Study of Concentrated Saline for People With Traumatic Shock Halted

03/26/09  Portland, Ore.

Study being conducted at OHSU and other sites nationwide has been stopped due to lack of survival benefit

One portion of a clinical trial testing hypertonic saline in people with traumatic injuries has been halted by the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health. The trial was stopped in people experiencing shock from severe blood loss because they were no more likely to survive than people who received normal saline solution.

 

The current standard of care in treating people with traumatic injuries includes administering normal saline solution intravenously in the field to compensate for blood loss and to buy time until a blood transfusion can be safely administered at a hospital. The hypertonic saline study was testing whether hypertonic saline (water with a higher salt content than blood) or hypertonic saline with dextran (an added sugar molecule) could improve survival or brain function recovery in people with traumatic brain injuries or shock from severe blood loss. Hypertonic saline is believed to compensate for blood loss more effectively, lessen excessive inflammatory responses and prevent brain swelling.

The NHLBI suspended enrollment in the shock portion of the hypertonic saline study on Aug. 25, 2008, due to concerns raised by ROC’s independent Data and Safety Monitoring Board (DSMB). The DSMB found no difference among the saline and the hypertonic saline treatment groups in 28-day mortality. However, more of the patients who received hypertonic saline died before reaching the hospital or in the emergency department, while more of the patients who received normal saline died during the remainder of the 28-day follow-up period.

Further analysis requested by the DSMB looked at in-hospital data from 545 people in the largest enrolling hospital from each site.  The results, presented to the DSMB on Feb. 25, 2009, confirmed the previous findings that deaths occurred earlier in patients who received hypertonic saline and that there was no significant difference in cumulative mortality between the hypertonic and normal saline groups at 28 days. However, the new analysis did not fully explain the mortality findings. The investigators are completing analyses of these results and will submit them for publication in a peer-reviewed scientific journal.

No similar concerns were found about earlier mortality in the traumatic brain injury portion of the trial, but it was also temporarily and voluntarily suspended last August so that emergency medical service (EMS) personnel could be retrained to enroll only brain injury patients, not those who would have been eligible for the shock study.  The traumatic brain injury study resumed in late November 2008 and continues to investigate whether hypertonic saline improves survival and brain function in patients six months after traumatic injury.

“Hypertonic saline has been shown to reduce swelling and improve blood flow to the brain in smaller studies, and we remain hopeful it will prove beneficial in improving recovery from traumatic brain injuries,” said the principal investigator of the Greater Portland ROC site Terri Schmidt, M.D. Schmidt is a professor of emergency medicine in the OHSU School of Medicine.

The greater Portland ROC site has enrolled a total of 160 people in the hypertonic saline trial. Of those, 98 have been enrolled in the traumatic brain injury study, and 62 were enrolled in the shock study.

Individuals eligible for enrollment in these studies are unable to provide consent to be in a research study due to the nature of their conditions.  Because of this, the studies are being conducted under Food and Drug Administration (FDA) guidelines that allow research in certain life-threatening situations without pretreatment authorization.

The hypertonic saline study is part of the National Institutes of Health-funded Resuscitation Outcomes Consortium (ROC). The ROC comprises 10 regional medical centers in the United States and Canada that seek to find promising scientific and clinical advances to improve survival from cardiac arrest and severe trauma. Portland was designated a ROC community in 2004. OHSU is also currently enrolling people in another ROC study testing methods of resuscitating victims of cardiac arrest.

Currently emergency medical services agencies across North America use slightly varying methods to treat patients. The ROC allows studies to be conducted in rural and urban areas simultaneously, thus allowing a large number of diverse individuals to be enrolled and results to more quickly guide future practice. EMS agencies and hospitals in Multnomah, Clackamas, Washington and Clark counties are working together to conduct this research.

The NHLBI is the lead sponsor of the ROC studies with additional funding provided by the NIH’s National Institute of Neurological Disorders and Stroke, the Institute of Circulatory and Respiratory Health of the Canadian Institutes of Health Research, U.S. Army Medical Research & Materiel Command, American Heart Association, Defence Research and Development Canada, and the Heart and Stroke Foundation of Canada.

Any community member who does not wish to be included in this or any future exception from informed consent studies can request a medical alert bracelet with the words “No Study” by calling 503 494-8083 or emailing roc@ohsu.edu with a full name and mailing address. More information about ROC can be found at: www.ohsu.edu/emergency/roc