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No pain benefit found for IV acetaminophen vs. oral in the neuro ICU




PHOENIX – Intravenous acetaminophen was no better than oral acetaminophen at relieving pain in neurocritical ICU patients with stroke and other conditions in a retrospective study at Virginia Commonwealth University in Richmond.

From May 2012 to April 2013, 312 patients – about a quarter of all neuroscience ICU admissions – got a median of three 1,000-mg doses of IV acetaminophen (Ofirmev), usually every 6 hours as needed. By 3 hours after their first dose, those with a median baseline pain score of 4 on a 10-point scale had dropped 1.5 points and remained there when reassessed at 6 hours. Pain was measured either by patient report or nurse assessment, using vital signs, grimacing, and other measures.

About the same number of patients received oral acetaminophen, usually 650 mg, also every 6 hours. At 3 hours, patients with an initial median score of 4 had dropped a mean of 1.7 points; at 6 hours, they had fallen by about 2 points from baseline. Many of the patients in both the intravenous and oral groups needed rescue opioids, usually fentanyl.

Intracranial hemorrhages were the most common diagnoses in both the oral and intravenous groups, followed by subarachnoid hemorrhages and traumatic brain injuries.

The study begins to answer a question on the minds of many health care providers: Is it worth paying $33 for a dose of intravenous acetaminophen when oral acetaminophen costs 5 cents a pill?

Dan Nichols Alex Otto/Frontline Medical News

Dan Nichols

“This was completely surprising to us. Everything that we learn in pharmacy school says IV is going to be more effective than oral. We thought we’d see a difference, but we didn’t,” said lead investigator Dan Nichols, a third-year pharmacy student at Virginia Commonwealth University, Richmond.

“In fact, oral was actually more effective in traumatic brain injury patients,” as well as in patients who received rescue opioids and the small number in whom acetaminophen was the only pain medication needed, he said at the Critical Care Congress, sponsored by the Society for Critical Care Medicine.

As with any intravenous drug, IV acetaminophen bypasses the vagaries of the gastrointestinal tract, so its pharmacokinetics are much quicker than oral formulations. Peak plasma concentrations come at the end of the 15 minute infusion.

That might translate to quicker pain relief; the investigators next plan to compare pain scores at 1 and 2 hours, and analyze whether Glasgow Coma Score, surgery, and other confounders make a difference.

Dr. Gretchen M. Brophy

Dr. Gretchen M. Brophy

In the meantime, “we and every institution I’ve spoken to have restricted its use, because we don’t have data saying it’s more effective. At $33 a dose” – recently up from $10 – “it’s harder to justify. At least in the 0-3 hour window, it didn’t have any additional benefit over oral. It might still be better at 1 hour; kinetically, that would make sense, but there’s nothing yet to say from what we did that it’s better,” said senior investigator Gretchen M. Brophy, Pharm.D., of the departments of pharmacy and neurosurgery at VCU.

For now, VCU has restricted intravenous acetaminophen to one dose per patient.

The mean age in the study was 55 years, and just over half the patients were men.

Dr. Brophy is a speaker for Cadence Pharmaceuticals, the maker of intravenous acetaminophen. There was no outside funding for the work.

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