Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial

To describe the short-term outcome of pediatric intensive care by quantifying overall functional morbidity and cognitive impairment, I developed the Pediatric Overall Performance Category (POPC) and the Pediatric Cerebral Performance Category (PCPC) scales, respectively. A total of 1469 subjects (1539 admissions) were admitted to the pediatric intensive care unit of Arkansas Children's Hospital from July 1989 through December 1990. Patients were assigned baseline POPC and PCPC scores derived from historical information and discharge scores at the time of discharge from the hospital (or from the pediatric intensive care unit for patients with multiple hospitalizations). Delta scores were calculated as the difference between the discharge scores and the baseline scores. The changes in POPC and PCPC scores were associated with several measures of morbidity (length of stay in the pediatric intensive care unit, total hospital charges, and discharge care needs) and with severity of illness (pediatric risk of mortality score) or severity of injury (pediatric trauma score) (p less than 0.0001). Interrater reliability was excellent (r = 0.88 to 0.96; p less than 0.001). The POPC and PCPC scales are apparently reliable and valid tools for assessing the outcome of pediatric intensive care.

The purpose of this study was to establish relationships between illness severity, length of stay, and functional outcomes in the pediatric intensive care unit (PICU) by using multi-institutional data. We hypothesized that a positive relationship exists between functional outcome scores, severity of illness, and length of stay. The study used a prospective multicentered inception cohort design. The study was conducted in 16 PICUs across the United States that were member institutions of the Pediatric Critical Care Study Group of the Society of Critical Care Medicine. In total, 11,106 patients were assessed, representing all admissions to these intensive care units for 12 consecutive months. Functional outcomes were measured by the Pediatric Overall Performance Category (POPC) and Pediatric Cerebral Performance Category (PCPC) scales. Both scales were assessed at baseline and discharge from the PICU. Delta scores were formed by subtracting baseline scores from discharge scores. Other measurements included admission Pediatric Risk of Mortality scores, age, operative status, length of stay in the PICU, and diagnoses. Interrater reliability was assessed by using a set of ten standardized cases on two occasions 6 months apart. Baseline, discharge, and delta POPC and PCPC outcome scores were associated with length of stay in the PICU and with predicted risk of mortality (p < .01). Incorporation of baseline functional status in multivariate length of stay analyses improved measured fit. Mild baseline cerebral deficits in children were associated with 18% longer PICU stays after controlling for other patient and institutional characteristics. Moderate and severe baseline deficits for both the POPC and PCPC score predict increased length of stay of between 30% and 40%. On the standardized cases, interrater consensus was achieved on 82% of scores with agreement to within one neighboring class for 99.7% of scores. These data establish current relationships for the POPC and PCPC outcome scales based on multi-institutional data. The reported relationships can be used as reference values for evaluating clinical programs or for clinical outcomes research.

Much has been learned recently about the structure and function of 55 kDa bactericidal/permeability-increasing protein (BPI), a member of a genomically conserved lipid-interactive protein family. Analysis of BPI fragments and the crystal structure of human BPI have established that BPI consists of two functionally distinct domains: a potently antibacterial and anti-endotoxin amino-terminal domain (approximately 20 kDa) and a carboxy-terminal portion that imparts opsonic activity to BPI. A recombinant amino-terminal fragment (rBPI21) protects animals against the effects of Gram-negative bacteria and endotoxin. In man, rBPI21 is nontoxic and non-immunogenic and is in Phase II/III clinical trials with apparent therapeutic benefit.