A randomized, single‐blind, increasing dose safety trial of an oxygen‐carrying plasma expander (Hemospan^®) administered to orthopaedic surgery patients with spinal anaesthesia

Abstract

The objective of this study was to further explore the safety of Hemospan (Sangart Inc., San Diego, CA, USA), an oxygen-carrying plasma expander. The aim of this study was to determine if Hemospan is well tolerated in orthopaedic surgery patients with spinal anaesthesia in doses up to 1 L. Hemospan was previously found to be well tolerated in normal volunteers and orthopaedic surgery patients with spinal anaesthesia in doses up to 500 mL. Five cohorts of six orthopaedic surgery patients, American Society of Anesthesiologists (ASA) I and II, were studied. In each cohort, four patients received Hemospan in doses ranging from 200 to 1000 mL, and two received Ringer's lactate immediately prior to induction of spinal anaesthesia. There were no serious adverse events (SAEs). Iohexol clearance measured before and 24 h after dosing was unaffected. There were 14 adverse events (AEs) in the 10 control patients (1.4 per patient) and 30 in the 20 patients receiving Hemospan (1.5 per patient). One patient in the group receiving 200 mL Hemospan had elevated mean arterial pressure after dosing, but there were no elevations in any of the other patients. The peak plasma Hemospan concentration in the 1000 mL group was 1.3 g dL(-1), with a dose-dependent clearance (T(1/2)) ranging from 14.1 to 23.0 h. Plasma methaemoglobin levels were independent of dose, reaching a maximum at 40 h after dosing and never exceeded 0.125 g dL(-1). Troponin T was transiently elevated in two patients receiving Hemospan without symptoms or electrocardiographic abnormalities or elevation of myocardial creatinine kinase isoenzyme. Hemospan was well tolerated in this group of patients at doses up to 1000 mL.

Comparison of the Pharmacokinetic Properties of Hemoglobin-Based Oxygen Carriers

“…Interestingly, serum Hp completely disappeared immediately after MP4 administration, suggesting that MP4 was captured by Hp and eliminated via CD163, similar to endogenous Hb [8], albeit PEG would be expected to prevent the interactions between Hp and Hb. Olofsson et al reported two randomized Phase II studies that were carried out to evaluate the safety and efficacy of MP4 at a dose of 100–500 mg/kg during spinal anesthesia in patients who were undergoing orthopedic surgery [57,58]. The half-life of MP4 in these patients ranged from 14 to 23 h, which was prolonged with increasing dose.…”

Blood Substitutes

“…In a phase II study of 90 patients undergoing orthopedic surgery under spinal anesthesia, the infusion of up to 500 mL Hemospan reduced the frequency of hypotensive episodes to 45-48% (vs. 87% in the control-group). Three serious adverse events, including two deaths were reported, but none was considered related to study treatment [67,68]. The effect of Hemospan™ on hypotension after induction of spinal anesthesia was also studied in a recently completed phase-III trial, which compared the volume expansion effect of Hemospan™ with a hydroxyethyl starch preparation (6% HES 130/0.4).…”

Cardioprotective Effect of a Hemoglobin-Based Oxygen Carrier on Cold Ischemia/Reperfusion Injury

“…However, nonclinical and clinical studies of HBOCs have raised questions about their safety, presenting an obstacle to their development [17,18,19]. Thus, in addition to improving the quality of HBOCs themselves, we have started to explore their alternative clinical uses [12,13,20].…”