Saul S. Bloomfield

Unreliability of conventional electrocardiography monitoring for arrhythmia detection in coronary care units

To evaluate the reliability of conventional coronary care unit electrocardiographic monitoring, a study was made of 31 consecutive patients with uncomplicated verified acute myocardial infarction. All patients were monitored routinely with conventional equipment, and at the same time the electrocardiogram for each patient was recorded continuously on electromagnetic tape and stored for later analysis by an automated arrhythmia detection system. All patients studied were within 24 hours of the onset of chest pain and on entry into study all were free of shock, heart block, bundle branch block, severe heart failure or an existing arrhythmia. By conventional monitoring, premature ventricular contractions were recognized in 64.5 percent of patients compared with 100 percent using the automated detection system (P <0.01). The corresponding percentages for recognition of premature atrial contractions were 45.2 vs. 96.8 percent (P < 0.001); serious ventricular arrhythmias, 16.1 vs. 93.5 percent (P <0.001); multifocal premature ventricular contractions, 6.5 vs. 87.1 percent (P < 0.001); and consecutive premature ventricular contractions, 13.0 vs. 77.5 percent (P < 0.001), respectively. The delay from the time of first occurrence as detected by the automated system to recognition by the conventional monitoring system averaged 18 hours for premature ventricular contractions, 10 hours for serious ventricular arrhythmias and 23 hours for premature atrial contractions. The on-line use of an automated arrhythmia detection system in the coronary care unit is suggested if further improvement in the elimination of arrhythmias as a primary cause of death after myocardial infarction is to be achieved. The presence of serious ventricular arrhythmias in virtually all patients after myocardial infarction suggests that prophylactic antiarrhythmic agents be used in this setting; however, none of the presently available antiarrhythmic agents have been shown to reduce mortality when given prophylactically following myocardial infarction.

Comparative efficacy of ibuprofen and aspirin in episiotomy pain.

Substitutes for aspirin devoid of troublesome effects are needed. A potential candidate, ibuprofen, heretofore marketed outside the United States as an antiarthritic, was compared in single oral doses of 300 and 900 mg with aspirin, 900 mg, and placebo in a parallel balanced randomized double‐blind design in 80 patients with pain due to episiotomy. Over the 6 hours of evaluation, there was pain reduction greater than 50 per cent in 17 of 20 patients treated with either dose of ibuprofen (p < 0.01), in 18 of 20 patients treated with aspirin (p < 0.001), and in only 6 of 20 patients treated with placebo. With the two doses of ibuprofen, pain relief, as measured by pain intensity differences (PID) was similar to that with aspirin with respect to time of onset, degree and duration of analgesia. Reported side effects with ibuprofen were insignificant.

TRANSCENDENTAL MEDITATION IN HYPERTENSION: Individual Response Patterns

Seven selected hypertensive patients were stabilized on drugs at a research clinic. Subjects learned transcendental meditation (T.M.), were seen weekly, and took their own blood pressure several times daily. After 12 weeks of T.M. six subjects showed psychological changes and reduced anxiety scores. Six subjects also showed significant reductions in home and four in clinic blood-pressures. Six months later four subjects continued to derive psychological benefit and two showed significant blood-pressure reductions attributable to T.M. at home and clinic.

Naproxen, aspirin, and codeine in postpartum uterine pain

The analgesic efficacy of oral naproxen and its sodium saft was compared with that of aspirin and codeine in two separate trials involving 140 and 90 patients, respectively, with postpartum uterine pain in a single‐dose, parallel, stratified, randomized, placebo‐controlled, double‐blind design. With 300 or 600 mg naproxen and with 275 mg naproxen sodium, significant analgesia, measured subjectively by pain intensity differences (PID), was prolonged at least 7 or 8 hr; onset tended to be delayed 2 hr or more. With 650 mg aspirin analgesia began within 1 hr and continued until the fifth hour, while with 60 mg codeine responses were indistinguishable fram placebo responses throughout the 8‐hr time course. Although time‐effect patterns with naproxen sodium and aspirin were different, summed analgesic effects (SPID) showed equal efficacy and superiority over placebo (p < 0.005). With each of the 2 doses of naproxen, SPID separation from placebo was comparable to that above (p < 0.02 and 0.005, respectively), but analgesic dose response, though measurable, was not significant. Side effects were not significant with any of the treatments. It appears that naproxen and naproxen sodium are analgesics with efficacy equal to aspirin and may prove to be rational substitutes for currently available analgesics in some painful states in which longer pain relief would be desireable.

Aspirin and codeine in two postpartum pain models

Aspirin and codeine, standard reference analgesics, are frequently used as positive controls in clinical trials of new oral analgesics. In randomized parallel double‐blind studies, single doses of aspirin and codeine were compared with placebo in episiotomy pain (99 patients) and in postpartum uterine pain (130 patients), common models in analgesic trials. With aspirin, 600 and 1,200 mg, in episiotomy pain, analgesia as measured by pain intensity difference (PID) scores began within 1 hr, peaked at the second hour (p < 0.01), and continued to the fifth hour (p < 0.01). In uterine pain, responses with aspirin, 650 mg, were observed to be equally good. With codeine, 60 mg, in episiotomy pain measurable analgesia was present by the second hour and was significant at the fourth hour (p < 0.05); in uterine pain, responses were indistinguishable from placebo throughout an 8‐hr time‐course. Codeine seemed ineffective and therefore unacceptable as a positive control in uterine pain. These data imply that the two postpartum pain models are qualitatively different: episiotomy pain seems sensitive to both aspirin alld codeine, while uterine pain appears sensitive to aspirin but not to codeine.

Evaluation of Bretylium Tosylate for the Treatment of Premature Ventricular Contractions

In a controlled setting bretylium tosylate was evaluated for efficacy, toxicity, onset, and duration of action in eight patients with frequent premature ventricular contractions (PVC). Four patients received a single im dose of bretylium, 4 mg/kg, with before and after control days; the other four patients received bretylium, 2 and 4 mg/kg, on different days with before and between control days. PVC were quantified from stored continuous ECG tape recordings by an automated arrhythmia-detection system. Five patients had 50% or more reduction of PVC frequency with bretylium 4 mg/kg, and one with 2 mg/kg. Bretylium 4 mg/kg but not 2 mg/kg reduced mean PVC frequency by half beginning at the sixth hour and continuing for 12 hours. Hypotension began within 1 hour. Maximum fall in mean supine blood pressure was 17/6 mm Hg with 2 mg/kg, and 25/12 mm Hg with 4 mg/kg. Plasma bretylium concentration was maximum at about 1 hour with a mean elimination half-life of 10 hours. A controlled quantitative method for evaluation of antiarrhythmic drugs in man demonstrated that bretylium can be effective in suppressing PVC frequency. The dissociation between hypotensive and antiarrhythmic effects of bretylium suggested that its antiarrhythmic effect was independent of adrenergic neuronal blockade.

Multicenter clinical evaluation of long-term efficacy and safety of labetalol in treatment of hypertension

The long-term efficacy and safety of labetalol, an antihypertensive agent with combined beta- and alpha-blocking activity, were evaluated alone (number = 193) and in combination with a diuretic (number = 144) in an open-label multicenter trial of 337 hypertensive patients aged 21 to 75 years, including initially 205 (61 percent) men and 219 (65 percent) Caucasians. There were 219 (65 percent) mild, 85 (25 percent) moderate, and 33 (10 percent) severe hypertensive patients. Labetalol (100 to 1,200 mg twice a day) alone or in combination with a diuretic reduced the mean standing blood pressure by 13/11 and 25/16 mm Hg to 135/88 and 130/91 mm Hg, respectively (p less than 0.01), and supine blood pressure by 6/7 and 18/13 mm Hg to 141/86 and 138/90 mm Hg (p less than 0.01), respectively. Blood pressure reductions observed at one month were maintained after one year; 206 (62 percent) patients had 10 mm Hg or greater reductions and 184 (56 percent) patients were maintained at diastolic blood pressures less than 90 mm Hg. Most frequently reported drug-related side effects included fatigue (14 percent), dizziness (12 percent), nausea (11 percent), nasal stuffiness (8 percent), headache (4 percent), and male sexual dysfunction (14 percent). Side effects were generally of mild to moderate intensity and often transient. In addition, in 27 (8 percent) patients reversible asymptomatic transaminase elevations to greater than twice normal developed at some time during the study. In 13 (4 percent) patients these alterations resolved during continued labetalol therapy, but in five (2 percent) patients these marked elevations led to discontinuation of the drug. A total of 32 (9.5 percent) patients were terminated prematurely due to side effects (most commonly genitourinary or gastrointestinal) possibly attributable to the drug. These findings indicate that labetalol with or without a diuretic is a potentially effective, safe, and relatively well-tolerated long-term antihypertensive therapy.

Nefopam and propoxyphene in episiotomy pain.

To evaluate relative efficacy, safety, and time course of analgesia, nefopam (45 and 90 mg), a new centrally acting nonnarcotic analgesic, was compared with propoxyphene (65 mg) and placebo in a single oral dose, parallel, stratified, randomized, double‐blind trial with 100 hospitalized postpartum women with medium or severe episiotomy pain. Using subjective reports as indices of response, patients rated pain intensity and side effects at periodic interviews for 6 hr. After 45 and 90 mg nefopam, 21 of 25 and 20 of 25 patients (p < 0.01) reported more than 50% reduction of pain, whereas after 65 mg propoxyphene 18 of 25 (p < 0.05) and after placebo 11 of 25 reported reduction in pain. Relative efficacy, based on summed pain intensity differences, showed measurable but modest dose‐dependent analgesia with nefopam, suggesting that the effectiveness of 65 mg propoxyphene lay between 45 mg nefopam and placebo. Side effects included mild dizziness and hypothermia after nefopam and mild elevation of diastolic arterial pressure after nefopam and propoxyphene. Our results suggest that 45‐ and 90‐mg doses of nefopam induced more analgesia than 65 mg propoxyphene in the relief of episiotomy pain.

Metkephamid and meperidine analgesia after episiotomy

Metkephamid is an analog of methionine enkephalin. The efficacy, safety, and time course of analgesia with 70 or 140 mg metkephamid were compared with those of 100 mg meperidine and placebo in 59 hospitalized women with severe postpartum episiotomy pain. There were two separate trials with single intramuscular doses and identical designs, including parallel groups, randomized blocks, and double‐blind conditions. Using subjective reports as indexes of response, patients rated pain intensity, pain relief, and side effects at periodic interviews for 6 hr. Almost all measures of summed and peak analgesia exhibited important differences among the three treatments in both trials. Metkephamid at the 140‐mg dose was the most effective and meperidine, 100 mg, was next, whereas metkephamid, 70 mg, and placebo were least effective. Only metkephamid, 140 mg, and meperidine were measurably superior to placebo. Both treatments took effect within 30 min and peaked at 1 to 2 hr; with 140 mg metkephamid, maximum analgesia was sustained 6 hr, i.e., 2 hr longer than with meperidine. Metkephamid, 70 mg, could not be distinguished from placebo throughout its entire time course. Although dizziness was experienced with meperidine, the two metkephamid doses induced other side effects, including sensation of heavy limbs, dry mouth, eye redness, and nasal stuffiness. None were distressing. Our results suggest that 140 mg metkephamid compares favorably with 100 mg meperidine for analgesia after episiotomy, but it induces minor side effects more frequently.

Flurbiprofen, aspirin, codeine, and placebo for postpartum uterine pain

Flurbiprofen (Ansaid, Upjohn), a substituted phenyl propionic acid, is a new analgesic/anti-inflammatory agent. To evaluate its relative efficacy in noninflammatory pain, 159 hospitalized women with moderate or severe postpartum uterine cramps were given single oral doses of 50 mg of flurbiprofen, 650 mg of aspirin, 60 or 120 mg of codeine sulfate, or placebo in a parallel, stratified, randomized block, placebo-controlled, double-blind trial. Patients rated pain intensity, pain relief, and side effects in uniform interviews for six hours after treatment. All measures of peak and summed analgesia exhibited significant differences among the five treatments. Flurbiprofen and aspirin showed the greatest analgesic response and were significantly superior to placebo. Results of codeine treatment were equivocal with no evidence of a positive dose response. Side effects were unremarkable except for dizziness and drowsiness after the 120-mg codeine dose. These findings suggest that flurbiprofen as an analgesic for patients with postpartum uterine pain is equivalent to aspirin and superior to codeine.