Thomas F. Imperiale

Do corticosteroids reduce mortality from alcoholic hepatitis? A meta-analysis of the randomized trials

PURPOSEnTo determine whether corticosteroids affect short-term mortality from alcoholic hepatitis.nnnDATA IDENTIFICATIONnStudies published from 1966 to 1989 were identified through a MEDLINE computer search and an extensive manual search of the bibliographies of identified articles.nnnSTUDY SELECTIONnWe found 11 randomized studies (10 of which were placebo controlled) that assessed mortality in hospitalized patients diagnosed with acute alcoholic hepatitis and treated with corticosteroids.nnnDATA EXTRACTIONnTwo critical appraisers independently evaluated trial quality and abstracted quantitative data on clinical characteristics of the populations, interventions, and all-cause mortality.nnnRESULTS OF DATA SYNTHESISnOverall, the protective efficacy (or percent reduction in mortality) of corticosteroids was 37% (95% CI, 20% to 50%). Protective efficacy was higher among trials with higher quality scores and trials that excluded subjects with active gastrointestinal bleeding. In subjects with hepatic encephalopathy, protective efficacy was 34% overall (CI, 15% to 48%). It was also higher among trials with higher quality scores and trials excluding subjects with acute gastrointestinal bleeding, but was not present among trials with lower quality scores or trials that did not exclude subjects with acute gastrointestinal bleeding. In subjects without hepatic encephalopathy, corticosteroids had no protective effect, and this lack of efficacy was consistent across all trial subgroups.nnnCONCLUSIONSnThese results suggest that corticosteroids reduce short-term mortality in patients with acute alcoholic hepatitis who have hepatic encephalopathy, that the protective effect depends on the exclusion criterion of acute gastrointestinal bleeding and is influenced by trial quality, and that corticosteroids are of no benefit in patients without hepatic encephalopathy.

A meta-analysis of somatostatin versus vasopressin in the management of acute esophageal variceal hemorrhage

BACKGROUND & AIMSnAlthough sclerotherapy is the current standard therapy for bleeding esophageal varices, the best method for initial control is unclear. The aim of this meta-analysis was to compare the efficacy and toxicity of somatostatin and vasopressin in short-term treatment of hemorrhage from esophageal varices.nnnMETHODSnUsing MEDLINE, all randomized trials comparing somatostatin with vasopressin in subjects with endoscopically documented acute esophageal variceal bleeding were identified. The quality of each study was critically and independently evaluated, and quantitative data for initial cessation of bleeding, sustained control of bleeding, and major adverse effects were abstracted. The relative risk (RR) and number needed to be treated were calculated.nnnRESULTSnThe RR or likelihood of achieving initial control of bleeding with somatostatin vs. vasopressin was 1.62 (95% confidence interval [CI], 1.37-1.93), and the number needed to be treated was 3.7, i.e., between 3 and 4 patients would have to be treated with somatostatin for 1 patient to derive additional benefit over vasopressin. For trials that measured sustained control of bleeding, somatostatin was superior to vasopressin (RR, 1.28 [95% CI, 1.00-1.65]; number needed to be treated, 8.8). The risk of adverse effects was greater for subjects given vasopressin (10% vs. 0%; P = 0.00007).nnnCONCLUSIONSnThis meta-analysis suggests that somatostatin is more efficacious in controlling acute hemorrhage from esophageal varices and has a lower risk of adverse effects than vasopressin.

Use of the alveolar-arterial oxygen gradient in the diagnosis of pulmonary embolism

BACKGROUNDnArterial blood gas (ABG) values and the alveolar-arterial oxygen (A-a) gradient are sensitive indicators of pulmonary pathology. Alone, they are not diagnostic of pulmonary embolism (PE), but they may be useful in excluding the diagnosis of PE if their values fall within the normal range. The purpose of this study was to determine the diagnostic value of a normal A-a gradient in ruling out PE.nnnPATIENTS AND METHODSnThe Derivation Set came from the records of all patients at Cleveland MetroHealth Medical Center who received a ventilation/perfusion (V/Q) scan for suspected PE in 1988 or 1989. Demographic and clinical data were obtained that included risk factors, symptoms, signs, and laboratory tests. A-a gradients were calculated using a standard equation; a normal gradient was defined as less than or equal to (age/4 + 4). The A-a gradient was examined before and after controlling for PE risk factors. The Validation Set was comprised of patients who had V/Q scans in 1987 and 1990.nnnRESULTSnAmong the 873 patients in the Derivation Set, 540 had simultaneous room air ABG determinations. Of these patients, 109 (20%) had a discharge diagnosis of PE. Only 1 of 57 (1.8%; 95% confidence interval [CI]: 0.9%-10.7%) patients without a history of PE or deep venous thrombosis (DVT) and with a normal A-a gradient had PE. Among the 805 V/Q patients in the Validation Set, 489 had simultaneous room air/ABG determinations. Of these, 75 (15%) had PE. Only 1 of 54 (1.9%; 95% CI: 0.1%-11.2%) patients without a history of PE or DVT and with a normal A-a gradient had PE.nnnCONCLUSIONSnA normal A-a gradient among patients without a history of PE or DVT makes the diagnosis of PE unlikely. Further diagnostic evaluation may be unnecessary in this subgroup of patients.

The acute effect of phenylpropanolamine and brompheniramine on blood pressure in controlled hypertension - A randomized double-blind crossover trial

Study objective:To determine the acute effect of phenylpropanolamine, 75 mg, and brompheniramine, 12 mg, in combination (PPA/B) on blood pressure in patients with controlled hypertension, using ambulatory blood pressure monitoring (ABPM).Design:Randomized double-blind crossover trial.Setting:Outpatient clinic at one medical center.Participants:13 healthy volunteers aged 36 to 64 years, receiving medication for hypertension.Interventions:Following 24-hour baseline ABPM, participants were randomized to receive either placebo or PPA/B every 12 hours for three doses, while ABPM continued. After a 24-hour washout period, all participants received the crossover regimen.Measurements and main results:No clinically important or statistically significant difference was noted for mean systolic and diastolic blood pressures during the baseline (125/75), PPA/B (127/72), and placebo (126/73) phases of the study. Within the first four hours of treatment, the mean change in systolic blood pressure from baseline between PPA/B and placebo phases was 1.7 mm Hg (95% CI −5.3 to 8.7), and mean change in diastolic blood pressure was 0.9 mm Hg (95% CI −1.6 to 3.5), excluding a first-dose pressor effect.Conclusion:When used as recommended, PPA/B, a commonly used over-the-counter cold medication, has no significant acute effect on blood pressure in patients with controlled hypertension.

Review: β-Blockers reduce first-time variceal hemorrhage but do not improve 2-year mortality

Source Citation Poynard T, Cales P, Pasta L, et al. Beta-adrenergic-antagonist drugs in the prevention of gastrointestinal bleeding in patients with cirrhosis and esophageal varices. An analysis of...