Frommelt Peter, Juern Anna, Siegel Dawn, Holland Kristen, Seefeldt Marcia, Yu JiaDe, Uhing Michael, Wade Kelly, Drolet Beth
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Department of Dermatology , Medical College of Wisconsin, Milwaukee, Wisconsin.
Pediatr Dermatol. 2016 Jul;33(4):405-14. doi: 10.1111/pde.12869. Epub 2016 May 31.
The success of oral propranolol for treatment of infantile hemangiomas (IHs) has led practitioners to use topical β-blockers. In preterm infants, clinicians frequently turn to topical timolol, with the presumption that topical application will result in less systemic absorption. We used Holter monitoring to assess for drug-induced bradycardia in high-risk infants.
We retrospectively reviewed the charts of 22 at-risk infants who received a Holter monitor to assess for association between timolol administration and development of significant bradycardia.
Four infants had episodic bradycardia detected by Holter monitoring. Two of these infants were full term; weighed more than 3,000 g; and had rare, brief, asymptomatic episodes unrelated to the timing of the timolol application. The other two infants had symptomatic bradycardia while on timolol and were the only two babies that weighed less than 2,500 g at initiation of therapy. Both were young (postmenstrual age [PMA] 34 and 37 wks) at initiation and had a timolol dose above the average exposure for the cohort.
In this cohort of at-risk infants, topical timolol appeared to provide safe treatment for IHs in full-term infants receiving a dose of less than 0.2 mg/kg/day, but infants with a PMA of less than 44 weeks and weight at treatment initiation of less than 2,500 g may be at risk of adverse events, including bradycardia, hypotension, apnea, and hypothermia. We recommend close monitoring of temperature, blood pressure, and heart rate in premature and low-birthweight infants with IHs at initiation of and during therapy with topical timolol.
口服普萘洛尔治疗婴儿血管瘤（IHs）取得成功后，临床医生开始使用局部β受体阻滞剂。对于早产儿，临床医生常选用局部用噻吗洛尔，认为局部用药全身吸收较少。我们使用动态心电图监测评估高危婴儿药物诱发的心动过缓情况。
我们回顾性分析了22例接受动态心电图监测的高危婴儿的病历，以评估噻吗洛尔给药与显著心动过缓发生之间的关联。
动态心电图监测发现4例婴儿有发作性心动过缓。其中2例为足月儿，体重超过3000克，发作罕见、短暂且无症状，与噻吗洛尔用药时间无关。另外2例婴儿在使用噻吗洛尔时出现症状性心动过缓，且是治疗开始时体重不足2500克的仅有的2例婴儿。二者开始用药时均较年幼（月经龄[PMA]分别为34周和37周），且噻吗洛尔剂量高于队列平均暴露量。
在这个高危婴儿队列中，局部用噻吗洛尔似乎能为接受剂量小于0.2毫克/千克/天的足月儿的婴儿血管瘤提供安全治疗，但月经龄小于44周且治疗开始时体重不足2500克的婴儿可能有发生心动过缓、低血压、呼吸暂停和体温过低等不良事件的风险。我们建议在使用局部用噻吗洛尔治疗婴儿血管瘤的早产儿和低体重儿开始治疗时及治疗期间密切监测体温、血压和心率。
