title: Initial evaluation of diaspirin cross-linked hemoglobin (DCLHb) as a vasopressor in critically ill patients.
abstract: OBJECTIVE
  To evaluate the hemodynamic effects and any toxicologic effects of diaspirin cross-linked hemoglobin (DCLHb) in critically ill patients.
  
  
  METHODS
  A prospective, observational study.
  
  
  METHODS
  A seven-bed intensive care unit (ICU) in a University teaching hospital.
  
  
  METHODS
  Fourteen critically ill patients requiring vasopressor therapy to maintain adequate mean arterial pressure (MAP). All patients had secondary organ dysfunction.
  
  
  METHODS
  Administration of 100 mL boluses of 10% diaspirin cross-linked hemoglobin, up to a maximum of 500 mL, given over 15 mins and separated by 60 to 90 mins.
  
  
  RESULTS
  Hemodynamic parameters, norepinephrine and inotropic requirements, arterial and mixed venous blood gases, urine output, and biochemical and hematologic analyses were measured before diaspirin cross-linked hemoglobin administration and at multiple time points up to 72 hrs. MAP was maintained at approximately preinfusion values and the reduction in norepinephrine requirements was used as the main end point to assess the efficacy of diaspirin cross-linked hemoglobin as a vasopressor. Diaspirin cross-linked hemoglobin demonstrated a marked vasopressor action, allowing norepinephrine requirements to be reduced from 0.29 +/- 0.15 (SD) microgram/kg/min to 0.15 +/- 0.14 and 0.07 +/- 0.10 microgram/kg/min after the first (at 1.5 hrs, p < .001) and last (at 7.5 hrs, p < .0001) boluses, respectively. These reductions in norepinephrine requirements were maintained at 24, 48, and 72 hrs (p < .01 at all time points). These hemodynamic changes began within 5 mins of starting the diaspirin cross-linked hemoglobin infusion. MAP, heart rate, central venous pressure, pulmonary artery occlusion pressure, mean pulmonary arterial pressure (MPAP), systemic vascular resistance index, and urine output did not demonstrate any significant changes from preinfusion values. Pulmonary vascular resistance index increased at 7.5 hrs despite nonsignificant increases in MPAP. Cardiac index and oxygen delivery index decreased significantly at 7.5 hrs and 24 hrs. Total plasma bilirubin increased significantly from baseline at 24 and 48 hrs, before returning to baseline values within 5 days. Platelet count was significantly reduced at 6 and 24 hrs. No other biochemical or hematologic analyses were altered significantly post diaspirin cross-linked hemoglobin.
  
  
  CONCLUSIONS
  This preliminary study demonstrated that diaspirin cross-linked hemoglobin is a potent vasopressor agent in critically ill patients with septicemic shock or systemic inflammatory response syndrome. This vasopressor characteristic of diaspirin cross-linked hemoglobin may have future clinical applications.
authors.affiliation: Anaesthetics Department, General Infirmary at Leeds, UK.
authors.forename: G
authors.initials: G
authors.lastname: Reah
authors.forename: A R
authors.initials: AR
authors.lastname: Bodenham
authors.forename: A
authors.initials: A
authors.lastname: Mallick
authors.forename: E K
authors.initials: EK
authors.lastname: Daily
authors.forename: R J
authors.initials: RJ
authors.lastname: Przybelski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003404:Creatinine / Q000097:blood; D016638:Critical Illness; D016903:Drug Monitoring; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006454:Hemoglobins / Q000627:therapeutic use*; D006801:Humans; D007022:Hypotension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D010976:Platelet Count / Q000187:drug effects; D011446:Prospective Studies; D013997:Time Factors
chemical_list: D006454:Hemoglobins; D003404:Creatinine; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin