Desai Jay, Key Logan, Swindall Alyson, Gaston Kan, Talati Ajay J
Department of Pediatrics, Division of Neonatal- Perinatal Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
Department of Pharmacy, Regional One Health Center, Memphis, TN, USA.
Ther Adv Drug Saf. 2021 May 18;12:20420986211011338. doi: 10.1177/20420986211011338. eCollection 2021.
The most common cause of persistent hypoglycemia in infancy is hyperinsulinemic hypoglycemia. When conservative measures fail, providers often use medications to treat persistent hypoglycemia. Diazoxide is first-line therapy for neonatal hypoglycemia and works by inhibiting insulin secretion. Diazoxide is associated with fluid retention, and less commonly with respiratory decompensation and pulmonary hypertension. Case reports documenting these severe adverse events exist in the literature, although the overall incidence, risk factors, and timing for these effects in a newborn are not clearly defined.
We performed a retrospective chart review of all infants admitted to the neonatal intensive care unit (NICU) at Regional One Health from 1 January 2013 until 15 August 2019, who received diazoxide as a treatment for persistent hypoglycemia secondary to hyperinsulinism. Patients were stratified as either having no adverse event or having an adverse outcome to the medication. A severe adverse outcome was defined as any known major side effect of the medication, which a patient developed within 2 weeks of medication initiation that led to medication discontinuation.
From our pharmacy database, we identified a total of 15 babies who received diazoxide for persistent hypoglycemia. Of these patients, eight (53%) were classified as having a complication requiring discontinuation of the medication. Six out of eight patients required intubation with mechanical ventilation and five out of eight patients developed pulmonary hypertension. All patients returned to their baseline respiratory support after drug discontinuation.
A total of 53% of our study population had an adverse outcome to diazoxide. Previous studies suggest 5% of patients may have respiratory decompensation and require ventilatory support while on diazoxide; however, 40% of our patients deteriorated and then required mechanical ventilation. Based on our data, respiratory deterioration may be more likely to occur when diazoxide is used in preterm infants, those with lower birth weight and intrauterine growth restriction.
Newborns could experience a transient period of low blood glucose levels soon after birth. However, some may progress to persistent low blood glucose levels that cannot be controlled with adequate glucose infusion and may require other ways of treatment. Diazoxide is the first-line drug approved by the US Food and Drug Administration (FDA) for this condition. However, certain cases have reported the development of respiratory deterioration, including increased blood pressure in lung circulation after its use. This prompted a black box warning in 2015 by the FDA. The incidence of neonatal low blood glucose levels seems to have increased and so has the use of this drug. Our study identifies 15 newborns who received diazoxide at Regional One Health neonatal intensive care unit in the past 6 years and reports a significantly higher rate of adverse events in our population leading to drug discontinuation in almost 53% of our cases.
婴儿持续性低血糖最常见的原因是高胰岛素血症性低血糖。当保守措施失败时，医疗人员通常会使用药物来治疗持续性低血糖。二氮嗪是新生儿低血糖的一线治疗药物，其作用机制是抑制胰岛素分泌。二氮嗪与液体潴留有关，较少见的是与呼吸代偿失调和肺动脉高压有关。文献中有记录这些严重不良事件的病例报告，尽管新生儿中这些影响的总体发生率、危险因素和发生时间尚不清楚。
我们对2013年1月1日至2019年8月15日期间在地区一号健康中心新生儿重症监护病房（NICU）住院的所有因高胰岛素血症继发持续性低血糖而接受二氮嗪治疗的婴儿进行了回顾性病历审查。患者被分为未发生不良事件或出现药物不良结局两类。严重不良结局定义为药物的任何已知主要副作用，患者在开始用药后2周内出现该副作用并导致停药。
从我们的药房数据库中，我们共识别出15名接受二氮嗪治疗持续性低血糖的婴儿。在这些患者中，8名（53%）被归类为出现了需要停药的并发症。8名患者中有6名需要插管并进行机械通气，8名患者中有5名出现了肺动脉高压。所有患者在停药后恢复到基线呼吸支持状态。
我们研究人群中共有53%的患者出现了二氮嗪的不良结局。先前的研究表明，5%的患者在使用二氮嗪时可能会出现呼吸代偿失调并需要通气支持；然而，我们的患者中有40%病情恶化，随后需要机械通气。根据我们的数据，在早产儿、低出生体重儿和宫内生长受限的婴儿中使用二氮嗪时，呼吸恶化可能更易发生。
新生儿出生后可能会经历一段短暂的低血糖期。然而，一些新生儿可能会发展为持续性低血糖，通过适当的葡萄糖输注无法控制，可能需要其他治疗方法。二氮嗪是美国食品药品监督管理局（FDA）批准用于这种情况的一线药物。然而，某些病例报告了使用后出现呼吸恶化，包括肺循环血压升高。这促使FDA在2015年发出黑框警告。新生儿低血糖水平的发生率似乎有所增加，这种药物的使用也增加了。我们的研究确定了过去6年在地区一号健康中心新生儿重症监护病房接受二氮嗪治疗的15名新生儿，并报告了我们人群中不良事件发生率显著更高，导致近53%的病例停药。
