Severe yellow fever in Brazil: clinical characteristics and management

Background: Little is known about clinical characteristics and management of severe yellow fever as previous yellow fever epidemics often occurred in times or areas with little access to intensive care units (ICU). We aim to describe the clinical characteristics of severe yellow fever cases requiring admission to the ICU during the 2018 yellow fever outbreak in Sao Paulo, Brazil. Furthermore, we report on preliminary lessons learnt regarding clinical management of severe yellow fever. Methods: Retrospective descriptive cohort study. Demographic data, laboratory test results on admission, clinical follow-up, and clinical outcomes were evaluated. Results: From 10 January to 11 March 2018, 79 patients with laboratory confirmed yellow fever were admitted to the ICU in a tertiary hospital in Sao Paolo because of rapid clinical deterioration. On admission, the median AST was 7,000 IU/L, ALT 3,936 IU/L, total bilirubin 5.3 ml/dL, platelet 74 x 10(3)/mm(3), INR 2.24 and factor V 37%. Seizures occurred in 24% of patients, even without substantial intracranial hypertension. The high frequency of pancreatitis and rapidly progressive severe metabolic acidosis were notable findings. 73% of patients required renal replacement therapy. The in-hospital fatality rate was 67%. Patients with diabetes mellitus had a higher case fatality rate (CFR) of 80%, while patients without diabetes had a CFR of 65%. Leading causes of death were severe gastrointestinal bleeding, epileptic status, severe metabolic acidosis, necrohemorrhagic pancreatitis, and multiorgan failure. Conclusions: Severe yellow fever is associated with a high CFR. The following management lessons were learnt: Anticonvulsant drugs in patients with any symptoms of hepatic encephalopathy or arterial ammonia levels >70 mu mol/L was commenced which reduced the frequency of seizures from 28% to 17%. Other new therapy strategies included early institution of plasma exchange. Due to the high frequency of gastric bleeding, therapeutic doses of intravenous proton pump inhibitors should be administered.