Cost-effectiveness of intravenous acetaminophen and ketorolac in adolescents undergoing idiopathic scoliosis surgery.

BACKGROUND: Enhanced recovery after surgery protocols increasingly use multimodal analgesia after major surgeries with intravenous acetaminophen and ketorolac, despite no documented cost-effectiveness of these strategies. AIMS: The goal of this prospective cohort study was to model cost-effectiveness of adding acetaminophen or acetaminophen + ketorolac to opioids for postoperative outcomes in children having scoliosis surgery. METHODS: Of 106 postsurgical children, 36 received only opioids, 26 received intravenous acetaminophen, and 44 received acetaminophen + ketorolac as analgesia adjuncts. Costs were calculated in 2015 US $. Decision analytic model was constructed with Decision Maker® software. Base-case and sensitivity analyses were performed with effectiveness defined as avoidance of opioid adverse effects. RESULTS: The groups were comparable demographically. Compared with opioids-only strategy, subjects in the intravenous acetaminophen + ketorolac strategy consumed less opioids (P = .002; difference in mean morphine consumption on postoperative days 1 and 2 was -0.44 mg/kg (95% CI -0.72 to -0.16); tolerated meals earlier (P < .001; RR 0.250 (0.112-0.556)) and had less constipation (P < .001; RR 0.226 (0.094-0.546)). Base-case analysis showed that of the 3 strategies, use of opioids alone is both most costly and least effective, opioids + intravenous acetaminophen is intermediate in both cost and effectiveness; and opioids + intravenous acetaminophen and ketorolac is the least expensive and most effective strategy. The addition of intravenous acetaminophen with or without ketorolac to an opioid-only strategy saves $510-$947 per patient undergoing spine surgery and decreases opioid side effects. CONCLUSION: Intravenous acetaminophen with or without ketorolac reduced opioid consumption, opioid-related adverse effects, length of stay, and thereby cost of care following idiopathic scoliosis in adolescents compared with opioids-alone postoperative analgesia strategy.

Postoperative ketorolac tromethamine use in infants aged 6-18 months: the effect on morphine usage, safety assessment, and stereo-specific pharmacokinetics.

BACKGROUND: Nonsteroidal antiinflammatory drugs have been useful for treating postoperative pain in children. The only parenteral nonsteroidal antiinflammatory drug currently available in the United States is ketorolac tromethamine with cyclooxygenase-1 and cyclooxygenase-2 effects. Information on the pharmacokinetics of ketorolac in infants is sparse, making dosing difficult. Ketorolac is administered as a racemic mixture with the S(-) isomer responsible for the analgesic effect. In this study, we describe the population pharmacokinetics of ketorolac in a group of 25 infants and toddlers who received a single IV administration of racemic ketorolac and evaluate the potential influence of patient covariates on ketorolac disposition. METHODS: In this double-blind, placebo-controlled study, ketorolac pharmacokinetic, safety, and analgesic effects were studied in 37 infants and toddlers (aged 6-18 mo) postoperatively. On postoperative day 1, infants were randomized to receive placebo, 0.5, or 1 mg/kg ketorolac as a 10-min IV infusion. Blood samples were collected up to 12-h after dosing. The data were analyzed using noncompartmental and compartmental (nonlinear mixed-effects model) means. The patient covariates, including body weight, age, and surgical procedure, were analyzed in a stepwise fashion to identify their potential influence on ketorolac pharmacokinetics. RESULTS: The data were best described by a two-compartmental model. Inclusion of covariates did not significantly decrease the nonlinear mixed-effects model objective function values and between-subject variability in the pharmacokinetic parameters of nested models. The mean and standard error of the estimates of the R(+) isomer were central volume of distribution 1200 +/- 163 mL (coefficient of variation of interindividual variability, 13.6%), peripheral volume of distribution 828 +/- 108 mL (13.0%), clearance from the central compartment 7.52 +/- 0.7 mL/min (9.3%), and extrapolated elimination half-life 238 +/- 48 min. Those of the S(-) isomer were 2320 +/- 34 (14.6%), 224 +/- 193 mL (86.2%), 45.3 +/- 5.5 mL/min (12.1%), and 50 +/- 42 min respectively. Dosing simulations, using population pharmacokinetic parameters, showed no accumulation of S(-) ketorolac but steady increases in R(+) ketorolac. Safety assessment showed no adverse effects on renal or hepatic function tests, surgical drain output, or continuous oximetry between placebo and ketorolac groups. Cumulative morphine administration showed large interpatient variability and was not different between groups. CONCLUSION: The stereo-isomer-specific clearance of ketorolac in infants and toddlers (aged 6-18 mo) shows rapid elimination of the analgesic S(-) isomer. No adverse effects on surgical drain output, oximetry measured saturations, renal or hepatic function tests were seen. Simulation of single dosing at 0.5 or 1 mg/kg every 4 or 6 h does not lead to accumulation of S(-) ketorolac, the analgesic isomer, but does result in increases in R(+) ketorolac. Shorter dose intervals may be needed in infants older than 6 mo.

Retrospective case-control evaluation of the use of parenteral ketorolac tromethamine in patients after surgery.

The aim of this study was to assess medication usage and to determine differences in selected outcomes in patients who received either parenteral ketorolac tromethamine or narcotics after surgery. A retrospective case-control study was used in patients on a surgery service who were postoperative. Forty patients who received parenteral ketorolac tromethamine as their primary postoperative pain medication were matched by surgical procedure, age, and sex to 40 patients who did not receive parenteral or oral ketorolac tromethamine. Patient data were collected by chart review, and fiscal information was obtained through hospital computer data bases. Simple t-tests were used to examine between-group differences in outcomes measured by interval scales, and contingency table analyses using the chi-square statistic were used to examine differences in dichotomous and ordinal scale outcomes. Parenteral ketorolac was prescribed in accordance with Food and Drug Administration (FDA)-approved guidelines 55% of the time, but actual patient use was in accordance with FDA guidelines 75% of the time. There were no differences between groups in any measure of analgesia prescription. Significant findings between patients receiving ketorolac tromethamine versus controls included a longer length of hospital stay (14.6 +/- 13.0 v 9.2 +/- 8.3 days), higher pharmacy cost ($69. 57 +/- $87.00 v $5.20 +/- $6.10), and higher use of histamine-2 antagonists (59.0% v 35.0%). Subgroup analysis showed that patients with a principle gastrointestinal diagnosis had the greatest differences in length of stay. Prospective studies are needed to assess patient outcomes when parenteral ketorolac tromethamine is prescribed for postoperative pain.