Protocol adherence when managing massive bleeding following complex cardiac surgery: a study design pilot.

OBJECTIVE: High-quality prospective trials of hemostatic "rescue" therapy to control massive bleeding in cardiac surgery are lacking. Wide variability in the care of patients with severe bleeding following cardiopulmonary bypass has precluded accurate comparison of treatment groups in previous studies. This study identified the use of a management protocol for early identification and uniform treatment of patients with massive bleeding for application in future trials of hemostatic rescue agents. DESIGN: A prospective, nonblinded, interventional feasibility study. SETTING: A university teaching hospital. PARTICIPANTS: Forty-three adult patients undergoing complex cardiac surgery. INTERVENTIONS: Study participants undergoing high-risk cardiac surgery received standardized treatment in accordance with a bleeding management protocol. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients (63%) had severe bleeding following heparin reversal and received conventional hemostatic resuscitation per protocol. Six patients had massive refractory bleeding. Compliance with protocol tasks was≥90% in 4 of 5 categories (anticoagulation, hemostasis scoring, recording blood loss, protocol transfusion) with the exception being submission of laboratory samples (76%). Measured bleeding rates (mL/h) following heparin reversal were clearly differentiated in those with hemostasis scores≥3 compared to those with scores≤2 (1,420±957 v 147±96; p<0.001). CONCLUSIONS: Adherence to a management protocol for massive bleeding is feasible and allows for homogenous treatment of patients before study arm randomization in future "rescue" therapy trials. The authors' protocol allowed for prompt and accurate identification of patients with severe bleeding refractory to conventional therapy. This review resolved several key barriers in the design of severe bleeding management trials.

Granulocyte colony stimulating factor alters the phenotype of neuroblastoma cells: implications for disease-free survival of high-risk patients.

INTRODUCTION: Granulocyte colony stimulating factor (GCSF) is commonly used for the treatment of chemotherapy-induced neutropenia. Despite high-dose intensive chemotherapy for advanced-stage neuroblastoma, the survival rate remains poor. Granulocyte colony stimulating factor therapy is quite common in these children; thus, we questioned its effect on neuroblastoma cells. We hypothesized that exogenous GCSF stimulates the proliferation and invasive character of neuroblastoma cells. METHODS: Expression of a GCSF receptor in 5 different neuroblastoma cell lines was determined by polymerase chain reaction. In addition, we determined the effect of increasing doses of GCSF (0, 1 ng/mL, 10 ng/mL, 1 microg/mL, and 10 microg/mL) on DNA synthesis (BrdU assay), invasiveness (Matrigel invasion chambers), and cell proliferation. RESULTS: We tested 5 neuroblastoma cell lines; all expressed the GCSF receptor. Granulocyte colony stimulating factor treatment resulted in significantly increased proliferation of SK-N-SH, SK-N-AS, and SHSY-5Y cells. Likewise, increased invasiveness of SK-N-SH cells was observed with GCSF treatment. CONCLUSIONS: Our results indicate that neuroblastoma cell lines express the GCSF receptor and respond to exogenous GCSF by increased proliferation and invasiveness. These findings suggest that GCSF may stimulate the growth of neuroblastoma cells in patients undergoing high-dose chemotherapy with GCSF rescue and could have a significant impact on the ability to eradicate these tumors.