A double-blind study to evaluate the safety of recombinant human hemoglobin in surgical patients during general anesthesia.

OBJECTIVE: To evaluate recombinant human hemoglobin (rHb1.1) in patients undergoing surgery involving general anesthesia; examine rHb1.1 for toxicity, including renal dysfunction and hypertension; and measure plasma concentrations of rHb1.1 over time. DESIGN: Prospective, double-blinded, randomized, placebo-controlled study. SETTING: University medical center hospital. PARTICIPANTS: Eighteen patients having surgery under general anesthesia. INTERVENTIONS: One of 4 escalating doses of rHb1.1 or normal saline (control) was administered by continuous infusion to patients receiving general anesthesia for elective surgical procedures. Total rHb1.1 doses ranged from 4.7 to 25.6 g. MEASUREMENTS AND MAIN RESULTS: Clinical and laboratory data, including vital signs monitoring, hematology (white blood cell and reticulocyte count, hemoglobin, hematocrit, erythrocyte sedimentation rates, and coagulation values), renal function (serum creatinine and blood urea nitrogen), hepatic function (mean and indirect bilirubin), pancreatic function (serum amylase and lipase), and antibodies (IgG and IgM) to Escherichia coli protein, were collected at specified intervals for 7 days after infusion of rHb1.1. No serious adverse events occurred. The most frequently observed clinical event occurred during the first 24 hours after infusion and was primarily associated with surgery and anesthetic administration. A slightly higher incidence of hypertension, symptoms suggestive of pyrogenicity, mildly elevated total and indirect bilirubin, and elevated pancreatic enzymes was observed in rHb1.1 treatment groups when compared with control. Hypertension resolved within 7 hours, and laboratory values returned to normal levels by day 7. CONCLUSION: Although the elevations in pancreatic enzymes seen in some rHb1.1-treated patients remain unexplained, the safety profile of rHb1.1 appears to be acceptable. These results support the continued clinical evaluation and development of rHb1.1.