The effect of critical illness and inflammation on midazolam therapy in children

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Objective: To determine the effect of inflammation and disease severity on midazolam pharmacokinetics (as surrogate marker of cytochrome 3A activity) and pharmacodynamics in critically ill children. Design: Analysis of prospectively collected pharmacokinetic and pharmacodynamic data from a midazolam study in critically ill children. Setting: Pediatric intensive care unit of a university hospital. Patients: Twenty-one critically ill children who needed midazolam for sedation. Interventions: None. Measurements and Main Results: We determined the relationship between inflammation (using C-reactive protein and leukocyte count as surrogate markers) and disease severity (Pediatric Logistic Organ Dysfunction and Pediatric Risk of Mortality scores) vs. the pharmacokinetics (clearance) and pharmacodynamics (COMFORT score, dose requirement) of midazolam. We found a significant negative correlation between disease severity and midazolam clearance corrected for body weight (r = -0.49, p = .02). Mid Conclusions: Results from this pilot study suggest that increased disease severity is associated with reduced midazolam clearance in critically ill children, most likely as a result of reduced cytochrome 3A activity. In contrast, reduced midazolam clearance does not seem to result in decreased midazolam dose requirements. (Pediatr Crit Care Med 2012; 13:e48-e50)
Original languageUndefined/Unknown
Pages (from-to)E48-E50
JournalPediatric Critical Care Medicine
Issue number1
Publication statusPublished - 2012

Research programs

  • EMC MGC-02-53-01-A
  • EMC OR-02-54-06

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