title: Metabolic acidemia with hypoxia attenuates the hemodynamic responses to epinephrine during resuscitation in lambs.
abstract: OBJECTIVE
  To examine the effects of metabolic acidemia and hypoxia on the hemodynamic responses to epinephrine in an intact neonatal animal model.
  
  
  METHODS
  Multi-experiment, randomized, controlled trial.
  
  
  METHODS
  Animal research laboratory of a university hospital.
  
  
  METHODS
  Sixteen lambs, ranging in age from 2 to 14 days.
  
  
  METHODS
  The lambs were chronically catheterized; the ductus arteriosus was ligated; and a pulmonary arterial flow probe was inserted to measure cardiac output, blood pressure (BP), and heart rate. In the first protocol, hemodynamic responses to epinephrine during pure metabolic acidemia or metabolic alkalosis were studied in eight lambs. Each lamb was studied on four different days at a different arterial pH: 6.9, 7.1, 7.4, and 7.6. Ventilation was controlled to maintain PCO2 at 35 to 45 torr (4.66 to 5.99 kPa). Acidemia was induced by the infusion of lactic acid and alkalosis by the infusion of sodium bicarbonate. When the appropriate arterial pH was achieved, 10 micrograms/kg of epinephrine was administered intravenously. In a second protocol, hemodynamic responses to epinephrine during metabolic acidemia or alkalosis plus hypoxia were studied in eight lambs. When the appropriate arterial pH was achieved, hypoxia was induced until cardiac output decreased to 40% of baseline. Epinephrine bolus was given, and after 90 secs, the lambs were resuscitated with oxygen.
  
  
  RESULTS
  Epinephrine administered during uncompromised hemodynamics led to hypertension, bradycardia, and decreased cardiac output that were unaffected by arterial pH values between 6.9 and 7.6. Acidemia with hypoxia compromised hemodynamics with decreases in heart rate and cardiac output. Epinephrine administered during this compromised condition did not improve cardiac output, heart rate, or BP before resuscitation with oxygen at any arterial pH studied. Resuscitation with epinephrine and oxygen during hemodynamically compromised states led to increases in heart rate, BP, and cardiac output with significant attenuation of these hemodynamic responses during metabolic acidemia at pH values of 6.9 and 7.1.
  
  
  CONCLUSIONS
  During the physiologic conditions associated with neonatal resuscitation, that is, hypoxia with a compromised hemodynamic state, metabolic acidemia significantly attenuates the hemodynamic responses to resuscitation with epinephrine and oxygen. Correction of metabolic acidosis may be warranted in newborn resuscitation.
authors.affiliation: Department of Pediatrics, University of Florida College of Medicine, Gainesville.
authors.forename: M P
authors.initials: MP
authors.lastname: Preziosi
authors.forename: J C
authors.initials: JC
authors.lastname: Roig
authors.forename: N
authors.initials: N
authors.lastname: Hargrove
authors.forename: D J
authors.initials: DJ
authors.lastname: Burchfield
mesh_terms: D000138:Acidosis / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000471:Alkalosis / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D001784:Blood Gas Analysis; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004195:Disease Models, Animal; D004837:Epinephrine / Q000494:pharmacology / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010102:Oxygen Inhalation Therapy; D011897:Random Allocation; D012756:Sheep
chemical_list: D004837:Epinephrine