A cost-effectiveness analysis for high versus standard (low) dose caffeine for the treatment of apnea in neonatal intensive care unit.

Objective: Preterm babies are prone to experiencing apnea of prematurity (AOP), mostly characterised by a pause in breathing lasting a minimum of 20 seconds. Recent literature supported higher maintenance doses of caffeine, indicating benefits. This study evaluated the cost-effectiveness of high maintenance dose (HD) versus low maintenance dose (LD) caffeine for AOP in neonates. Methods: From the hospital perspective of Hamad Medical Corporation (HMC), Qatar, a cost-effectiveness decision-analytic model was constructed to follow the use of a HD maintenance caffeine of 20 mg/kg/dose versus a LD maintenance caffeine of 10 mg/kg/dose, in a simulated cohort of AOP neonates, over a therapy follow-up duration of six weeks, until neonatal intensive care (NICU) discharge. The clinical inputs were primarily literature-based, while the resource cost and utilisation were locally extracted in HMC. The cost-effectiveness outcome measure was calculated per therapy success, defined as survival with no apnea and successful extubation removal within 72 hours, with or without adverse events. One-way and multivariate sensitivity analyses were performed to confirm the robustness of the results. Results: With 0.23 (95% CI, 0.23-0.23) enhancement in success rate, at United States dollar (US$) 3869 (95% CI, US$ 3823-3915) added infant cost, the HD caffeine was between dominant (34.8%) and cost-effective (63.7%), with an average incremental cost-effectiveness ratio of US $16,895 (95% CI, US$ 15,242-18,549) relative to LD caffeine per additional case of success. The hospitalisation contributed the most to the total infant cost, and the probability of patent ductus arteriosus was the model input that influenced the results most. Conclusion: This is the first literature economic evaluation of caffeine for AOP. Despite increasing the cost of therapy, HD maintenance caffeine seems to be a cost-effective alternative to LD caffeine in Qatar. Our results support the recent global trends of increased use of HD caffeine for AOP in NICU.

Clinical pharmacists' interventions for preventing adverse events in critically ill neonates in Qatar: an economic impact analysis.

Objective: This study aimed to assess the overall economic impact of clinical pharmacist interventions in the neonatal ICU (NICU) in Qatar. Methods: A retrospective review of neonates' records was performed over a 3-month duration in the NICU of Qatar to determine the total economic benefit of clinical pharmacist interventions. The total benefit of interventions was calculated by considering the cost avoidance due to preventable adverse drug events (ADEs) and the cost savings associated with the revised resource use due to interventions. Sensitivity analyses were conducted to ensure the robustness and generalizability of the results. Results: A total of 513 interventions were analyzed, involving 150 neonates. Most of the drug-related problems were related to therapy dosing, followed by drug choice appropriateness, the addition of prophylactic treatment, and administration frequency. The overall annual benefit was estimated at QAR 4,178,352 (1,147,584), which consisted of cost avoidance of QAR 1,050,680 (USD 288,648) and an overall cost saving of QAR -6091 (USD -1673). Conclusions: While the clinical pharmacist interventions led to increased resource utilisation and associated costs, when considering the avoided costs of ADEs, the overall clinical pharmacist practices in the NICU setting were economically beneficial.

Cost-Effectiveness Analysis of Ibuprofen Versus Indomethacin or Paracetamol for the Treatment of Patent Ductus Arteriosus in Preterm Neonates.

This was a first-time evaluation that sought to analyze the cost-effectiveness of oral paracetamol and intravenous (IV) indomethacin as alternatives to ibuprofen for PDA in neonates. Decision-analytic, literature-based, economic simulation models were constructed, to follow up the use and consequences of oral/IV ibuprofen versus IV indomethacin, and oral/IV ibuprofen versus oral paracetamol, as first-line therapies for PDA closure. Model outcomes of interest were "success", defined as PDA closure with/without adverse events, or "failure" due to no response to the first course of treatment, death or premature discontinuation of therapy due to adverse events. Oral ibuprofen is dominant/cost-effective over IV indomethacin in 97.9% of simulated cases, but oral paracetamol was 75.2% dominant/cost-effective over oral ibuprofen. Against IV ibuprofen, IV indomethacin was 55.3% dominant/cost-effective, whereas oral paracetamol was dominant/cost-effective in 98.5% of the cases. Sensitivity analyses confirmed the robustness of the study results. For PDA closure, while IV indomethacin was cost-effective against IV ibuprofen, oral paracetamol was cost-effective against both oral and IV ibuprofen.

Neonatal Simulation Program: A 5 Years Educational Journey From Qatar.

We describe the process of implementation, adaptation, expansion and some related clinical intuitional impacts of the neonatal simulation program since its launch in 2016 in a non-simulation neonatal unit. The team has developed 6 types of curricula: 1 full-day course and 5 half-day workshops. A total of 35 free of charge simulation courses/workshops were conducted, 32 in Qatar and 3 abroad with a total of 799 diverse participants. There was a steady increase in the overall success rate of PICC insertion from 81.7% (309/378) to 97.6% (439/450) across 3 years (P < 0.0001). The first attempt PICC insertion success rate has been also increased from 57.7% (218/378) to 66.9% (301/450) across 3 years. The mean duration of PICC insertion has been improved from 39.7 ± 25 to 34.9 ± 12.4 min after implementing the program (P = 0.33). The mean duration of the LISA catheter insertion at the beginning of the workshop was 23.5 ± 15.9 compared to 12.1 ± 8.5 s at the end of the workshop (P = 0.001). When it came to clinical practise in real patients by the same participants, the overall LISA catheter insertion success rate was 100% and the first attempt success rate was 80.4%. The mean duration of LISA catheter insertion in real patients was 26.9 ± 13.9 s compared to the end of the workshop (P = 0.001). The mean duration of the endotracheal intubation at the beginning of the workshop was 12.5 ± 9.2 compared to 4.2 ± 3.8 s at the end of the workshop (P = 0.001). In real patients, the first-attempt intubation success rate has been improved from 37/139 (26.6%) in the first year to 141/187 (75.5%) in the second year after the program implementation (P = 0.001). The mean duration of successful endotracheal intubation attempts has been improved from 39.1 ± 52.4 to 20.1 ± 9.9 s (P = 0.78). As per the participants, the skills learned in the program sessions help in protecting neonates from potential harm and improve the overall neonatal outcome. Implementing a neonatal simulation program is a promising and feasible idea. Our experience can be generalised and replicated in other neonatal care institutions.

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.

Clinical and Economic Analysis of Morphine Versus Fentanyl in Managing Ventilated Neonates With Respiratory Distress Syndrome in the Intensive Care Setting.

PURPOSE: Morphine and fentanyl opioids are common analgesic agents for consideration in the neonatal intensive care unit (NICU) for neonates with respiratory distress syndrome (RDS) and undergoing mechanical ventilation (MV). The aim of this study was to evaluate the clinical and economic impact of morphine versus fentanyl in neonates with RDS undergoing MV. METHODS: Retrospective cost-effectiveness analysis of critically ill neonates with RDS receiving standard doses of morphine versus fentanyl at Women's Wellness and Research Center, Qatar. Clinical data of neonates were extracted from medical records of patients from 2014 to 2016. A decision analytic model based on the hospital's perspective was constructed to follow possible consequences of the initial dosing of analgesia, before potential titration. Primary end points were successful pain relief rate based on the Premature Infant Pain Profile scale and overall direct medical cost of therapy. Study population of 126 neonates was used to achieve results with 80% power and 0.05 significance. Sensitivity analysis was conducted to enhance robustness of conclusions against input uncertainties and to increase generalizability of results. FINDINGS: Morphine achieved a success of 68% versus 43% with fentanyl (risk ratio = 1.72; 95% CI, 1.16-2.56; P = 0.0075). Morphine was associated with a minimal incremental cost-effectiveness ratio of USD 135 per additional case of successful pain relief over fentanyl. Higher morphine cost was reported in 2% of cases. Sensitivity analysis found model insensitivity to input uncertainties except NICU stay and cost of MV. IMPLICATIONS: This is the first cost-effectiveness evaluation of morphine versus fentanyl in the NICU. Morphine significantly improved the relieve of pain over fentanyl. It had 98% probability of dominance over fentanyl. Results in this study support the use of morphine over fentanyl as first-line monotherapy with MV in NICU settings.

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

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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 240/7-296/7 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. RESULTS: 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. CONCLUSIONS: 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.