Fluid resuscitation in emergency patients with sepsis and hypotension (ARISE Fluids)

The question of fluid volume in resuscitation has been identified as the top priority in sepsis research by emergency physicians in the United Kingdom, Australia and New Zealand. Guidelines and sepsis pathways recommend an initial intravenous (IV) fluid bolus of 30ml/kg isotonic crystalloid for patients with sepsis and hypotension. However, there is a lack of evidence from clinical trials to support this strategy. Both observational data as well as randomised studies suggest there may be harm associated with injudicious use of fluids in sepsis. Since there is equipoise regarding a more liberal or restricted fluid volume resuscitation as first line treatment for sepsis-related hypotension, we conducted the pilot multicentre REstricted Fluid REsuscitation in Sepsis-associated Hypotension (REFRESH) trial comparing a restricted fluid protocol with early initiation of vasopressor support against standard guideline care.

The data from REFRESH will inform feasibility of a large, multicentre phase III study. However, further ground work is essential for the optimal design of a Phase III trial that will provide valuable information on feasibility (road test recruitment rate and screening processes) as well as refinement of the protocol (sample size estimation, processes of care, prevalence of the population of interest, real world clinical practice regarding fluid use).

In this ARISE Fluids study, we aim to provide more insight into current practice by conducting a bi-national multi-site prospective observational study of fluid administration in (suspected) sepsis and hypotension in the Emergency Departments of Australia and New Zealand hospitals. Sites have been selected on the basis of having expressed interest in participating in a phase III trial.

Is prednisolone an effective treatment for Bell’s Palsy in children?

Bell’s palsy or acute idiopathic lower motor neurone facial paralysis is characterised by sudden onset paralysis or weakness of the muscles to one side of the face controlled by the facial nerve. It is the third most common neurological reason for children to present acutely to hospital.

In adults, there is conclusive evidence from two major recent trials that a short course of prednisolone, a cheap, widely available and safe steroid, can significantly increase the number of Bell’s palsy patients who completely recover. While the medical problems associated with Bell’s palsy are similar, in children there is no good evidence that prednisolone is an effective treatment.

Many neurological conditions progress differently in children and treatment methods sometimes vary. Children may react differently to prednisolone and without paediatric evidence; treatment guidelines for children with Bell’s palsy remain absent or vague, with variable and overall low rates of steroid use in children by physicians.

The lack of evidence and clinical uncertainty in the treatment of Bell’s palsy in children warrants a definitive trial to determine the efficacy of prednisolone as a treatment for this condition in children. The aim of this study is to assess the utility of steroids in Bell’s palsy in children in a large multicentre randomised, placebo-controlled, trial. The trial will take place in at least 10 hospitals within Australia and New Zealand, involving more than 500 children.

ConSEPT: Convulsive Status Epilepticus Paediatric Trial

Convulsive Status Epilepticus (CSE) is the most common childhood neurological emergency, sometimes resulting in death or serious disability. CSE is managed with anticonvulsant medications in a step-wise approach until seizures stop. While some management strategies for CSE are well supported by evidence (e.g. initial administration of benzodiazepines), subsequent strategies are based on expert consensus and not evidence. Phenytoin, the traditional second line agent for CSE has a high failure rate, causes adverse events and must be administered slowly. Levetiracetam, a newer anticonvulsant, has a favourable adverse events profile, can be administered quickly and has good efficacy for various seizure types.

This research project proposes to undertake a randomised controlled trial of the second line anticonvulsants phenytoin and levetiracetam for CSE in children. This multi-centre study was a world first and is likely to have a profound impact on the management of CSE in children in New Zealand, Australia and worldwide, in either confirming the current second line medication used or recommending a newer second line medication.