Post hoc analysis of calfactant use in immunocompromised children with acute lung injury: Impact and feasibility of further clinical trials.

OBJECTIVE: To assess the impact of calfactant (a modified natural bovine lung surfactant) in immunocompromised children with acute lung injury and to determine the number of patients required for a definitive clinical trial of calfactant in this population. DESIGN: Post hoc analysis of data from a previous randomized, control trial. SETTING: Tertiary care pediatric intensive care units. PATIENTS: All children, defined as immunocompromised, enrolled in a multicenter, masked, randomized, control trial of calfactant for acute lung injury conducted between July 2000 and July 2003. INTERVENTIONS: Patients received either an intratracheal instillation of calfactant or an equal volume of air placebo in a protocolized manner. MEASUREMENTS AND MAIN RESULTS: Eleven of 22 (50%) calfactant-treated patients died when compared with 18 of 30 (60%) placebo patients (absolute risk reduction 10.0%, 95% confidence interval [CI] -17.3, 37.3). Among the 23 patients with an initial oxygen index (OI) >/=13 and

Clinical review: alternative vascular access techniques for continuous hemofiltration.

Obtaining or maintaining vascular access for continuous hemofiltration can sometimes be problematic, especially in the child or adult in multiple organ failure with edema and/or coagulopathy. Problems commonly encountered include obstruction of the femoral vein by the catheter, insertion difficulties, safety concerns when cannulating the subclavian vein in coagulopathy, and catheter and circuit occlusion due to disseminated intravascular coagulation. For access in infants we describe a technique utilizing two single-lumen thin-walled vascular sheaths. For infants and small children initial access to the vein may be difficult due to edema or poor perfusion. For this situation we describe the 'mini-introducer' technique of securing the vein and facilitating subsequent insertion of a relatively large guide wire. At any age an alternative route to the subclavian vein, from above the clavicle, is potentially 'compressible' in the event of hemorrhage during the procedure. We remind the reader of the utility of ultrasound guidance for cannulation of the internal jugular and subclavian veins. And lastly we review the options for venous return via the umbilical vein in infants, and via the antecubital vein in larger children and adults.

Effect of exogenous surfactant (calfactant) in pediatric acute lung injury: a randomized controlled trial.

CONTEXT: Despite evidence that patients with acute lung injury (ALI) have pulmonary surfactant dysfunction, trials of several surfactant preparations to treat adults with ALI have not been successful. Preliminary studies in children with ALI have shown that instillation of a natural lung surfactant (calfactant) containing high levels of surfactant-specific protein B may be beneficial. OBJECTIVE: To determine if endotracheal instillation of calfactant in infants, children, and adolescents with ALI would shorten the course of respiratory failure. DESIGN, SETTING, AND PATIENTS: A multicenter, randomized, blinded trial of calfactant compared with placebo in 153 infants, children, and adolescents with respiratory failure from ALI conducted from July 2000 to July 2003. Twenty-one tertiary care pediatric intensive care units participated. Entry criteria included age 1 week to 21 years, enrollment within 48 hours of endotracheal intubation, radiological evidence of bilateral lung disease, and an oxygenation index higher than 7. Premature infants and children with preexisting lung, cardiac, or central nervous system disease were excluded. INTERVENTION: Treatment with intratracheal instillation of 2 doses of 80 mL/m2 calfactant or an equal volume of air placebo administered 12 hours apart. MAIN OUTCOME MEASURES: Ventilator-free days and mortality; secondary outcome measures were hospital course, adverse events, and failure of conventional mechanical ventilation. RESULTS: The calfactant group experienced an acute mean (SD) decrease in oxygenation index from 20 (12.9) to 13.9 (9.6) after 12 hours compared with the placebo group's decrease from 20.5 (14.7) to 15.1 (9.0) (P = .01). Mortality was significantly greater in the placebo group compared with the calfactant group (27/75 vs 15/77; odds ratio, 2.32; 95% confidence interval, 1.15-4.85), although ventilator-free days were not different. More patients in the placebo group did not respond to conventional mechanical ventilation. There were no differences in long-term complications. CONCLUSIONS: Calfactant acutely improved oxygenation and significantly decreased mortality in infants, children, and adolescents with ALI although no significant decrease in the course of respiratory failure measured by duration of ventilator therapy, intensive care unit, or hospital stay was observed.

Continuous veno-venous hemofiltration may improve survival from acute respiratory distress syndrome after bone marrow transplantation or chemotherapy.

PURPOSE: Acute respiratory distress syndrome (ARDS) may result from immunologic activity triggered by irradiation and/or chemotherapy. Hemofiltration removes plasma water and soluble components below 25 kilodaltons. The authors hypothesized that early hemofiltration might attenuate the inflammatory component of ARDS, resulting in increased survival in immunocompromised children and young adults. METHODS: Ten children (6 bone marrow transplantation, 3 chemotherapy, 1 lymphoma/hemophagocytosis) with ARDS (Pao2/Fio2 94 +/- 37 torr) received early continuous veno-venous hemodiafiltration as adjunctive therapy for respiratory failure, regardless of renal function. Six children had normal urine output and initial serum creatinine (range 0.1-1.2 mg/dL); four had renal insufficiency (initial creatinine 1.7-2.4 mg/dL). Hemofiltration was instituted coincident with intubation. Respiratory failure was precipitated by Enterobacter sepsis in two patients and by Aspergillus in one. RESULTS: Hemodiafiltration was performed for 13 +/- 9 days. A high rate of clearance was achieved (52 +/- 17 mL/min/1.73 m2). Duration of mechanical ventilation was 14 +/- 9 days. Nine of the 10 children were successfully extubated; 8 survived. CONCLUSIONS: Early hemofiltration may improve survival from ARDS following bone marrow transplantation or chemotherapy. Possible mechanisms include strict fluid balance, immunomodulation through filtration of inflammatory constituents, and immunomodulation through intensive extracellular water exchange that delivers biochemicals to organs of metabolism as well as the hemofilter.