Extracorporeal membrane oxygenation exposes infants to the plasticizer, di(2-ethylhexyl)phthalate
Extracorporeal membrane oxygenation exposes infants to the plasticizer, di(2-ethylhexyl)phthalate
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DOI：
10.1097/00003246-199704000-00023
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发表时间：
1997-04-01
影响因子：
8.8
通讯作者：
Rubin, RJ
中科院分区：
文献类型：
--
作者：
Karle, VA;Short, BL;Rubin, RJ
目的：为了确定暴露，并评估潜在的毒性，增塑剂，邻苯二甲酸二（2-乙基己基）酯（DEHP）在体外膜肺氧合（ECMO）therapy.Design：协议1包括一个前瞻性比较三个ECMO电路设计在体外。方案2包括一项前瞻性、比较性临床研究，评价ECMO与非ECMO呼吸衰竭患者的DEHP血浆浓度。设置：华盛顿儿童国家医学中心的新生儿重症监护室。患者：在方案2中，28名连续足月婴儿接受ECMO治疗。18名婴儿需要ECMO; 10名对照患者接受常规通气，并且在没有ECMO的情况下得到改善。干预：在方案1中，三种ECMO回路设计在体外用生理盐水、白蛋白和人血预充，人血维持在37 ℃并以400 mL/min再循环48小时。在时间0、1小时和每6小时获得血浆样品。在方案2中，由主治医生对研究中的患者进行治疗和心血管管理。当患者符合ECMO治疗的机构标准时，他们被置于ECMO上。在ECMO组中，收集奶牛血浆DEHP浓度，直至体外循环拔管后3天。对照组患者每天采样，直至拔管。通过ECMO组第1天、第3天和拔管当天或对照组拔管时的胸部放射学评分、肝功能检查和超声心动图，评价心脏、肝脏或肺毒性的证据。镇静，血液制品输血，抗生素，高营养管理，所有patients. Measures和主要结果：所有DEHP血浆浓度测定气相色谱法。在方案1中，研究了三个回路：回路A（小表面积）;回路B（大表面积）;和回路C（A的表面积，但回路中有肝素粘合管路）。从回路A中沥滤的DEHP为0.32 +/- 0.12 μ g/mL/hr，而回路B中为0.57 +/- 0.14 μ g/mL/hr（p <0.05）。在ECMO患者中，DEHP的这一量外推到其他医疗器械或程序（如输血、透析或短期心肺转流）的潜在暴露量的20至70倍。回路C显示几乎没有从回路中浸出; DEHP浓度以0.2 +/- 0.04 μ g/mL/hr的速率下降。在方案2中，对照患者中未检测到DEHP。ECMO患者的DEHP浓度在ECMO早期更高。然而，大多数患者在拔管前从血浆中清除了该化合物。与方案1中的体外结果相反，在体外循环任何时间的平均最高浓度为8.3 +/- 5.7 μ g/mL或2 mg/kg.Conclusions：DEHP来自ECMO回路，潜在暴露浓度与ECMO回路中管路的表面积相关。管路的肝素粘合消除了该风险。尽管随着时间的推移，非肝素结合回路中的DEHP浓度显著增加，但我们的体内研究表明，DEHP血浆浓度低于先前报告的值，并且与任何可观察到的短期毒性无关。这种化合物可以被新生儿有效地代谢，或者重新分布到各种组织中。尽管在本研究中未发现毒性迹象，但尚未确定长期暴露于DEHP的长期并发症。
Objectives: To determine the exposure to, and evaluate the potential toxicity from, the plasticizer, di(2-ethylhexyl)phthalate (DEHP) during extracorporeal membrane oxygenation (ECMO) therapy.Design: Protocol 1 consisted of a prospective comparison of three ECMO circuit designs in vitro. Protocol 2 consisted of a prospective, comparative clinical study evaluating DEHP plasma concentrations in ECMO vs. non-ECMO patients with respiratory failure.Setting: Neonatal intensive care unit at The Children's National Medical Center, Washington, DC.Patients: In protocol 2, 28 consecutive term infants were referred for ECMO therapy. Eighteen infants required ECMO; ten control patients received conventional ventilation and improved without ECMO.Interventions: In protocol 1, three ECMO circuit designs were primed in vitro with normal saline, albumin, and human blood, which was maintained at 37 degrees C and recirculated at 400 mL/min far 48 hrs. Plasma samples were obtained at time 0, 1 hr, and every 6 hrs. In protocol 2, ventilatory and cardiovascular management of the patients in the study was conducted by the attending physician. Patients were placed on ECMO when they met the institutional criteria far ECMO therapy. Dairy plasma concentrations for DEHP were collected until 3 days after decannulation from bypass in the ECMO group. Control patients were sampled daily until extubation. Evidence of cardiac, liver, or lung toxicity was evaluated by Chest Radiographic Scores, liver function studies, and echocardiograms obtained on day 1, day 3, and the day of decannulation in the ECMO group, or at the time of extubation in the control group. Sedation, blood product transfusions as indicated, antibiotics, and hyperalimentation were administered to all patients.Measurements and Main Results: All DEHP plasma concentrations were measured by gas chromatography. In protocol 1, three circuits were studied: circuit A (small surface area); circuit B (larger surface area); and circuit C (surface area of A but with heparin-bonded tubing in the circuit). DEHP leached from circuit A at 0.32 +/- 0.12 mu g/mL/hr, compared with 0.57 +/- 0.14 mu g/mL/hr from circuit B (p < .05). This amount of DEHP extrapolates in the ECMO patient to a potential exposure of 20 to 70 times that exposure from other medical devices or procedures, such as transfusions, dialysis, or short-term cardiopulmonary bypass. Circuit C showed almost no leaching from the circuit; DEHP concentrations decreased at a rate of 0.2 +/- 0.04 mu g/mL/hr. In protocol 2, DEHP was undetected in the control patients. DEHP concentrations in ECMO patients were greater in the early course of ECMO. However, most patients cleared this compound from the plasma before decannulation. In contrast to the in vitro results in protocol 1, the average highest concentration at any time on bypass was 8.3 +/- 5.7 mu g/mL or 2 mg/kg.Conclusions: DEHP teaches from ECMO circuits, with potential exposure concentrations related to the surface area of the tubing in the ECMO circuit. Heparin bonding of the tubing eliminates this risk. Although significant concentrations of DEHP leach from the nonheparin-bonded circuits over time, our in vivo studies showed that the DEHP plasma concentrations were less than the previously reported values and do not correlate with any observable short-term toxicity. This compound may be either efficiently metabolized by the newborn, or redistributed into various tissues. Although signs of toxicity were not found in this study, long term complications from chronic exposure to DEHP have not been determined.