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LITERATURE REVIEW 711 amiodarone for control of ventricular dysrhythmias, the authors were unable to demonstrate a correlation between symptoms or chest radiographic changes and the decreased pulmonary diffusing capacity occurring after amiodarone administration. Pulmonary toxicity was defined as respira- tory tract symptoms such as cough or dyspnea lasting >4 weeks in stable patients in whom other casues could be eliminated. Diffusing capacity decreased 20% and more than one-half of the 33 patients demonstrated decreased diffusion. Symptoms of pulmonary toxicity developed in 27% of patients. However, lung toxicity could not be predicted by preexisting cardiopulmonary dysfunction as seven patients had mild obstructive defects and 11 had restrictive defects on preliminary testing. Patients with the greatest decrease in diffusing capacity had a longer duration of time on a daily maintenance dose r600 mg of amiodarone. Thus, toxicity can be correlated with higher maintenance doses, since patients treated with ~400 mg/day have an insignificant reduction of diffusing capacity. Reilly LAG,FitzGerald GA: Aspirin in car- diovascular disease. Drugs 35~134176,1988 The antithrombotic effects of aspirin, mediated through irreversible acetylation of a serine residue at the active site of the platelet enzyme cyclooxygenase, are well known to anesthesiologists. Platelet cyclooxygenase is -90% inactivated by a single 325mg dose. Since platelets have no capacity for protein synthesis, new cyclooxygenase cannot be produced and the defect persists for the life of the platelet. The principal effect on platelet function is inhibition of platelet aggregation, the platelet release reaction in response to epinephrine, adenosine diphosphate, collagen, or arachi- donic acid, and platelet thromboxane formation. Other anti- thrombotic mechanisms for aspirin include its effects on the platelet lipcoxygenase pathway of arachidonic acid metabo- lism. Aspirin reduces the synthesis and activity of vitamin K-dependent coagulation factors, although only in large doses. It also enhances fibrinolytic activity. Aspirin is rapidly absorbed from the small intestine and stomach. Absorption half-life (trb) is 15 to 20 minutes. It undergoes hydrolysis to salicylate in the gastrointestinal tract and in its first passage through the liver (50% inactivation). After hydrolysis, salicylate is further metabolized and elimi- nated as glucuronic acid, glycine conjugates, and dihydroxy acids, or by renal excretion of unchanged salicylate. This review details the clinical trials and future appli- cations of aspirin therapy in cardiac, vascular, and cerebral disease. Although individual trials of aspirin in myocardial infarction suggest a reduction in total mortality, it is only when all seven trials are considered together that aspirin appears to have a protective effect against acute myocardial infarction and death. Reasons for the failure of beneficial effects in individual trials include defects in study designs, variation in aspirin dose, failure of aspirin to inhibit platelet activation, or the inability of aspirin to affect platelet- independent factors contributing to the pathogenesis of infarction. Similarly, in nine trials, aspirin doses of 100 to 975 mg daily, started within the first 24 hours postoperatively, decreased coronary bypass graft occlusion. Aspirin may also be useful in patients with prosthetic vascular grafts because increased platelet turnover, platelet deposition on graft surfaces early after placement, and long- term platelet deposition occur. Aspirin alone in doses of 900 to 1300 mg daily decreases the incidence of complications from transient ischemic attacks. Future uses of aspirin may include prevention of increased thromboxane production after thrombolytic therapy or coronary angioplasty. Overall, its greatest benefit occurs with early application in situations in which thrombosis is dependent on platelet mechanisms. Salama A, Hugo F, Heinrich D, et al: Deposition of terminal C5b-9 complement com- plexes on erythrocytes and leukocytes during cardiopulmonary bypass. N Engl J Med 318:408- 414,1988 The postperfusion syndrome includes hemolysis, leu- kopenia, nonspecific systemic reactions, and hemostatic defects in patients undergoing cardiopulmonary bypass (CPB). Activation of the terminal complement sequence may be important in the pathogenesis of this syndrome. Comple- ment activation is a well-recognized feature of extracorporeal circulation. During bypass, C3a and C5a anaphylatoxins are generated and converted to their desArg forms by plasma carboxypeptidase. After the cleavage of C5, the complement sequence proceeds to completion with generation of CSb-9 complexes on target membranes such as erythrocytes and leukocytes, or of cytolytically inactive SCSb-9 complexes in the fluid phase. In 48 unselected patients undergoing cardiac surgery for coronary or valvular heart disease or both with a bubble oxygenator at a perfusion flow of 4.1 to 4.8 L/min at 2S0 to 34’C, plasma-free hemoglobin, cell-bound C5b-9 from eryth- rocyte ghosts and granulocytes, and platelet-associated C3d were determined before, during, and after CPB. The plasma concentration of inactive complement components C5b-9 was always normal prior to CPB. However, it increased three- to eightfold with onset of bypass. The presence of C5b-9 on leukocytes and erythrocytes, but not platelets, was docu- mented by double-immunofluorescent labeling and enzyme- linked immunosorbent assays. Erythrocyte membranes with attached CSb-9 disappeared from the circulation within 30 minutes of termination of bypass. Two hours after discontin- uation of bypass, the SCSb-9 returned to normal. The pres- ence of CSb-9 complexes always coincided with hemoglobi- nemia, indicating hemolysis. Autologous CSb-9 attack may be another important factor causing hemolysis during CPB. Veltri EP, Mower MM, Mirowski M: Ambulatory monitoring of the automatic implant- able cardioverter-defibrillator: A practical guide. Pace 11:315-325,1988 Anesthesiologists must be prepared to manage patients with automatic implanted cardioverter-defibrillators (AICDs) during cardiac or noncardiac surgery. This article details the long-term management of these patients and indicates essential clinical and laboratory evaluation that is necessary prior to elective or emergency surgery. Like patients with pacemakers, patients with implanted defibrilla- tors require careful evaluation before surgery. Intraoperative

Aspirin in cardiovascular disease

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LITERATURE REVIEW 711

amiodarone for control of ventricular dysrhythmias, the authors were unable to demonstrate a correlation between symptoms or chest radiographic changes and the decreased pulmonary diffusing capacity occurring after amiodarone administration. Pulmonary toxicity was defined as respira- tory tract symptoms such as cough or dyspnea lasting >4 weeks in stable patients in whom other casues could be eliminated. Diffusing capacity decreased 20% and more than one-half of the 33 patients demonstrated decreased diffusion. Symptoms of pulmonary toxicity developed in 27% of patients. However, lung toxicity could not be predicted by preexisting cardiopulmonary dysfunction as seven patients had mild obstructive defects and 11 had restrictive defects on preliminary testing. Patients with the greatest decrease in diffusing capacity had a longer duration of time on a daily maintenance dose r600 mg of amiodarone. Thus, toxicity can be correlated with higher maintenance doses, since patients treated with ~400 mg/day have an insignificant reduction of diffusing capacity.

Reilly LAG, FitzGerald GA: Aspirin in car- diovascular disease. Drugs 35~134176,1988

The antithrombotic effects of aspirin, mediated through irreversible acetylation of a serine residue at the active site of the platelet enzyme cyclooxygenase, are well known to anesthesiologists. Platelet cyclooxygenase is -90% inactivated by a single 325mg dose. Since platelets have no capacity for protein synthesis, new cyclooxygenase cannot be produced and the defect persists for the life of the platelet. The principal effect on platelet function is inhibition of platelet aggregation, the platelet release reaction in response to epinephrine, adenosine diphosphate, collagen, or arachi- donic acid, and platelet thromboxane formation. Other anti- thrombotic mechanisms for aspirin include its effects on the platelet lipcoxygenase pathway of arachidonic acid metabo- lism. Aspirin reduces the synthesis and activity of vitamin K-dependent coagulation factors, although only in large doses. It also enhances fibrinolytic activity.

Aspirin is rapidly absorbed from the small intestine and stomach. Absorption half-life (trb) is 15 to 20 minutes. It undergoes hydrolysis to salicylate in the gastrointestinal tract and in its first passage through the liver (50% inactivation). After hydrolysis, salicylate is further metabolized and elimi- nated as glucuronic acid, glycine conjugates, and dihydroxy acids, or by renal excretion of unchanged salicylate.

This review details the clinical trials and future appli- cations of aspirin therapy in cardiac, vascular, and cerebral disease. Although individual trials of aspirin in myocardial infarction suggest a reduction in total mortality, it is only when all seven trials are considered together that aspirin appears to have a protective effect against acute myocardial infarction and death. Reasons for the failure of beneficial effects in individual trials include defects in study designs, variation in aspirin dose, failure of aspirin to inhibit platelet activation, or the inability of aspirin to affect platelet- independent factors contributing to the pathogenesis of infarction. Similarly, in nine trials, aspirin doses of 100 to 975 mg daily, started within the first 24 hours postoperatively, decreased coronary bypass graft occlusion.

Aspirin may also be useful in patients with prosthetic

vascular grafts because increased platelet turnover, platelet deposition on graft surfaces early after placement, and long- term platelet deposition occur. Aspirin alone in doses of 900 to 1300 mg daily decreases the incidence of complications from transient ischemic attacks. Future uses of aspirin may include prevention of increased thromboxane production after thrombolytic therapy or coronary angioplasty. Overall, its greatest benefit occurs with early application in situations in which thrombosis is dependent on platelet mechanisms.

Salama A, Hugo F, Heinrich D, et al: Deposition of terminal C5b-9 complement com- plexes on erythrocytes and leukocytes during cardiopulmonary bypass. N Engl J Med 318:408- 414,1988

The postperfusion syndrome includes hemolysis, leu- kopenia, nonspecific systemic reactions, and hemostatic defects in patients undergoing cardiopulmonary bypass (CPB). Activation of the terminal complement sequence may be important in the pathogenesis of this syndrome. Comple- ment activation is a well-recognized feature of extracorporeal circulation. During bypass, C3a and C5a anaphylatoxins are generated and converted to their desArg forms by plasma carboxypeptidase. After the cleavage of C5, the complement sequence proceeds to completion with generation of CSb-9 complexes on target membranes such as erythrocytes and leukocytes, or of cytolytically inactive SCSb-9 complexes in the fluid phase.

In 48 unselected patients undergoing cardiac surgery for coronary or valvular heart disease or both with a bubble oxygenator at a perfusion flow of 4.1 to 4.8 L/min at 2S0 to 34’C, plasma-free hemoglobin, cell-bound C5b-9 from eryth- rocyte ghosts and granulocytes, and platelet-associated C3d were determined before, during, and after CPB. The plasma concentration of inactive complement components C5b-9 was always normal prior to CPB. However, it increased three- to eightfold with onset of bypass. The presence of C5b-9 on leukocytes and erythrocytes, but not platelets, was docu- mented by double-immunofluorescent labeling and enzyme- linked immunosorbent assays. Erythrocyte membranes with attached CSb-9 disappeared from the circulation within 30 minutes of termination of bypass. Two hours after discontin- uation of bypass, the SCSb-9 returned to normal. The pres- ence of CSb-9 complexes always coincided with hemoglobi- nemia, indicating hemolysis. Autologous CSb-9 attack may be another important factor causing hemolysis during CPB.

Veltri EP, Mower MM, Mirowski M: Ambulatory monitoring of the automatic implant- able cardioverter-defibrillator: A practical guide. Pace 11:315-325,1988

Anesthesiologists must be prepared to manage patients with automatic implanted cardioverter-defibrillators (AICDs) during cardiac or noncardiac surgery. This article details the long-term management of these patients and indicates essential clinical and laboratory evaluation that is necessary prior to elective or emergency surgery. Like patients with pacemakers, patients with implanted defibrilla- tors require careful evaluation before surgery. Intraoperative