Objectives

The purpose of this study was to evaluate the effectiveness of a dexamethasone regimen with decreasing dosage over time at reducing hospitalization and recovery time in people with sickle cell disease and acute chest syndrome.

Background

Sickle cell disease (SCD) is an inherited blood disorder. Symptoms include anemia, infections, organ damage, and intense episodes of pain, which are called "sickle cell crises." Acute chest syndrome (ACS) is a life-threatening, lung-related complication of SCD that can lower the level of oxygen in the blood. Repeat occurrences of ACS can cause lung damage. It is the second most common cause of hospitalizations among people with SCD and accounts for more than 25% of premature deaths in people with SCD. Symptoms of ACS include fever, chest pain, cough, and breathing difficulties. ACS can appear suddenly and often requires immediate hospitalization and treatment, including antibiotics, supplemental oxygen, and blood transfusions. Previous studies have shown that dexamethasone, a type of steroid medication that blocks inflammation, can decrease hospitalization time for people with ACS; however, some participants in these earlier studies were re-hospitalized due to new sickle cell pain. Slowly decreasing the dosage of dexamethasone over time may decrease the chance that new sickle cell pain will occur. This study was initiated to evaluate hospitalization and recovery time in individuals with SCD and ACS receiving a dexamethasone regimen with decreasing dosage over time.

Participants

Eligible participants had a diagnosis of sickle cell anemia (Hgb SS) or sickle-β0-thalassemia (Hgb Sβ0), along with an episode of ACS diagnosed within 24 hours prior to study entry. ACS was defined as a new lobar or segmental pulmonary infiltrate observed on a chest radiograph, accompanied by at least two of the following findings: a temperature of 38.5°C or higher, tachypnea, dyspnea or increased work of breathing, chest wall pain, or oxygen saturation below 90% on room air as measured by pulse oximetry. Exclusion criteria included the presence of any medical condition likely to be worsened by corticosteroid therapy, recent corticosteroid use, or a chronic lung condition.

A total of 12 participants were enrolled (9 children and 3 adults). 6 were randomized to receive dexamethasone and 6 were randomized to receive placebo.

Design

Eligible participants were randomly assigned to receive either dexamethasone (0.3 mg/kg [12 mg maximum single dose]) or placebo. Participants, investigators, and outcome accessors were blinded to treatment assignments. The study drug was given by mouth every 12 hours until discharge from the hospital or for a maximum of 4 doses (2 days), whichever occurred first. Thereafter, study drug was tapered over 6 days for a total duration of therapy not to exceed 8 days. While in the hospital, participants received usual care for ACS, including antibiotics, pain control medication, intravenous fluids, and other needed treatments. Each day, participants underwent a physical exam, a pain assessment score, a test to measure the oxygen level in the body, blood collection, and, if needed, a chest x-ray. Vital signs and blood pressure measurements were taken every 4 hours. Study staff documented the amount of pain medication, blood transfusions, oxygen, and breathing treatments participants received. Upon leaving the hospital, follow-up visits occurred 1 week after participants were originally admitted to the hospital (participants who were still hospitalized at this time did not attend this visit) and 1 month after hospital discharge. At both visits, information on hospital visits for pain treatment and blood transfusions were collected, and evaluations performed earlier in the study were repeated. The second visit also included lung function tests. The study was terminated early because of slow accrual.

The primary outcome was duration of signs and symptoms of ACS or duration of hospitalization, whichever was less.

Conclusions

In individuals with sickle cell disease and acute chest syndrome, a dexamethasone regimen with decreasing dosage over time decreased duration of hospitalization by 20.8 hours compared to placebo.

Quinn CT, Stuart MJ, Kesler K, et al. Tapered oral dexamethasone for the acute chest syndrome of sickle cell disease. Br J Haematol. 2011;155(2):263-267. doi:10.1111/j.1365-2141.2011.08827.x

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