Early Vasopressor Use in Trauma Linked to Increased Mortality Risk

BOSTON – In critically injured patients, early treatment with vasopressors was associated with more than an 11-fold increase in risk of death, and this risk was independent of the patient’s fluid status, reported Dr. David Plurad.

An analysis of outcomes of 1,349 patients treated over an 8-year period showed that among all patients who received vasopressors within 24 hours of admission, those with low scores (less than 8) on the Glasgow Coma Scale (GCS) had a more than fourfold increased risk for death, and those who received more than one vasopressor had a risk nearly as large, reported Dr. Plurad of the Los Angeles County Hospital/University of Southern California Medical Center.

“While we know that these vasopressors are necessary many times, they should be used with caution regardless of the presumed adequacy of resuscitation. Further investigation is necessary to develop evidence-based strategies that maximize beneficial, and minimize detrimental, effects when these agents become necessary after trauma,” he said at the annual meeting of the American Association for the Surgery of Trauma.

In trauma cases, vasopressors are typically used early in the course of treatment when a patient experiences traumatic arrest requiring thoracotomy or becomes hypotensive during surgery while the team is attempting to control bleeding, or during damage-control resuscitation while the team attempts to correct physiologic parameters.

The use of vasopressors is decades old, as are warnings to clinicians about their indiscriminate use. But recent evidence from animal studies, short human clinical trials, and case reports suggests that vasopressors might be useful for maintaining critical central perfusion and delaying cardiac arrest because of hemorrhaging, Dr. Plurad said.

To study whether vasopressors were associated with increased risk of death, the investigators conducted a retrospective database/registry search on all trauma patients older than 15 years admitted to their ICU in 2001-2008 who had central venous pressure monitoring. They excluded from their analyses all patients with traumatic brain injury (defined as an Abbreviated Injury Scale score greater than 3), and all patients with spinal cord injuries.

The two-stage analysis looked at all patients, and the subset of patients who received vasopressors during the first 24 hours after ICU admission. The agents included dopamine, epinephrine, norepinephrine, vasopressin, and phenylephrine. Patients who received dobutamine or milrinone were included in the vasopressor-negative group.

Of the 1,349 total patients – nearly 80% of whom were male victims of blunt trauma – 351 (26.0%) received at least one vasopressor, and 150 (11.1%) received multiple agents. The most commonly used vasopressor was dopamine, in 22.5% of all patients, followed by norepinephrine in 6.4%, epinephrine in 5.9%, vasopressin in 4.4%, and phenylephrine in 2.4%. Overall, 195 patients (14.5%) died.

Patients who received vasopressin were significantly more likely than those who did not to have blunt mechanism of trauma (odds ratio [OR], 1.98), to be admitted to the ICU with hypovolemia (OR, 9.55), to have an emergency department GCS score of 8 or less (OR, 3.7), and to die in the hospital (OR, 17.6); they were also older and had higher mean injury severity scores.

Factors independently associated with death among all patients were vasopressor use (OR, 11.51), emergency department GCS score of 8 or less (OR, 4.1), injury severity score of 35 or greater (OR, 2.71), and age of 55 or older (OR, 2.3; P value for all comparisons less than .01).

In logistic regression analysis of all patients who received vasopressors, an emergency department GCS score of 8 or lower was significantly associated with mortality (OR, 4.33, P less than .01), as was multiple vasopressor use (OR, 3.93, P less than 0.01). In contrast, hypovolemia was not significantly associated with increased risk of death in these patients (OR, 1.29).

Commenting on the study, invited discussant Dr. Patrick Offner of St. Anthony Central Hospital in Denver noted that trauma guidelines emphasize that vasopressors should be used with caution in trauma patients.

“This is, however, a retrospective study, and as such, suffers from several limitations,” he said. “In particular, the specific indications and timing of vasopressor use are unknown.”

He added that although hypovolemic and nonhypovolemic patients in the study seemed to be relatively well matched, with similar anatomic injury severity scores and rates of hypotension, potentially important physiologic information was missing.

“Ultimately, I think it remains unclear whether early vasopressor use is in itself detrimental or merely a marker for outcome in these patients,” Dr. Offner said.

The funding source for the study was not disclosed. Dr. Offner reported that he had no conflicts of interest.