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Adenosine versus verapamil in the treatment of supraventricular tachycardia: A randomized double-crossover trial
LITERATURE REVIEW Frederick W Campbell, MD, Editor
SCIENTIFIC
ARTICLES
Eisenberg MJ, London MJ, L.eung JM, et al: Monitoring for myocardial ischemia during noncardisc surgery. A technology assessment of transesophageal echocardiography and 12-lead electrocardiography. J Am Med Assoc 268:210-216,1992 This is one of six articles published in this journal issue focusing on the problem of perioperative myocardial ischemia. Two hundred and eighty-five men with evidence of coronary artery disease or clinical risk factors for coronary artery disease undergoing vascular and nonvascular noncardiac surgery underwent intraoperative monitoring with transesophageal echocardiographic (TEE) monitoring and continuous 12-lead and two-lead ECG monitoring. Intraoperative myocardial ischemia detected by one or more techniques occurred in 39% of patients. When TEE and 12-lead ECG monitoring results were added to a multivariate model that included preoperative clinical data and two-lead ECG results, the incremental predictive value of TEE was small and of 1Zlead ECG nonsignificant. Intraoperative myocardial ischemia (detected by each of the three monitoring techniques) was associated with a two-fold to three-fold increased likelihood for adverse cardiac outcome (cardiac death, myocardial infarction, unstable angina, congestive heart failure and ventricular tachycardia) than without ischemia.
Grant RP, Dolman JF, Harper JA, et al: Patientcontrolled lumbar epidural fentanyl compared with patient-controlled intravenous fentanyl for postthoracotomy pain. Can J Anaesth 39:214-9,1992 Thirty-four patients were studied in a randomized, double-blind, placebo-controlled comparison of intravenousversus lumbar epidural fentanyl for the first 20 hours after thoracotomy. Fentanyl was delivered in a patient-controlled bolus plus infusion protocol. The cumulative fentanyl requirements were significantly lower in the epidural than the intravenous group (mean 1,857 v 2,573 p,g). There were no differences between the groups with respect to measures of analgesia or pulmonary function. There is obviously some pharmacokinetic difference between the two methods of administering fentanyl that permits equal analgesia with lower dosage in the epidural group. The logical conclusion is a direct neuraxial effect of fentanyl. However, in this group of patients, over the period studied, there is no obvious clinical benefit to using the highly lipophilic opioid fentanyl via the lumbar epidural rather than the intravenous route.
ment (group II, n = 25) of reperfusion-induced ventricular fibrillation. Time to onset of cardiac activity upon reperfitsion was similar in the two groups. There were no significant differences in acid-base or blood gas data, aortic cross-clamp time, CPK-MB, or myoglobin levels between the two groups. Patients who developed reperfusion ventricular fibrillation had significantly higher myocardial temperature (27.6” v 25.6”C) at the onset of electrical activity, higher levels of serum sodium (126.1 v 123.9 mMol/L), and significantly lower serum potassium levels (3.55 v 3.98 mMol/L) and lower serum potassium-to-calcium ratios (4.29 v 4.94).
Goto M, Flynn AE, Doucette JW, et al: Effect of intracoronary nitroglycerin administration on phasic pattern and transmural distribution of flow during coronary artery stenosis. Circulation 852296-2304, 1992 Coronary perfusion pressure, phasic pattern of myocardial blood flow (Doppler ultrasound flowmeter), and transmyocardial blood flow distribution (radioactive microspheres) were measured in a canine model during intracoronary administration of nitroglycerin. Nitroglycerin decreased poststenotic coronary arterial pressure and increased diastolic blood flow velocity, augmented systolic reverse velocity, and increased the subepicardial flow, but failed to increase subendocardial blood flow. Subendocardial-to-subepicardial flow ratio decreased from 0.73 to 0.32. Nitroglycerin clearly relieves angina by reducing myocardial oxygen consumption through its venodilating action. The drug’s effects on the coronary circulation are still debated and depend on the model studied. The model did not examine the contribution of collateral vessels to subendocardial blood flow.
Perondi R, Saino A, Totio RA, et al: ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. Circulation 85:2004-2013,1992 Diving and cold pressor tests were administered to nine patients with angiographic coronary atherosclerosis during control conditions and 30 minutes after captopril, 25 mg, orally. Both sympathetic stimulating tests increased blood pressure, rate-pressure product, and coronary vascular resistance during control measurements. Coronary blood flow (thermodilution method) decreased under control conditions in response to diving and was unchanged after cold pressor tests. Captopril administration did not change blood pressure, heart rate, or rate-pressure product responses to both stimuli; however, increases in coronary vascular resistance were significantly attenuated.
Kinoshita K, Mitani A, Tsuruhara Y, et al: Analysis of determinants of ventricular fibrillation induced by reperfusion: Dissociation between electrical instability and myocardial damage. Ann Thorac Surg 53:9991005,1992
Hood MA, Smith WM: Adenosine versus verapamil in the treatment of supraventricular tachycardia: A randomized double-crossover trial. Am Heart J 123: 1543-1549,1992
Sixty-two patients undergoing open heart surgery were divided into two groups based on absence (group I, n = 37) or develop-
Of 32 patients with narrow complex tachycardia, 22% experienced conversion to sinus rhythm with carotid sinus massage. The
Journalof Cardiorhoracic and VascularAnesthesia,
Vol7, No 1 (February), 1993: pp 117-l19
117
118
other 25 patients were randomly assigned to receive adenosine (successive 40 ug/kg increments to maximum dose of 20 mg) or verapamil (70 kg/kg repeated to maximum dose of 15 mg). Conversion to sinus rhythm occurred in 100% of patients for adenosine versus 73% for verapamil (P = NS). Indications for crossover from verapamil to adenosine were hypotension (one patient) and treatment failure with maximum drug dose (two patients). Reinitiation of tachycardia occurred in two adenosinetreated patients; in both, sinus rhythm was restored by a second injection of the previously effective adenosine dose. Transient mild symptoms, including flushing and chest tightness, occurred in 76% of adenosine patients.
Wickey JC, Keifer JC, Larach DR, et al: Heparin resistance after interoperative platelet-rich plasma harvesting. J Thorac Cardiovasc Surg 103:1172-1176, 1992 The effect of plateletpheresis and preoperative heparin therapy on heparin dose requirements were studied by review of records of 58 patients undergoing coronary artery surgery. Compared to patients undergoing prebypass autologous whole blood harvesting or no blood withdrawal, plateletpheresis insignificantly increased the heparin dose necessary to achieve anticoagulation (ACT 480 seconds), and significantly increased the total heparin dose during cardiopulmonary bypass. Preoperative heparin therapy significantly increased heparin dose to achieve anticoagulation (338 v 273 U/kg) and total heparin dose (499 v 422 U/kg).
Yau TM, Carson S, Weisel RD, et al: The effect of warm heart surgery on postoperative bleeding. J Thorac Cardiovasc Surg 103:1155-1163,1992 One hundred forty-six patients undergoing coronary artery surgery were randomly assigned to normothermic or hypothermic (25” to 29°C) systemic perfusion and nonrandomly to receive tranexamic acid (10 gm IV, n = 63) epsilon-aminocaproic acid (15 gm IV, n = 63) or no drug (controls, n = 20). Postoperative blood loss was significantly less in warm perfused control patients at 6 and 12 hours postoperatively than in cold perfused control patients. The difference was not statistically significant at twenty-four hours. Patients receiving either antifibrinolytic agent, regardless of perfusion temperature, bled less after all time periods than did cold control patients. Frequency of blood transfusion was not different between perfusion temperature groups, and insignificantly reduced in antifibrinolytic agent-treated patients compared to warm and cold controls. Postoperative platelet count was reduced in the hypothermic control group compared to all other groups.
Khuri SF, Wolfe JA, Josa M, et al: Hematologic changes during and after cardiopulmonary bypass and their relationship to the bleeding time and nonsurgical blood loss. J Thorac Cardiovasc Surg 104:94-107,1992 Measurement of blood loss and bleeding time in 85 patients during and after cardiopulmonary bypass demonstrated correlation between postoperative bleeding time and blood loss; both parameters were directly related to duration of cardiopulmonary bypass. Postoperative bleeding time correlated with patient’s skin temperature and plasma level of D-dimer; blood loss correlated with temperature and plasma C3 levels. Improvement in bleeding
LITERATURE REVIEW
time postoperatively is associated with increases in mean platelet volume and thromboxane B2 levels in shed blood. Fibrinolytic activity and complement activation play a role in bypass-induced platelet dysfunction, which may be alleviated postoperatively by rewarming and release of larger, younger platelets into circulation. Inverse relationship between skin temperature and bleeding time in cardiac surgical patients is also demonstrated in another article in the same journal: Valeri CR, Kahbbaz K, Kahuri SF. et al: Effect of skin temperature on platelet function in patients undergoing extracorporeal bypass. J Thorac Cardiovasc Surg 104:108-116. 1992.
Ansell J, Klassen V, Lew R, et al: Does desmopressin acetate prophylaxis reduce blood loss after valvutar heart operations? A randomized, double-blind study. J Thorac Cardiovasc Surg 104:117-123,1992 Eighty-three patients undergoing valvular heart operations were randomized to receive desmopressin (0.3 kg/kg) or placebo after cardiac bypass. There were no significant differences in 24 hour blood loss (1,064 v 844 mL), red blood cell, platelet or fresh frozen plasma transfusion. or reexploration for hemorrhage between the desmopressin or control groups. Factor VIII activity was higher in the desmopressin group immediately after operation than in placebo group. Factor VIII activity, von Willebrand factor, or von Willebrand factor multimers did not correlate with blood loss. The authors also review the previously published literature on desmopressin acetate in cardiac operations.
Pearson PJ, Evora PRR, Ayrancioglu K, Schaff Hv: Protamine releases endothelium-derived relaxing factor from systemic arteries. A possible mechanism of hypotension during heparin neutralization. Circulation 86:289-294,1992 Canine coronary, femoral and renal artery rings, with and without endothelium, were exposed to increasing concentrations of protamine in vitro. Protamine caused only a modest decrease in tension in arterial segments without endothelium. Concentrationdependent relaxation occurred in all endothelialized segments. which was significantly greater than in segments without endothelium. Endothelium-dependent relaxation induced by protamine was inhibited by L-NMMA, an inhibitor of endothelium-derived relaxing factor synthesis.
Tuman KJ, MC Carthy RJ, March RJ, et al: Morbidity and duration of ICU stay after cardiac surgery. A model for preoperative risk assessment. Chest 102:36-44,1992 Eleven variables were identified by univariate analysis of risk factors in 3,156 operations and logistic regression as important predictors of morbidity. Correlation was found between a simplified additive model for clinical use and the logistic regression model. Both models were then tested prospectively in 394 patients demonstrating increasing morbidity, greater frequency of individual complications, and prolonged ICU stays with ascending scores similar to that predicted by the reference group. Preoperative variables associated with increased risk of morbidity include emergency surgery, multivalve and combined coronary valve procedures, age greater than 75 years, recent myocardial infarction, and renal dysfunction.
SCIENTIFIC
ARTICLES
Eisenberg MJ, London MJ, L.eung JM, et al: Monitoring for myocardial ischemia during noncardisc surgery. A technology assessment of transesophageal echocardiography and 12-lead electrocardiography. J Am Med Assoc 268:210-216,1992 This is one of six articles published in this journal issue focusing on the problem of perioperative myocardial ischemia. Two hundred and eighty-five men with evidence of coronary artery disease or clinical risk factors for coronary artery disease undergoing vascular and nonvascular noncardiac surgery underwent intraoperative monitoring with transesophageal echocardiographic (TEE) monitoring and continuous 12-lead and two-lead ECG monitoring. Intraoperative myocardial ischemia detected by one or more techniques occurred in 39% of patients. When TEE and 12-lead ECG monitoring results were added to a multivariate model that included preoperative clinical data and two-lead ECG results, the incremental predictive value of TEE was small and of 1Zlead ECG nonsignificant. Intraoperative myocardial ischemia (detected by each of the three monitoring techniques) was associated with a two-fold to three-fold increased likelihood for adverse cardiac outcome (cardiac death, myocardial infarction, unstable angina, congestive heart failure and ventricular tachycardia) than without ischemia.
Grant RP, Dolman JF, Harper JA, et al: Patientcontrolled lumbar epidural fentanyl compared with patient-controlled intravenous fentanyl for postthoracotomy pain. Can J Anaesth 39:214-9,1992 Thirty-four patients were studied in a randomized, double-blind, placebo-controlled comparison of intravenousversus lumbar epidural fentanyl for the first 20 hours after thoracotomy. Fentanyl was delivered in a patient-controlled bolus plus infusion protocol. The cumulative fentanyl requirements were significantly lower in the epidural than the intravenous group (mean 1,857 v 2,573 p,g). There were no differences between the groups with respect to measures of analgesia or pulmonary function. There is obviously some pharmacokinetic difference between the two methods of administering fentanyl that permits equal analgesia with lower dosage in the epidural group. The logical conclusion is a direct neuraxial effect of fentanyl. However, in this group of patients, over the period studied, there is no obvious clinical benefit to using the highly lipophilic opioid fentanyl via the lumbar epidural rather than the intravenous route.
ment (group II, n = 25) of reperfusion-induced ventricular fibrillation. Time to onset of cardiac activity upon reperfitsion was similar in the two groups. There were no significant differences in acid-base or blood gas data, aortic cross-clamp time, CPK-MB, or myoglobin levels between the two groups. Patients who developed reperfusion ventricular fibrillation had significantly higher myocardial temperature (27.6” v 25.6”C) at the onset of electrical activity, higher levels of serum sodium (126.1 v 123.9 mMol/L), and significantly lower serum potassium levels (3.55 v 3.98 mMol/L) and lower serum potassium-to-calcium ratios (4.29 v 4.94).
Goto M, Flynn AE, Doucette JW, et al: Effect of intracoronary nitroglycerin administration on phasic pattern and transmural distribution of flow during coronary artery stenosis. Circulation 852296-2304, 1992 Coronary perfusion pressure, phasic pattern of myocardial blood flow (Doppler ultrasound flowmeter), and transmyocardial blood flow distribution (radioactive microspheres) were measured in a canine model during intracoronary administration of nitroglycerin. Nitroglycerin decreased poststenotic coronary arterial pressure and increased diastolic blood flow velocity, augmented systolic reverse velocity, and increased the subepicardial flow, but failed to increase subendocardial blood flow. Subendocardial-to-subepicardial flow ratio decreased from 0.73 to 0.32. Nitroglycerin clearly relieves angina by reducing myocardial oxygen consumption through its venodilating action. The drug’s effects on the coronary circulation are still debated and depend on the model studied. The model did not examine the contribution of collateral vessels to subendocardial blood flow.
Perondi R, Saino A, Totio RA, et al: ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. Circulation 85:2004-2013,1992 Diving and cold pressor tests were administered to nine patients with angiographic coronary atherosclerosis during control conditions and 30 minutes after captopril, 25 mg, orally. Both sympathetic stimulating tests increased blood pressure, rate-pressure product, and coronary vascular resistance during control measurements. Coronary blood flow (thermodilution method) decreased under control conditions in response to diving and was unchanged after cold pressor tests. Captopril administration did not change blood pressure, heart rate, or rate-pressure product responses to both stimuli; however, increases in coronary vascular resistance were significantly attenuated.
Kinoshita K, Mitani A, Tsuruhara Y, et al: Analysis of determinants of ventricular fibrillation induced by reperfusion: Dissociation between electrical instability and myocardial damage. Ann Thorac Surg 53:9991005,1992
Hood MA, Smith WM: Adenosine versus verapamil in the treatment of supraventricular tachycardia: A randomized double-crossover trial. Am Heart J 123: 1543-1549,1992
Sixty-two patients undergoing open heart surgery were divided into two groups based on absence (group I, n = 37) or develop-
Of 32 patients with narrow complex tachycardia, 22% experienced conversion to sinus rhythm with carotid sinus massage. The
Journalof Cardiorhoracic and VascularAnesthesia,
Vol7, No 1 (February), 1993: pp 117-l19
117
118
other 25 patients were randomly assigned to receive adenosine (successive 40 ug/kg increments to maximum dose of 20 mg) or verapamil (70 kg/kg repeated to maximum dose of 15 mg). Conversion to sinus rhythm occurred in 100% of patients for adenosine versus 73% for verapamil (P = NS). Indications for crossover from verapamil to adenosine were hypotension (one patient) and treatment failure with maximum drug dose (two patients). Reinitiation of tachycardia occurred in two adenosinetreated patients; in both, sinus rhythm was restored by a second injection of the previously effective adenosine dose. Transient mild symptoms, including flushing and chest tightness, occurred in 76% of adenosine patients.
Wickey JC, Keifer JC, Larach DR, et al: Heparin resistance after interoperative platelet-rich plasma harvesting. J Thorac Cardiovasc Surg 103:1172-1176, 1992 The effect of plateletpheresis and preoperative heparin therapy on heparin dose requirements were studied by review of records of 58 patients undergoing coronary artery surgery. Compared to patients undergoing prebypass autologous whole blood harvesting or no blood withdrawal, plateletpheresis insignificantly increased the heparin dose necessary to achieve anticoagulation (ACT 480 seconds), and significantly increased the total heparin dose during cardiopulmonary bypass. Preoperative heparin therapy significantly increased heparin dose to achieve anticoagulation (338 v 273 U/kg) and total heparin dose (499 v 422 U/kg).
Yau TM, Carson S, Weisel RD, et al: The effect of warm heart surgery on postoperative bleeding. J Thorac Cardiovasc Surg 103:1155-1163,1992 One hundred forty-six patients undergoing coronary artery surgery were randomly assigned to normothermic or hypothermic (25” to 29°C) systemic perfusion and nonrandomly to receive tranexamic acid (10 gm IV, n = 63) epsilon-aminocaproic acid (15 gm IV, n = 63) or no drug (controls, n = 20). Postoperative blood loss was significantly less in warm perfused control patients at 6 and 12 hours postoperatively than in cold perfused control patients. The difference was not statistically significant at twenty-four hours. Patients receiving either antifibrinolytic agent, regardless of perfusion temperature, bled less after all time periods than did cold control patients. Frequency of blood transfusion was not different between perfusion temperature groups, and insignificantly reduced in antifibrinolytic agent-treated patients compared to warm and cold controls. Postoperative platelet count was reduced in the hypothermic control group compared to all other groups.
Khuri SF, Wolfe JA, Josa M, et al: Hematologic changes during and after cardiopulmonary bypass and their relationship to the bleeding time and nonsurgical blood loss. J Thorac Cardiovasc Surg 104:94-107,1992 Measurement of blood loss and bleeding time in 85 patients during and after cardiopulmonary bypass demonstrated correlation between postoperative bleeding time and blood loss; both parameters were directly related to duration of cardiopulmonary bypass. Postoperative bleeding time correlated with patient’s skin temperature and plasma level of D-dimer; blood loss correlated with temperature and plasma C3 levels. Improvement in bleeding
LITERATURE REVIEW
time postoperatively is associated with increases in mean platelet volume and thromboxane B2 levels in shed blood. Fibrinolytic activity and complement activation play a role in bypass-induced platelet dysfunction, which may be alleviated postoperatively by rewarming and release of larger, younger platelets into circulation. Inverse relationship between skin temperature and bleeding time in cardiac surgical patients is also demonstrated in another article in the same journal: Valeri CR, Kahbbaz K, Kahuri SF. et al: Effect of skin temperature on platelet function in patients undergoing extracorporeal bypass. J Thorac Cardiovasc Surg 104:108-116. 1992.
Ansell J, Klassen V, Lew R, et al: Does desmopressin acetate prophylaxis reduce blood loss after valvutar heart operations? A randomized, double-blind study. J Thorac Cardiovasc Surg 104:117-123,1992 Eighty-three patients undergoing valvular heart operations were randomized to receive desmopressin (0.3 kg/kg) or placebo after cardiac bypass. There were no significant differences in 24 hour blood loss (1,064 v 844 mL), red blood cell, platelet or fresh frozen plasma transfusion. or reexploration for hemorrhage between the desmopressin or control groups. Factor VIII activity was higher in the desmopressin group immediately after operation than in placebo group. Factor VIII activity, von Willebrand factor, or von Willebrand factor multimers did not correlate with blood loss. The authors also review the previously published literature on desmopressin acetate in cardiac operations.
Pearson PJ, Evora PRR, Ayrancioglu K, Schaff Hv: Protamine releases endothelium-derived relaxing factor from systemic arteries. A possible mechanism of hypotension during heparin neutralization. Circulation 86:289-294,1992 Canine coronary, femoral and renal artery rings, with and without endothelium, were exposed to increasing concentrations of protamine in vitro. Protamine caused only a modest decrease in tension in arterial segments without endothelium. Concentrationdependent relaxation occurred in all endothelialized segments. which was significantly greater than in segments without endothelium. Endothelium-dependent relaxation induced by protamine was inhibited by L-NMMA, an inhibitor of endothelium-derived relaxing factor synthesis.
Tuman KJ, MC Carthy RJ, March RJ, et al: Morbidity and duration of ICU stay after cardiac surgery. A model for preoperative risk assessment. Chest 102:36-44,1992 Eleven variables were identified by univariate analysis of risk factors in 3,156 operations and logistic regression as important predictors of morbidity. Correlation was found between a simplified additive model for clinical use and the logistic regression model. Both models were then tested prospectively in 394 patients demonstrating increasing morbidity, greater frequency of individual complications, and prolonged ICU stays with ascending scores similar to that predicted by the reference group. Preoperative variables associated with increased risk of morbidity include emergency surgery, multivalve and combined coronary valve procedures, age greater than 75 years, recent myocardial infarction, and renal dysfunction.