Variability in insulin pharmacokinetics following high-dose insulin therapy

Abstract

Introduction: High dose insulin (HDI) therapy for cardiogenic shock from acute poisoning can be complicated by treatable hypoglycemia which persists following poisoning recovery. Glucose requirements post-HDI reflect supraphysiological insulin plasma concentration. A publication reported a patient treated with HDI with plasma insulin concentrations >1000 µU/mL and elimination half-life 10-18 h requiring intravenous glucose replacement for >5 days. We report two cases treated with HDI (Actrapid; soluble or regular insulin) with shorter elimination half-lives.

Case reports: A man ingesting diltiazem received HDI for approximately 60 h (maximum dose 10 U/kg/h) and supplemental intravenous dextrose for 44 h post-HDI. Post-HDI the maximum measured plasma insulin concentration was 6345 µU/mL and elimination half-life 5.5 h. A man ingesting propranolol received HDI for approximately 12 h (maximum dose 1.5 U/kg/h) and supplemental intravenous dextrose for 4 h post-HDI. Post-HDI the maximum measured plasma insulin concentration was 368 µU/mL and elimination half-life 2.2 h.

Discussion: Markedly different insulin pharmacokinetics post-HDI is observed in two cases and a previously published report, and factors contributing to the interpatient differences are poorly defined. This pharmacokinetic variability impacts on the severity and duration of treatable hypoglycemia post-HDI. Analytical factors impacting on the measured plasma insulin concentrations include appropriate sample dilution and differing analytical specificity for the type of insulin.

Keywords: HDI; HIET; Insulin; assay; diltiazem; inotrope; overdose; poisoning; propranolol; shock; toxicity.