Jul 202018
 

Quick Take: This small (n=100), two-center, industry-funded (Hospira) study showed a remarkable 80% prevention rate of ICU delirium (compared to 20% with placebo) with patients given dexmedetomidine prophylactically during their ICU stay. Although associated with poor outcomes in critically ill patients, delirium is not known to be an independent predictor of those outcomes. This small study was not designed or powered to detect improved outcomes other than delirium (mortality, ventilator days, etc.) in the patients whose delirium was prevented -- and it did not show any. Nevertheless, delirium is undesirable in itself. If subsequently validated, this finding could be practice-changing, with a push for dexmedetomidine to be "bundled" into routine ICU care. Dexmedetomidine is already considered preferable to benzodiazepines for ICU sedation.  --PulmCCM


by Nicole Lou, Contributing Writer, MedPage Today

Low-dose dexmedetomidine (Precedex) prevented delirium in the intensive care unit (ICU) in critically ill adults requiring sedation, according to a trial.

Night-time administration of the drug to patients allowed 80% of them to remain delirium-free during their stay in the ICU, as evaluated by the Intensive Care Delirium Screening Checklist every 12 hours (versus 20% of those randomized to placebo, RR 0.44, 95% CI 0.23-0.82), researchers led by Yoanna Skrobik, MD, of McGill University Health Centre in Montreal, reported online in the American Journal of Respiratory and Critical Care Medicine.

Sleep quality evaluated by the Leeds Sleep Evaluation Questionnaire was no different between the dexmedetomidine and placebo groups. Fewer patients randomized to dexmedetomidine required a fentanyl infusion during their ICU stay (76% versus 94%, P=0.02), however.

"The lower proportion of patients requiring a fentanyl infusion during the ICU stay in the intervention group may be related to a dexmedetomidine-associated analgesic effect, particularly since fentanyl infusions at the time of randomization were frequent and similar between the two groups," the team speculated. "This potential co-analgesia and opioid-sparing effect is important to study further, given increasing concerns about opioid consumption during hospitalization.

"In conclusion, nocturnal administration of low-dose dexmedetomidine in critically ill adults helps prevent ICU delirium and reduces both days spent with coma and opiate requirements. While patient-reported sleep quality appears unchanged, future investigations incorporating polysomnography may better characterize the relationship between ICU delirium and sleep quality."

Skrobik added in a statement: "We believe this is a practice-altering study and that dexmedetomidine should be used with patients at high risk for delirium."

The phase II trial was conducted at two centers with delirium-screening protocols dating back more than a decade. A total of 100 consecutive eligible and consenting adults were enrolled, all of whom were critically ill but free of delirium at the time. Participants were randomized to the intervention or placebo until ICU discharge.

The two groups ended up having similar durations of mechanical ventilation, ICU stay, and hospital stay; rates of ICU and hospital mortality were statistically no different as well.

"Safety concerns associated with dexmedetomidine were consistent with its pharmacological profile; while it had to be down-titrated or temporarily held in some instances due to bradycardia and/or hypotension, no patients were removed from the study due to safety issues," the investigators noted.

Caveats to the trial, they acknowledged, included the fact that only 26% of screened patients were enrolled and that changes in clinical practice may have occurred over the 3 years needed to complete the study. Moreover, delirium "was not evaluated after ICU discharge, and its subsequent occurrence may have been missed in patients with shorter ICU stays.

"To our knowledge, this is the first pharmacologic intervention study shown to prevent delirium in critically ill adults," the team wrote. "We used a rigorous study design, meticulously titrated the study intervention during the nocturnal period, and evaluated two groups of patients with a similar risk for delirium at baseline."

The researchers added that prior studies had suggested that dexmedetomidine was associated with less delirium compared with benzodiazepines and better sleep compared with benzodiazepines or propofol.

The study was supported by a grant from Hospira Canada.

Source: Society journal

--from MedPage Today

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Prophylactic Precedex prevented delirium in ICU patients