained by pre-existing EG shedding or overlap between the fluid volumes administered in the two groups in this clinical trial. Trial registration Australia New Zealand Clinical Trials Registry ACTRN126160000006448 Registered 12 January 2016.

Management of adult cardiac arrest in the COVID-19 era: consensus statement from the Australasian College for Emergency Medicine.

INTRODUCTION: The global pandemic of coronavirus disease 2019 (COVID-19) has caused significant worldwide disruption. Although Australia and New Zealand have not been affected as much as some other countries, resuscitation may still pose a risk to health care workers and necessitates a change to our traditional approach. This consensus statement for adult cardiac arrest in the setting of COVID-19 has been produced by the Australasian College for Emergency Medicine (ACEM) and aligns with national and international recommendations. MAIN RECOMMENDATIONS: In a setting of low community transmission, most cardiac arrests are not due to COVID-19. Early defibrillation saves lives and is not considered an aerosol generating procedure. Compression-only cardiopulmonary resuscitation is thought to be a low risk procedure and can be safely initiated with the patient's mouth and nose covered. All other resuscitative procedures are considered aerosol generating and require the use of airborne personal protective equipment (PPE). It is important to balance the appropriateness of resuscitation against the risk of infection. Methods to reduce nosocomial transmission of COVID-19 include a physical barrier such as a towel or mask over the patient's mouth and nose, appropriate use of PPE, minimising the staff involved in resuscitation, and use of mechanical chest compression devices when available. If COVID-19 significantly affects hospital resource availability, the ethics of resource allocation must be considered. CHANGES IN MANAGEMENT: The changes outlined in this document require a significant adaptation for many doctors, nurses and paramedics. It is critically important that all health care workers have regular PPE and advanced life support training, are able to access in situ simulation sessions, and receive extensive debriefing after actual resuscitations. This will ensure safe, timely and effective management of the patients with cardiac arrest in the COVID-19 era.

A 20-year analysis of compressed gas diving-related deaths in Tasmania, Australia.

INTRODUCTION: This study reviews diving deaths that occurred in Tasmanian waters over a 20-year period. METHODS: Detailed analysis was undertaken of deaths that occurred from 01 January 1995 to 31 December 2014. The cases were collated from numerous sources. Utilising a chain of events analysis, factors were identified and assigned to predisposing factors, triggers, disabling agents, disabling injuries and cause of death. These were then scrutinised to ascertain regional variables, remediable factors and linkages which may benefit from targeted risk mitigation strategies. RESULTS: Seventeen deaths were identified across this 20-year period, which included one additional case not previously recorded. All were recreational divers and 15 were male. Five were hookah divers, 12 were scuba divers. Important predisposing factors identified included equipment (condition and maintenance), pre-existing health conditions, diver experience and training. These factors can now be used to promote public health messages for divers. CONCLUSIONS: This 20-year study highlighted regional variations for Tasmanian deaths and presents opportunities for strategies to prevent diving deaths in the future. Of particular concern was the diving practice of 'hookah' diving, which has no governing regulations. The study highlighted the importance of applying a structured methodology such as chain of events analysis to scrutinise diving deaths.

Restricted fluid resuscitation in suspected sepsis associated hypotension (REFRESH): a pilot randomised controlled trial.

PURPOSE: To determine if a regimen of restricted fluids and early vasopressor compared to usual care is feasible for initial resuscitation of hypotension due to suspected sepsis. METHODS: A prospective, randomised, open-label, clinical trial of a restricted fluid resuscitation regimen in the first 6 h among patients in the emergency department (ED) with suspected sepsis and a systolic blood pressure under 100 mmHg, after minimum 1000 ml of IV fluid. Primary outcome was total fluid administered within 6 h post randomisation. RESULTS: There were 99 participants (50 restricted volume and 49 usual care) in the intention-to-treat analysis. Median volume from presentation to 6 h in the restricted volume group was 2387 ml [first to third quartile (Q1-Q3) 1750-2750 ml]; 30 ml/kg (Q1-Q3 32-39 ml/kg) vs. 3000 ml (Q1-Q3 2250-3900 ml); 43 ml/kg (Q1-Q3 35-50 ml/kg) in the usual care group (p < 0.001). Median duration of vasopressor support was 21 h (Q1-Q3 9-42 h) vs. 33 h (Q1-Q3 15-50 h), (p = 0.13) in the restricted volume and usual care groups, respectively. At 90-days, 4 of 48 (8%) in the restricted volume group and 3 of 47 (6%) in the usual care group had died. Protocol deviations occurred in 6/50 (12%) in restricted group and 11/49 (22%) in the usual care group, and serious adverse events in four cases (8%) in each group. CONCLUSIONS: A regimen of restricted fluids and early vasopressor in ED patients with suspected sepsis and hypotension appears feasible. Illness severity was moderate and mortality rates low. A future trial is necessary with recruitment of high-risk patients to determine effects on clinical outcomes in this setting.

REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH): study protocol for a pilot randomised controlled trial.

BACKGROUND: Guidelines recommend an initial intravenous (IV) fluid bolus of 30 ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this. Accumulating observational data suggest harm associated with the injudicious use of fluids in sepsis. There is currently equipoise regarding liberal or restricted fluid-volume resuscitation as first-line treatment for sepsis-related hypotension. A randomised trial comparing these two approaches is, therefore, justified. METHODS/DESIGN: The REstricted Fluid REsuscitation in Sepsis-associated Hypotension trial (REFRESH) is a multicentre, open-label, randomised, phase II clinical feasibility trial. Participants will be patients presenting to the emergency departments of Australian metropolitan hospitals with suspected sepsis and a systolic blood pressure of < 100 mmHg, persisting after a 1000-ml fluid bolus with isotonic crystalloid. Participants will be randomised to either a second 1000-ml fluid bolus (standard care) or maintenance rate fluid only, with the early commencement of a vasopressor infusion to maintain a mean arterial pressure of > 65 mmHg, if required (restricted fluid). All will receive further protocolised fluid boluses (500 ml or 250 ml, respectively), if required during the 6-h study period. The primary outcome measure is total volume administered in the first 6 h. Secondary outcomes include fluid volume at 24 h, organ support 'free days' to day 28, 90-day mortality, and a range of feasibility and process-of-care measures. Participants will also undergo serial measurement, over the first 24 h, of biomarkers of inflammation, endothelial cell activation and glycocalyx degradation for comparison between the groups. DISCUSSION: This is the first randomised trial examining fluid volume for initial resuscitation in septic shock in an industrialised country. A pragmatic, open-label design will establish the feasibility of undertaking a large, international, multicentre trial with sufficient power to assess clinical outcomes. The embedded biomarker study aims to provide mechanistic plausibility for a larger trial by defining the effects of fluid volume on markers of systemic inflammation and the vascular endothelium. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry, ID: ACTRN12616000006448. Registered on 12 January 2016.

First episode schizophrenia in general practice: a national survey.

OBJECTIVE: We sought to establish the views of general practitioners about detecting and managing patients with a first episode of schizophrenia in Ireland. METHOD: Twenty per cent of GPs were invited to participate in a cross-sectional postal survey. RESULTS: Sixty-two per cent (n = 261) participated. Almost all (99.2%) see at least one case of suspected first episode schizophrenia annually. The most commonly (80.7%) encountered symptom is 'bizarre behaviour'. Many (47.7%) rarely or never prescribe antipsychotics to patients whom they suspect have a first episode of schizophrenia. However, 80.6% of GPs reported that they 'always' refer this group of patients to psychiatric services. Over half (57.8%) advised patients with schizophrenia to continue medication for less than a year. A large number of respondents reported that it is difficult to obtain a rapid psychiatric assessment. CONCLUSIONS: GPs want more information about identifying early psychosis, a closer liaison with psychiatric services and a rapid intervention service.