心血管药物在危重症和急救治疗中应用的再评价.doc

心血管药物在危重症和急救治疗中应用的再评价东南大学附属中大医院麻醉科景亮一、多巴胺的再认识n 自1960以来，沿用多年n 用于术中的低血压仍然是首选n 心脏手术后的低心排n ICU,各种休克导致的顽固性低血压 多巴胺的药理学特征n This endogenous catecholamine influences different catecholamine receptors in a dose-dependent manner. n 0.5 to 2 g kg-1 min-1 induce primarily dopaminergic effectsn 2 to 5 g kg-1 min-1, the actions are mainly dopaminergic (80% - 100%)，beta adrenergic effects (5% to 20%). n 5 to 10 g kg-1 min-1, beta-adrenergic effects predominaten 10 to 20 g kg-1 min-1 produce primarily alpha- and beta-adrenergic effects 二、对肾脏作用的再评价n protective effect of low-dose DA (LDD, 5 g kg-1 min-1 -兴奋beta-受体-CO -肾血流n 上述理论多基于健康志愿者或动物实验n 一些临床应用n 没进行正确的循证医学验证nn absence of concurrent control groups, absence of randomization, and relatively small sample sizes, which prevented adequate statistical analysis and conclusions n 多个临床循证医学调查表明LDD治疗ARF效果不好，甚至有害n LDD导致的尿量增加并未伴有平行的肾功改善n ARF时的低灌注可因尿量的增加而加重n 实际上LDD的增尿作用可能主要仍源于CO增加。因为多数认为LDD无全身心血管作用的报道实际未测COnn first large, prospective, randomized, double-blinded, placebo-controlled trial investigating the potential of LDD (2 g kg-1 min-1) n Australian and New Zealand Intensive Care Society group clearly showed that LDD does not prevent or reverse ARF, nor does it improve outcome. -Bellomo R, et al. Lancet. 2000, 356:2139-43.n 对象：324例 SIRS+Early ARFn 项目：死亡率、肾替代治疗率、肾功能恢复率、血浆肌酐n 同样的结果也为其他研究证实n North American Septic Shock Trial (NORASEPT)-II, LDD did not reduce the incidence of ARF, the need for hemodialysis, or the 28-day mortality in septic shock patients with oliguria n 是否对感染性休克应用NE导致的肾血管收缩有益？n 在健康动物和志愿者出现此效果n 感染性休克动物或病人尽管LDD可使尿量一定程增加，但没有出现肾功能保护作用n 结论：LDD应用于ICU或休克病人的肾保护没有实际的临床意义，反可因尿量排泄导致循环不稳定三、对内脏灌注的再评价n 一度认为LDD可兴奋Dop-受体增加内脏血灌流，同样主要为实验动物n 但在休克和感染动物模型上，LDD减少粘膜血灌注，O2摄取，加重缺O2性损伤n 也有相反的结论！ 主要是动物种属、剂量、 时间等差别n 在临床应用中，表现极大的差异： -to increase splanchnic blood flow in septic shock and cardiac surgery patients -Meier-Hellmann A, et al. Intensive Care Med. 1997,23: 31-7. -it decreases the gastric mucosal flow -Neviere R, Am J Respir Crit Care Med. 1996, 154:1684-8. n 结论： There is no evidence that LDD has beneficial effects on the splanchnic function or reduces the progression to multiple organ failure in sepsis. Recent data even suggest a potentially detrimental effect of LDD on splanchnic oxygen uptake. -Debaveye YA，et al. Aneth Analg. 2004.四、对呼吸道的作用再评价n LDD 的两个有害作用经常被忽视 -抑制颈动脉体的化学感受器，而致对缺氧和高碳酸血症呼吸代偿能力减弱 -抑制肺局部的通气/血流比，而减低动脉血氧张力呼吸道的作用再评价-2n 机械呼吸时此弊不明显n 但脱机时/后有降低血氧的顾虑，往往会考虑为脱机后的呼吸代偿不足n In summary, also from a respiratory point of view, the use of LDD cannot be advised 五、对作为升压药的再评价n DA仍作为升压药的首选 -出于对NE的恐惧 -以前认为的肾保护、心脏正性肌力作用n 这种观点受到挑战 -感染性休克病人应用DA不能维持稳定的循环，而NE做到了，且少并发症 n 感染性休克病人用NE迅速稳定了循环机能，且减少了血乳酸水平，稳定了胃肠道粘膜Phi，效果优于DA -Marik PE, et al. JAMA.272: 1354-7,1994.n 感染性休克动物和患者的研究中证明NE在改善肾功、胃肠道屏障、内脏氧摄取等方面优于DA -LeDoux D, et al. Crit Care Med.2000, 28:2729-32. -Treggiari MM. et al. Crit Care Med.2002, 30:1334-9.n 亦有应用NE使感染性休克病人的生存率优于DA 的报道 -Martin C. et al. Crit Care Med.2000, 28:2758-65. norepinephrine may be emerging as the vasopressor of choice for severe hypotension in adequately volume-resuscitated septic shock patients. 小结n DA 仍作为临床一线升压药，尤其是心功低下者n 感染性休克时LDD无肾保护、内脏保护作用，反而有害n DA作为ICU的心血管活性药的地位开始让位于其他的药物心血管药物在CPR中的再评价n 为什么重视心血管药物在CPR的应用？n 心脏复苏是前提n 胸外挤压只能提供25-30%的冠状血流n 需要适度减少主动脉的口径n 增大舒张期压力n 体内的内源性神经内分泌减少，循环张力失调，需要外源性药物支持一、Epinephrine（EP）n 沿用40年，仍为教科书列为首选n 一直认为主要是兴奋a1-，b1-受体n There is unequivocal evidence that its efficacy is owing to its a2 -adrenergic vasopressor effects. -Tang W, et al.: Epinephrine increases the severity of post-resuscitation myocardial dysfunction. Circulation 1995, 92:30893093. n This study brought the reconsideration of the routine use of epinephrine during CPR.n 心肌氧耗增加n 增加心肌乳酸浓度n 减少心肌ATP储量n 数个多中心临床验证表明： 1. 增加复苏后心肌损伤，减少复苏成功率。与并用b1-拮抗剂相比 2. 反复大剂量与1mg的复苏量相比，在复苏预后及神经系并发症上没有差别 n AHA Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency - for Advanced Cardiac Life Support call for 1 mg of intravenously injected epinephrine as an appropriate initial dose.There has been disappointing experience with repetitive doses of epinephrine because these have little added pressor effect -Cardiovascular Care. Circulation 2000, 8(suppl): I-86I-89.二、Norepinephrinen 与EP相比： 升压作用 心脏和脑灌注 心肌变力和变时 心肌氧耗n 相同剂量在早期复苏和院内存活率方面 无差异n 不主张作为EP的替代药 三、a2 -adrenergic agonistsn 兴奋突触前a2-受体可减少内源性CAn 兴奋突触后a2-受体可促使NO释放，对抗过量的CAn 减少心肌的缺氧n a2A , a2B ,and a2Cn a-methylnorepinephrine，选择性a2-激动剂，因对a2A ， a2C作用弱而最具希望，在动物CPR中有较好的效果四、Vasopressinn 研究源于CPR成功的病人有较高的血浆Vasopressin水平n Lindner KH, et al. Br Heart J 1996,75:145150.n 与EP相比： -气体交换，心肌血流，肾上腺血流，神经学体征等优于EP（动物模型）n 40 U vasopressin restored spontaneous circulation in each instance,and three of eight were discharged from the hospital with normal neurologic function -Lindner KH, Ann Intern Med 1996, 124:10611064. A larger study of 40 patients also showed a better initial resuscitation and 24-hour survival after the use of vasopressin rather than epinephrine -Lindner KH, Lancet 1997, 349:535538. n American Heart Association Advan