口服普萘洛尔治疗婴儿血管瘤第一周不良反应研究
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摘要
目的:研究口服普萘洛尔治疗婴儿血管瘤第一周发生不良反应的比率及严重程度,评估住院流程是否必须。方法:回顾性分析502例高风险婴儿血管瘤患儿口服普萘洛尔治疗第一周的临床资料,分析不良反应发生的种类、比率及相关因素。结果:502例患儿中男152例,女350例,男∶女=1∶2.3;平均年龄(3.29±2.22)个月。皮损主要分布于头颈(315例,占62.75%)、躯干(97例,占19.32%)、四肢(40例,占7.97%),多发性血管瘤(≥5个病灶)26例(5.18%),其中2例累及肝脏。合并溃疡7例(1.39%)。有早产史38例(7.57%),有低出生体重史17例(3.39%),有心脏病史47例(9.36%)。服药前发现肝功能异常21例(4.18%),TSH增高31例(6.18%)。总不良反应发生率为18.52%(93/502),其中心动过缓4.58%(23/502)、Ⅰ度房室传导阻滞0.40%(2/502),均无临床症状;胃肠道反应12.55%(63/502);食欲减退0.40%(2/502);嗜睡0.20%(1/502);手足湿冷0.40%(2/502)。比较不同性别、年龄患儿以及是否有早产史或低出生体重史、是否存在先天性心脏病史、服药前TSH是否升高、肝功能是否异常患儿在服用普萘洛尔1周后发生心动过缓和胃肠道反应的百分比,差异均无统计学意义(P值均>0.05)。结论:口服普萘洛尔治疗高风险婴儿血管瘤相对安全、不良反应发生率低,非特殊人群、无明显禁忌症的患儿可选择在门诊服药后短期监测、定期随诊调整剂量的模式,免去住院流程。
Objective:To investigate the side effects of oral propranolol for infantile hemangiomas in the first week of treatment, and to assess the necessity of hospitalization. Methods: Data from 502 inpatients with high-risk infantile hemangiomas in the first week of treatment with oral propranolol were retrospectively analyzed. Results: The patient male to female ratio was 1 ∶2.3(152 versus 350), with mean age of 3.29±2.22 months. Lesions on the head/neck, trunk and limbs accounted for 62.75 %(315), 19.32%(97) and 7.97%(40), respectively. Among 26(5.18%) patients with multiple hemangiomas(≥5 lesions), 2 patients exhibited liver involvement. Seven cases were complicated with ulcers. Premature birth and low birth weight accounted for 7.57%(38) and 3.39%(17), respectively. Forty seven(9.36%) patients had a history of heart diseases. Prior to the treatment, 21(4.18%) cases displayed abnormal liver function and 31(6.18%) with high level of blood TSH. The total adverse reaction rate was 18.52%(93/502), including 4.58%(23/502) with bradycardia and 0.40%(2/502) with grade Ⅰ atrioventricular block, all of which were asymptomatic. Gastrointestinal reactions were observed in 12.55%(63/502) of patients, while 0.40%(2/502) of patients had poor appetite. Other adverse reactions included hypersomnia(1/502, 0.20%) and cold extremities(2/502, 0.40%). Following treatment with oral propranolol, the rates of bradycardia and gastrointestinal reactions did not differ between genders, ages and with or without premature birth, low birth weight, elevated basal TSH, abnormal basal liver function or a history of congenital heart disease(all P>0.05). Conclusions: Oral propranolol for high-risk infantile hemangiomas is relatively safe, with minor side effects. Patients without special conditions or contraindications can be treated in the clinic, without necessity of hospitalization. Dosage can be adjusted at regular follow-up visit.
Objective:To investigate the side effects of oral propranolol for infantile hemangiomas in the first week of treatment, and to assess the necessity of hospitalization. Methods: Data from 502 inpatients with high-risk infantile hemangiomas in the first week of treatment with oral propranolol were retrospectively analyzed. Results: The patient male to female ratio was 1 ∶2.3(152 versus 350), with mean age of 3.29±2.22 months. Lesions on the head/neck, trunk and limbs accounted for 62.75 %(315), 19.32%(97) and 7.97%(40), respectively. Among 26(5.18%) patients with multiple hemangiomas(≥5 lesions), 2 patients exhibited liver involvement. Seven cases were complicated with ulcers. Premature birth and low birth weight accounted for 7.57%(38) and 3.39%(17), respectively. Forty seven(9.36%) patients had a history of heart diseases. Prior to the treatment, 21(4.18%) cases displayed abnormal liver function and 31(6.18%) with high level of blood TSH. The total adverse reaction rate was 18.52%(93/502), including 4.58%(23/502) with bradycardia and 0.40%(2/502) with grade Ⅰ atrioventricular block, all of which were asymptomatic. Gastrointestinal reactions were observed in 12.55%(63/502) of patients, while 0.40%(2/502) of patients had poor appetite. Other adverse reactions included hypersomnia(1/502, 0.20%) and cold extremities(2/502, 0.40%). Following treatment with oral propranolol, the rates of bradycardia and gastrointestinal reactions did not differ between genders, ages and with or without premature birth, low birth weight, elevated basal TSH, abnormal basal liver function or a history of congenital heart disease(all P>0.05). Conclusions: Oral propranolol for high-risk infantile hemangiomas is relatively safe, with minor side effects. Patients without special conditions or contraindications can be treated in the clinic, without necessity of hospitalization. Dosage can be adjusted at regular follow-up visit.
引文
[1] FRIEDEN I J,HAGGSTROM A N,DROLET B A,et al.Infantile hemangiomas:current knowledge,future directions.Proceedings of a research workshop on infantile hemangiomas,April 7-9,2005,Bethesda,Maryland,USA[J].Pediatr Dermatol,2005,22(5):383-406.
[2] LUU M,FRIEDEN I J.Hemangioma:clinical course,complications,and management[J].Br J Dermatol,2013,169(1):20-30.
[3] MACISAAC Z M,NAYAR H S,GEHRIS R,et al.Treatment for infantile hemangiomas:selection criteria,safety,and outcomes using oral propranolol during the early phase of propranolol use for hemangiomas[J].J Craniofac Surg,2016,27(1):159-162.
[4] HAIDER K M,PLAGER D A,NEELY D E,et al.Outpatient treatment of periocular infantile hemangiomas with oral propranolol[J].J AAPOS,2010,14(3):251-256.
[5] DYME J L,THAMPAN A,HAN E J,et al.Propranolol for infantile haemangiomas:initiating treatment on an outpatient basis[J].Cardiol Young,2012,22(4):424-429.
[6] CHANG L,YE X,QIU Y,et al.Is propranolol safe and effective for outpatient use for infantile hemangioma?A prospective study of 679 cases from one center in China[J].Ann Plast Surg,2016,76(5):559-563.
[7] PUTTGEN K B,SUMMERER B,SCHNEIDER J,et al.Cardiovascular and blood glucose parameters in infants during propranolol initiation for treatment of symptomatic infantile hemangiomas[J].Ann Otol Rhinol Laryngol,2013,122(9):550-554.
[8] LIU X,QU X,ZHENG J,et al.Effectiveness and safety of oral propranolol versus other treatments for infantile hemangiomas:a meta-analysis[J].Plos One,2015,10(9):e0138100.
[9] DROLET B A,FROMMELT P C,CHAMLIN S L,et al.Initiation and use of propranolol for infantile hemangioma:report of a consensus conference[J].Pediatrics,2013,131(1):128-140.
[10] STILES J,AMAYA C,PHAM R,et al.Propranolol treatment of infantile hemangioma endothelial cells:a molecular analysis[J].Exp Ther Med,2012,4(4):594-604.
[11] HOEGER P H,HARPER J I,BASELGA E,et al.Treatment of infantile haemangiomas:recommendations of a European expert group[J].Eur J Pediatr,2015,174(7):855-865.
[12] MARQUELING A L,OZA V,FRIEDEN I J,et al.Propranolol and infantile hemangiomas four years later:a systematic review[J].Pediatr Dermatol,2013,30(2):182-191.
[13] YUN Y J,GYON Y H,YANG S,et al.A prospective study to assess the efficacy and safety of oral propranolol as first-line treatment for infantile superficial hemangioma[J].Korean J Pediatr,2015,58(12):484-490.
[14] KHOURI C,JOUVE T,BLAISE S,et al.Peripheral vasoconstriction induced by β-adrenoceptor blockers:a systematic review and a network meta-analysis[J].Br J Clin Pharmacol,2016,82(2):549-560.
[15] HOGELING M,ADAMS S,WARGON O.A randomized controlled trial of propranolol for infantile hemangiomas[J].Pediatrics,2011,128(2):e259-e266.
[16] PéPIN V,GAGNé N,ROTTEMBOURG D.Recurrent hypoglycaemia in a toddler on β-blocker therapy[J].Cardiol Young,2018,28(3):511-513.
[2] LUU M,FRIEDEN I J.Hemangioma:clinical course,complications,and management[J].Br J Dermatol,2013,169(1):20-30.
[3] MACISAAC Z M,NAYAR H S,GEHRIS R,et al.Treatment for infantile hemangiomas:selection criteria,safety,and outcomes using oral propranolol during the early phase of propranolol use for hemangiomas[J].J Craniofac Surg,2016,27(1):159-162.
[4] HAIDER K M,PLAGER D A,NEELY D E,et al.Outpatient treatment of periocular infantile hemangiomas with oral propranolol[J].J AAPOS,2010,14(3):251-256.
[5] DYME J L,THAMPAN A,HAN E J,et al.Propranolol for infantile haemangiomas:initiating treatment on an outpatient basis[J].Cardiol Young,2012,22(4):424-429.
[6] CHANG L,YE X,QIU Y,et al.Is propranolol safe and effective for outpatient use for infantile hemangioma?A prospective study of 679 cases from one center in China[J].Ann Plast Surg,2016,76(5):559-563.
[7] PUTTGEN K B,SUMMERER B,SCHNEIDER J,et al.Cardiovascular and blood glucose parameters in infants during propranolol initiation for treatment of symptomatic infantile hemangiomas[J].Ann Otol Rhinol Laryngol,2013,122(9):550-554.
[8] LIU X,QU X,ZHENG J,et al.Effectiveness and safety of oral propranolol versus other treatments for infantile hemangiomas:a meta-analysis[J].Plos One,2015,10(9):e0138100.
[9] DROLET B A,FROMMELT P C,CHAMLIN S L,et al.Initiation and use of propranolol for infantile hemangioma:report of a consensus conference[J].Pediatrics,2013,131(1):128-140.
[10] STILES J,AMAYA C,PHAM R,et al.Propranolol treatment of infantile hemangioma endothelial cells:a molecular analysis[J].Exp Ther Med,2012,4(4):594-604.
[11] HOEGER P H,HARPER J I,BASELGA E,et al.Treatment of infantile haemangiomas:recommendations of a European expert group[J].Eur J Pediatr,2015,174(7):855-865.
[12] MARQUELING A L,OZA V,FRIEDEN I J,et al.Propranolol and infantile hemangiomas four years later:a systematic review[J].Pediatr Dermatol,2013,30(2):182-191.
[13] YUN Y J,GYON Y H,YANG S,et al.A prospective study to assess the efficacy and safety of oral propranolol as first-line treatment for infantile superficial hemangioma[J].Korean J Pediatr,2015,58(12):484-490.
[14] KHOURI C,JOUVE T,BLAISE S,et al.Peripheral vasoconstriction induced by β-adrenoceptor blockers:a systematic review and a network meta-analysis[J].Br J Clin Pharmacol,2016,82(2):549-560.
[15] HOGELING M,ADAMS S,WARGON O.A randomized controlled trial of propranolol for infantile hemangiomas[J].Pediatrics,2011,128(2):e259-e266.
[16] PéPIN V,GAGNé N,ROTTEMBOURG D.Recurrent hypoglycaemia in a toddler on β-blocker therapy[J].Cardiol Young,2018,28(3):511-513.