Methods to enhance hemodynamic stability using oxygen carrying compositions

Abstract

The present invention relates to methods for enhancing the hemodynamic stability of an individual undergoing surgery by administering a composition comprising a hemoglobin-based oxygen carrier. In one embodiment, the present invention relates to the use of polyalkylene oxide modified hemoglobins with reduced cooperativity and a high oxygen affinity to enhance oxygen offloading as a preventative measure to avoid hemodynamic stability-related complications during surgery.

1 . A method for enhancing hemodynamic stability of a normovolemic subject undergoing surgery comprising: 
 a) administering a composition containing a hemoglobin-based oxygen carrier (HBOC) with an oxygen affinity higher than whole blood to the subject in connection with the surgery; and    b) monitoring the hemodynamic stability of the patient.    
     
     
         2 . The method according to  claim 1 , wherein the composition is administered prior to surgery.  
     
     
         3 . The method according to  claim 1 , wherein the composition is administered during surgery.  
     
     
         4 . The method according to  claim 1 , wherein the composition is administered after surgery.  
     
     
         5 . The method according to  claim 1 , wherein step b) is performed before surgery.  
     
     
         6 . The method according to  claim 1 , wherein step b) is performed during surgery.  
     
     
         7 . The method according to  claim 1 , wherein step b) is performed after surgery.  
     
     
         8 . The method according to  claim 1 , wherein the HBOC further comprises a polyalkylene oxide modified natural hemoglobin.  
     
     
         9 . The method according to  claim 1 , wherein the HBOC further comprises a polyalkylene oxide modified synthetic hemoglobin.  
     
     
         10 . The method according to  claim 1 , wherein the HBOC further comprises recombinant hemoglobin.  
     
     
         11 . The method according to  claim 1 , wherein the HBOC further comprises human hemoglobin.  
     
     
         12 . The method according to  claim 1 , wherein the HBOC further comprises human hemoglobin from a non-human animal.  
     
     
         13 . The method according to  claim 1 , wherein the HBOC has an oxygen affinity greater than twice that of whole blood.  
     
     
         14 . The method according to  claim 1 , wherein the HBOC has a P50 between 4 and 15.  
     
     
         15 . The method according to  claim 1 , wherein the HBOC further comprises hemoglobin that has been modified by covalent attachment of malemidyl-activated polyethylene glycol.  
     
     
         16 . The method according to  claim 1 , wherein step b) further comprises monitoring blood pressure of the subject.  
     
     
         17 . The method of  claim 16 , wherein hemodynamic stabilization is characterized by the subject maintaining a systolic pressure above 90 mm Hg.