Approximately 500,000 children suffer critical illness every year in the United States and more than one third will receive a continuous infusion of a sedative-analgesic medication such as an opioid or dexmedetomidine. Such drugs are commonly administered to ease the burden of critical illness by treating serious pain and anxiety associated with invasive organ support delivery and procedures in the intensive care unit. However, there are no widely-accepted standards for the administration of these potent neuroactive medications and several studies have demonstrated that children receive too little or too much of these medications nearly half of the time they are administered. This imprecision in conventional dosing strategies leads to adverse events, including acute physiologic deterioration, drug tolerance and dependency, prolonged illness and hospitalization and life-threatening complications of invasive support such as unplanned extubation and post-extubation airway obstruction. Evidence also indicates that relatively short exposures to these medications may be detrimental to long-term neurodevelopment. More precise strategies for administering these medications to children are needed and this is an issue of major
Clinicians caring for critically ill children routinely struggle to harmonize the tension between giving too much versus too little sedation-analgesia. This work will (1) identify patterns of sedation-analgesia associated with outcome; (2) identify genotypes associated with sedation-analgesia administration; (3) characterize PK parameters of common sedative-analgesic mediations; and (4) promote the development of the PI as an independent Learning Health System researcher. The aggregate results of this work will inform development of a predictive model for sedation-analgesia dose response for critically ill children that will be the focus of future, prospective investigations
