Objectives: 

Objective of this study was to determine if bivalirudin resulted in less circuit interventions than unfractionated heparin. A secondary objective was to examine associations between bivalirudin dose and partial thromboplastin time, international normalized ratio, and activated clotting time.

Design: 

Prospective observational.

Setting: 

Medical-surgical and cardiac PICUs.

Patients: 

Neonatal and pediatric extracorporeal membrane oxygenation patients who received bivalirudin anticoagulation.

Interventions: 

None.

Measurements and Main Results: 

Twenty extracorporeal membrane oxygenation runs in 18 patients used bivalirudin; 90% were venoarterial. Median (interquartile range) age was 4.5 months (1.6–35 mo). Thirteen patients (72%) had an underlying cardiac diagnosis. Of the 20 runs using bivalirudin, 16 (80%) were initially started on unfractionated heparin and transitioned to bivalirudin due to ongoing circuit thrombosis despite therapeutic anti-Xa levels (n = 13), ongoing circuit thrombosis with unfractionated heparin greater than or equal to 40 U/kg/hr (n = 2), or absence of increase in ACT after bolus of 100 U/kg of unfractionated heparin and escalation of unfractionated heparin infusion (n = 1). Initial bivalirudin dose ranged from 0.2 to 0.5 mg/kg/hr; no bolus doses were used. Median (range) bivalirudin dose was 0.9 mg/kg/hr (0.15–1.6 mg/kg/hr). Median (interquartile range) time on extracorporeal membrane oxygenation was 226.5 hours (150.5–393.0 hr) including 84 hours (47–335 hr) on bivalirudin. Nonparametric results are as follows: the rate of circuit intervention was significantly lower in patients on bivalirudin than on unfractionated heparin (median [interquartile range]: 0 [0–1] and 1 [1–2], respectively; Wilcoxon p = 0.0126). Bivalirudin dose was correlated to PTT (r_s = 0.4760; p < 0.0001), INR (r_s = 0.6833; p < 0.0001), and ACT (r_s = 0.6161; p < 0.0001). Four patients had a significant bleeding complication on bivalirudin. Survival to hospital discharge was 56%.

Conclusions: 

Bivalirudin appears to be a viable option for systemic anticoagulation in pediatric extracorporeal membrane oxygenation patients who have failed unfractionated heparin, but questions remain namely its optimal monitoring strategy. This pilot study supports the need for larger prospective studies of bivalirudin in pediatric extracorporeal membrane oxygenation, particularly focusing on meaningful monitoring variables.

中文翻译：

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小儿体外膜氧合中比伐卢定抗凝的前瞻性探索性经验

目标： 

本研究的目的是确定比伐卢定是否比普通肝素导致更少的回路干预。次要目标是检查比伐卢定剂量与部分促凝血酶原激酶时间、国际标准化比率和活化凝血时间之间的关联。

设计： 

前瞻性观察。

环境： 

医疗外科和心脏 PICU。

患者： 

接受比伐卢定抗凝治疗的新生儿和儿童体外膜肺氧合患者。

干预： 

没有任何。

测量和主要结果： 

18 名使用比伐卢定的患者进行了 20 次体外膜肺氧合；90% 为静脉动脉。中位（四分位距）年龄为 4.5 个月（1.6-35 个月）。13 名患者 (72%) 有潜在的心脏诊断。在使用比伐卢定的 20 次试验中，16 次 (80%) 最初开始使用普通肝素，但由于抗 Xa 治疗水平（n = 13）持续循环血栓形成而转换为比伐卢定，使用普通肝素大于或等于40 U/kg/hr ( n = 2)，或推注 100 U/kg 普通肝素和升级普通肝素输注后 ACT 没有增加 ( n= 1)。初始比伐卢定剂量范围为 0.2 至 0.5 mg/kg/hr；没有使用推注剂量。中位（范围）比伐卢定剂量为 0.9 mg/kg/hr（0.15–1.6 mg/kg/hr）。体外膜氧合的中位（四分位距）时间为 226.5 小时（150.5-393.0 小时），其中比伐卢定为 84 小时（47-335 小时）。非参数结果如下：使用比伐卢定的患者的回路干预率显着低于使用普通肝素的患者（中位数 [四分位距]：分别为 0 [0-1] 和 1 [1-2]；Wilcoxon p = 0.0126） . 比伐卢定剂量与 PTT ( r _s = 0.4760; p < 0.0001)、INR ( r _s = 0.6833; p < 0.0001) 和 ACT ( r _s= 0.6161; p < 0.0001)。4 名患者在服用比伐卢定时出现了明显的出血并发症。出院生存率为 56%。

结论： 

比伐卢定似乎是对普通肝素失败的儿科体外膜肺氧合患者进行全身抗凝治疗的可行选择，但仍存在问题，即其最佳监测策略。这项初步研究支持对比伐卢定在儿科体外膜肺氧合中进行更大规模前瞻性研究的需要，特别关注有意义的监测变量。