According to a National Institutes of Health sponsored clinical trial that was conducted at several North American hospitals and was led by clinician-scientists at the University of Pittsburgh and University of Colorado schools of medicine, reversibly paralysing and sedating hospitalised patients with severe breathing problems does not prove improve patient outcomes in a large majority of cases. Findings were presented at the American Thoracic Society's Annual Meeting and are published in the New England Journal of Medicine.
This trial was conducted to settle an ongoing debate within the critical care medicine community as to whether it is better to paralyse and sedate patients in acute respiratory distress or to avoid heavy sedation to improve the patient’s recovery. According to senior author Derek Angus, Chair of PITT's Department of Critical Care Medicine, this issue has always been a dilemma for clinicians since many well-done clinical studies show that temporarily paralysing patients to improve mechanical breathing could save lives. But it is not possible to paralyse a patient without heavy sedation. As per the findings of the trial, sedation results in worse recovery, hence providing the answer to this long-standing debate that sedation with intermittent short-term paralysis is as good as deep sedation with continuous paralysis.
The trial - Re-evaluation Of Systemic Early neuromuscular blockade (ROSE) is the first of the National Heart, Lung, and Blood Institute's (NHLBI) Prevention & Early Treatment of Acute Lung Injury (PETAL) Network. The network conducts clinical trials designed to prevent diseases or treat patients who are at risk for acute lung injury or acute respiratory distress syndrome (ARDS). One of the key areas of emphasis for the PETAL Network is early detection, and that is why every member institute of this network is required to include critical care, emergency medicine, acute care or trauma principal investigators. This is to ensure that critical issues are recognised and triaged, and the odds of patient recovery are improved before they even get to the intensive care unit.
The ROSE trial has already enrolled 1006 patients in 48 US and Canadian hospitals. The patients were enrolled within hours after the onset of moderate to severe ARDS. Half of the patient population was given a 48-hour continuous neuromuscular blockade and heavy sedation while the other half was given light sedation. Study clinicians had the option of giving a small dose of neuromuscular blockade that would wear off within an hour to ease respiratory intubation.
James Kiley, Director of the Division of Lung Diseases at the NHLBI, explains that the PETAL network wants to conduct trials that would help answer these important questions. The results of these trials can help clinicians make decisions early on so that they can provide better care for patients with ARDS.
The idea for the ROSE trial originated because of findings from another trial in 2010 that reported reduced mortality with neuromuscular blockade. All participants in that French trial were heavy sedated, whether they received the neuromuscular blockade or not. But in North America, clinicians have been trying to stay away from heavy sedation as it is associated with cardiovascular complications, delirium, and increased difficulty weaning patients from mechanical ventilation.
Findings from the ROSE trial show that patients who received the neuromuscular blockade and were highly sedated developed more cardiovascular issues while in the hospital. However, no significant difference was found in mortality between the two groups at three months, six months, or 12 months follow-up.
The study has completed enrolment ahead of schedule, and it is believed that findings will soon be available for healthcare providers, which could result in rapid implementation of enhanced care for ARDS patients. Derek Angus has said that so far, the results suggest that avoiding paralysis and deep sedation is the best practice for most patients who are hospitalised for breathing problems. But future trials will have to test whether there is a subpopulation of patients with ARDS who could still benefit from neuromuscular blockade.