A review of therapeutic hypothermia examined disposition across several medicines. A change in a midazolam-metabolite parameter was not a uniform reduction in clearance of every drug.
The reviewed evidence
The review included thirty-six studies involving fifteen compounds in neonates with hypoxic-ischemic encephalopathy. Some showed decreased clearance during cooling, particularly for selected elimination routes.
The summarized midazolam-related finding concerned a metabolite, while other drugs showed different magnitudes or no measured difference. The review emphasized drug-specific disposition.
Cooling and illness are intertwined
Organ dysfunction, developmental maturation, treatment, and sampling can all influence neonatal pharmacokinetics. Studies varied, and the underlying encephalopathy complicates causal attribution.
The paper cannot establish one universal cooling correction for benzodiazepines or infer neurologic effect from a metabolite-clearance percentage. A forensic account should distinguish parent drug, active metabolites, renal and hepatic function, temperature phase, and actual infusion history. A neonatal review also cannot be transferred directly to hypothermic adults.
Source paper
Original analysis of the supplied journal article, identified as PMC7299043.
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