Association between total dose of ritodrine hydrochloride and pulmonary oedema in twin pregnancy: a retrospective cohort study in Japan

OBJECTIVE Pulmonary oedema is recognised as a severe side effect of ritodrine hydrochloride. Recently, the number of twin pregnancies has been increasing. Few studies have reported the association between total dose of ritodrine hydrochloride prior to delivery and pulmonary oedema in twin pregnancy. We aimed to examine this association and determine the optimal cut-off threshold of total ritodrine hydrochloride dose to predict the incidence of pulmonary oedema in twin pregnancy based on obstetric records. DESIGN Retrospective cohort study. SETTING Yamanashi Prefectural Central Hospital, Japan. PARTICIPANTS Two hundred and twenty-six women with twin pregnancy who delivered at Yamanashi Prefectural Central Hospital between September 2009 and November 2016. METHODS The obstetric records of the participants were analysed. We defined 1 unit of ritodrine hydrochloride as 72 mg per 24 hours continuous transfusion at 50 µg/min to calculate the dose of ritodrine used for tocolysis. OUTCOME MEASURES Multivariable logistic regression analysis was performed to examine the association between total dose of ritodrine hydrochloride used for threatened preterm labour and pulmonary oedema, while controlling for potential confounding factors. Then, a receiver-operating characteristic curve was used to determine the optimal cut-off of total ritodrine dose to predict pulmonary oedema incidence. RESULTS Mean maternal age was 32 (range, 18-46) years; 143 participants were nulliparous (63.3%), 109 had (48.2%) term deliveries and 194 (85.8%) had caesarean deliveries. The overall incidence of pulmonary oedema was 13.7% (31/226). Multivariable analysis showed that the total dose of ritodrine was significantly associated with pulmonary oedema (adjusted OR 1.02; 95% CI 1.004 to 1.03). The best cut-off point to predict the incidence of pulmonary oedema was 26 units (1872 mg) (sensitivity, 61.3%; specificity, 87.8%). CONCLUSION Our results suggest that consideration of the total dose of ritodrine hydrochloride is helpful in the management of patients with threatened preterm labour in twin pregnancy.