Risk of Mortality in Immunocompromised Children With Severe Sepsis and Septic Shock

Abstract

Objectives: To assess the prevalence of immunocompromised diagnoses among children with severe sepsis and septic shock, and to determine the association between immunocompromised diagnoses and clinical outcomes after adjustment for demographics and illness severity.

Design: Retrospective multicenter cohort study.

Setting: Eighty-three centers in the Virtual Pediatric Systems database.

Patients: Children with severe sepsis or septic shock admitted to a participating PICU between January 1, 2012, and December 31, 2016.

Interventions: None.

Measurements and main results: Across 83 centers, we identified 10,768 PICU admissions with an International Classification of Diseases, 9th Revision, Clinical Modification code for severe sepsis or septic shock; 3,021 of these patients (28%) had an immunocompromised diagnosis. To evaluate variation across centers and determine factors associated with PICU mortality, we used mixed-effect logistic regression models. Among patients without hematopoietic cell transplant, congenital immunodeficiency (adjusted odds ratio, 1.90; 95% CI, 1.24-2.92), multiple prior malignancies (adjusted odds ratio, 1.86; 95% CI, 1.15-2.99), and hemophagocytic lymphohistiocytosis (adjusted odds ratio, 3.09; 95% CI, 1.91-4.98) were associated with an increased odds of PICU mortality. Among patients with prior hematopoietic cell transplant, liquid malignancy (adjusted odds ratio, 3.15; 95% CI, 2.09-4.74), congenital immunodeficiency (adjusted odds ratio, 6.94; 95% CI, 3.84-12.53), multiple prior malignancies (adjusted odds ratio, 3.54; 95% CI, 1.80-6.95), and hemophagocytic lymphohistiocytosis (adjusted odds ratio, 2.79; 95% CI, 1.36-5.71) were associated with an increased odds of PICU mortality. PICU mortality varied significantly by center, and a higher mean number of sepsis patients per month in a center was associated with lower PICU mortality (adjusted odds ratio, 0.94; 95% CI, 0.90-0.98). PICU resource utilization varied by immunocompromised diagnosis and history of hematopoietic cell transplant, and among survivors immunocompromised patients have shorter median PICU length of stay compared with patients without immunocompromised diagnoses (p < 0.001).

Conclusions: Immunocompromised diagnoses are present in 28% of children with severe sepsis or septic shock. Multiple prior malignancies, hemophagocytic lymphohistiocytosis, congenital immunodeficiency, and hematopoietic cell transplant are independently associated with an increased odds of PICU mortality in children with severe sepsis or septic shock. Significant variation exists in PICU mortality among centers despite adjustment for immunocompromised diagnoses, known risk factors for sepsis-related mortality, and center-level sepsis volume.

Figure 1.

Association between IC diagnoses are PICU mortality among patients with severe sepsis or septic shock, after adjustment for a priori covariates in the final mixed effects model.

Figure 2.

Center-level variation in PICU mortality for patients with severe sepsis or septic shock. Panel A depicts the mortality by hospital, ordered from lowest to highest. Panel B depicts the volume-outcome relationship between center-level volume of septic patients and PICU mortality. For both panels, the size of the point estimate corresponds to the volume of patients from each participating hospital. Error bars indicate the 95% confidence interval. The observed mortality rate for the entire cohort is indicated by a broken line at 15.5%.