December 14, 2007

Study targets new options for sedating ICU respirator patients

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Pratik Pandharipande, M.D., and colleagues are studying sedation options for intensive care patients on respirators that result in more days without delirium or coma. (photo by Anne Rayner)

Study targets new options for sedating ICU respirator patients

Vanderbilt University Medical Center researchers have conducted a study that offers a better sedation option for intensive care unit patients on respirators.

Their findings were published this week in the Journal of the American Medical Association.

Pratik Pandharipande, M.D., assistant professor of Anesthesiology, and colleagues compared the standard sedative, lorazepam, which is a benzodiazepine, with the drug dexmedetomidine and found that the patients on dexmedetomidine had more days alive without delirium or coma.

In addition, patients experienced better sedation. There was also a slight decrease in mortality.

There are between 60,000 and 70,000 people in ICUs who are on respirators, said Wes Ely, M.D., associate professor of Medicine and senior author on the study. The standard of care mandates that basically everyone receive heavy sedatives to keep them safe, comfortable and unaware of the ICU experience.

“Historically, benzodiazepines are what we use to keep people deeply sedated,” Pandharipande said. “Our group's interest has been in trying to figure out the factors that impede people coming off ventilation. Delirium plays a role in getting people off mechanical ventilation. They seem to be ready from the respiratory system standpoint, but their brains have taken a hit.”

When Pandharipande began to look at risk factors for delirium, he found that the class of benzodiazepine drugs is a major one. These drugs act on the GABA receptors in the brain, which may be responsible for people having a high risk for acute brain dysfunction.

“If GABA receptors predispose people to delirium, we have to have an alternative,” Pandharipande said.

Dexmedetomidine was a fairly new drug on the market, and it targets the alpha-2 receptor.

“We began to wonder if we changed sedation paradigms by targeting alpha-2 receptors instead of GABA receptors, would that reduce acute brain dysfunction in the ICU, time on mechanical ventilation, days in ICU and mortality?” he said.

Pandharipande and Ely enrolled 106 surgical and medical ICU patients at Vanderbilt and Washington Hospital in Washington, D.C. Half received lorazepam and half received dexmedetomidine over a five-day period. Patients were evaluated for acute brain dysfunction for 12 days.

“What we found was that by using a sedation regimen that incorporated dexmedetomidine, these patients had four more days free of delirium and coma. If you are free of delirium and coma, it presents more days of normal cognitive status. That is what is most important,” Pandhari-pande said.

Fewer patients on dexmedetomidine were comatose; they had more days free of delirium, and there was a 10 percent reduction in mortality. Their level of sedation was also more easily controlled while on dexmedetomidine.

“We need to start realizing that a balance between patient comfort and the risk associated with sedatives is important,” Pandharipande said.

Ely said this is the first study of its kind to look at reducing brain dysfunction in critically ill people by using an alpha-2 drug instead of a GABA drug.

“We have the first data to say there is possibly a way to debunk the current standard of care. It's a completely different mindset of how we approach these patients,” Ely said.