Editorial: Sepsis in the immunocompromised child: The least studied with the most to gain

Itis common knowledge among practitioners of pediatric critical care that the frequently cited randomized trials treating septic patients with activated protein C (1), goal-directed therapy (2), and corticosteroids (3) do not include any subjects younger than 18 yrs of age. What is not as well known is that, by and large, these trials also excluded a large proportion of immunocompromised patients, as have most other sepsis trials. The activated protein C study excluded those with a history of bone marrow, lung, liver, pancreas, or small-bowel transplantation and those with human immunodeficiency virus (HIV) and a CD4 count <50 cells/mm3 (although 18% of the subjects did have cancer as an underlying condition) (1). The goal-directed therapy study of Rivers et al. (2) excluded those with “uncured cancer (during chemotherapy)” or “immunosuppression (because of organ transplantation or systemic disease).” The corticosteroid trial of Annane and colleagues (3) excluded patients with “evidence for…advanced forms of cancer or acquired immunodeficiency syndrome (AIDS) infection, and contraindication or formal indication for steroids.” Given the fact that these trials are the underpinnings of several of the key recommendations of the Surviving Sepsis Campaign (4), we are left asking whether we can legitimately apply the results of those trials to immunocompromised patients with sepsis. Also, immunocompromised children and adults make up a substantial proportion of patients with severe sepsis (5, 6). These considerations underscore the critical gaps in knowledge regarding the treatment of sepsis in the immunocompromised host and the importance of seeking that knowledge through clinical trials. The articles presented in the section on the immunocompromised host during the International Sepsis Forum on Sepsis in Infants and Children and included in this supplement are an important step in addressing the need to include immunocompromised patients in sepsis trials. The goals of the session are listed in Table 1. Dr. Upton Allen, a specialist in pediatric infectious diseases from the Hospital for Sick Children in Toronto, presents the broad categories of acquired immunodeficiencies unrelated to HIV infection, including cancer, hematopoietic stem cell and solid organ transplantation, and immunomodulating agents. His article highlights the difficulties encountered when including immunocompromised patients in sepsis trials and will be highly useful for any investigator designing such trials. Dr. Robert Tamburro, a pediatric intensivist formerly at St. Jude Research Hospital for Children (currently at Penn State Children’s Hospital) discusses the published literature involving pediatric cancer patients with sepsis and concludes that pediatric cancer patients account for a relatively high proportion of severe sepsis episodes in children and that outcomes of sepsis in the pediatric oncology population (excluding those who have undergone hematopoietic stem cell transplantation) are not substantially different from that of the general population. He also points out that the generally poor outcomes of pediatric hematopoietic stem cell transplantation patients with sepsis should not preclude their participation in clinical trials but rather should be a call to action for their widespread participation in clinical trials. Dr. Mark Hatherill, a pediatric intensivist at the Red Cross Children’s Hospital in Cape Town, discusses the heterogeneity of pediatric HIV infection in the era of highly active antiretroviral therapy and outlines important clinical aspects that will prove to be invaluable for stratification in sepsis trials. Finally, Dr. Jordan Orange, a pediatric immunologist at Children’s Hospital of Philadelphia, provides a comprehensive, detailed overview of congenital immunodeficiencies, with a focus on bacteremic sepsis as a presenting or characteristic feature. An understanding of these disorders will be important for the design of sepsis trials in children to ensure that proper evaluation for congenital immunodeficiencies in children with sepsis is undertaken.Table 1: Focus questions in the session on the immunocompromised host of the International Sepsis Forum on Sepsis in Infants and Children, Boston, MA, 2004As a whole, the articles presented in this section of the International Sepsis Forum on Sepsis in Infants and Children will allow clinical trials involving immunocompromised children with sepsis to move forward more efficiently and more successfully. This, in turn, will likely lead to important clinical advances for this understudied patient population having very much to gain. Gregory P. Priebe, MD Division of Critical Care Department of Anesthesiology Division of Infectious Diseases Department of Medicine Children’s Hospital Boston Channing Laboratory Department of Medicine Brigham and Women’s Hospital Boston, MA

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