Sinclair D Barry, Berg Marjorie, Breault Rene
Division of Pediatric Neurology, 2C3 Walter MacKenzie Health Sciences Centre, University of Alberta, Edmonton, AB T6G 2R7, Canada.
J Child Neurol. 2004 Jul;19(7):498-502. doi: 10.1177/08830738040190070401.
In the past 6 years, 11 children on valproic acid have developed pancreatitis in our children's hospital. Valproic acid has been used as one of the primary anticonvulsants for generalized seizures in children for the past 25 years. A literature review reveals mostly singular reports of pancreatitis over the past decade. The charts of the 11 patients with valproic acid-induced pancreatitis were reviewed. Dosage, valproic acid serum levels, duration of therapy, and concomitant medications were examined. Families were contacted by telephone to determine the formulation (brand name vs generic) of valproic acid at the time of diagnosis. Six girls and five boys were studied. The ages ranged from 4 to 16 years. Eight of 11 children presented with an acute abdomen. Unexpectedly, three children presented with a flulike illness. Serum lipase values ranged from 341 to 5576 U/L (normal range < 190 U/L). The dose of valproic acid ranged from 20 to 50 mg/kg. Serum levels ranged from 334 to 884 micromol/L (therapeutic range 350-800 micromol/L). Six of the patients were on monotherapy. Seven children were on brand-name drugs. Four of the children had an abnormal neurologic syndromic diagnosis (West syndrome, Rett syndrome, Lowe syndrome, and Angelman's syndrome). Six of the children had a history of drug allergies with a skin rash. Valproic acid was reintroduced in one child and resulted in a second episode of pancreatitis. Resolution of symptoms usually took several weeks following discontinuation of the drug. No association was found with valproic acid dosage, type of preparation, serum levels, duration of therapy, or presence of concomitant medications. Pancreatitis is a severe adverse effect of valproic acid use in children. Dose, duration of treatment, serum valproic acid levels, generic preparation, and the presence of concomitant antiepileptic drugs do not appear to be risk factors. Children with known drug sensitivity might be at risk. Lipase levels at the time of an acute abdomen or a flulike illness in epileptic children taking valproic acid can reveal early stages of pancreatitis and are recommended.
在过去6年里，我院有11名服用丙戊酸的儿童患上了胰腺炎。在过去25年中，丙戊酸一直是治疗儿童全身性癫痫的主要抗惊厥药物之一。文献综述显示，在过去十年中，关于胰腺炎的报道大多为个别病例。我们回顾了11例丙戊酸所致胰腺炎患者的病历。检查了剂量、丙戊酸血清水平、治疗持续时间和同时服用的药物。通过电话联系患者家属，以确定诊断时丙戊酸的剂型（品牌药还是仿制药）。共研究了6名女孩和5名男孩。年龄范围为4至16岁。11名儿童中有8名表现为急腹症。出乎意料的是，有3名儿童表现为流感样疾病。血清脂肪酶值在341至5576 U/L之间（正常范围<190 U/L）。丙戊酸剂量在20至50 mg/kg之间。血清水平在334至884 μmol/L之间（治疗范围350 - 800 μmol/L）。6名患者接受单一疗法。7名儿童服用品牌药。4名儿童有异常神经综合征诊断（韦斯特综合征、雷特综合征、洛氏综合征和天使综合征）。6名儿童有药物过敏史伴皮疹。1名儿童再次服用丙戊酸后引发了第二次胰腺炎发作。停药后症状通常需要数周才能缓解。未发现丙戊酸剂量、制剂类型、血清水平、治疗持续时间或同时服用药物之间存在关联。胰腺炎是儿童使用丙戊酸的严重不良反应。剂量、治疗持续时间、血清丙戊酸水平、仿制药剂型以及同时服用抗癫痫药物似乎都不是危险因素。已知有药物敏感性的儿童可能有风险。对于服用丙戊酸的癫痫儿童，在出现急腹症或流感样疾病时检测脂肪酶水平可发现胰腺炎的早期阶段，因此建议进行检测。
