Outcomes of Pediatric Patients with Respiratory Failure Following Hematopoietic Cell Transplant (HCT); 8 Years’ Experience with High Frequency Oscillatory Ventilation (HFOV).

Background: Pediatric hematopoietic cell transplant (HCT) patients requiring mechanical ventilation have historically had poor outcomes with high mortality rates. However, recent studies have shown an improvement in the overall outcomes for patients requiring mechanical ventilation (18% improved to 59% survival, Kache S et al 2006). One subset that has persistently had poor outcomes is the patient group requiring high frequency oscillatory ventilation (HFOV) with published mortality rates of 89–100% (Kache S et al 2006, Hagen S et al 2003). However, Hagen et al also noted that patients placed on HFOV within 6 hours of intubation had better survival than those managed with conventional ventilation for longer intervals before conversion to HFOV. We report our experience at a large pediatric HCT center with mechanical ventilation and, more specifically, the largest single center experience with HFOV.

Methods: Records of all pediatric HCT patients from 1/2000 through 7/2007 (n=522) who required mechanical ventilation (n=139) and/or HFOV (n=36) were retrospectively reviewed to identify conditions of the patient at the time of initial intubation, as well as co-morbidities during the period of intubation.

Results: At one year after HCT, 69.7% (364/522) of all patients were alive. For nonventilated patients, 79.6% (305/383) were alive at one year compared to 42.4% (59/139) of all patients over the entire interval who required mechanical ventilation. For patients who required mechanical ventilation but not HFOV, 47.6% (49/103) survived compared to 27.8% (10/36) of patients who required HFOV. With respect to patients requiring HFOV, renal replacement therapy at any point was associated with a significant (p=0.04) risk for in-hospital mortality. No other significant factors associated with increased mortality were identified in patients requiring HFOV, including age, gender, initial diagnosis, stem cell source, etc. Specifically, no increase in mortality was seen with umbilical cord blood transplants in contrast to the experience of Hagen et al. When comparing 1 year survival of patients who were transplanted in the earliest interval 2000–2001 versus those transplanted in current years 2005–2007, we did note a significant increase in survival for all HCT patients (62.5% increased to 77.7%, p = 0.01) and for those HCT patients that required mechanical ventilation (38.3% increased to 58.5%, p=0.04). There was a trend toward improvement in survival over time for those patients who required HFOV (22.2% 2000–2001 to 33.3% 2005–2007), but the difference was not significant due to the small number of patients. 50% of all patients converted to HFOV within one day of initiating mechanical ventilation survived; of the HFOV survivors, 67% were converted to HFOV within one day of intubation and all but 2 survivors were converted within 2 days of intubation.

Conclusions: Despite the historically poor outcomes of HCT recipients who require HFOV, our data suggests HCT patients with respiratory failure managed with HFOV can have reasonable expectations for survival, including umbilical cord blood transplant patients. The need for renal replacement therapy in patients requiring HFOV significantly increases the risk of mortality. We identified no additional risk factors contributing to mortality comparing other demographic data or other co-morbidities. Institution of HFOV early in HCT patients’ ventilator course may improve survival. Further definition of optimal HFOV management strategies remains to be investigated as well as the pathophysiology underlying the apparent enhanced survival with earlier HFOV use.