Al-Salam Zakariya, Johnson Scott, Abozaid Sameh, Bigam David, Cheung Po-Yin
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Shock. 2007 Sep;28(3):317-25. doi: 10.1097/shk.0b013e318048554a.
Asphyxiated neonates usually have myocardial stunning and hypotension and require inotropic support. A randomized controlled study was designed to examine the dose-response effect of dobutamine (5-20 microg x kg(-1) x min(-1)) on systemic and regional circulations and oxygen metabolism in a neonatal swine model of hypoxia/reoxygenation. Thirty-eight anesthetized newborn piglets were acutely instrumented for continuous monitoring of heart rate, systemic and pulmonary arterial pressures, and pulmonary (surrogate for cardiac index), right common carotid, and superior mesenteric and left renal arterial flows. After stabilization, they were exposed to normocapnic alveolar hypoxia (10%-15% oxygen) for 2 h followed by reoxygenation with 100% oxygen for 1 h, then 21% for 3 h. Piglets were block randomized to receive dobutamine infusion (5, 10, or 20 microg x kg(-1) x min(-1)) or saline (control) at 2 to 4 h of reoxygenation (n = 8 each). A nonasphyxiated, sham-operated group was included (n = 6). Blood samples were collected for blood gas analysis, arterial and venous co-oximetry, and plasma lactate concentration determination. At 2-h reoxygenation after hypoxia, there was hypotension (systemic arterial pressure, 27 to 36 mmHg) and myocardial dysfunction (cardiac index from 178-209 to 134-156 mL x kg(-1) x min(-1)). Cardiac index improved significantly with 20 microg x kg(-1) x min(-1) of dobutamine (P < 0.05) and modestly in the treatment groups of 5 and 10 microg x kg(-1) x min(-1) (P < 0.1) (at 120 min, 172 +/- 35, 160 +/- 30, and 158 +/- 56 mL x kg(-1) x min(-1) vs. 119 +/- 33 mL x kg(-1) x min(-1) of controls, respectively), with corresponding increases in stroke volume. Pulmonary vascular resistance was lower in all dobutamine-treated groups (vs. controls, P < 0.05) There were no differences in heart rate, systemic and pulmonary arterial pressures, systemic vascular resistance, and regional flows between groups. The group of 20 mug.kg.min of dobutamine also had higher systemic oxygen delivery (at 120 min, 18 +/- 5 vs. 11 +/- 3 O(2) mL x kg(-1) x min(-1) of controls, P < 0.05) with no significant differences in systemic oxygen consumption and regional oxygen delivery between groups. After the reoxygenation of newborn piglets with severe hypoxia, high dose of dobutamine is effective to treat myocardial stunning and low cardiac output with no significant effect on blood pressure or regional circulation. Further clinical studies are needed to confirm these findings in the human neonate.
窒息新生儿通常会出现心肌顿抑和低血压，需要使用正性肌力药物支持。一项随机对照研究旨在检测多巴酚丁胺（5 - 20微克·千克⁻¹·分钟⁻¹）对缺氧/复氧新生猪模型的全身和局部循环及氧代谢的剂量反应效应。38只麻醉的新生仔猪被急性植入仪器，以连续监测心率、体循环和肺动脉压，以及肺循环（作为心脏指数的替代指标）、右颈总动脉、肠系膜上动脉和左肾动脉血流。稳定后，使其暴露于正常碳酸血症性肺泡缺氧（10% - 15%氧气）2小时，随后用100%氧气复氧1小时，再用21%氧气复氧3小时。仔猪在复氧2至4小时时被随机分组接受多巴酚丁胺输注（5、10或20微克·千克⁻¹·分钟⁻¹）或生理盐水（对照组）（每组n = 8）。纳入一组未窒息的假手术组（n = 6）。采集血样进行血气分析、动脉和静脉血氧定量分析以及血浆乳酸浓度测定。缺氧后复氧2小时时，出现低血压（体循环动脉压，27至36毫米汞柱）和心肌功能障碍（心脏指数从178 - 209降至134 - 156毫升·千克⁻¹·分钟⁻¹）。20微克·千克⁻¹·分钟⁻¹的多巴酚丁胺使心脏指数显著改善（P < 0.05），5和10微克·千克⁻¹·分钟⁻¹治疗组有适度改善（P < 0.1）（在120分钟时，分别为172 ± 35、160 ± 30和158 ± 56毫升·千克⁻¹·分钟⁻¹，而对照组为119 ± 33毫升·千克⁻¹·分钟⁻¹），同时每搏输出量相应增加。所有多巴酚丁胺治疗组的肺血管阻力均较低（与对照组相比，P < 0.05）。各组之间在心率、体循环和肺动脉压、体循环血管阻力以及局部血流方面无差异。20微克·千克⁻¹·分钟⁻¹多巴酚丁胺组的全身氧输送也更高（在120分钟时，18 ± 5与对照组的11 ± 3毫升·千克⁻¹·分钟⁻¹·氧相比，P < 0.05），各组之间在全身氧消耗和局部氧输送方面无显著差异。新生仔猪严重缺氧复氧后，高剂量多巴酚丁胺可有效治疗心肌顿抑和低心输出量，对血压或局部循环无显著影响。需要进一步的临床研究来在人类新生儿中证实这些发现。
