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Severe yellow fever in Brazil: clinical characteristics and management.

BACKGROUND
Previous yellow fever epidemics occurred in times and areas in which intensive care was not available and in conditions with scarce medical support. This report aims to describe the clinical and laboratory findings of a cohort of patients who required admission to an intensive care unit (ICU) during the 2018 yellow fever outbreak in São Paulo, Brazil.


METHODS
Retrospective descriptive cohort study. Demographic data, laboratory test results on admission, clinical follow-up, and clinical outcomes were evaluated. Additionally, new strategies for clinical management are described.


RESULTS
From 10 January to 11 March 2018, 79 patients with laboratory confirmed yellow fever were admitted to intensive care unit (ICU) 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 74x103/mm3, INR 2.24 and factor V 37%. Seizures occurred in 24% of patients, even without substantial intracranial hypertension. It was decided to commence anticonvulsant drugs in patients with any symptoms of hepatic encephalopathy or arterial ammonia levels >70μmol/L. Before this decision was made, 14 of 50 (28%) patients developed seizure. After initiation of prophylactic anticonvulsant therapy, 5 of 29 (17%) patients developed seizures. The high frequency of pancreatitis and rapidly progressive severe metabolic acidosis were notable findings. 73% of patients required renal replacement therapy. New therapy strategies included plasma exchange. Due to the high frequency of gastric bleeding, therapeutic doses of intravenous proton pump inhibitors were administered. The in-hospital fatality rate was 67. Patients with diabetes mellitus had a higher case fatality rate of 80%, while patients without diabetes had a CFR of 65%.


CONCLUSIONS
Severe yellow fever is associated with high mortality; with a higher risk of fatal outcomes in diabetic patients. Leading causes of death were severe gastrointestinal bleeding, epileptic status, severe metabolic acidosis, necrohemorrhagic pancreatitis, and multi-organ failure.