Background: Military guidelines call for two 500-mL boluses of Hextend for resuscitation in far-forward environments. This study compared a hemoglobin-based oxygen carrier (HBOC-201; Hemopure) to Hextend when used to treat hemorrhagic shock in situations of delayed definitive care military operations. Methods: Yorkshire swine (55-65 kg) were hemorrhaged to a mean arterial blood pressure (MAP) of 30 mmHg. Hypotension was maintained for 45 minutes followed by resuscitation with either Hextend (HEX) (n = 8) or HBOC-201 (HBOC) (n = 8). Over 8 hours, animals received up to 1,000 mL of either fluid in an effort to sustain an MAP of 60 mmHg. At the end of 8 hours, HEX animals received 2 L of lactated Ringer's solution followed by shed blood. HBOC animals received 4 L of lactated Ringer's solution only. Animals were killed and necropsied on postprocedure day 5. Hemodynamic data were collected during shock and resuscitation. Complete blood counts, amylase, lactate, coagulation studies, and renal and liver function were measured throughout the experiment. Results: Equivalent volumes were hemorrhaged from each group (HBOC, 44.3 ± 2.2 mL/kg; HEX, 47.4 ± 3.0 mL/ kg). The HBOC group achieved the goal MAP (HBOC, 60.0 ± 2.3 mmHg; HEX, 46.4 ± 2.3 mmHg; p < 0.01) and required less volume during the initial 8 hours (HBOC, 12.4 ± 1.4 mL/kg; HEX, 17.3 ± 0.3 mL/kg; p < 0.01). The HBOC group had lower SvO 2 (HBOC, 46.3 ± 2.4%; HEX, 50.7 ± 2.5%; p = 0.12) and cardiac output (HBOC, 5.8 ± 0.4 L/min; HEX, 7.2 ± 0.6 L/min; p = 0.05), but higher systemic vascular resistance (HBOC, 821.4 ± 110.7 dynes · s · cm-5; HEX, 489.6 ± 40.6 dynes · s · cm-5; p = 0.01). Base excess, pH, lactate, and urine output did not differ between groups. HEX group survival was 50% (four of eight) versus 88% for the HBOC group (seven of eight). All animals survived the initial 8 hours. Animals surviving 5 days displayed no clinical or laboratory evidence of organ dysfunction in either group. Conclusion: HBOC-201 more effectively restored and maintained perfusion pressures with lower volumes, and allowed for improved survival. These data suggest that hemoglobin-based oxygen carriers are superior to the current standard of care for resuscitation in far-forward military operations. Copyright © 2005 by Lippincott Williams & Wilkins, Inc.