Landmark Australasian Study Finds No Survival Benefit from Earlier Vasopressors Compared with a Fluid-First Approach in Septic Shock

A major international study, published in The New England Journal of Medicine, has found that outcomes for critically unwell patients with severe infections were the same, regardless of which of the two different treatment approaches were started in the Emergency Department (ED). The ARISE FLUIDS study was led in New Zealand by Associate Professor Peter Jones, University of Auckland and Director of Emergency Medicine Research at Te Toka Tumai Auckland City Hospital and project managed by Sally Hurford, Senior Project Manager at MRINZ. 

The research was conducted across 51 hospitals in Australia, New Zealand and Ireland, enrolling 1,000 adults presenting to emergency departments with septic shock (dangerously low blood pressure due to infection). Septic shock is one of the leading causes of critical illness and death worldwide. 

Vasopressors (medicines that raise the blood pressure), and fluids, through an intravenous line, are given to improve circulation when patients have septic shock. Before the study, there was uncertainty around how much fluid should be given and when to start vasopressors in septic shock.  

The researchers compared a restricted-fluid, early-vasopressor strategy with a liberal-fluid, later-vasopressor approach during the first 24 hours of treatment. 

The study found no difference in the primary outcome: the number of days patients spent in hospital during the three months following enrolment. Survival rates at 90 days were also similar between the two treatment approaches. 

Importantly, patients who got vasopressors early were given less intravenous fluid and experienced lower rates of fluid on the lungs (0.6% versus 5.0%). 

Lead investigators said the findings provide high-quality evidence to guide the early management of septic shock.  

Associate Professor Peter Jones says the results suggest clinicians can safely use either strategy, tailoring treatment to individual patient needs and local resources. 

“There has been considerable uncertainty about the best way to initially resuscitate patients with septic shock, particularly around how much fluid to give and when to start vasopressors. This trial provides important evidence that clinicians can use either approach, depending on the individual patient and clinical circumstances. Most importantly, it gives us better evidence to guide decisions in those critical early hours of septic shock,” he says. 

The New Zealand Sepsis Trust has welcomed the results of the study, with the Chair of its Clinical & Scientific Committee, Dr. Paul Huggan, saying it answers some important questions for frontline clinicians. 

“Despite the significant burden of sepsis, many key questions about how best to prevent, recognise and treat it remain unanswered. High-quality research like this is critical to generating the evidence needed to improve outcomes and reduce the devastating short- and long-term impact of sepsis,” he says. 

The New Zealand Sepsis Trust’s CEO, Ally Hossain, acknowledges the significant contribution this research will make to the international evidence on how we treat sepsis. 

“Having this research led from New Zealand, involving hospitals across Australasia, demonstrates the strength of our emergency and critical care research community. The study offers high-quality evidence to inform clinical decision-making at the bedside; decisions which we know are time-critical in sepsis cases,” she says. 

The ARISE FLUIDS trial was funded by the Australian Medical Research Future Fund and the New Zealand Health Research Council and represents a collaboration between the Australian and New Zealand Intensive Care Society Clinical Trials Group, the Australasian College for Emergency Medicine Clinical Trials Network, the New Zealand Emergency Medicine Network and the Australian and New Zealand Intensive Care Research Centre.