Renal dysfunction and intravascular coagulation with aprotinin and hypothermic circulatory arrest
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126 LITERATURE REVIEW thrombocytopenia was 51 hours and recovery occurred 54 hours after cessation of therapy. Fessatidis IT, Thomas VL, Shore DF, et al: Brain damage after profoundly hypothermic circulatory ar- rest: Correlation between neurophysiologic and neu- ropathologic findings. An experimental study in verte- brates. J Thorac Cardiovasc Surg 106:32-41,1993 Intraoperative somatosensory evoked potential monitoring and postoperative brain microscopy were evaluated in neonatal pigs placed on cardiopulmonary bypass with circulatory arrest periods from 70 to 120 minutes. Microscopic cellular damage appeared in all animals with circulatory arrest of more than 70 minutes. These changes involve mainly Purkinje’s cells of the cerebellum. The prolongation of latency in the somatosensory cortical responses reflecting a hypothermia-induced slowing of neural transmission occurred in all animals. Late evoked potentials remained absent in all piglets with circulatory arrest periods of 90 minutes or greater, but were fully recovered in all piglets of the control group and those with 70-minute arrest times. In a retrospective clinical study in the same journal issue (Svensson LG, Crawford ES, Hess KR, et al: Deep hypothermia with circulatory arrest. Determinants of stroke and early mortality in 656patients.JThoruc Cardiovusc Sung 106:19-31,1993), multivari- ate predictors of postoperative neurologic injury were a history of cerebrovascular disease, previous descending aortic surgery and cardiopulmonary bypass time. Circulatory arrest time was a univari- able predictor of postoperative stroke although not an independent variable by logistic regression analysis. The occurrence of stroke was observed to increase after 40 minutes of circulatory arrest and mortality increased markedly after 65 minutes of arrest. Tobe CE, Vocelka C, Sepulvada R, et al: Infusion of autologous platelet-rich plasma does not reduce blood loss and product use after coronary artery bypass. A prospective randomized blinded study. J Thorac Car- diovasc Surg 105:1007-1014,1993 Platelet-rich plasma (8-10 mL/kg) was collected from 51 pa- tients undergoing primary coronary artery surgery. After random- ization, the platelet-rich plasma was reinfused immediately in the control group or after heparin reversal in the treatment group. Surgeons’ subjective assessment of hemostasis was not different between control and treatment groups after bypass. No statistically significant differences were found in the use of any blood product or in the percentage of patients receiving transfusion. Chest tube drainage was not significantly different between the groups at any interval but tended toward significance 6 to 12 hours postopera- tively in favor of the treatment group. Prothrombin time immedi- ately after reinfusion of platelet-rich plasma was significantly lower in the treatment group but there were no differences in thromboelas- tography, partial thromboplastin time, activated clotting time, fibrinogen, platelet counts, and hematocrit between groups at each time interval. Wachtfogel YT, Cucich U, Hack CE, et al: Aproti- nin inhibits the contact, neutrophil, and platelet activation systems during simulated extracorporeal perfusion. J Thorac Cardiovasc Surg 106:1-lo,1993 Platelet and leukocyte counts, platelet response to ADP, plasma levels of l3-thromboglobulin, kallikrein-Cl-inhibitor complexes, Cl-Cl-inhibitor complexes, and neutrophil elastase were mea- sured during 2 hours of recirculation of fresh heparinized human blood at 37” in a spiral coil membrane oxygenator-roller pump perfusion circuit with five doses (0 to 0.12 mg/mL) of aprotinin. Aprotinin did not alter the decrease in platelet count occurring during recirculation but did prevent the decrease in sensitivity of platelets to ADP and reduced @thromboglobulin release. In the absence of aprotinin, kallikrein-Cl-inhibitor and Cl-Cl-inhibitor complexes increased significantly during recirculation. Kallikrein- Cl-inhibitor complexes were completely inhibited and CI-CI- inhibitor complexes partially inhibited at aprotinin concentration of 0.03 mg/mL or greater. Release of neutrophil elastase was partially inhibited at the highest aprotinin dose and was 50% inhibited at the does of 0.03 mg/mL. Data showed that aprotinin does not directly affect platelet adhesion or aggregation but indirectly preserves platelet sensitivity to agonists and attenuates release of platelet granules. Aprotinin in high doses completely inhibited kallikrein-induced neutrophil activation and partially inhibited complement-induced activation. These changes were independent of inhibition of plasmin because activation of fibrino- lytic system does not occur in this model because endothelium is not present to release tissue plasminogen activator. Huang H, Ding W, Su Z, Zhang W: Mechanism of the preserving effect of aprotinin on platelet function and its use in cardiac surgery. J Thorac Cardiovasc 106:11-18,1993 In in vitro studies, urokinase (40 units/ml) was added to platelet-rich plasma and plasmin (0.3 units/ml) was added to washed platelets with and without aprotinin (250 KlUlmL). Control samples demonstrated a reduction in platelet membrane glycoprotein Ib to 76% of initial values and a decline in ristocetin- induced agglutination to one third of initial values. With aprotinin pretreatment of platelet-rich plasma or washed platelets the changes in agglutination were not statistically significant and the reduction in glycoprotein lb less marked. In related clinical studies, high-dose aprotinin-preserved plasma az-antiplasmin and platelet glycoprotein lb, and attenuated reduction in platelet agglutination compared to non-aprotinin-treated patients. Sundt TM, Kouchoukos NT, Saffitz JE, et al: Renal dysfunction and intravascular coagulation with apro- tinin and hypothermic circulatory arrest. Ann Thorac Surg 5514181424,1993 Mortality and morbidity in 20 adult patients undergoing primary or repeat operations on the thoracic or thoracoabdominal aorta using cardiopulmonary bypass and hypothermic circulatory arrest were compared with that in 20 age-matched controls. In the 20 aprotinin-treated patients, reoperation for bleeding was required in 3,7 patients died, and renal dysfunction occurred in 13 patients, 5 of whom required hemodialysis. Postmortem examination in 5 patients revealed platelet-fibrin thrombi in multiple organs includ- ing coronary arteries of 4 patients with myocardial infarction or failure, the pulmonary arteries of 2 patients, one of whom died of acute right ventricular failure, the brains of 2 patients who sustained a stroke, and the kidneys of 4 patients, 3 of whom developed renal dysfunction. Among the age-matched controls there was 1 hospital death from myocardial infarction and renal dysfunction occurred in 1 patient who did not require dialysis. None of the control patients required reoperation for bleeding. Boldt J, Knothe C, Zickman B, et al: Aprotinin in pediatric cardiac operations: Platelet function, blood
Transcript of Renal dysfunction and intravascular coagulation with aprotinin and hypothermic circulatory arrest
126 LITERATURE REVIEW
thrombocytopenia was 51 hours and recovery occurred 54 hours after cessation of therapy.
Fessatidis IT, Thomas VL, Shore DF, et al: Brain damage after profoundly hypothermic circulatory ar- rest: Correlation between neurophysiologic and neu- ropathologic findings. An experimental study in verte- brates. J Thorac Cardiovasc Surg 106:32-41,1993
Intraoperative somatosensory evoked potential monitoring and postoperative brain microscopy were evaluated in neonatal pigs placed on cardiopulmonary bypass with circulatory arrest periods from 70 to 120 minutes. Microscopic cellular damage appeared in all animals with circulatory arrest of more than 70 minutes. These changes involve mainly Purkinje’s cells of the cerebellum. The prolongation of latency in the somatosensory cortical responses reflecting a hypothermia-induced slowing of neural transmission occurred in all animals. Late evoked potentials remained absent in all piglets with circulatory arrest periods of 90 minutes or greater, but were fully recovered in all piglets of the control group and those with 70-minute arrest times.
In a retrospective clinical study in the same journal issue (Svensson LG, Crawford ES, Hess KR, et al: Deep hypothermia with circulatory arrest. Determinants of stroke and early mortality in 656patients.JThoruc Cardiovusc Sung 106:19-31,1993), multivari- ate predictors of postoperative neurologic injury were a history of cerebrovascular disease, previous descending aortic surgery and cardiopulmonary bypass time. Circulatory arrest time was a univari- able predictor of postoperative stroke although not an independent variable by logistic regression analysis. The occurrence of stroke was observed to increase after 40 minutes of circulatory arrest and mortality increased markedly after 65 minutes of arrest.
Tobe CE, Vocelka C, Sepulvada R, et al: Infusion of autologous platelet-rich plasma does not reduce blood loss and product use after coronary artery bypass. A prospective randomized blinded study. J Thorac Car- diovasc Surg 105:1007-1014,1993
Platelet-rich plasma (8-10 mL/kg) was collected from 51 pa- tients undergoing primary coronary artery surgery. After random- ization, the platelet-rich plasma was reinfused immediately in the control group or after heparin reversal in the treatment group. Surgeons’ subjective assessment of hemostasis was not different between control and treatment groups after bypass. No statistically significant differences were found in the use of any blood product or in the percentage of patients receiving transfusion. Chest tube drainage was not significantly different between the groups at any interval but tended toward significance 6 to 12 hours postopera- tively in favor of the treatment group. Prothrombin time immedi- ately after reinfusion of platelet-rich plasma was significantly lower in the treatment group but there were no differences in thromboelas- tography, partial thromboplastin time, activated clotting time, fibrinogen, platelet counts, and hematocrit between groups at each time interval.
Wachtfogel YT, Cucich U, Hack CE, et al: Aproti- nin inhibits the contact, neutrophil, and platelet activation systems during simulated extracorporeal perfusion. J Thorac Cardiovasc Surg 106:1-lo,1993
Platelet and leukocyte counts, platelet response to ADP, plasma levels of l3-thromboglobulin, kallikrein-Cl-inhibitor complexes, Cl-Cl-inhibitor complexes, and neutrophil elastase were mea-
sured during 2 hours of recirculation of fresh heparinized human blood at 37” in a spiral coil membrane oxygenator-roller pump perfusion circuit with five doses (0 to 0.12 mg/mL) of aprotinin. Aprotinin did not alter the decrease in platelet count occurring during recirculation but did prevent the decrease in sensitivity of platelets to ADP and reduced @thromboglobulin release. In the absence of aprotinin, kallikrein-Cl-inhibitor and Cl-Cl-inhibitor complexes increased significantly during recirculation. Kallikrein- Cl-inhibitor complexes were completely inhibited and CI-CI- inhibitor complexes partially inhibited at aprotinin concentration of 0.03 mg/mL or greater. Release of neutrophil elastase was partially inhibited at the highest aprotinin dose and was 50% inhibited at the does of 0.03 mg/mL. Data showed that aprotinin does not directly affect platelet adhesion or aggregation but indirectly preserves platelet sensitivity to agonists and attenuates release of platelet granules. Aprotinin in high doses completely inhibited kallikrein-induced neutrophil activation and partially inhibited complement-induced activation. These changes were independent of inhibition of plasmin because activation of fibrino- lytic system does not occur in this model because endothelium is not present to release tissue plasminogen activator.
Huang H, Ding W, Su Z, Zhang W: Mechanism of the preserving effect of aprotinin on platelet function and its use in cardiac surgery. J Thorac Cardiovasc 106:11-18,1993
In in vitro studies, urokinase (40 units/ml) was added to platelet-rich plasma and plasmin (0.3 units/ml) was added to washed platelets with and without aprotinin (250 KlUlmL). Control samples demonstrated a reduction in platelet membrane glycoprotein Ib to 76% of initial values and a decline in ristocetin- induced agglutination to one third of initial values. With aprotinin pretreatment of platelet-rich plasma or washed platelets the changes in agglutination were not statistically significant and the reduction in glycoprotein lb less marked. In related clinical studies, high-dose aprotinin-preserved plasma az-antiplasmin and platelet glycoprotein lb, and attenuated reduction in platelet agglutination compared to non-aprotinin-treated patients.
Sundt TM, Kouchoukos NT, Saffitz JE, et al: Renal dysfunction and intravascular coagulation with apro- tinin and hypothermic circulatory arrest. Ann Thorac Surg 5514181424,1993
Mortality and morbidity in 20 adult patients undergoing primary or repeat operations on the thoracic or thoracoabdominal aorta using cardiopulmonary bypass and hypothermic circulatory arrest were compared with that in 20 age-matched controls. In the 20 aprotinin-treated patients, reoperation for bleeding was required in 3,7 patients died, and renal dysfunction occurred in 13 patients, 5 of whom required hemodialysis. Postmortem examination in 5 patients revealed platelet-fibrin thrombi in multiple organs includ- ing coronary arteries of 4 patients with myocardial infarction or failure, the pulmonary arteries of 2 patients, one of whom died of acute right ventricular failure, the brains of 2 patients who sustained a stroke, and the kidneys of 4 patients, 3 of whom developed renal dysfunction. Among the age-matched controls there was 1 hospital death from myocardial infarction and renal dysfunction occurred in 1 patient who did not require dialysis. None of the control patients required reoperation for bleeding.
Boldt J, Knothe C, Zickman B, et al: Aprotinin in pediatric cardiac operations: Platelet function, blood
