Prehospital Hypertonic Saline Resuscitation Not Helpful for Hypotensive Patients with Severe Traumatic Brain Injury

Abstract & Commentary

Source: Cooper DJ, et al for the HTS study investigators. Prehospital hypertonic saline resuscitation of patients with hypotension and severe traumatic brain injury – a randomized controlled trial. JAMA 2004;291:1350-1357.

Patients with hypotension following severe traumatic brain injury (TBI) have a higher mortality rate and worse neurological outcome for survivors. Resuscitation with intravenous hypertonic saline (HTS) may have theoretical benefits in this setting by increasing blood pressure and decreasing intracranial pressure compared with isotonic resuscitation fluids.

In this well-designed, double-blind, controlled study, investigators in Australia randomized 229 patients with severe TBI (i.e., Glasgow Coma Scale score less than 9) and hypotension (i.e., systolic blood pressure less than 100 mmHg) to receive either HTS or isotonic saline fluid administered in the pre-hospital setting. One hundred-fourteen patients in the HTS group received 250 mL of 7.5% saline, while 115 control patients received 250 mL of Ringer’s lactate solution. All patients then received standard resuscitation fluids and other care in the prehospital setting. Patients with penetrating trauma or traumatic arrest were excluded. Investigators followed patients through their hospital course and at three and six months to assess survival and neurologic outcome.

In both groups, prehospital hypotension had resolved on arrival to the emergency department. However, the HTS group did have a higher mean serum sodium level (149 vs 141 mEq/L). Despite this difference, there was no survival difference between the HTS and control group at hospital discharge (55% vs. 57%, p =0.32), at three-month follow-up (55% vs. 48%, p =0.26), and at six-month follow-up (55% vs. 47%, p =0.23), respectively.

There also was no difference in neurologic outcome for survivors as measured by a number of parameters including the extended Glasgow Outcome Scale (GOSE), which measures neurologic recovery on an eight-step scale (one = dead; eight = upper good recovery). In addition, there was no significant difference in the proportion of patients with a good recovery (i.e., GOSE greater than 4), and no difference in the rates of return to work between the two groups. Based upon their findings, the authors conclude that prehospital HTS does not improve mortality rates or long-term neurologic function in patients with severe TBI and hypotension compared with conventional resuscitation fluids.

Commentary by Theodore C. Chan, MD, FACEP

This is an excellent study from a number of standpoints. First, it is one of the few examples of a blinded, randomized controlled study of therapies in critically ill patients conducted in the prehospital setting with excellent long-term follow-up. In fact, patient loss to follow-up at six months was only 1%. Second, while there were only 229 subjects, this study had 80% power to detect a one-grade change in the neurologic outcome score (GOSE).

A number of points should be kept in mind regarding this study. First, patients also received standard therapies in the prehospital setting, which included fluid resuscitation. Thus, both groups received other resuscitation fluids (median 1250 mL)—including both isotonic fluid and colloid—which may have had a diluting effect on the 250 mL of HTS. Second, more than 90% of patients had multi-system trauma, as opposed to isolated head injury, which may have affected mortality and neurologic outcomes in both groups. Third, prehospital transport times were relatively long (median time 60 minutes), which may have affected their results, though a subgroup analysis suggested no difference between HTS and control groups when looking at time of transport. Fourth, recent studies have suggested that a combination of HTS and colloid (HTS-dextran) may have additive benefits that this study did not investigate. Finally, it should be noted that while not statistically significant, there was a trend toward improved survival in the HTS group, indicating the need for further study in the future.

Dr. Chan, Associate Clinical Professor of Medicine, Emergency Medicine, University of California, San Diego, is on the Editorial Board of Emergency Medicine Alert.