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

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.The authors acknowledge the funds provided by Qatar University, Qatar, through the internal grant QUUG-CPH-CPH-15/16-8

Prophylactic Sildenafil in Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Pilot Randomized, Double-Blinded, Placebo-Controlled Trial.

Bronchopulmonary dysplasia (BPD) is the need for oxygen therapy at 36 weeks postmenstrual age (PMA). Sildenafil has been shown to enhance the lung alveolarization and vascularization in newborn animal models after lung injury and has possible therapeutic potential for the prevention of BPD. To perform a proof-of-concept, Phase II, pilot randomized, double-blind, clinical trial to study the efficacy of sildenafil in preventing BPD, in postnatal (< 24 h), extremely and very preterm infants. This Phase II, pilot randomized, double-blind, clinical trial was conducted in the Neonatal Intensive Care Unit of Women's Wellness and Research Center, Doha, Qatar during 2012-2014. Infants of 24-29 weeks' gestation were eligible if they needed respiratory or oxygen support ≥ 25% at randomization, and if they were at a postnatal age of < 24 h at randomization. Forty preterm infants were randomly assigned to receive off-label oral sildenafil (0.5 mg/kg every 6 h) or a placebo solution, for one week. The primary endpoints were the incidence of BPD and death at 36 weeks PMA, and the side effects. Secondary outcomes included the incidence of BPD and the respiratory support at day 28 of life, duration of oxygen use, fraction of inspired oxygen use at 36 weeks and 28 days of life, duration of hospitalization, and the incidence of significant retinopathy of prematurity, severe intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, patent ductus arteriosus, and late sepsis. No significant differences were observed between the sildenafil and placebo study groups in mortality at 36 weeks PMA (10% vs 20%, p = 1), respiratory support at 36 weeks (30% vs 25%, p = 0.57), and side effects (0% vs 0%). For all other secondary outcomes, no significant differences were detected. While not associated with side effects, off-label oral sildenafil did not demonstrate benefits in the prevention of BPD or death in the extreme and very preterm infants. Future studies of dosing and efficacy that target different regimens of sildenafil are warranted before sildenafil is recommended for the prevention of BPD.The study was supported by Medical Research Center, Hamad Medical Corporation [Grant number RP#11087/11]

Prophylactic Sildenafil in Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Pilot Randomized, Double-Blinded, Placebo-Controlled Trial

Bronchopulmonary dysplasia (BPD) is the need for oxygen therapy at 36 weeks postmenstrual age (PMA). Sildenafil has been shown to enhance the lung alveolarization and vascularization in newborn animal models after lung injury and has possible therapeutic potential for the prevention of BPD. To perform a proof-of-concept, Phase II, pilot randomized, double-blind, clinical trial to study the efficacy of sildenafil in preventing BPD, in postnatal (Other Information Published in: Clinical Drug Investigation License: https://creativecommons.org/licenses/by-nc/4.0See article on publisher's website: http://dx.doi.org/10.1007/s40261-019-00834-0</p