Dados do Trabalho

Título

Prophylactic minocycline for delirium in critically ill patients: a randomized controlled pilot trial

Objetivo

Delirium is a potentially severe form of acute brain dysfunction. Minocycline has neuroprotective effects in animal models of neurological diseases; however, data from human studies remain scarce. Since brain inflammation is thought to be one of the major pathophysiological mechanisms of delirium, it was hypothesized that suppression of microglial activation by minocycline could be a potential target to prevent delirium.

Métodos

This study was a randomized, placebo-controlled, double-blind trial (NCT04219735) conducted in four Intensive Care Units (ICUs). Patients aged 18 years or older were eligible, and randomized to receive minocycline (100 mg twice a day) or placebo. The primary outcome was delirium incidence within 28 days or before ICU discharge. Secondary outcomes included days in delirium during ICU stay, delirium/coma free days, length of mechanical ventilation, ICU length of stay, ICU mortality, and hospital mortality. The kinetics of different inflammatory (interleukin-1b, interleukin-6, interleukin-10, and C-reactive protein) and brain-related biomarkers (brain-derived neurotrophic factor and S-100B) were used as exploratory outcomes.

Resultados

A total of 159 patients were randomized (minocycline, n=84; placebo, n=75). There was a small but significant decrease in delirium incidence (26 patients in the minocycline arm compared to 17 patients in the placebo arm, P=0.043). No other delirium-related outcomes were modified by minocycline treatment. Unexpectedly, there was a significant decrease in hospital mortality (39% vs. 23%, P=0.029). Among all analyzed biomarkers, only plasma levels of C-reactive protein decreased significantly after minocycline treatment (F=0.75, P=0.78 within time; F=4.09, P=0.045 group⋅time).

Conclusão

Minocycline administration can prevent delirium in critically ill patients.