Clinical and Economic Evaluation of the Impact of Midazolam on Morphine Therapy for Pain Relief in Critically Ill Ventilated Infants with Respiratory Distress Syndrome

Abstract

Background: The impact of midazolam on the overall performance of morphine therapy for pain in ventilated neonates with respiratory distress syndrome (RDS) has never been investigated. Objective: This study is a clinical and economic analysis of morphine monotherapy versus morphine plus midazolam in ventilated infants with RDS. Methods: A decision-analytic model from the hospital perspective was developed to follow the consequences of the use of the study drugs. Clinical and resource utilization data were extracted based on a retrospective cohort study of 104 neonates with RDS receiving morphine alone versus in combination with midazolam at the main neonatal intensive care unit (NICU) in Qatar, from 2014 to 2019. Primary outcome measures were the analgesia success rate, via the Premature Infant Pain Profile scale, and overall costs of therapies. Multivariate statistical analyses confirmed no significant variations in baseline characteristics between study groups. Results: With 0.05 significance and 80% power, morphine had a higher rate of successful analgesia (65.4 vs. 34.6%; risk ratio 1.91; 95% confidence interval 1.11–3.28; p = 0.019). Overall costs were also in favor of morphine compared with its combination with midazolam, with cost savings of 40,959 Qatari Riyal ($US11,222), year 2019/20 values. The Monte Carlo analyses confirmed the economic advantage of morphine alone in 100% of cases and demonstrated that it is not sensitive to uncertainties in study model inputs. Conclusions: Morphine monotherapy enabled enhanced pain relief over its combination with midazolam in the NICU, at a reduced overall cost. Morphine alone, therefore, seems to be a dominant analgesia strategy.