Sedation in Critically Ill Children with Respiratory Failure

Abstract

This article discusses the rationale of sedation in respiratory failure, sedation goals, how to assess the need for sedation as well as effectiveness of interventions in critically ill children, with validated observational sedation scales. The drugs and non-pharmacological approaches used for optimal sedation in ventilated children are reviewed, and specifically the rationale for drug selection, including short- and long-term efficacy and safety aspects of the selected drugs. The specific pharmacokinetic and pharmacodynamic aspects of sedative drugs in the critically ill child and consequences for dosing are presented. Furthermore, we discuss different sedation strategies and their adverse events, such as iatrogenic withdrawal syndrome and delirium. These principles can guide clinicians in the choice of sedative drugs in pediatric respiratory failure.

Keywords: PICU; critically ill child; pharmacodynamics; pharmacokinetics; respiratory failure; sedation.

Figure 1

Illustration of the effect of critical illness on pharmacokinetics of analgosedative drugs. With intravenous administration (upper left), drugs are injected directly into the central compartment: bioavailability is complete. With oral administration (lower left), gut absorption and first by-pass metabolism limit bioavailability. Analgosedative drugs are metabolized by the liver into more water-soluble metabolites that are excreted by the kidneys. Some analgosedatives have active metabolites (e.g., morphine and midazolam) that may accumulate with decreased renal function. A graphical representation of drug concentration over time depicts pharmacokinetics changes induced by critical illness: the dashed line represents the curve of a healthy individual while the solid line shows the change induced by critical illness. *Liver flow affects clearance of drugs with a high hepatic extraction ratio (e.g., propofol).