Neumar R W, Bircher N G, Sim K M, Xiao F, Zadach K S, Radovsky A, Katz L, Ebmeyer E, Safar P
Safar Center For Resuscitation Research, University of Pittsburgh, PA 15260, USA.
Resuscitation. 1995 Jun;29(3):249-63. doi: 10.1016/0300-9572(94)00827-3.
Although high-dose epinephrine during CPR improves coronary perfusion pressure (CoPP) and rate of return of spontaneous circulation (ROSC) in some models, its impact on long term outcome (> or = 72 h) has not been evaluated. Previous studies of sodium bicarbonate (NaHCO3) therapy during CPR indicate that beneficial effects may be dependent on epinephrine (EPI) dose. We hypothesized that EPI and NaHCO3 given during CPR have a significant impact on long term outcome. One hundred male Sprague-Dawley rats were prospectively studied in a block randomized placebo controlled trial. Rats were anesthetized, paralyzed, mechanically ventilated, instrumented, and each underwent 10 min of asphyxia, resulting in 6.8 +/- 0.4 min of circulatory arrest. Resuscitation was performed by mechanical ventilation and manual external chest compressions. EPI 0.0 (placebo), 0.01, 0.1, or 1.0 mg/kg IV was given at the onset of CPR, followed by NaHCO3 0.0 (placebo) or 1.0 mEq/kg IV. Successfully resuscitated rats were monitored and ventilated for 1 h without hemodynamic support. Neurologic deficit scores (NDS), cerebral histopathologic damage scores (CHDS) and myocardial histopathologic damage scores (MHDS) were determined in rats that survived 72 h. EPI improved CoPP and ROSC in a dose-dependent manner up to 0.1 mg/kg. Rats receiving EPI 0.1 and 1.0 mg/kg during CPR exhibited prolonged post-ROSC hypertension and metabolic acidemia, increased A-a O2 gradient, and an increased incidence of post-ROSC ventricular tachycardia or fibrillation. Overall survival was lower with EPI 0.1 and 1.0 mg/kg compared to 0.01 mg/kg. Although NDS was significantly less with EPI 0.1 mg/kg compared to placebo, there was no difference in CHDS between groups. In contrast, MDS was significantly higher with EPI 0.1 mg/kg compared to placebo or EPI 0.01 mg/kg. There was an overall trend toward improved survival at 72 h in rats that received NaHCO3 which was most evident in the EPI 0.1 mg/kg group. We conclude that (1) EPI during CPR has a biphasic dose/response curve in terms of survival, when post-resuscitation effects are left untreated and (2) NaHCO3 doses greater than 1.0 mEq/kg may be necessary to treat the side-effects of high-dose EPI. Further work is needed to determine if treating the immediate post-resuscitation effects of high-dose EPI can prevent detrimental effects on long-term outcome.
尽管在某些模型中，心肺复苏期间使用大剂量肾上腺素可提高冠状动脉灌注压（CoPP）和自主循环恢复率（ROSC），但其对长期预后（≥72小时）的影响尚未得到评估。先前关于心肺复苏期间碳酸氢钠（NaHCO3）治疗的研究表明，有益效果可能取决于肾上腺素（EPI）剂量。我们假设心肺复苏期间给予EPI和NaHCO3对长期预后有显著影响。在一项整群随机安慰剂对照试验中，对100只雄性Sprague-Dawley大鼠进行了前瞻性研究。大鼠麻醉、麻痹、机械通气、插管，每只大鼠经历10分钟窒息，导致6.8±0.4分钟的循环骤停。通过机械通气和手动胸外按压进行复苏。在心肺复苏开始时静脉注射EPI 0.0（安慰剂）、0.01、0.1或1.0mg/kg，随后静脉注射NaHCO3 0.0（安慰剂）或1.0mEq/kg。成功复苏的大鼠在无血流动力学支持的情况下监测和通气1小时。对存活72小时的大鼠测定神经功能缺损评分（NDS）、脑组织病理损伤评分（CHDS）和心肌组织病理损伤评分（MHDS）。EPI以剂量依赖方式提高CoPP和ROSC，最高可达0.1mg/kg。心肺复苏期间接受EPI 0.1和1.0mg/kg的大鼠复苏后出现高血压和代谢性酸中毒持续时间延长、肺泡-动脉血氧分压差（A-a O2）增加，复苏后室性心动过速或颤动发生率增加。与0.01mg/kg相比，EPI 0.1和1.0mg/kg组的总体生存率较低。尽管与安慰剂相比，EPI 0.1mg/kg组的NDS显著降低，但各组之间的CHDS没有差异。相比之下，与安慰剂或EPI 0.01mg/kg相比，EPI 0.1mg/kg组的MDS显著更高。接受NaHCO3的大鼠在72小时时总体生存有改善趋势，这在EPI 0.1mg/kg组最为明显。我们得出结论：（1）在不治疗复苏后效应的情况下，心肺复苏期间的EPI在生存方面具有双相剂量/反应曲线；（2）可能需要大于1.0mEq/kg的NaHCO3剂量来治疗大剂量EPI的副作用。需要进一步研究以确定治疗大剂量EPI的复苏后即时效应是否能预防对长期预后的有害影响。
