Clinical and Economic Evaluation of Surfactant Use in the Management of Meconium Aspiration Syndrome in the Intensive: Care Setting In Qatar

Abstract

Background. Surfactant replacement therapy is widely used in the management of the life-threatening condition of Meconium Aspiration Syndrome (MAS), with no clear guidance on its best use. This thesis constitutes two phases. Phase one was to conduct a systematic overview of literature systematic reviews (SRs) and randomized clinical trials (RCTs) on surfactant therapy in neonatal MAS. Phase two was to evaluate the clinical and economic impact of surfactant use in MAS management in the NICU setting in Qatar, including different surfactant dosing regimens. Methods. For the SR, we searched EMBASE, PROQUEST and PubMed to summarize the different effects of surfactant lung lavage (SLL) and bolus surfactant (BS) therapies in neonates with MAS. Phase two of the thesis was a retrospective cost-effectiveness analyses to evaluate critically ill neonates with MAS receiving surfactant versus standard care, and those receiving single versus multiple dosing surfactant therapy at NICUs in Hamad Medical Corporation (HMC), Qatar. Available medical records in the duration from 2014 to 2019 were utilized. Decision-analytic models from the hospital perspective were designed to measure all the possible consequences of all comparisons. The base case of the model was analyzed based on a multivariate analysis via Monte Carlo simulation. Primary endpoints were treatment success defined as improvements in oxygenation over baseline 24 h after treatment, evaluated by the reduction of oxygen index (OI) to less than 10, and the overall direct medical cost of therapy. Sample size was calculated to achieve results with 80% power and a significance level of 0.05. Sensitivity analyses were conducted to enhance the robustness and generalizability of the results. Results. With a total of 1,377 patients, three SRs and two RCTs were included in our SR analysis. Surfactant effectiveness was concluded by low-quality SRs, with high risk of bias, which was contradicted by high-quality SRs, with low risk of bias. In SRs, the SLL reduced mortality, need for extracorporeal membrane oxygenation, and hospitalization, while the BS did not. In recent high-quality RCTs, however, the two modalities did not significantly differ. For the cost-effectiveness evaluation in phase two of the thesis, the standard care achieved a success of 75% versus 51% with surfactant (odd ratio = 2.84; P = 0.029). The surfactant use was dominated by the standard care in MAS, with cost-saving of QAR 48,653 per patient in favor of the latter. Single dose surfactant dominated the multiple doses regimen, with a cost saving of QAR 12,582 per patient and a 57% treatment success, compared to 33% (odd ratio = 1.2; P = 0.839). Here, the study groups did not achieve the calculated sample size and, hence, the evaluation was piloting in nature. Sensitivity analyses demonstrated the robustness of all study conclusions. Conclusion. The literature evidence on surfactant effectiveness and its method of administration is sparse and inconsistent. Based on the first cost-effectiveness evaluations of surfactant use in MAS in the literature. Standard care was cost effective and dominant over surfactant therapy in both clinical and economic outcomes. A cost analysis of single dose surfactant therapy versus the multiple dosing approach demonstrated overall cost savings with the single dosing approach. The results support the recent trend by some HMC practitioners of favoring standard care over surfactant in the NICU practices of HMC.