Ketorolac in Postoperative Infants: Pharmacokinetics and Safety

Infants handle ketorolac differently than adults. Study of handling of this pain medication given to infants following surgery. Detailed analysis of how the drug is eliminated from age 2 months to 18 months. Compared morphine use in infants who received the drug to the group getting placebo. Safety testing for kidney and liver function, breathing measured by continuous oximetry, and any bleeding issues.

Population kinetic analysis of ketorolac stereo-isomer concentrations after single dose given postoperatively in infants aged 2-18 months. Safety assessments of renal and hepatic function tests by blood tests before and after drug administration, urinalysis pre- and post-drug, continuous oximetry before and for 12 hours after drug. Morphine use between active drug groups and placebo group in the first 24 hours after surgery was assessed as a surrogate analgesic measure in these non-verbal infants. A modified infant pain scale was used to assure consistent pain management.

Ketorolac Tromethamine 1 mg/kg infusion over 10 minutes intravenous (IV) infusion. Blood sampling in for up to 12 hours after infusion for analysis of ketorolac concentrations and safety assessments.

Ketorolac Tromethamine 0.5 mg/kg infusion over 10 minutes intravenous (IV) infusion. Blood sampling for up to 12 hours after infusion for analysis of ketorolac concentrations and safety assessments.

Dextrose in water (D5W) infusion over 10 minutes intravenous (IV) infusion. Blood sampling for up to 12 hours after infusion for analysis of ketorolac concentrations and safety assessments.

stereo-specific ketorolac analysis using population-based analysis (NONMEM)for ketorolac given intravenously 24 hours after surgery in 2-6 month old infants

peripheral volume of distribution for ketorolac stereo-isomers determined by population kinetic analysis (NONMEM)

half-life calculated from non-compartmental analysis of ketorolac isomers in 2-6 month old infants given intravenous ketorolac following surgery

population-based kinetic analysis of ketorolac isomers following intravenous infusion in infants after surgery

noncompartmental pharmacokinetic analysis of ketorolac stereo-isomers after intravenous infusion in postoperative infants

total morphine given intravenously in the 12 hours following receiving intravenous ketorolac or placebo

continuous oximetry monitoring of room air saturation was collected for 12 hours after intravenous infusion of ketorolac or placebo

Total Morphine Use in 6-18 Month Old Infants After Ketorolac or Placebo Intravenous Infusion After Surgery

total amount of morphine given for 12 hours after ketorolac or placebo infusion in 6-18 month old infants after surgery

continuous oximetry monitoring for 12 hours after ketorolac or placebo intravenous infusion in 6-18 month old infants after surgery

Inclusion Criteria: Non-prematurely-born infants admitted to hospital following surgery ages 2-18 months, studied by age group 12-18 months, 6-12 months, < 6 months Exclusion Criteria: Bleeding history in infant or family Coagulopathy Gastrointestinal bleeding history Renal or hepatic disease assessed by history and by pre-drug blood tests Premature birth (<36 weeks gestation)

Lynn AM, Bradford H, Kantor ED, Seng KY, Salinger DH, Chen J, Ellenbogen RG, Vicini P, Anderson GD. Postoperative ketorolac tromethamine use in infants aged 6-18 months: the effect on morphine usage, safety assessment, and stereo-specific pharmacokinetics. Anesth Analg. 2007 May;104(5):1040-51, tables of contents. doi: 10.1213/01.ane.0000260320.60867.6c.

Lynn AM, Bradford H, Kantor ED, Andrew M, Vicini P, Anderson GD. Ketorolac tromethamine: stereo-specific pharmacokinetics and single-dose use in postoperative infants aged 2-6 months. Paediatr Anaesth. 2011 Mar;21(3):325-34. doi: 10.1111/j.1460-9592.2010.03484.x. Epub 2010 Dec 29.