Kerry Kaplan

Intravenous nitroglycerin for the treatment of angina at rest unresponsive to standard nitrate therapy.

Thirty-five patients who had angina at rest that was unresponsive to standard therapy comprised of oral or topical nitrates and beta-blocking drugs were treated with a continuous infusion of intravenous nitroglycerin (IVNTG). The infusion was started at 10 micrograms/min and increased by 10 micrograms/min increments every 5 minutes until an infusion rate of 50 micrograms/min was reached. After each episode of rest angina, the infusion was increased by 50 micrograms/min in the same stepwise manner. Data from a 24-hour baseline control period were compared with those from a 24-hour IVNTG endpoint period at which time the highest IVNTG infusion rate was administered. The average IVNTG infusion rate was 140 +/- 15 micrograms/min. With IVNTG therapy, the number of episodes of angina at rest decreased from 3.5 +/- 0.4 to 0.3 +/- 0.1, sublingual nitroglycerin use decreased from 1.9 +/- 0.3 to 0.4 +/- 0.1 mg/day, and morphine sulfate administration decreased from 5.5 +/- 1.3 to 0.4 +/- 0.2 mg/day (all p less than 0.001). When each patients response on the endpoint day was analyzed, 25 were defined as complete (no rest angina), 8 as partial (greater than 50% decrease in the number of episodes/day from control values), and 2 as nonresponders. No significant drug-induced adverse effects occurred. IVNTG appears to be effective therapy for angina at rest refractory to standard oral and topical medications.

Prophylaxis of Supraventricular Tachyarrhythmia after Coronary Bypass Surgery with Oral Verapamil: A Randomized, Double-Blind Trial

This study investigated the efficacy of oral administration of verapamil, started 24 hours after coronary artery bypass grafting (CABG), in reducing the incidence of postoperative supraventricular tachyarrhythmia (SVT). Two hundred patients were randomly assigned in a double-blind fashion to receive a one-week course of either a placebo or 80 mg of verapamil every 6 hours. Overall, SVT developed in 23 control and 14 verapamil-treated patients, a 39% reduction in incidence (p less than 0.10). Of the patients who received at least four doses and continued to receive the study drug, 17 in the control and 7 in the verapamil group experienced SVT, a 53% decrease in incidence (p less than 0.06). Atrial fibrillation constituted 34 of the 37 SVT episodes and was associated with a slower ventricular response in the group given verapamil (115 +/- 8 versus 156 +/- 4 beats per minute; p less than 0.001). No evidence was found linking postoperative SVT with the withdrawal of beta-blocking drugs. Adverse effects required that 20 patients in the verapamil and 6 in the placebo group be removed from the study. Hypotension or pulmonary edema or both developed in 13 of the patients receiving verapamil, but in only 1 of the control patients (p less than 0.001). We conclude that although verapamil has potential merit for the prophylaxis of SVT after CABG, its use in this setting is associated with a high incidence of unacceptable hemodynamic side effects.

Role of heparin after intravenous thrombolytic therapy for acute myocardial infarction.

The optimal approach to management of patients after thrombolytic therapy for acute myocardial infarction (AMI) is unclear. The role of anticoagulation with heparin was evaluated in 75 consecutive patients who received intravenous streptokinase for AMI. Heparin therapy was titrated to keep the partial thromboplastin time (PTT) between 90 and 120 seconds. Seventeen episodes of definite myocardial ischemia (associated with reversible electrocardiographic changes) were observed in 13 patients. When episodes of probable myocardial ischemia are included (typical chest pain relieved by nitroglycerin or associated with more than a 15-mm Hg change in blood pressure but without electrocardiographic changes), 52 episodes occurred in 28 patients. Four episodes of definite and 4 of probable myocardial ischemia occurred within 24 hours of discontinuation of heparin. Analysis of the level of anticoagulation as assessed by PTT at the time of the ischemic events shows that ischemia occurred more often at lower PTTs. Nine hemorrhagic complications occurred, all within 24 hours of streptokinase infusion. In 4 patients bleeding was believed to be major and heparin administration was discontinued; 2 patients with gastrointestinal bleeding required blood transfusions. Our data suggest that after thrombolytic therapy for AMI, the level of anticoagulation is inversely related to the frequency of recurrent ischemic events; that discontinuation of heparin is frequently associated with ischemia; and that administration of heparin is associated with a low incidence of hemorrhagic complications.

Allergic reactions to streptokinase consistent with anaphylactic or antigen-antibody complex-mediated damage☆

Streptokinase used as a thrombolytic agent may produce immunologic drug reactions. We report a second case of IgE-mediated anaphylaxis and a late reaction to streptokinase. This late reaction was consistent with an IgG-mediated antigen-antibody disease with transient renal involvement, fever, and cutaneous lesions. The second case responded to prednisone therapy.

The effect of clonidine on the cessation of cigarette smoking

The effect of clonidine on smoking cessation was studied by randomly assigning 186 smokers in a double‐blind fashion to either placebo or clonidine. Abstinence from smoking was reported more frequently by subjects receiving clonidine, but the difference was statistically significant only at the end of the first week (34.4% vs 21.5%; p < 0.05). Bothersome side effects were common and resulted in the early discontinuation of the study medication by 23 of the subjects taking clonidine and eight taking placebo (p < 0.05). Although this study did not demonstrate a significant effect of clonidine on smoking cessation, a beneficial trend was detected and therefore further trials with transcutaneous delivery of this agent in combination with behavior modification techniques are warranted.

Clinical Evaluation of the Relative Effectiveness of Multidose Crystalloid and Cold Blood Potassium Cardioplegia in Coronary Artery Bypass Graft Surgery: A Nonrandomized Matched-Pair Analysis

Controversy exists concerning the most effective method of myocardial protection during coronary artery bypass graft operations. Accordingly, we performed a matched-pair analysis between 25 patients receiving multidose hypothermic potassium crystalloid cardioplegia and 25 other patients receiving cold blood potassium cardioplegia. Patients were matched on the basis of preoperative ejection fraction (EF) and the number of anatomically similar stenotic coronary arteries. The adequacy of myocardial protection was assessed by serial perioperative determinations of radionuclide ventriculography, hemodynamic measurements, analyses of electrocardiograms and serum levels of MB-CK. We found that the level of myocardial protection was similar between unstratified groups. However, when subgroups were selected on the basis of prolonged aortic cross-clamp time (greater than ninety minutes) or impaired preoperative left ventricular function (EF less than 40%), there was a suggestion that cold blood cardioplegia may be advantageous.

Association of methemoglobinemia and intravenous nitroglycerin administration

Significant elevation of arterial methemoglobin levels has been reported with the administration of intravenous (i.v.) nitroglycerin (NTG). To determine the incidence and clinical significance of this side effect of i.v. NTG, serial arterial methemoglobin levels were determined in 50 consecutive patients receiving i.v. NTG for 48 hours or longer. The mean i.v. NTG infusion rate was 290 +/- 13 micrograms/min (4.1 +/- 0.2 micrograms/kg/min) and the mean duration of infusion was 7.1 +/- 0.5 days. The mean methemoglobin level for the 141 samples was 1.57 +/- 0.08%, which differs from the control mean value in our laboratory of 0.44 +/- 0.01%. Although no patient had clinical symptoms from methemoglobin, 20 patients had elevated (greater than 1%) levels on at least 1 measurement. Seventy-eight of the 141 samples analyzed were in the normal range; 63 determinations were between 2 and 5%. Patients with normal methemoglobin levels differed from those with abnormal levels in the dose of i.v. NTG (mean infusion rate 244 +/- 16 vs 351 +/- 17 micrograms/min; total cumulative dose 1,612 +/- 153 vs 3,398 +/- 308 mg). Age, weight, renal and hepatic function, and arterial oxygen saturation were not different between the groups. In conclusion, clinically significant methemoglobinemia is uncommon with i.v. NTG infusion; however, when large doses of NTG are administered, this complication is more likely.

Frequency of pericardial effusion as determined by M-mode echocardiography in acute myocardial infarction

A pericardial friction rub occurs in 6 to 16% of patients after acute myocardial infarction (AMI), but the incidence of pericardial effusion (PE) is not known. M-mode echocardiography was done 1, 3 and 5 days after AMI in 43 consecutive patients admitted within 24 hours of AMI, and PE was detected in 16 (37%). The PE was small in 7 patients, moderate in 6 and large in 3. A pericardial friction rub developed in 8 (19%), of whom only 4 had PE. Pleuritic chest pain diminished by sitting up and relieved by antiinflammatory agents developed in 12 (28%), of whom only 5 had PE. The peak creatine kinase level was significantly higher in patients with PE (1,769 +/- 1,003 U) than in those without (1,181 +/- 838 units). More patients with PE were in Killip classification II, III or IV (11 of 16 [69%] vs 9 of 27 [33%]). The presence of PE was not associated with age, site of AMI, development of Q waves, use of heparin or previous AMI. In conclusion, PE as detected by M-mode echocardiography is frequently present after AMI, and its presence is not closely associated with the occurrence of a pericardial friction rub or typical pericardial pain.

Pulmonary Emboli from a Platelet‐rich Thrombus Attached to a Pacemaker Electrode

A patient with recurrent, fatal pulmonary emboli originating from thrombus attached to a permanently‐implanted pacemaker electrode is described. While most throm‐boemboli are composed predominantly of fibrin and erythrocytes. histologic and immunologic studies showed this thrombus to be rich in platelets. A possible therapeutic approach to this rare situation is discussed.

Efficacy of Esmolol in the Treatment and Transfer of Patients with Supraventricular Tachyarrhythmias to Alternate Oral Antiarrhythmic Agents

The efficacy and safety of esmolol, a titratable intravenous beta‐adrenergic blocking agent with a short elimination hall‐life (t1/2 = 9.0 min) was evaluated in a multicenter open‐label study for the treatment of supraventricular tachyarrhythmias (heart rate greater than 100 bpm). The study also investigated the feasibility of transferring patients from esmolol to alternate oral antiarrhythmic agents without loss of therapeutic response. Of the 113 patients studied, 95 (84%) achieved therapeutic response (reduction in heart rate of 15% or more or conversion to sinus rhythm). Most of these patients (93%) achieved the therapeutic response at esmolol doses of 200 μg/kg/min or lower. Transfer from esmolol to an oral antiarrhythmic agent(s) was studied in 76 patients. Alternate antiarrhythmic agents used in this study were digoxin (N = 25), propranolol (N = 21), verapamil (N = 10), metoprolol (N = 11), quinidine (N = 2), and a combination of two antiarrhythmic agents (N = 7). Sixty‐seven (88%) patients were successfully transferred to oral antiarrhythmic agents without loss of the therapeutic response obtained with esmolol. The most frequent adverse effect observed during the study was hypotension, which resolved quickly (16 ± 14 min) either by decreasing the dose or by discontinuation of esmolol infusion. This study supports previous observations concerning the safety and efficacy of esmolol in the treatment of supraventricular tachyarrhythmias. Furthermore, it demonstrates that the majority of patients successfully treated with esmolol can be safely and effectively transferred to oral therapy with alternate antiarrhythmic agents.