Outcomes of adult critically ill patients with hemophagocytic lymphohistiocytosis in united states-analysis from an administrative database from 2007 to 2015

Background: Severe infections caused by the novel coronavirus 2 display similarities to secondary hemophagocytic lymphohistiocytosis (HLH). However, HLH is a rare disease and has not been well described in critically ill patients. Methods: We used the Nationwide Inpatient Sample (NIS), the largest all-payer inpatient care database publicly available in the United States to identify all adult discharges with Hemophagocytic syndrome (ICD-9 CM code 288.4) between 2007 and 2015. Critical illness was considered present if patient had either ICD-9 CM code indicating the requirement of invasive mechanical ventilation or the presence of shock. We used ICD-9-CM codes to identify various infections (inf-HLH), malignancies (mal-HLH) and autoimmune diseases associated with HLH (MAS-HLH) and classified them in their respective groups. Primary outcome was in-hospital mortality in critically ill patients. We developed multivariable regression model to examine variables associated with mortality in critically ill HLH patients. P value was kept at < 0.05. Results: Of the 7420 (95% CI 6959-7881) estimated discharges with HLH, 2313 (31%) were critically ill. Of the critically ill patients, 442 (34%) were mal-HLH, 422 (43.3%) were inf-HLH, 403 (30.7%) were MAS-HLH and 1046 (27.3%) were unable to be classified. In hospital mortality rates were 6.4% in non-critically ill and 48.4% in critically ill patients. Among the subtypes of HLH, in-hospital mortality was 53% in mal-HLH, 49.4% in inf-HLH, 26% in MAS-HLH and 54.6% in unclassified group. On multivariable regression analysis, development of acute renal failure requiring hemodialysis (OR 2.06, 95% CI 1.29-3.3, P=0.002) and acute hepatic failure (OR 2.21, 95% CI 1.38-3.52, P=0.001) were significantly associated with higher mortality. Conclusion: Inpatient mortality of critically ill patients is remarkably high. Patients with MAS-HLH had better outcomes when compared to other groups of HLH.