The Most Vulnerable SPROUTs: Severe Sepsis in the Pediatric Hematopoietic Cell Transplantation Population*

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Severe sepsis remains an important etiology of both morbidity and mortality among pediatric patients (1). Within the pediatric patient population, there are identifiable subgroups at higher risk for developing severe sepsis, as well as having poor outcomes from this disease process. Patients with immunologic dysfunction are a well-recognized group particularly vulnerable to severe sepsis, and those who have undergone hematopoietic stem cell transplantation (HCT) are at even greater risk. HCT has become the standard of care for patients with several malignant and some nonmalignant conditions over the past 50 years (2). In 2012, approximately 68,000 HCT were reported from 77 countries, with an estimated 2,500 performed annually in the United States in patients less than 20 years old (3–5). The growing population of patients who have undergone HCT make up an important population of children at high risk for complications like severe sepsis.
In this issue of Pediatric Critical Care Medicine, Lindell et al (6) describe the epidemiology, morbidity, and mortality of severe sepsis, for patients who have received HCT, using the previously published data from the Sepsis Prevalence Outcomes and Therapies (SPROUT) international point prevalence study. In the original report, 6.5% (n = 37) of patients with severe sepsis had received an HCT (1). Patients with HCT and severe sepsis were twice as likely to be admitted to the PICU from inpatient units and experienced a four-fold higher mortality rate, compared to those without HCT, despite similar PICU length of stay and use of vasoactive agents. They were more likely to have nosocomial sepsis and end organ dysfunction. Specifically, patients with HCT were more likely to have renal dysfunction and to require renal replacement therapy than patients without HCT. Additionally, patients with HCT received less enteral nutrition and more parenteral nutrition than patients without HCT. Of note, 78% of the comparison group for these analyses had at least one comorbidity, and thus patients in both groups would be considered at-risk. When the patients with HCT were compared with those who were immunocompromised but had not received HCT, higher mortality was again noted despite similar ventilator-free days and vasoactive infusion-free days.
One relevant question is whether the morbidity and mortality of patients with HCT can be fully understood without taking into account key variables that describe patients with HCT who may be at greater risk for nonrelapse and overall mortality. One such tool is the HCT-comorbidity index that provides an evidence-based index score of risk (7). HCT-CI scores of greater than or equal to 3 were associated with higher risks for morbidity and mortality in both allogeneic (e.g., high dose allogeneic, reduced intensity, and nonmyeloablative allogeneic) and autologous HCT, regardless of diagnoses, age, and conditioning intensity. The score includes cardiovascular and cerebrovascular disease, psychiatric, hepatic and renal dysfunctions, obesity, rheumatologic, and pulmonary comorbidity. Many of these elements were not gathered during the SPROUT study but provide intriguing options for future studies of pediatric HCT recipients who may be at greater risk for severe sepsis.
The reasons for poor outcome in the HCT population remain unclear, as immune dysfunction alone does not explain the increased morbidity and mortality. Lindell et al (6) suggest several hypotheses for their findings of increased morbidity and mortality including limited enteral nutrition use and details about type, reasons, conditioning regimen, and source of cells for HCT. Understanding why patients who undergo HCT are at greater risk for poor outcomes associated with severe sepsis will be key in improving survival in this at-risk population.
Lindell et al (6) identified that the majority of HCT patients admitted to the PICU with severe sepsis (73%) were admitted from inpatient units.

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