A multicenter clinical study of the safety and activity of maleimide-polyethylene glycol-modified Hemoglobin (Hemospan) in patients undergoing major orthopedic surgery.
BACKGROUND
Hemospan (Sangart Inc., San Diego, CA), a polyethylene glycol-modified hemoglobin with unique oxygen transport properties, has successfully completed a phase I trial in healthy volunteers. Because adverse events are expected to increase with age, the authors conducted a phase II safety study of Hemospan in elderly patients undergoing elective hip arthroplasty during spinal anesthesia.


METHODS
Ninety male and female patients, American Society of Anesthesiologists physical status I-III, aged 50-89 yr, in six Swedish academic hospitals were randomly assigned to receive either 250 or 500 ml Hemospan or Ringer's acetate (30 patients/group) before induction of spinal anesthesia. Safety assessment included vital signs and Holter monitoring from infusion to 24 h, evaluation of laboratory values, and fluid balance. The hypothesis to be tested was that the incidence of adverse events would be no more frequent in patients who received Hemospan compared with standard of care (Ringer's acetate).


RESULTS
Three serious adverse events were noted, none of which was deemed related to study treatment. Liver enzymes, amylase, and lipase increased transiently in patients in all three groups. There were no significant differences in electrocardiogram or Holter parameters, but there was a suggestion of more bradycardic events in the treated groups. Hypotension was less frequent in the treated patients compared with controls.


CONCLUSIONS
In comparison with Ringer's acetate, Hemospan mildly elevates hepatic enzymes and lipase and is associated with less hypotension and more bradycardic events. The absence of a high frequency of serious adverse events suggests that further clinical trials should be undertaken.
Olofsson
Christina
C
Karolinska University Hospital, Solna, Stockholm, Sweden.
Ahl
Torbjörn
T
Johansson
Torsten
T
Larsson
Sune
S
Nellgård
Per
P
Ponzer
Sari
S
Fagrell
Bengt
B
Przybelski
Robert
R
Keipert
Peter
P
Winslow
Nancy
N
Winslow
Robert M
RM
D000368:Aged; D000369:Aged, 80 and over; D000775:Anesthesia, Spinal; D019644:Arthroplasty, Replacement, Hip; D016063:Blood Loss, Surgical; D001802:Blood Substitutes / Q000009:adverse effects* / Q000627:therapeutic use*; D001803:Blood Transfusion; D001835:Body Weight / Q000502:physiology; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D015716:Electrocardiography, Ambulatory; D004798:Enzymes / Q000097:blood; D005260:Female; D006454:Hemoglobins / Q000009:adverse effects* / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D007552:Isotonic Solutions; D008297:Male; D008301:Maleimides / Q000009:adverse effects* / Q000627:therapeutic use*; D008875:Middle Aged; D019637:Orthopedic Procedures; D011092:Polyethylene Glycols / Q000009:adverse effects* / Q000627:therapeutic use*; D000077331:Ringer's Solution; D014882:Water-Electrolyte Balance / Q000502:physiology
D001802:Blood Substitutes; D004798:Enzymes; D006454:Hemoglobins; D007552:Isotonic Solutions; D008301:Maleimides; C043592:maleimide; D011092:Polyethylene Glycols; D000077331:Ringer's Solution