The prognoses and outcomes for pediatric oncologic patients have improved considerably over recent decades. However, improved outcomes for pediatric cancer patients admitted to the intensive care unit (ICU) have lagged behind these advancements; little progress was made until the last decade. Earlier published reports indicated pessimistic outcomes for oncologic patients admitted to the pediatric intensive care unit (PICU), and some even questioned if these patients should be admitted to the PICU at all, as treatment frequently was viewed as futile.1 Even more recently, some authors suggested denying PICU admission for some patients with pulmonary dysfunction after stem cell transplantation.2 As a result, pediatric oncology units, especially those that offered stem cell transplants, developed a very broad therapeutic repertoire. These units started to treat patients with a severity-of-illness that ordinarily would have dictated a PICU admission. In some cases, this included attempts at hemodynamic support for early septic or hypovolemic shock and renal replacement therapies.3 PICU admissions were reserved for children who required mechanical ventilation, usually for acute respiratory failure. This philosophy often resulted in delayed PICU admission, if it was offered at all. Appropriately aggressive interventions also were delayed until “late in the spiral of multi-system organ failure.” 4

Recent studies suggest that a more aggressive therapeutic approach and early application of invasive therapies may improve outcomes for those admitted to the PICU. Outcomes for patients with liquid and solid tumors (excepting stem cell transplantation) who receive mechanical ventilation for respiratory disease or shock now are comparable to those of the general PICU population (See Figure 1). In addition, Kutko et al. noted that oncologic illness, in the absence of bone marrow transplantation, does not appear to be associated with an increased mortality for children with septic shock.5

Comparing studies to identify factors associated with improved outcomes is difficult at best. Studies often include variations in patient populations (e.g., some include transplants for genetic and metabolic disorders in addition to oncologic patients), PICU admission criteria, severity of illness, and clinical thresholds for implementing intensive therapies. In addition, most studies usually are retrospective, conducted in a single institution and lack the power to identify significant risk factors for mortality. Thus, using evidenced-based methods to identify treatment strategies associated with decreased mortality often proves difficult. However, there are recurring themes in the conclusions. Studies by Hallahan and Rossi suggest that early interventions for patients who have low Pediatric Risk of Mortality (PRISM)6 scores when entering the PICU can produce improved outcomes.4,7 Although the inclusion of less severely ill patients in these studies cannot be ruled out as a factor contributing to this success, these studies are consistent in finding that mortality increases as more organ systems fail. It seems reasonable that intervention before end-stage organ failure has occurred is a prudent therapeutic goal. Once three or more organ systems fail, survival rates markedly decrease. Those statistics have changed little in the past two decades.8,9

Some of the most challenging cases among PICU cancer patients are those where a patient receives stem cell transplantation. A review of recent literature on this population indicates improved PICU and short-term hospital outcomes (See Table 1).7,10 Treatment for acute respiratory failure for patients with stem cell transplantations can be improved, especially with early intervention. Traditionally, patients who received endotracheal intubation for acute respiratory failure, especially in the presence of pneumonia, had poor outcomes. 8,11,12 Recently, some have postulated that the use of “lung protective” conventional ventilation strategies may be associated with improved outcomes. The subsequent application of alternative therapies, such as high-frequency oscillatory ventilation (HFOV) after failure of “lung protective” conventional ventilation, appeared to be associated with probable mortality.8,10 However, in the study by Hagen, use of HFOV within the first six hours of respiratory failure was associated with improved survival, once again suggesting that earlier intervention in the acute lung injury process may improve survival rates.8

Care for the pediatric oncologic patient requires ongoing multiprofessional communication and planning. Of all the patients admitted to the PICU, those with bone marrow suppression often require the most resources. Often, these patients have multi-system organ dysfunction secondary to the treatment or progression of an underlying disease and require specialists. The combination of multiple antibiotics (including antiviral and antifungal agents) and the replacement of blood products in addition to the patient's other needs may require additional vascular access and renal replacement therapy for positive fluid balance even when kidneys are functioning normally.10 In addition, frequent fevers or signs of possible sepsis require particular and frequent attention by the critical care team and infectious disease specialists. Close assessment by critical care pharmacists becomes paramount for monitoring drug interactions and potential toxicities of therapeutic agents. Unfortunately, end-of-life decision making is needed frequently. These situations can tax the emotional resources of team members, especially when long-term relationships have been established. However, the strength, grace and gratitude often exhibited by these patients and their families can serve to validate the hard work of the multiprofessional team.

In summary, except for stem cell transplantation patients, mortality and morbidity rates for pediatric cancer patients in the PICU should be approaching those of the general PICU population. Many studies have identified clinical variables that predict poor patient outcomes, but presently there are no such variables that reliably predict mortality with certainty, especially at the time of PICU admission. Based on current knowledge, the consideration of PICU admission and the application of aggressive supportive therapies should occur as early as possible in the context of a child's declining clinical course and impending multi-system organ dysfunction. Decisions on therapy should be continuously re-evaluated based on the patient's clinical course to ensure a more informed discussions among caregivers, patients and families concerning the continuation, limitations or even withdrawal of PICU care.

 


















Figure 1: Intensive care unit (ICU) survival of respiratory failure in pediatric oncologic patients at St. Judes Children’s Research Hospital.*

Non-BMT a patients outcome 64% vs. BMT patients 36% (p<0.0001)

Odds ratio of ICU survival 99-01 vs. 93-98: 1.45% (95% C.I. 1.09, 1.98) a Bone marrow transplantation

*Adapted with permission RF Tamburro