Richard Davison

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.

The use of epinephrine in the treatment of older adult asthmatics.

Three subcutaneous doses of 0.3 mL 1:1,000 epinephrine were given 20 minutes apart to 95 adult asthmatics 15 to 96 years old during 108 asthma exacerbations. Patients with a history of recent myocardial infarction or of angina were excluded from our study. Heart rhythm and rate, blood pressure, respiratory rate, and clinical response were prospectively evaluated before, during, and after the administration of epinephrine. There was no significant difference in the occurrence of ventricular arrhythmias between patients less than 40 and more than 40 years old. The mean systolic and diastolic blood pressures, mean heart rate, and mean respiratory rate decreased with treatment in the older population. Our results suggest that epinephrine is safe to use in acute asthmatics of any age.

Estimation of central venous pressure by examination of jugular veins

Abstract Attempts were made in 39 seriously ill patients to estimate the central venous pressure (measured through an intrathoracic venous catheter) by clinical examination of the jugular veins. Internal jugular veins were usually not visible. Inspection of the external jugular veins resulted in 103 measurements. These correlated poorly with the actual CVP, since only 47 per cent of the pooled observations were within 2 cm. of the recorded value. To obtain a 90 per cent coincidence, an error of up to 4 cm. had to be allowed. Moreover, large discrepancies were noted in individual cases. The central venous pressure cannot be reliably estimated by inspection of the jugular veins.

Excessive serum lidocaine levels during maintenance infusions: Mechanisms and prevention

Clinical and pharmacokinetic data were reviewed in 72 patients who developed excessive lidocaine serum levels during maintenance infusions. Fifty-one of the 72 (70%) were cardiac patients who had mean lidocaine excretory clearances less than one half of normal. Forty percent of these became toxic in spite of a reduced infusion rate (30 micrograms/kg/min). Seven patients with normal excretory mechanisms became toxic when they received large doses of lidocaine. The remaining 14 cases lacked an identifiable cause to explain the development of higher than therapeutic serum levels. Inordinately high serum levels of monoethylglycinexylidide (MEGX), an active lidocaine metabolite, were found in seven patients, but in only one was MEGX greater than lidocaine. Prolonged infusions (24 hours or greater) were not clearly associated with the worst lidocaine elimination clearances. Lidocaine toxicity was life-threatening or significantly complicated the management of 15 patients. Based on the data presented, guidelines are offered as an approach to the prevention of toxicity from maintenance lidocaine infusions.

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.

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.

Reassessment of the assumed A-V oxygen content difference in the shunt calculation.

A study was undertaken in 15 patients to compare measured and assumed arteriovenous oxygen (A-V O2) content differences and their effects on resultant shunt calculations. All patients were on volume ventilators and demonstrated a stable cardiovascular state. Simultaneous measurements of the O2 content of a pulmonary artery (PA) and of a superior rena cava (SVC) sample were compared. A mean A-V O2 content difference of 3.5 ± 0.8 volumes percent was obtained from the PA and 2.6 ± 1.1 volumes percent from the SVC. The resultant shunt calculations derived from measured A-V O2 content differences were compared with the calculation based on an assumed A-V O2 content difference of 5 volumes percent. A method for extrapolating a “true” A-V O2 content difference from an SVC blood sample was obtained. The extrapolated value resulted in a more representative “true shunt” calculation in 13 of the 15 patients.