Precision dosing is expected to improve patient outcomes, however, models developed in one patient population may perform poorly when translated to a new patient population. Continuous learning has been proposed as a strategy to improve model-informed precision dosing (MIPD) by tailoring a model to the intended use population as more data become available.

Objective To examine the impact of a change in the empiric gentamicin dose from 5 mg/kg every 24h to 5 mg/kg every 36h on target drug concentration achievement in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. Study Design Gentamicin drug concentrations in neonates with HIE receiving therapeutic hypothermia were examined during two time periods in a retrospective chart review. During the initial treatment period (November 2007 to March 2010; n=29), neonates received gentamicin 5 mg/kg every 24h (Q24h period). During the second treatment period (January 2011 to May 2012; n=23), the dose was changed to 5 mg/kg every 36h (Q36h period). Cooling criteria and protocol remained the same between treatment periods. Gentamicin drug concentrations including achievement of target trough concentrations (<2 mg/L) were compared between treatment periods. Individual Bayesian estimates of gentamicin clearance were also compared. Result Neonates with an elevated trough concentration >2 mg/L decreased from 38% to 4% with implementation of a Q36h dosing interval (P<0.007). The mean gentamicin trough concentration was 2.0 ± 0.8 mg/L during the Q24h period and 0.9 ± 0.4 mg/L during the Q36h period (P<0.001). Peak concentrations were minimally impacted (Q24h 11.4 ± 2.3 mg/L vs. Q36h 10.0 ± 1.9 mg/L; P=0.05). The change in gentamicin trough concentration could not be accounted for by differences in gentamicin clearance between treatment periods (P=0.9). Conclusion A 5 mg/kg every 36h gentamicin dosing strategy in neonates with HIE receiving therapeutic hypothermia improved achievement of target trough concentration <2 mg/L while still providing high peak concentration exposure.

In the cardiac ICU, management of the cardiac patient requires an individualized sedative and analgesic strategy that maintains hemodynamic stability. Multiple pharmacological therapies exist to achieve these goals and should be selected based on the patient's underlying physiology, hemodynamic vulnerabilities, desired level of sedation and analgesia, and the projected short- or long-term recovery trajectory.