Abstract
To clarify the relevant factors to the tolerance for continuous sedation by midazolam and flunitrazepam with or without propofol, multifactorial retrospective observational case-controlled study was introduced. The subjects were 70 critically-ill patients admitted to ICU of our critical care and emergency center from June 1995 to January 1998. We examined the differences in clinical variables between 14 patients resisting continuous sedation (R group) and 56 patients successfully sedated with standard-dose sedatives (non-R group).
Patients in R group experienced significantly longer stay in ICU, longer mechanical ventilation, more prevalence of systemic inflammatory response syndrome (SIRS), more flunitrazepam as a choice of sedative, more continuous renal replacement therapy, and longer use of steroid and erythromycin than non-R group. We speculate, from these results, that strong inflammation or infection may lead to develop pharmacokinetic tolerance for sedative within a few days and long duration of mechanical ventilation accompanied by long-term sedation may lead to develop the pharmacodynamic tolerance in late phase about two weeks after. Further prospective study will determine the clinical risk factors of tolerance for sedative drugs.
