肾上腺素持续给药与间断给药对室颤兔血流动力学及脑循环灌注的影响
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摘要
目的:研究肾上腺素采用电脑微量注射泵持续给药与间断人工静脉推注对室颤兔血流动力学及脑循环灌注的影响。
方法:将实验兔22只随机抽取两只作为假手术组,只进行外科手术操作,不给予致颤和心肺复苏(CPR);其余20只随机分成两组,分别为肾上腺素持续给药组(实验组,A组)与间断给药组(对照组,B组)。采用开胸心外膜下电刺激法制备室颤动物模型,A组,首先20μg/kg人工推注一次,而后持续泵注10μg/kg/min 9min;B组20μg/kg每3min人工推注1次,共计4次。实验过程中测主动脉收缩压(ASP)、主动脉舒张压(AOD)、平均动脉压(MAP)、中心静脉压(CVP)、颅内压(ICP),计算冠状动脉灌注压(CoPP)、脑灌注压(CePP)及观察两组对室颤兔自主循环恢复(ROSC)率的影响。ROSC后30min注入10%的异硫氰酸荧光素-白蛋白标记全身血液(0.3g/kg),循环30min后将动物断头取脑。每只家兔切片三张,在100倍荧光显微镜下观察并拍照。用IMAGEJ1.36图像处理软件计算脑灌注区域,用百分数表示。
结果:应用SPSS11.5统计软件进行统计分析,显示实验组的ASP、AOD、MAP、CoPP、CePP均高于对照组(室颤前均无差异),两组CoPP、CePP显示均有差异(p<0.05)。实验组10例复苏成功8例,对照组10例复苏成功6例,采用Fisher确切概率法统计分析,结果两组ROSC率无差异(p=0.628,p>0.05)。A组中的脑灌注面积为62.35±3.51%、B组31.92±3.86%,两组差异显著(P<0.01),而两只假手术组的动物显示了均匀一致的脑循环灌注。
结论:肾上腺素持续给药与间断给药相比有更佳的血流动力学效果及脑循环灌注,因此,采用电脑微量泵持续给药优于传统的肾上腺素给药方式。
Objective:To study the effects of continuously administered epinephrine(Epi) with computer micro pump, compared to intermittent bolus doses, on hemodynamic and cerebral circulation perfusion in ventricular fibrillation rabbits during cardiopulmonary resuscitation (CPR) .
Methods:Two of 22 rabbits were served as sham operated group ,which were not induced ventricular fibrillation and implemented of CPR .Other animals were randomized into two groups. A group was received an initial bolus of 20μg/kg epinephrine followed by an infusion of 10μg/kg/min epinephrine for 9 minutes. B group was received a bolus of 20μg/kg epinephrine every other 3 minutes, to amount to 4 times. Ventricular fibrillation was induced with epicardium electric current shock in 20 anaesthetised rabbits. aortic systolic pressure(ASP) ,aortic diastolic pressure (AOD),mean arterial pressure(MAP),central venous pressure(CVP),intracranial pressure(ICP) was measured. coronary perfusion pressure(CoPP), cerebral perfusion pressure(CePP),restoration of spontaneous circulation (ROSC) was calculated. The cerebral microcirculation perfusion was markded by injection of 0.3/kg 10% fluorescent isothiocyanate- albumin(FITC) after ROSC 30 minutes and the animals were decapitated 30 minutes later. At different levels three slices of the rabbit brain were observaed using 100 times fluorescence microscopy.Capillary filling with FITC areas were identified and calculated,quantified using image processing software IMAGEJ.
Results:The data were analyzed with SPSS 11.5 statistical software, Group A was higher than Group B in ASP、AOD、MAP、CoPP、CePP (they had no difference between two groups before ventricular fibrillation). CoPP and CePP had difference (P<0.05) , a continuous epinephrine infusion compared with repeated bolus doses. 8 of 10 animals could survive to the end of the experimental in A group, while 6 of 10 animals could survive to the end of the experimental in B group. According to Fisher exact propability, rate of ROSC had no difference between two groups(p=0.628,p>0.05). the difference of the cerebral perfusion area (P<0.01)was also significant between A group(62.35±3.51%) and B group (31.92±3.86%).The two sham operated animals showed homogeneous cerebral microcirculation perfusion.
Conclusions:Continuous infusion of epinephrine generated a better hemodynamics and cerebral circulation perfusion during CPR as compared to intermittent bolus doses. Thus, continuous infusion with computer micro pump was superior to intermittent bolus doses administering epinephrine during CPR.
方法:将实验兔22只随机抽取两只作为假手术组,只进行外科手术操作,不给予致颤和心肺复苏(CPR);其余20只随机分成两组,分别为肾上腺素持续给药组(实验组,A组)与间断给药组(对照组,B组)。采用开胸心外膜下电刺激法制备室颤动物模型,A组,首先20μg/kg人工推注一次,而后持续泵注10μg/kg/min 9min;B组20μg/kg每3min人工推注1次,共计4次。实验过程中测主动脉收缩压(ASP)、主动脉舒张压(AOD)、平均动脉压(MAP)、中心静脉压(CVP)、颅内压(ICP),计算冠状动脉灌注压(CoPP)、脑灌注压(CePP)及观察两组对室颤兔自主循环恢复(ROSC)率的影响。ROSC后30min注入10%的异硫氰酸荧光素-白蛋白标记全身血液(0.3g/kg),循环30min后将动物断头取脑。每只家兔切片三张,在100倍荧光显微镜下观察并拍照。用IMAGEJ1.36图像处理软件计算脑灌注区域,用百分数表示。
结果:应用SPSS11.5统计软件进行统计分析,显示实验组的ASP、AOD、MAP、CoPP、CePP均高于对照组(室颤前均无差异),两组CoPP、CePP显示均有差异(p<0.05)。实验组10例复苏成功8例,对照组10例复苏成功6例,采用Fisher确切概率法统计分析,结果两组ROSC率无差异(p=0.628,p>0.05)。A组中的脑灌注面积为62.35±3.51%、B组31.92±3.86%,两组差异显著(P<0.01),而两只假手术组的动物显示了均匀一致的脑循环灌注。
结论:肾上腺素持续给药与间断给药相比有更佳的血流动力学效果及脑循环灌注,因此,采用电脑微量泵持续给药优于传统的肾上腺素给药方式。
Objective:To study the effects of continuously administered epinephrine(Epi) with computer micro pump, compared to intermittent bolus doses, on hemodynamic and cerebral circulation perfusion in ventricular fibrillation rabbits during cardiopulmonary resuscitation (CPR) .
Methods:Two of 22 rabbits were served as sham operated group ,which were not induced ventricular fibrillation and implemented of CPR .Other animals were randomized into two groups. A group was received an initial bolus of 20μg/kg epinephrine followed by an infusion of 10μg/kg/min epinephrine for 9 minutes. B group was received a bolus of 20μg/kg epinephrine every other 3 minutes, to amount to 4 times. Ventricular fibrillation was induced with epicardium electric current shock in 20 anaesthetised rabbits. aortic systolic pressure(ASP) ,aortic diastolic pressure (AOD),mean arterial pressure(MAP),central venous pressure(CVP),intracranial pressure(ICP) was measured. coronary perfusion pressure(CoPP), cerebral perfusion pressure(CePP),restoration of spontaneous circulation (ROSC) was calculated. The cerebral microcirculation perfusion was markded by injection of 0.3/kg 10% fluorescent isothiocyanate- albumin(FITC) after ROSC 30 minutes and the animals were decapitated 30 minutes later. At different levels three slices of the rabbit brain were observaed using 100 times fluorescence microscopy.Capillary filling with FITC areas were identified and calculated,quantified using image processing software IMAGEJ.
Results:The data were analyzed with SPSS 11.5 statistical software, Group A was higher than Group B in ASP、AOD、MAP、CoPP、CePP (they had no difference between two groups before ventricular fibrillation). CoPP and CePP had difference (P<0.05) , a continuous epinephrine infusion compared with repeated bolus doses. 8 of 10 animals could survive to the end of the experimental in A group, while 6 of 10 animals could survive to the end of the experimental in B group. According to Fisher exact propability, rate of ROSC had no difference between two groups(p=0.628,p>0.05). the difference of the cerebral perfusion area (P<0.01)was also significant between A group(62.35±3.51%) and B group (31.92±3.86%).The two sham operated animals showed homogeneous cerebral microcirculation perfusion.
Conclusions:Continuous infusion of epinephrine generated a better hemodynamics and cerebral circulation perfusion during CPR as compared to intermittent bolus doses. Thus, continuous infusion with computer micro pump was superior to intermittent bolus doses administering epinephrine during CPR.
引文
[1] 康舟军,杨瑞和,霍正禄.心肺复苏药物治疗新进展.中国急救医学,2004,24(7):508～509.
[2] Berkowitz ID, Gervais H, Schleien CL,et al.Epinephrine dosage effects on cerebral and myocardial blood flow in an infant swine model of cardiopulmonary resuscitation. Anesthesiology. 1991,75(6):1041~1050.
[3] Guidelines 2000 for CPR and emergency cardiovascular care: international consensus on science. Part 6: Advanced cardiovascular life support; Section 6: Pharmacology II. Agents to optimize cardiac output and blood pressure. Circulation 2000,102 (Suppl. I): 1129~1135.
[4] 石海明,李颖,梁勇,等.加强心脏按压与大剂量肾上腺素在心肺复苏中的应用[J].中国危重病急救医学,1998,10(7):436—437.
[5] Johansson J, Gedeborg R, Basu S,et al. Increased cortical cerebral blood flow by continuous infusion of epinephrine during experimental cardiopulmonary resuscitation. Resuscitation 2003,57(3):299~307.
[6] D.J. Callans.Out-of-hospital cardiac arrest—the solution is shocking.N Engl J Med ,2004, 35(1): 632~634.
[7] Rogove FU, Safar P, Suton 一 Tyrrel K, et al.Old age does not negate good cerebral outcome after cardiopulmonary resuscitation: analysis from the brain resuscitation clinical trials IJI .The Brain Resuscitation Clinical Trial I and II Study Groups. Crit Care Med, 1995, 23(l):18~25.
[8] Johansson J, Gedeborg R, Rubertsson S.Vasopressin versus continuous epinephrine during experimental cardiopulmonary resuscitation.Resuscitation. 2004 ,62(1):61~69.
[9] 李涛,李玲莉,李承晏,等.低温高渗盐水配合低温等渗盐水治疗兔脑梗死的实验研究.中华物理医学与康复杂志,2005,27(7):438~439.
[10] Fischer M,Hossman KA.No-reflow after cardiac arrest. Intensive Care Med,1995,21(2):132~141.
[11] WalravenC V,StiellL C,WellsG A,et al. Do advanced cardiac life support during increase resuscitation rate from in hospital cardiac?BrJAnasth,1999,82:738.
[12] LinderK H,AhnfedldFW,GrunertA.Epinephrine versus norpinephrine in Prehospital ventricular fibrillation.Lancet,1999,354:505.
[13] Chai P, Skaryak L, Ungerleider R, et al. Jugular ligation does not increase intracranial pressure but does increase bihemispheric cerebral Baumann G, Dingman J. Distribution, blood transport and degradation of antidiuretic hormone in man. J Clin Invest 1976,57:1109~1116.
[14] Tang W, Weil M, Sun S, etal. Epinephrine increases the severity of post-resuscitation myocardial dysfunction.Circulation 1995,92:3089~3093.
[15] Gedeborg R, Silander HC, Ronne-Engstr?m E,et al. Adverse effects of high-dose epinephrineon cerebral blood flow during experimental cardiopulmonary resuscitation. Crit Care Med 2000,28(5):1423~1430.
[16] Berg R, Otto C, Kern K, et al. A randomized, blinded trial of high-dose epinephrine versus standard-dose epinephrine in a swine model of pediatric asphyxial arrest. Crit Care Med 1996,24(1)695~700.
[17] Biondi-Zoccai G, Abbate A, Parisi Q, et al. Is vasopressin superior to epinephrine or placebo in the management of cardiac arrest? Ameta-analysis. Resuscitation 2003,59:221–224.
[1] 康舟军,杨瑞和,霍正禄.心肺复苏药物治疗新进展.中国急救医学,2004,24(7):508～509.
[2] Berkowitz ID, Gervais H, Schleien CL,et al.Epinephrine dosage effects on cerebral and myocardial blood flow in an infant swine model of cardiopulmonary resuscitation. Anesthesiology. 1991,75(6):1041~1050.
[3] Guidelines 2000 for CPR and emergency cardiovascular care: international consensus on science. Part 6: Advanced cardiovascular life support; Section 6: Pharmacology II. Agents to optimize cardiac output and blood pressure. Circulation 2000,102 (Suppl. I): 1129~1135.
[4] LinderK H,AhnfedldFW,GrunertA.Epinephrine versus norpinephrine in Prehospital ventricular fibrillation.Lancet,1999,354:505.
[5] Chai P, Skaryak L, Ungerleider R, et al. Jugular ligation does not increase intracranial pressure but does increase bihemispheric cerebral Baumann G, Dingman J. Distribution, blood transport and degradation of antidiuretic hormone in man. J Clin Invest 1976,57:1109~1116.
[6] Tang W, Weil M, Sun S, etal. Epinephrine increases the severity of post-resuscitation myocardial dysfunction.Circulation 1995,92:3089~3093.
[7] 石海明,李颖,梁勇,等.加强心脏按压与大剂量肾上腺素在心肺复苏中的应用[J].中国危重病急救医学,1998,10(7):436—437.
[8] Johansson J, Gedeborg R, Basu S,et al. Increased cortical cerebral blood flow by continuous infusion of epinephrine during experimental cardiopulmonary resuscitation. Resuscitation 2003,57(3):299~307.
[9] Rogove FU, Safar P, Suton 一 Tyrrel K, et al.Old age does not negate good cerebral outcome after cardiopulmonary resuscitation: analysis from the brain resuscitation clinical trials IJI .The Brain Resuscitation Clinical Trial I and II Study Groups. Crit Care Med, 1995, 23(l):18~25.
[10] McCrirrick A,Kestin J.Haemodynamic effects of trachealcompare with intrayenousadrenalin. Lancet,2000,356:988.
[11] Prengel A W,Linder K H,Kelle A,etal.Cardiovascular function during the Postresuscitation phase after cardic arrest in pages: acomparion of epinephrine versus vasopression.Crit Care Med,1997,23(12):2014.
[12] European Epinephrine Study Group. A comparison high doses and repeated standard doses of epinephrine for cardiac Arrest outside the hospital. N Engl J Med,1998,339(22):1595.
[13] 周荣斌,檀桥.心肺复苏的药物应用.中国急救医学,2000,20(1).
[14] The AHA in association with ILCOR. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. An international consensus on science. Resuscitation 2000; 46:1–448.
[15] Berg R, Otto C, Kern K, et al. A randomized, blinded trial of high-dose epinephrine versus standard-dose epinephrine in a swine model of pediatric asphyxial arrest. Crit Care Med 1996,24(1)695~700.
[16] Wortsman J, Paradis N A,Martine GB,etal.Functional responses to extremely high plasma epinephrine concentration in Cardiac arrest .Crit Care Med,2002,28:692.
[17] WalravenC V,StiellL C,WellsG A,et al. Do advanced cardiac life support during increase resuscitation rate from in hospital cardiac?BrJAnasth,1999,82:738.
[18] EnsingerH,WeichelT,LinderKH,etal.Are the effects of norepinephrine,epinephrine and dopamine infusions on VO2 and metabolism transient?IntensiveCareMed,1998,24:50.
[19] McleanA S.Vasopressor therapy in cardiac resuscitation.Am HeartJ,2002,139(1):111.
[20] Voelckel WG.Lurie KG,Lindner KH,et a1.Vasopressin improves survival after cardiac arrest in hypovolemic shock.Anesth Analg,2000.91(3):627—634.
[21] Prengel A, Lindner K, Keller A. Cerebral oxygenation during cardiopulmonary resuscitation with epinephrine and vasopressin in pigs.Stroke 1996;27:1241–1248.
[2] Berkowitz ID, Gervais H, Schleien CL,et al.Epinephrine dosage effects on cerebral and myocardial blood flow in an infant swine model of cardiopulmonary resuscitation. Anesthesiology. 1991,75(6):1041~1050.
[3] Guidelines 2000 for CPR and emergency cardiovascular care: international consensus on science. Part 6: Advanced cardiovascular life support; Section 6: Pharmacology II. Agents to optimize cardiac output and blood pressure. Circulation 2000,102 (Suppl. I): 1129~1135.
[4] 石海明,李颖,梁勇,等.加强心脏按压与大剂量肾上腺素在心肺复苏中的应用[J].中国危重病急救医学,1998,10(7):436—437.
[5] Johansson J, Gedeborg R, Basu S,et al. Increased cortical cerebral blood flow by continuous infusion of epinephrine during experimental cardiopulmonary resuscitation. Resuscitation 2003,57(3):299~307.
[6] D.J. Callans.Out-of-hospital cardiac arrest—the solution is shocking.N Engl J Med ,2004, 35(1): 632~634.
[7] Rogove FU, Safar P, Suton 一 Tyrrel K, et al.Old age does not negate good cerebral outcome after cardiopulmonary resuscitation: analysis from the brain resuscitation clinical trials IJI .The Brain Resuscitation Clinical Trial I and II Study Groups. Crit Care Med, 1995, 23(l):18~25.
[8] Johansson J, Gedeborg R, Rubertsson S.Vasopressin versus continuous epinephrine during experimental cardiopulmonary resuscitation.Resuscitation. 2004 ,62(1):61~69.
[9] 李涛,李玲莉,李承晏,等.低温高渗盐水配合低温等渗盐水治疗兔脑梗死的实验研究.中华物理医学与康复杂志,2005,27(7):438~439.
[10] Fischer M,Hossman KA.No-reflow after cardiac arrest. Intensive Care Med,1995,21(2):132~141.
[11] WalravenC V,StiellL C,WellsG A,et al. Do advanced cardiac life support during increase resuscitation rate from in hospital cardiac?BrJAnasth,1999,82:738.
[12] LinderK H,AhnfedldFW,GrunertA.Epinephrine versus norpinephrine in Prehospital ventricular fibrillation.Lancet,1999,354:505.
[13] Chai P, Skaryak L, Ungerleider R, et al. Jugular ligation does not increase intracranial pressure but does increase bihemispheric cerebral Baumann G, Dingman J. Distribution, blood transport and degradation of antidiuretic hormone in man. J Clin Invest 1976,57:1109~1116.
[14] Tang W, Weil M, Sun S, etal. Epinephrine increases the severity of post-resuscitation myocardial dysfunction.Circulation 1995,92:3089~3093.
[15] Gedeborg R, Silander HC, Ronne-Engstr?m E,et al. Adverse effects of high-dose epinephrineon cerebral blood flow during experimental cardiopulmonary resuscitation. Crit Care Med 2000,28(5):1423~1430.
[16] Berg R, Otto C, Kern K, et al. A randomized, blinded trial of high-dose epinephrine versus standard-dose epinephrine in a swine model of pediatric asphyxial arrest. Crit Care Med 1996,24(1)695~700.
[17] Biondi-Zoccai G, Abbate A, Parisi Q, et al. Is vasopressin superior to epinephrine or placebo in the management of cardiac arrest? Ameta-analysis. Resuscitation 2003,59:221–224.
[1] 康舟军,杨瑞和,霍正禄.心肺复苏药物治疗新进展.中国急救医学,2004,24(7):508～509.
[2] Berkowitz ID, Gervais H, Schleien CL,et al.Epinephrine dosage effects on cerebral and myocardial blood flow in an infant swine model of cardiopulmonary resuscitation. Anesthesiology. 1991,75(6):1041~1050.
[3] Guidelines 2000 for CPR and emergency cardiovascular care: international consensus on science. Part 6: Advanced cardiovascular life support; Section 6: Pharmacology II. Agents to optimize cardiac output and blood pressure. Circulation 2000,102 (Suppl. I): 1129~1135.
[4] LinderK H,AhnfedldFW,GrunertA.Epinephrine versus norpinephrine in Prehospital ventricular fibrillation.Lancet,1999,354:505.
[5] Chai P, Skaryak L, Ungerleider R, et al. Jugular ligation does not increase intracranial pressure but does increase bihemispheric cerebral Baumann G, Dingman J. Distribution, blood transport and degradation of antidiuretic hormone in man. J Clin Invest 1976,57:1109~1116.
[6] Tang W, Weil M, Sun S, etal. Epinephrine increases the severity of post-resuscitation myocardial dysfunction.Circulation 1995,92:3089~3093.
[7] 石海明,李颖,梁勇,等.加强心脏按压与大剂量肾上腺素在心肺复苏中的应用[J].中国危重病急救医学,1998,10(7):436—437.
[8] Johansson J, Gedeborg R, Basu S,et al. Increased cortical cerebral blood flow by continuous infusion of epinephrine during experimental cardiopulmonary resuscitation. Resuscitation 2003,57(3):299~307.
[9] Rogove FU, Safar P, Suton 一 Tyrrel K, et al.Old age does not negate good cerebral outcome after cardiopulmonary resuscitation: analysis from the brain resuscitation clinical trials IJI .The Brain Resuscitation Clinical Trial I and II Study Groups. Crit Care Med, 1995, 23(l):18~25.
[10] McCrirrick A,Kestin J.Haemodynamic effects of trachealcompare with intrayenousadrenalin. Lancet,2000,356:988.
[11] Prengel A W,Linder K H,Kelle A,etal.Cardiovascular function during the Postresuscitation phase after cardic arrest in pages: acomparion of epinephrine versus vasopression.Crit Care Med,1997,23(12):2014.
[12] European Epinephrine Study Group. A comparison high doses and repeated standard doses of epinephrine for cardiac Arrest outside the hospital. N Engl J Med,1998,339(22):1595.
[13] 周荣斌,檀桥.心肺复苏的药物应用.中国急救医学,2000,20(1).
[14] The AHA in association with ILCOR. Guidelines 2000 for cardiopulmonary resuscitation and emergency cardiovascular care. An international consensus on science. Resuscitation 2000; 46:1–448.
[15] Berg R, Otto C, Kern K, et al. A randomized, blinded trial of high-dose epinephrine versus standard-dose epinephrine in a swine model of pediatric asphyxial arrest. Crit Care Med 1996,24(1)695~700.
[16] Wortsman J, Paradis N A,Martine GB,etal.Functional responses to extremely high plasma epinephrine concentration in Cardiac arrest .Crit Care Med,2002,28:692.
[17] WalravenC V,StiellL C,WellsG A,et al. Do advanced cardiac life support during increase resuscitation rate from in hospital cardiac?BrJAnasth,1999,82:738.
[18] EnsingerH,WeichelT,LinderKH,etal.Are the effects of norepinephrine,epinephrine and dopamine infusions on VO2 and metabolism transient?IntensiveCareMed,1998,24:50.
[19] McleanA S.Vasopressor therapy in cardiac resuscitation.Am HeartJ,2002,139(1):111.
[20] Voelckel WG.Lurie KG,Lindner KH,et a1.Vasopressin improves survival after cardiac arrest in hypovolemic shock.Anesth Analg,2000.91(3):627—634.
[21] Prengel A, Lindner K, Keller A. Cerebral oxygenation during cardiopulmonary resuscitation with epinephrine and vasopressin in pigs.Stroke 1996;27:1241–1248.