Clicar no título para visualizar o abstract do artigo.
"Patients receiving mechanical ventilation in an intensive care unit (ICU) who were given dexmedetomidine for sedation had more days without delirium or coma and significantly more time at the desired level of sedation vs similar patients who received the standard sedative lorazepam, according to a study in the December 12 issue of the Journal of the American Medical Association.
The study also reported less mortality among patients receiving dexmedetomidine vs those receiving lorazepam, although this result was not statistically significant.
Lorazepam, a benzodiazepine drug, is routinely given to patients in ICU to reduce pain and anxiety and to allow them to tolerate invasive procedures, but these study results may change that treatment approach. "I think these data suggest that changing sedation paradigms is something that we need to do," said Pratik P. Pandharipande, MD, MSCI, assistant professor of anesthesiology and critical care, Vanderbilt University Medical Center in Nashville, Tennessee, who was lead author for the study."In previous research, investigators had noted that delirium occurs in up to 80% of patients on a respirator in the ICU, said Dr. Pandharipande. They also observed that lorazepam may contribute to an increased risk for delirium and coma. Lorazepam may cause such brain dysfunction by activating γ-aminobutyric acid central nervous system receptors that alter levels of neurotransmitters such as dopamine and serotonin. Benzodiazepine drugs also impair the quality of sleep by suppressing slow-wave (deep non–rapid eye movement) sleep, thereby perhaps contributing to delirium, said the authors.
Dexmedetomidine works on different receptors — alpha-2 receptors — and preserves slow-wave sleep.
This double-blind trial enrolled 106 adult patients in an ICU who needed mechanical ventilation between August 2004 and April 2006. They were randomized to receive sedation with either dexmedetomidine (52 patients) or lorazepam (51 patients) for as long as 120 hours at Washington Hospital Center or Vanderbilt University Medical Center (3 patients were withdrawn after randomization). Nurses treated pain with doses of fentanyl based on physiological parameters including blood pressure, heart and respiratory rates, facial expression, and limb movement.
Delirium was measured with use of the Confusion Assessment Method for the ICU (CAM-ICU). Patients were categorized as having delirium if they had a Richmond Agitation-Sedation Scale (RASS) score of –3 or greater. Coma was defined as a RASS score of –4 (responsive only to physical touch) or –5 (unresponsive to physical stimulus).
More Days Without Delirium
The researchers found that approximately 30% fewer patients experienced coma in the dexmedetomidine vs the lorazepam group (63% vs 92%) and that the patients receiving dexmedetomidine had more days alive without delirium or coma (median, 7 vs 3).
"We found that in a 12-day evaluation period . . . even though the groups were balanced as far as their age, demographics, etc, were concerned, patients on dexmedetomidine had a median or an average duration of being free of delirium and coma about 4 days more than the lorazepam group," commented Dr. Pandharipande.
As well, patients sedated with dexmedetomidine spent more time at the level of sedation targeted by both nurses and physicians, and although this was not statistically significant, they had more ventilator-free days than patients receiving the standard drug (22 vs 18 days).
As for pain control, patients treated with dexmedetomidine received more fentanyl than those treated with lorazepam. This could be because they were less likely to be delirious or in a coma and thus were more able to communicate their need for an analgesic, or because the pain drug was being used for its sedating properties, said the study authors.
Patients in the study who were not delirious or in a coma underwent neuropsychological testing within 72 hours of discharge from ICU. In the dexmedetomidine group, 42% of patients could be tested but only 31% in the lorazepam group, noted Dr. Pandharipande.
Changing Sedation May Improve Mortality Rate
The investigators also looked at 28-day mortality and reported a 10% reduction in the dexmedetomidine group (17% vs 27% in the lorazopam group). "We were not powered to study mortality so from a statistical standpoint, it was not significant, but I think if we had more patients in the study group, that would have been a very significant result," said Dr. Pandharipande. He added that researchers are planning a larger study "to look at whether changing sedation paradigms actually improves mortality."
Although there was a higher cost of care associated with patients in the dexmedetomidine group before their enrolment in the study, the total cost of care in the ICU was comparable for the 2 groups. "If you look at ICU costs, if you look at pharmacy bills, if you look at respiratory care costs, they were comparable in the 2 groups because those factor in only after a patient hits the ICU," Dr. Pandharipande told Medscape Neurology and Neurosurgery. So although dexmedetomidine is a more expensive drug than lorazepam, "the other costs were reduced and therefore they balanced out," he said.