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 un dergoing surgery involving general anesthesia; examine rHb1.1 for toxicity, including renal dysfunction and hypertension; and measure plasma concentra tions 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 (contro l) was administered by continuous infusion to patients receiving general an esthesia 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 vita l signs monitoring, hematology (white blood cell and reticulocyte count, he moglobin, hematocrit, erythrocyte sedimentation rates, and coagulation valu es), renal function (serum creatinine and blood urea nitrogen), hepatic fun ction (mean and indirect bilirubin), pancreatic function (serum amylase and lipase), and antibodies (IgG and IgM) to Escherichia coli protein, were co llected at specified intervals for 7 days after infusion of rHb1.1. No seri ous adverse events occurred. The most frequently observed clinical event oc curred during the first 24 hours after infusion and was primarily associate d with surgery and anesthetic administration. A slightly higher incidence o f hypertension, symptoms suggestive of pyrogenicity, mildly elevated total and indirect bilirubin, and elevated pancreatic enzymes was observed in rHb 1.1 treatment groups when compared with control. Hypertension resolved with in 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 appear s to be acceptable. These results support the continued clinical evaluation and development of rHb1.1. Copyright (C) 2001 by W.B. Saunders Company.