IV Corticosteroids Increase Deaths From Traumatic Brain Injury

Findings from the Corticosteroid Randomization After Significant Head Injury (CRASH) trial that intravenous corticosteroids increased mortality among patients with traumatic brain injury should put to rest once and for all questions about the role of steroids for this indication, Donald Marion, M.D., told this newspaper.

Current guidelines on the management and prognosis of severe head injury do not recommend use of intravenous corticosteroids, said Dr. Marion, a Boston-based senior research fellow at the Brain Trauma Foundation, New York.

Intravenous steroid use for this indication has been on the decline for at least 10 years in the United States. A decade ago, 60%–70% of physicians used steroids in the treatment of traumatic brain injury (TBI); today that has dropped to about 20%.

Negative findings from the unusually large British CRASH trial of more than 10,000 patients should end debate over use of corticosteroids after head injuries, according to Dr. Marion.

Investigators in the United Kingdom randomized 10,008 adult TBI patients to a 48-hour infusion of methylprednisolone or placebo. They reported 25.7% of the corticosteroid group but only 22.3% of the placebo group died within 6 months of entering the CRASH trial.

Although fewer patients developed severe disability on corticosteroids, the combined outcome of death or severe disability still favored the placebo. In the corticosteroid arm, 38.1% were dead or severely disabled at 6 months, compared with 36.3% of the control group (Lancet 2005;365:1957–9).

“These analyses lend support to the conclusion … that corticosteroids should not routinely be used in the treatment of head injury,” the CRASH trial collaborators stated in a research letter.

The results provide “clear evidence that treatment with corticosteroids following head injury affords no material benefit,” according to the investigators.

“The absence of evidence of any neurologic benefit from corticosteroid treatment might also have implications for the use of corticosteroids in spinal cord injury, which should remain an area for debate.”

The trial randomized patients with a Glasgow Coma Scale score of 14 or less within 8 hours of head injury. All patients received a 48-hour infusion of either placebo or methylprednisolone, which Pfizer provided.

The 6-month analysis was based on follow-up data for 9,673 patients (96.7%): 4,854 on corticosteroids and 4,819 patients on placebo.

At that point, a total of 1,248 corticosteroid patients and 1,075 placebo patients had died.

Conversely, 2,213 placebo patients (45.9%), but only 2,120 corticosteroid patients (43.7%), had made a good recovery. Stratification by severity of head injury and time from injury produced no substantial differences.

Dr. Marion noted in his interview with this newspaper that “the question they [the CRASH researchers] really needed to answer was not whether steroids were bad, but whether steroids improve outcome.

“They not only proved steroids did not improve outcome but also that people who had steroids had worse outcomes. … Those people who are following evidence-based medicine are not likely to use steroids.”

Findings from the Corticosteroid Randomization After Significant Head Injury (CRASH) trial that intravenous corticosteroids increased mortality among patients with traumatic brain injury should put to rest once and for all questions about the role of steroids for this indication, Donald Marion, M.D., told this newspaper.

Current guidelines on the management and prognosis of severe head injury do not recommend use of intravenous corticosteroids, said Dr. Marion, a Boston-based senior research fellow at the Brain Trauma Foundation, New York.

Intravenous steroid use for this indication has been on the decline for at least 10 years in the United States. A decade ago, 60%–70% of physicians used steroids in the treatment of traumatic brain injury (TBI); today that has dropped to about 20%.

Negative findings from the unusually large British CRASH trial of more than 10,000 patients should end debate over use of corticosteroids after head injuries, according to Dr. Marion.

Investigators in the United Kingdom randomized 10,008 adult TBI patients to a 48-hour infusion of methylprednisolone or placebo. They reported 25.7% of the corticosteroid group but only 22.3% of the placebo group died within 6 months of entering the CRASH trial.

Although fewer patients developed severe disability on corticosteroids, the combined outcome of death or severe disability still favored the placebo. In the corticosteroid arm, 38.1% were dead or severely disabled at 6 months, compared with 36.3% of the control group (Lancet 2005;365:1957–9).

“These analyses lend support to the conclusion … that corticosteroids should not routinely be used in the treatment of head injury,” the CRASH trial collaborators stated in a research letter.

The results provide “clear evidence that treatment with corticosteroids following head injury affords no material benefit,” according to the investigators.

“The absence of evidence of any neurologic benefit from corticosteroid treatment might also have implications for the use of corticosteroids in spinal cord injury, which should remain an area for debate.”

The trial randomized patients with a Glasgow Coma Scale score of 14 or less within 8 hours of head injury. All patients received a 48-hour infusion of either placebo or methylprednisolone, which Pfizer provided.

The 6-month analysis was based on follow-up data for 9,673 patients (96.7%): 4,854 on corticosteroids and 4,819 patients on placebo.

At that point, a total of 1,248 corticosteroid patients and 1,075 placebo patients had died.

Conversely, 2,213 placebo patients (45.9%), but only 2,120 corticosteroid patients (43.7%), had made a good recovery. Stratification by severity of head injury and time from injury produced no substantial differences.

Dr. Marion noted in his interview with this newspaper that “the question they [the CRASH researchers] really needed to answer was not whether steroids were bad, but whether steroids improve outcome.

“They not only proved steroids did not improve outcome but also that people who had steroids had worse outcomes. … Those people who are following evidence-based medicine are not likely to use steroids.”

Findings from the Corticosteroid Randomization After Significant Head Injury (CRASH) trial that intravenous corticosteroids increased mortality among patients with traumatic brain injury should put to rest once and for all questions about the role of steroids for this indication, Donald Marion, M.D., told this newspaper.

Current guidelines on the management and prognosis of severe head injury do not recommend use of intravenous corticosteroids, said Dr. Marion, a Boston-based senior research fellow at the Brain Trauma Foundation, New York.

Intravenous steroid use for this indication has been on the decline for at least 10 years in the United States. A decade ago, 60%–70% of physicians used steroids in the treatment of traumatic brain injury (TBI); today that has dropped to about 20%.

Negative findings from the unusually large British CRASH trial of more than 10,000 patients should end debate over use of corticosteroids after head injuries, according to Dr. Marion.

Investigators in the United Kingdom randomized 10,008 adult TBI patients to a 48-hour infusion of methylprednisolone or placebo. They reported 25.7% of the corticosteroid group but only 22.3% of the placebo group died within 6 months of entering the CRASH trial.

Although fewer patients developed severe disability on corticosteroids, the combined outcome of death or severe disability still favored the placebo. In the corticosteroid arm, 38.1% were dead or severely disabled at 6 months, compared with 36.3% of the control group (Lancet 2005;365:1957–9).

“These analyses lend support to the conclusion … that corticosteroids should not routinely be used in the treatment of head injury,” the CRASH trial collaborators stated in a research letter.

The results provide “clear evidence that treatment with corticosteroids following head injury affords no material benefit,” according to the investigators.

“The absence of evidence of any neurologic benefit from corticosteroid treatment might also have implications for the use of corticosteroids in spinal cord injury, which should remain an area for debate.”

The trial randomized patients with a Glasgow Coma Scale score of 14 or less within 8 hours of head injury. All patients received a 48-hour infusion of either placebo or methylprednisolone, which Pfizer provided.

The 6-month analysis was based on follow-up data for 9,673 patients (96.7%): 4,854 on corticosteroids and 4,819 patients on placebo.

At that point, a total of 1,248 corticosteroid patients and 1,075 placebo patients had died.

Conversely, 2,213 placebo patients (45.9%), but only 2,120 corticosteroid patients (43.7%), had made a good recovery. Stratification by severity of head injury and time from injury produced no substantial differences.

Dr. Marion noted in his interview with this newspaper that “the question they [the CRASH researchers] really needed to answer was not whether steroids were bad, but whether steroids improve outcome.

“They not only proved steroids did not improve outcome but also that people who had steroids had worse outcomes. … Those people who are following evidence-based medicine are not likely to use steroids.”