Newburger J W, Takahashi M, Beiser A S, Burns J C, Bastian J, Chung K J, Colan S D, Duffy C E, Fulton D R, Glode M P
Department of Cardiology, Children's Hospital, Boston, MA 02115.
N Engl J Med. 1991 Jun 6;324(23):1633-9. doi: 10.1056/NEJM199106063242305.
Treatment of acute Kawasaki syndrome with a four-day course of intravenous gamma globulin, together with aspirin, has been demonstrated to be safe and effective in preventing coronary-artery lesions and reducing systemic inflammation. We hypothesized that therapy with a single, very high dose of gamma globulin would be at least as effective as the standard regimen.
We conducted a multicenter, randomized, controlled trial involving 549 children with acute Kawasaki syndrome. The children were assigned to receive gamma globulin either as a single infusion of 2 g per kilogram of body weight over 10 hours or as daily infusions of 400 mg per kilogram for four consecutive days. Both treatment groups received aspirin (100 mg per kilogram per day through the 14th day of illness, then 3 to 5 mg per kilogram per day).
The relative prevalence of coronary abnormalities, adjusted for age and sex, among patients treated with the four-day regimen, as compared with those treated with the single-infusion regimen, was 1.94 (95 percent confidence limits, 1.01 and 3.71) two weeks after enrollment and 1.84 (95 percent confidence limits, 0.89 and 3.82) seven weeks after enrollment. Children treated with the single-infusion regimen had lower mean temperatures while hospitalized (day 2, P less than 0.001; day 3, P = 0.004), as well as a shorter mean duration of fever (P = 0.028). Furthermore, in the single-infusion group the laboratory indexes of acute inflammation moved more rapidly toward normal, including the adjusted serum albumin level (P = 0.004), alpha 1-antitrypsin level (P = 0.007), and C-reactive protein level (P = 0.017). Lower IgG levels on day 4 were associated with a higher prevalence of coronary lesions (P = 0.005) and with a greater degree of systemic inflammation. The two groups had a similar incidence of adverse effects (including new or worsening congestive heart failure in nine children), which occurred in 2.7 percent of the children overall. All the adverse effects were transient.
In children with acute Kawasaki disease, a single large dose of intravenous gamma globulin is more effective than the conventional regimen of four smaller daily doses and is equally safe.
已证明静脉注射γ球蛋白并联合阿司匹林进行为期四天的治疗，对于预防急性川崎综合征的冠状动脉病变和减轻全身炎症是安全有效的。我们推测单次大剂量γ球蛋白治疗至少与标准治疗方案同样有效。
我们进行了一项多中心、随机、对照试验，纳入549例急性川崎综合征患儿。这些患儿被分配接受γ球蛋白治疗，一种是在10小时内单次输注2克/千克体重，另一种是连续四天每天输注400毫克/千克体重。两个治疗组均接受阿司匹林治疗（疾病第14天前每天100毫克/千克体重，之后每天3至5毫克/千克体重）。
与单次输注治疗组相比，接受四天治疗方案的患者在入组两周后，经年龄和性别调整的冠状动脉异常相对患病率为1.94（95%置信区间为1.01和3.71），入组七周后为1.84（95%置信区间为0.89和3.82）。接受单次输注治疗方案的患儿住院期间平均体温较低（第2天，P<0.001；第3天，P = 0.004），发热平均持续时间也较短（P = 0.028）。此外，在单次输注组中，急性炎症的实验室指标恢复正常的速度更快，包括校正后的血清白蛋白水平（P = 0.004）、α1-抗胰蛋白酶水平（P = 0.007）和C反应蛋白水平（P = 0.017）。第4天较低的IgG水平与冠状动脉病变的较高患病率（P = 0.005）和更严重的全身炎症程度相关。两组不良反应发生率相似（包括9例患儿出现新的或加重的充血性心力衰竭），总体发生率为2.7%。所有不良反应均为短暂性。
对于急性川崎病患儿，单次大剂量静脉注射γ球蛋白比传统的每日四次小剂量治疗方案更有效，且安全性相同。
