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Adverse Effects of Ribavirin and Outcome in Severe Acute Respiratory Syndrome^*

Experience in Two Medical Centers

Hsueh-Erh Chiou, MS; Ching-Lung Liu, MD; Mary Jeanne Buttrey, MD; Han-Pin Kuo, MD; Hui-Wen Liu, MS; Hsu-Tah Kuo, MD, FCCP and Yen-Ta Lu, MD, PhD

^* From the Pharmacy Department (Ms. Chiou and Ms. H.-W. Liu), the Division of Chest Medicine, Department of Internal Medicine (Drs. C.-L. Liu and H.-T. Kuo), and the Department of Internal Medicine (Dr. Buttrey), Mackay Memorial Hospital, Taipei, Taiwan; the Department of Respiratory Care (Dr. Lu), Taipei Medical University, Taipei, Taiwan; and the Department of Thoracic Medicine II (Dr. H.-P. Kuo), Chang Gung Memorial Hospital, Linkou, Taiwan. Principal coinvestigators who jointly wrote this report.

Correspondence to: Yen-Ta Lu, MD, PhD, Division of Chest Medicine, Department of Internal Medicine, Mackay Memorial Hospital, 92, Sec 2, Chung-Shan North Rd, Taipei, 10449, Taiwan; e-mail: ytlhl{at}ms2.mmh.org.tw

Study objectives: To assess the effect of ribavirin-induced anemia on the outcome of severe acute respiratory syndrome (SARS).

Design: A retrospective observational study.

Setting: Two medical centers in Taiwan.

Patients: Forty-four patients with SARS who received ribavirin and 7 patients with SARS who did not receive ribavirin.

Measurements and results: The mean peak C-reactive protein and lactate dehydrogenase levels were higher in SARS patients who were receiving ribavirin therapy than in SARS patients who were not receiving ribavirin therapy. The mortality was also higher, but the difference was not statistically significant. On multivariate analysis, hemoglobin level was an independent prognostic correlate of hypoxemia or mortality (odds ratio, 2.0; 95% confidence interval, 1.1 to 3.8; p = 0.03). The hemoglobin began decreasing in two thirds of SARS patients (32 of 44 patients; 73%) who were receiving ribavirin 3 days after therapy with the antiviral drug was started. Patients with a drop in hemoglobin level of > 2 g/dL had a significantly higher mortality rate than the other patients. Hypoxemia developed in one third of SARS patients (17 of 44 patients; 39%) who were receiving ribavirin, all of whom were anemic. Of the 17 hypoxemic patients, 11 (65%) had a drop in hemoglobin of > 2 g/dL, and 4 patients (24%) required a blood transfusion. The mean slope of the hemoglobin decrease was significantly steeper (p = 0.001) in hypoxemic patients with SARS who were receiving ribavirin than in the nonhypoxemic patients with SARS who were receiving ribavirin. Only one of seven SARS patients (14%) who was not receiving ribavirin became anemic, but this individual was not hypoxemic. Eventually, 5 of 17 hypoxemic and anemic SARS patients (29%) who were receiving ribavirin died. The combination of hypoxia with anemia was thus significantly associated with a higher mortality (p < 0.001).

Conclusions: Hypoxia combined with anemia increased the risk for death in SARS patients. Unless ribavirin can be shown to be effective against SARS-coronavirus, the risk of anemia posed by this drug argues against its use in SARS patients.

Key Words: anemia • hypoxemia • ribavirin • severe acute respiratory syndrome

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