Corticosteroids for Pulmonary Sarcoidosis

MARK H. EBELL, M.D., M.S.

Clinical Question

Do inhaled or oral corticosteroids improve outcomes for patients with pulmonary sarcoidosis?

Evidence-Based Answer

Patients who take oral corticosteroids are more likely to show improvement in their chest radiographs than those taking placebo, although improvements in symptoms and lung function are less certain. The typical dosage used in randomized trials was 20 mg daily or 40 mg every two days tapered over several months.

Practice Pointers

Sarcoidosis is a multisystem disease that often affects the lungs. Pulmonary sarcoidosis is characterized by cough, breathlessness, and progressive respiratory failure. Corticosteroids are the most widely used treatment, but until now, the evidence had not been reviewed systematically. Other treatments, such as methotrexate, antimalarial drugs, cyclosporine (Sandimmune), and the immunomodulator infliximab (Remicade), have been less well studied.1

Paramothayan and associates found 12 randomized controlled trials using different doses and routes of administering corticosteroids. Only two were double-blinded, and only two used adequate concealment of allocation. The 1,051 participants involved in the studies were at various stages of histology-confirmed disease. The studies used a variety of outcomes, primarily symptoms, lung function, and chest radiograph findings. Few data were available for more than two years of follow-up, and none of the studies measured the impact on mortality. In general, studies were small, most with fewer than 50 participants.

Four studies compared oral steroids with placebo, and two compared oral steroids with no treatment. Of the two largest studies, one used a tapering dose of 20 to 10 mg daily and the other a tapering dose of 40 to 20 mg every two days. The researchers found a consistent benefit in terms of improved chest radiograph appearance at the end of follow-up (70 versus 49 percent, P = .04, number needed to treat = 5). However, they found no consistent evidence of symptomatic improvement or improvement in measures of lung function. Comparisons of inhaled steroids with placebo did not show any consistent benefit.

Acute Treatment of Hyperkalemia

Clinical Question

What is the best acute treatment of an elevated serum potassium level?

Evidence-Based Answer

According to disease-oriented evidence, insulin and intravenous glucose, inhaled albuterol (Ventolin), and dialysis are the best treatment options; the first two may be given in combination. Bicarbonate or resins are not recommended for routine use, particularly without one of the more effective agents listed above.

Practice Pointers

Acute treatment of hyperkalemia falls into the still considerable “widely used but little studied” category of medical interventions. No study has reported outcomes that matter to patients, such as the likelihood of death or cardiac arrhythmias. The available literature focuses largely on the ability of interventions to lower serum potassium levels acutely. The Cochrane review by Mahoney and colleagues applies to patients with a significantly elevated potassium level (i.e., greater than 6.5 to 7.0 mEq per L [6.5 to 7.0 mmol per L]).

The researchers identified 12 randomized, quasirandomized, or crossover studies comparing different approaches to the treatment of hyperkalemia. In a quasirandomized study, assignment to treatment groups is based on the day of the week or time of day rather than true randomization, making bias more likely. The crossover studies typically involved a series of interventions in the same small group of hemodialysis patients. Each patient acts as his or her own control, so it is possible to have a much smaller sample size and still obtain statistically significant results. Only four studies used blinding, and only four concealed allocation to treatment groups adequately. Most of the patients studied had acute or chronic renal failure and were receiving hemodialysis.

Nebulized or inhaled albuterol proved effective; a dose of 20 mg was more effective than 10 mg in lowering potassium levels, and both doses were better than placebo. Intravenous albuterol and levalbuterol (Xopenex) were no more effective than inhaled albuterol. The combination of insulin with intravenous glucose was effective, as was dialysis. In one study, the combination of insulin, glucose, and inhaled albuterol was more effective than insulin and glucose alone. Although potassium-binding polystyrene resins such as Kayexalate are widely used, only one study evaluated their effectiveness in the acute setting, and they proved ineffective. Adding bicarbonate to insulin and glucose was helpful in one study but not in another.

A review of the National Guideline Clearinghouse Web site (http://www.guidelines.gov) did not identify any practice guidelines for the management of hyperkalemia. Recommendations from textbooks vary considerably. For example, Griffith’s 5-Minute Clinical Consult 20051 recommends dextrose and insulin, sodium bicarbonate, and polystyrene resins but does not mention inhaled beta agonists.