Steroid-Dopamine Combination May Be Fatal in Septic Shock

Fran Lowry

January 25, 2011

January 25, 2011 (San Diego, California) — The combination of steroids and dopamine is associated with an increased 28-day mortality in patients with shock, in particular those with septic shock, researchers reported here at the Society of Critical Care Medicine 40th Critical Care Congress. The principal investigator advised discontinuing the use of dopamine as a vasopressor in these patients.

"In patients receiving steroids, the 28-day mortality rate was 56% in patients who were randomized to dopamine, compared with 49% in patients who were randomized to norepinephrine. But in patients who were not receiving steroids, the 28-day mortality was virtually the same, at 49%," Daniel De Backer, MD, professor of medicine at Erasme University Hospital in Brussels, Belgium, announced.

The finding comes from a secondary analysis of the Sepsis Occurrence in Acutely Ill Patients (SOAP) trial, which was led by Dr. De Backer and published in March 2010 (N Engl J Med. 2010362:779-789).

Both dopamine and norepinephrine are recommended as first-line vasopressor agents for the treatment of shock. The SOAP trial was undertaken to determine whether one agent was superior to the other in restoring and maintaining blood pressure.

The trial assigned 858 patients with shock to receive dopamine and 821 patients to receive norepinephrine. Dopamine was associated with a nonsignificant increase in 28-day mortality, compared with norepinephrine (52.5% vs 48.5%; odds ratio [OR], 1.17; 95% confidence interval [CI], 0.97 to 1.42; P = .10).

Dopamine was also associated with significantly more arrhythmic events. There were 207 events (rate 24.1%) with dopamine and 102 events (rate 12.4%) with norepinephrine (P < .001).

"We asked ourselves whether there could be confounding factors or some potential interaction with other drugs that these patients may have received. We decided to focus on steroid use, as steroids are frequently used in shock patients and could alter the outcome in some way," Dr. De Backer explained.

They went back and looked at the information on prednisolone and hydrocortisone use within 24 hours of randomization to dopamine or norepinephrine. Steroid use was not randomized and was left to the discretion of the attending physician.

In total, 885 (53.2%) of the SOAP patients received steroids, the most common of which was hydrocortisone (670 patients). Steroid use was well balanced between the dopamine and norepinephrine groups.

The study found that overall, 28-day mortality tended to be higher in patients receiving steroids than in those not receiving steroids (52.4% vs 48.8%, OR, 1.16; 95% CI, 0.95 to 1.40; P = .15).

The 28-day mortality rate was significantly higher in patients receiving steroids plus dopamine than in those receiving steroids plus norepinephrine (55.8% vs 48.8%; OR 1.33; 95% CI, 1.01 - 1.74; < .05); it was similar in patients receiving dopamine or norepinephrine without steroids (48.9 vs 48.8%; OR, 1.01; 95% CI, 0.76 o 1.32; P = .99), Dr. De Backer said.

"Dopamine should not be used anymore as a vasopressor. Period. At least that's my opinion," he told Medscape Medical News in an interview after his presentation. "You have more side effects and you face an increase in mortality rates, so it is of no benefit and is potentially more disadvantageous [and therefore] probably not a good idea to use it."

Richard H. Savel, MD, from Montefiore Medical Center and the Albert Einstein College of Medicine, in the Bronx, New York, agreed that the implications from this report go against dopamine in this setting.

"This is a famous and important group that has been studying optimal pressors in critically ill patients. Their finding that patients who received dopamine and steroids had a worse outcome, combined with the recent results of the CORTICUS trial, say don't use steroids and dopamine together. That is the clinical implication of this retrospective analysis," Dr. Savel stated.

Dr. De Backer and Dr. Savel have disclosed no relevant financial relationships.

Society of Critical Care Medicine (SCCM) 40th Critical Care Congress: Abstract 55. Presented January 16, 2011.


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