Prevention of venous thromboembolism: adherence to the 1995 American College of Chest Physicians consensus guidelines for surgical patients.

BACKGROUND: The American College of Chest Physicians addressed the dilemma of identifying optimal therapy for venous thromboembolism (VTE) prophylaxis and published their Fourth Consensus Conference on Antithrombotic Therapy in 1995, with recommendations for prophylactic therapy. Despite these recommendations, appropriate VTE prophylactic therapy is underused. OBJECTIVES: To examine routine practices in the prevention of VTE in high-risk surgical patients and to determine the extent of adoption of grade A prophylactic therapies as recommended by the American College of Chest Physicians. METHODS: Retrospective medical record review in 10 teaching or community-based hospitals located in the United States. Medical charts of 1907 patients were randomly selected for review from the population of patients who underwent high-risk major abdominal surgery, total hip replacement, hip fracture repair, or total knee replacement between January 1, 1996, and February 28, 1997. RESULTS: Of 1907 patients, VTE prophylaxis was used in 89.3%; use was 93.7% in each of the 3 orthopedic surgery groups and 75.2% in the high-risk major abdominal surgery group. The percentage of patients receiving grade A therapy was highest in the hip replacement group (84.3%) vs. the other groups (knee replacement, 75.9%; hip fracture repair, 45.2%; abdominal surgery, 50.3%). CONCLUSIONS: The use of grade A prophylaxis was related to the type of surgery, with the highest use seen in total hip replacement and the lowest in hip fracture repair. One in 4 patients who underwent high-risk major abdominal surgeries failed to receive any form of VTE prophylaxis. Publication of consensus statements alone may be insufficient to ensure the incorporation of important new clinical information into routine practice.

Chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease is indeed a multifaceted illness. The obstructive picture is the result of multiple pathologic processes. The most common cause is cigarette smoking. The key to decreasing the incidence of this disease is education to prevent people from starting to smoke and to educate those who do smoke to stop. The therapeutic management involves numerous medications, oxygen, and physiotherapy. Unfortunately, the pharmacologic management remains largely empiric with sympathomimetics, anticholinergics, methylxanthines, and corticosteroids. These agents, especially methylxanthines and corticosteroids, are not without considerable toxicity. Therefore, embarking on a pharmacologic plan requires weighing the risk to benefit ratio carefully and having a comprehensive plan to assess subjectively and objectively the efficacy and toxicity of the chosen therapy.

Short-course drug therapy for tuberculosis.

The cost, patient compliance considerations, and toxicity of short-course chemotherapy (SCC) and conventional 18- to 24-month treatment regimens for pulmonary tuberculosis are compared; studies of the efficacy of SCC regimens are evaluated; and the future of SCC in the United States is examined. SCC is defined as treatment for nine months or less. A definite advantage of SCC over conventional therapy in terms of cost, patient compliance, or adverse effects has not been established. A series of studies conducted by the East African-British Medical Research Council documented the efficacy of various six-month, multiple-drug regimens that contain rifampin and verified the sterilizing activity of pyrazinamide during the first two months of therapy. The studies of the Hong Kong Chest Service and British Medical Research Council documented the efficacy of several intermittent drug regimens. Acceptable relapse rates were achieved with streptomycin, isoniazid, and pyrazinamide given two or three times a week for four or six months, preceded by a two-month, multiple-drug, daily regimen, and various four-drug, pyrazinamide-containing intermittent regimens. The benefit of pyrazinamide in reducing the relapse rate with SCC was confirmed by studies of the British Thoracic and Tuberculosis Association. Few studies of SCC have been conducted in the United States. Treatment practices in the United States are becoming more uniform, and SCC is being used more frequently for uncomplicated pulmonary tuberculosis. SCC will probably be used more widely in the future. Current guidelines of the Centers for Disease Control recommend treatment for nine months with isoniazid and rifampin, plus ethambutol in areas where resistance to isoniazid is common. In vitro data suggest that the addition of pyrazinamide may be more effective, but clinical experience with this drug in the United States is limited.

Drug-induced systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) induced by drugs, primarily hydralazine and procainamide, is reviewed and compared with idiopathic SLE, and the use of these drugs in patients with idiopathic SLE is discussed. The etiology of SLE is unclear, but genetic predisposition is an important factor. Although more than 25 drugs have been suggested as causes of SLE, the majority of confirmed cases of drug-induced SLE involve hydralazine or procainamide. Parts of these chemical compounds apparently interact with nucleoproteins, causing stimulation of antinuclear antibody (ANA) production. The average age of patients with drug-induced SLE is nearly twice that of patients with idiopathic SLE. Approximately half the patients with drug-induced SLE are women, compared with 92% of patients with idiopathic SLE. For SLE induced by hydralazine or procainamide, musculoskeletal symptoms (especially arthritis in the hands and wrists) are the most common clinical manifestation. In patients with SLE induced by these drugs, ANAs and LE cells are present, erythrocyte sedimentation rate is often elevated, and a false-positive serologic test for syphilis is seen more frequently than in idiopathic SLE. Baseline ANA status should be determined before therapy with these drugs, and patients should be observed carefully for signs and symptoms of SLE. Hydralazine-induced SLE may be dose related; limiting the daily dose to 200 mg is recommended. Some drugs have been shown to exacerbate idiopathic SLE; these include estrogen-containing oral contraceptives and ibuprofen. Hydralazine and procainamide are probably safe for use in patients with idiopathic SLE, but alternative therapy should be considered. The clinical and laboratory manifestations of drug-induced SLE are similar to those of idiopathic SLE, but central nervous system and renal involvement are rare in drug-induced SLE.

Use of nitrates in patients with acute myocardial infarction.

The use of nitrates in treating acute myocardial infarction is reviewed; proposed mechanisms of action and pertinent pathophysiology are discussed. Oral and sublingual nitrates were first tested in acute myocardial infarction patients with mixed results. Later studies with sublingual nitroglycerin followed by phenylephrine infusion indicated that nitrates were effective in limiting myocardial ischemia and necrosis. I.V. nitroglycerin was then studied; beneficial results were documented by quantifying ECG changes and visualizing the areas of myocardial necrosis with radioisotopes. Mortality was also reduced in nitrate-treated patients. Patients who developed left ventricular failure after acute myocardial infarction benefitted the most from nitrate therapy. The preferred route of nitroglycerin administration is intravenous infusion. The dose is initially 5 micrograms/min and is increased by 5-10 micrograms/min every 5-10 minutes until mean arterial pressure is reduced 10-20% or pulmonary capillary wedge pressure is reduced to 15 mm Hg. Final infusion rates average 40-60 micrograms/min. Nitrates appear to have a role in reducing morbidity and mortality from acute myocardial infarction.

Antihypertensive effect of hydrochlorothiazide administered once or twice daily.

The antihypertensive effect of once and twice daily hydrochlorothiazide administration was compared in 24 ambulatory patients with essential hypertension. Hydrochlorothiazide 100 mg daily taken as a single morning dose or as a twice daily divided dose was administered to 24 previously diagnosed hypertensive patients in a double-blind cross-over fashion for 12 weeks. No patient received other antihypertensive agents or medications known to influence blood pressure. Sitting and standing blood pressure, weight, pulse, tablet count, and subjective complaints of side effects were obtained at study weeks 3 and 6 on each treatment schedule. There was no significant difference between the mean sitting systolic (133 and 131 mm Hg) or diastolic (85 and 84 mm Hg) blood pressure measurements at study weeks 3 and 6 for each treatment schedule. Comparison of standing mean systolic and diastolic blood pressure and mean arterial pressure produced similar results. Subjective complaints of medication side effects, including orthostasis or urinary frequency, did not differ between treatment schedules. This study suggests that hydrochlorothiazide may be effectively administered once daily for the treatment of hypertension.

Effect of antacids on phenytoin bioavailability.

Eight subjects were studied in a randomized crossover design to determine the effect of aluminum-magnesium hydroxide (AMH), calcium carbonate (CC), and aluminum hydroxide-magnesium trisilicate (AHMT) on the bioavailability of a single, 600-mg dose of phenytoin administered orally. Each subject received phenytoin alone on two separate occasions and phenytoin plus each of the three antacids on three other occasions. Each antacid was administered as 160 mEq at 1 and 3 hr after each meal and at bedtime on the day phenytoin was given. The mean area under the curve (AUC) was significantly decreased by AMH (p less than 0.005) and CC (p less than 0.05). AHMT had a similar trend but did not reach statistical significance (p = 0.1). Large inter- and intrasubject variability in AUC was observed when phenytoin was administered alone. In two subjects, cumulative urinary 5-(4-hydroxyphenyl)-5-phenylhydantoin at 72 hr (HPPH72) was determined. The amount of HPPH recovered had similar trends as the AUC with antacid treatments but not the same magnitude. In this study, antacids altered not only the extent of absorption but also appeared to alter the rate of absorption. Antacids administered in a peptic ulcer regimen may decrease the AUC of a single dose of phenytoin. Patients should be cautioned against concomitant use of antacids and phenytoin.

Hypertensive crisis and phencyclidine abuse.

This report of a case in Virginia suggests linkage between the abuse of a "street drug" by a young woman and an acute episode of hypertension resulting in coma and blindness. The authors warn of the potential dangers of phencyclidine and describe its mechanisms.