The NIH COVID-19 Treatment Guidelines Panel (the Panel) on June 25, published recommendations on the use of dexamethasone in patients with COVID-19.
In patients with severe COVID-19, an exaggerated systemic inflammatory response, or “cytokine storm, ” can cause significant pulmonary injury and multisystem organ dysfunction. Use of corticosteroids has been proposed to prevent or mitigate the effects of this response. According to a statement from the Panel, results to date from several small, retrospective cohort studies on use of corticosteroids are conflicting, with effects both beneficial* and harmful* reported based on evaluation of short courses of the drugs in COVID-19-infected patients.
Preliminary, unpublished results from the RECOVERY trial, a large, multicenter, randomized, open-label trial for hospitalized patients in the United Kingdom, showed reduced mortality in patients randomized to receive dexamethasone compared to those who received standard of care. The benefit was observed in patients with severe COVID-19 (defined as those who required supplemental oxygen) and was greatest in those who required mechanical ventilation at enrollment. No benefit of dexamethasone was observed in patients who did not require supplemental oxygen at enrollment.
Given the preliminary results, the Panel:
- Recommends using dexamethasone (at a dose of 6 mg per day for up to 10 days) in patients with COVID-19 who are mechanically ventilated (AI) and in patients with COVID-19 who require supplemental oxygen but who are not mechanically ventilated (BI).
- Recommends against using dexamethasone in patients with COVID-19 who do not require supplemental oxygen (AI).
NIH Recommendation Rating Scheme
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II = One or more well-designed, nonrandomized trials or observational cohort studies; III = Expert opinion
Before prescribing dexamethasone for a patient with COVID-19, however, the Panel provides a comprehensive list of Additional Considerations for clinicians to review.
Additional considerations from the NIH COVID-19 Treatment Guidelines Panel
- The results of the RECOVERY trial have not yet been published in a peer-reviewed journal.
- Remdesivir was not part of the treatment in the RECOVERY trial; therefore, the safety and efficacy of coadministering remdesivir and dexamethasone are not known.
- Very few pediatric or pregnant patients with COVID-19 were included in the RECOVERY trial; therefore, the safety and efficacy of using dexamethasone in these patients are unknown.
- It should be noted that in the RECOVERY trial, patients were not enrolled into the dexamethasone study arm (or included in the analysis) if their physicians decided that they were not suitable for corticosteroid therapy for any reason. Before initiating dexamethasone, clinicians should review the patient’s medical history and assess the potential risks and benefits of administering corticosteroids to the patient.
- Clinicians should closely monitor patients with COVID-19 who are receiving dexamethasone for adverse effects (eg, hyperglycemia, secondary infections).
- Using systemic corticosteroids may increase the risk of reactivation of latent infections (eg, hepatitis B virus, herpesviruses, strongyloidiasis, tuberculosis).
- Dexamethasone is a moderate cytochrome P450 (CYP) 3A4 inducer, which may reduce the concentration and potential efficacy of concomitant medications that are CYP3A4 substrates. Clinicians should review a patient’s medication regimens to assess potential interactions.
- At this time, it is not known whether other corticosteroids, such as prednisone, methylprednisolone, or hydrocortisone, will have a similar benefit to dexamethasone. Of note, the dose equivalencies for dexamethasone 6 mg daily are prednisone 38 mg, methylprednisolone 32 mg, and hydrocortisone 160 mg.
- In outbreaks of other novel coronavirus infections (ie, MERS, SARS) corticosteroid therapy was associated with delayed virus clearance.
The Panel may modify these recommendations based on the final published results of this study and the results of other ongoing studies.
*Please see original NIH recommendations for background, information sources.
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