Hypertonic Saline Lacks Benefit in TBI; Trial Shut Down
By Michele G. Sullivan
Elsevier Global Medical News
A randomized trial exploring the benefit of hypertonic saline resuscitation in patients with traumatic brain injury has been halted, after an interim analysis determined that the intervention was not significantly better than resuscitation with normal saline.
The National Heart, Lung and Blood Institute--the study's main federal sponsor--stopped enrollment in the trial on May 12 on the recommendation of the Data Safety and Monitoring Board, according to a statement. The statement said safety concerns did not play a role in the decision, despite a finding that patients who received hypertonic saline died earlier than those who received normal saline. Mortality rates at 28 days, however, were similar. Data from the 6-month follow-up analysis of 1,073 patients did not show any trend toward earlier death in those who received the hypertonic solutions.
The finding of no benefit was a disappointment, said Dr. Elizabeth G. Nabel, director of the NHLBI. "Improving treatment and survival of traumatic injury are critical public health problems," she said in the statement. "While these study results did not show the expected benefit of one type of treatment, other findings by the resuscitation consortium researchers--and hundreds of emergency and fire services teams they are working with--may lead to new life-saving intervention strategies."
The study, the largest randomized clinical trial ever conducted for severely brain injured patients, was being conducted by the Resuscitation Outcomes Consortium, a network of clinical research sites in the United States and Canada.
It randomized trauma patients with severe traumatic brain injury to one of three fluid treatment strategies for prehospital resuscitation: a single 250-mL intravenous dose of either 7.5% saline in 6% Dextran-70; 7.5% saline; or normal saline. In-hospital data collection lasted up to 28 days. Patients had neurologic outcome measurements at discharge, and at 1 and 6 months post injury.
In March, the NHLBI also stopped a parallel study examining the effect of the three solutions in patients with shock from severe bleeding. Enrollment in that trial ceased in August 2008, after an interim analysis found that more patients receiving the hypertonic solution died before reaching the hospital.
However, no significant overall mortality difference was found at 28 days. A further analysis of 545 patients confirmed these findings, but did not fully explain them, according to an NHLBI statement.
Investigators hoped the trials would support earlier studies, which suggested that resuscitation with hypertonic fluids might aid in rapid restoration of cerebral perfusion and prevent extravascular fluid sequestration, thus limiting secondary brain injury. Other data suggested that hypertonicity could decrease the activation of inflammatory cells, and reduce subsequent organ injury from ischemia-reperfusion and, possibly, nosocomial infection (www.clinicaltrials.gov; trial identifier number NCT00316004).n