NEW YORK (Reuters Health) – Prophylactic haloperidol does not improve survival of critically ill adults at high risk of delirium, according to results from the REDUCE trial.
“Based on our large-scale study, including 1,800 ICU patients, we found in none of the patient groups that prophylactic haloperidol is useful to reduce delirium or other delirium-related outcomes, but also there is no effect on reducing mortality,” Dr. Mark van den Boogaard from Radboud University Medical Center, Nijmegen, the Netherlands, told Reuters Health by email.
Delirium emerges in up to half of patients admitted to intensive care units and is associated with adverse clinical outcomes, including mortality. Prophylactic haloperidol has had beneficial effects on delirium outcomes of patients who were not critically ill, but its role in ICU patients remains unclear.
Dr. van den Boogaard and colleagues investigated the effects of two different doses of haloperidol (1 mg and 2 mg) given prophylactically, compared with placebo, on 28-day survival among 1,789 ICU patients cared for in a setting where non-pharmacological prevention strategies had already been adopted.
About 46% of patients were surgical admissions, about 50% medical, and 4% trauma-related.
The survival rate at 28 days did not differ significantly among the haloperidol 1-mg (81.7%), haloperidol 2-mg (83.3%), and placebo groups (82.7%), according to the February 20 JAMA online report.
Survival at 90 days also was similar among the three randomized groups, as were the numbers of delirium-free and coma-free days, the duration of mechanical ventilation, the incidence of unplanned removal of tubes, the incidence of ICU readmission, and the lengths of ICU and in-hospital stay.
“The most interesting and, in my opinion, the most relevant findings are the very consistent results over all groups of patients,” Dr. van den Boogaard said. “We determined that in none of the subgroups is there a beneficial effect of prophylactic haloperidol for ICU patients.”
“We recommend stopping the use of prophylactic haloperidol in ICU patients,” he said. “This is really important, because we know from other studies that this is still common practice in several ICUs in the USA and Canada.”
Dr. van den Boogaard added, “We cannot rule out that other antipsychotic agents may have beneficial effects. However, based on other studies, we believe that the use of nonpharmacological preventive interventions, like early mobilization, cognitive training, reducing noise, improving patients’ visibility and hearing, are probably more effective, especially when this is offered as a bundle of interventions (multi-component interventions). But this needs to be investigated and confirmed in a well-designed, large-scale study.”
Dr. Anthony Delaney from Royal North Shore Hospital, St. Leonards, New South Wales, Australia, who coauthored a related editorial, told Reuters Health by email, “I can’t see any role for prophylactic haloperidol in this setting. There are trials on the near horizon (the SPICE trial, which is assessing the efficacy of dexmedetomidine in a similar role) that offer some hope. But as we mentioned in the editorial, the answer may be doing less for patients rather than more and doing simpler things well rather than more complicated things.”
“Delirium is a major problem,” he said. “It can be terrifying for patients, families, and staff. Patients, particularly those with agitated delirium, are very difficult to deal with and are the cause of a lot of stress for families and staff. It may also be the harbinger of poor long-term functional recovery following critical illness.”
“As the acute mortality rate from most critical illness falls, survivors are facing long-term health consequences, and I think this paper is part of the recognition on the part of the ICU community that we need to try to prevent the long-term consequences of critical illness at the earliest possible time,” Dr. Delaney concluded.
Dr. John W. Devlin from Northeastern University and critical care pharmacist at Tufts Medical Center, Boston, who earlier reported the sparsity of evidence supporting the use of antipsychotics to prevent or treat delirium, told Reuters Health by email, “Currently, there is no role to administer an antipsychotic to reduce delirium in any patient setting.”
“Pharmacologic strategies to prevent or treat delirium remain very limited,” he said. “Instead, ICU clinicians should focus on aggressively reducing modifiable risk factors for delirium (e.g., avoidance of benzodiazepines, maintenance of wakefulness) and applying non-medication strategies known to reduce it (e.g., early mobilization, sleep protocol).”
SOURCES: http://bit.ly/2Guc2eR and http://bit.ly/2ofohoE
JAMA 2018.
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