Johns Hopkins All Children's Hospital, Johns Hopkins University School of Medicine St. Petersburg, Florida, United States
Abstract:
Introduction: Inadequate pain control after cardiac surgery may increase metabolic demand. However, reliance upon opioids for pain control poses concerns, given association with respiratory depression, extubation failure, increased length of stay, and adverse neurodevelopmental sequelae. Data on the safety and efficacy of ketorolac is limited particularly among neonates and infants post-cardiac surgery. Accordingly, we sought to assess the safety and efficacy of a standardized ketorolac regimen.
Methods: We performed a single-center retrospective cohort study of neonates and infants (age < 12months) who received ketorolac in the immediate post cardiac surgery period, from November 2020 through November 2021 (inclusive). Exclusion criteria included: 1) preterm birth; 2) allergy to non-steroidal anti-inflammatory drugs, 3) mechanical circulatory support, 4) estimated glomerular filtration rate < 10mL/min/1.73m2; 5) active bleeding; 6) disseminated intravascular coagulation or platelet count < 100,000/microliter; 7) history of gastrointestinal bleed/ulceration/perforation, necrotizing enterocolitis, or intraventricular hemorrhage. Ketorolac was administered at 0.5mg/kg every 6 hours. Safety was defined by absence of clinically significant decline in renal function (i.e. increase in serum creatinine [SCr] by ≥0.3mg/dL from baseline within 48 hours or urine output ≤0.5mL/kg/hour for six hours) and absence of clinically significant bleeding (defined as major by International Society on Thrombosis and Hemostasis pediatric criteria or Severe/Fatal Bleeding Events by Nellis et al, 2019). Efficacy measures included pain scores and opioid utilization. Descriptive statistics summarized patient clinical characteristics by age category (neonates, 1- < 6months, 6- < 12months). Two-sided Wilcoxon signed-rank tests were used to determine statistically significant differences in clinical measurements over time.
Results: Fifty-six patients met eligibility criteria: 11 neonates, 31 infants aged 1 to < 6 months, and 14 infants aged 6 to < 12 months. The majority (80.3%) of patients underwent STAT 1 and 2 operations, and 87.5% were extubated in the operating room. The median (range) duration of ketorolac administration was 48 6(-90) hours. There was not a statistically significant difference in median SCr within 48 hours of baseline (p>0.9) among the entire sample. Specifically, 48.2% of patients had a decrease in SCr, 42.9% had an increased SCr, and 8.9% had no change in SCr. Of those with an increased SCr, the median (range) increase in SCr from baseline within 48 hours of ketorolac initiation was 0.06 (0.01-0.3) mg/dL. One patient (1.8%) met the renal dysfunction definition. There were no major or severe bleeding events; 4 (7.1%) patients received blood transfusion following ketorolac initiation. The cumulative median (range) opioid administration (morphine equivalents) within 48 hrs of ketorolac initiation was 0.25 (0-7.9) mg/kg.
Conclusions: Our findings suggest that a ketorolac regimen 0.5 mg/kg/dose every 6 hours in neonates and infants post-cardiac surgery may be safe with regards to renal function and bleeding risk, and effective regarding opioid-sparing capacity. Further prospective studies are warranted to confirm and extend these findings.
