title: Effects of vasoactive drugs on crystalloid fluid kinetics in septic sheep.
abstract: OBJECTIVE
  Crystalloid fluid and vasoactive drugs are used in the early treatment of sepsis. The purpose of the present study was to examine how these drugs alter plasma volume expansion, peripheral edema, and urinary excretion.
  
  
  METHODS
  Twenty-five anesthetized sheep were made septic by cecal puncture and a short infusion of lipopolysaccharide. After 50 min, a slow infusion of isotonic saline was initiated: the saline either contained no drug, norepinephrine (1 μg/kg/min), phenylephrine (3 μg/kg/min), dopamine (50 μg/kg/min), or esmolol (50 μg/kg/min). Ten min later, 20 mL/kg Ringer´s lactate solution was given over 30 min. Central hemodynamics, acid-base balance, and the urinary excretion were monitored. Frequent measurements of the blood hemoglobin concentration were used as input in a kinetic analysis, using a mixed effects modeling software.
  
  
  RESULTS
  The fluid kinetic analysis showed slow distribution and elimination of Ringer´s lactate, although phenylephrine and dopamine accelerated the distribution. Once distributed, the fluid remained in the peripheral tissues and did not equilibrate adequately with the plasma. Overall, stimulation of adrenergic alpha1-receptors accelerated, while beta1-receptors retarded, the distribution and elimination of fluid. A pharmacodynamic Emax model showed that Ringer´s lactate increased stroke volume by 13 ml/beat. Alpha1-receptors, but not beta1-receptors, further increased stroke volume, while both raised the mean arterial pressure. Modulation of the beta1-receptors limited the acidosis.
  
  
  CONCLUSIONS
  Stimulation of adrenergic alpha1-receptors with vasoactive drugs accelerated, while beta1-receptors retarded, the distribution and elimination of fluid. The tendency for peripheral accumulation of fluid was pronounced, in particular when phenylephrine was given.
authors.affiliation: Department of Anesthesiology, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, PR of China.|Research Center, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, PR of China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: The Department of Anesthesiology, Zhejiang Hospital, Hangzhou, Zhejiang Province, PR of China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiaozhu
authors.affiliation: Research Center, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, PR of China.
authors.forename: Ru
authors.initials: R
authors.lastname: Guomei
authors.affiliation: Research Center, Shaoxing People's Hospital, Shaoxing, Zhejiang Province, PR of China.
authors.forename: Ding
authors.initials: D
authors.lastname: Qiannan
authors.affiliation: Research Unit, Södertälje Hospital, Södertälje, Sweden.
authors.forename: Robert G
authors.identifier: http://orcid.org/0000-0002-1528-3803
authors.initials: RG
authors.lastname: Hahn
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000077324:Crystalloid Solutions; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects*; D007552:Isotonic Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000077325:Ringer's Lactate; D018805:Sepsis / Q000097:blood / Q000188:drug therapy*; D012756:Sheep; D012965:Sodium Chloride / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D002316:Cardiotonic Agents; D000077324:Crystalloid Solutions; D007552:Isotonic Solutions; D011412:Propanolamines; D000077325:Ringer's Lactate; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D012965:Sodium Chloride; C036604:esmolol; D004298:Dopamine; D009638:Norepinephrine