title: Comparison of equipressor doses of norepinephrine, epinephrine, and phenylephrine on septic myocardial dysfunction.
abstract: BACKGROUND
  Myocardial depression is a frequent event during septic shock and may mimic a cardiogenic shock state with decreased cardiac output. Nevertheless, data are scarce regarding the myocardial effects of vasopressors used to treat hypotension. In this study, the authors compared the effects of three commonly used vasopressors acting on different adrenergic receptors on myocardial function in a rodent model of septic shock, as explored with conductance catheter and positron emission tomography.
  
  
  METHODS
  Septic shock was induced in rats by peritonitis. Eighteen hours after septic insult, vasopressors were titrated to increase mean arterial pressure by 20% compared with baseline values.
  
  
  RESULTS
  We observed that peritonitis was associated with arterial hypotension and systolodiastolic dysfunction. Norepinephrine and epinephrine improved mean arterial pressure, cardiac output, and preload recruitable stroke work, a load-independent measure of systolic function, as well as diastolic function and ventriculoarterial coupling. Heart rate, myocardial oxygen consumption, and arrhythmia incidence were furthermore increased in the epinephrine group. Conversely, phenylephrine, a peripheral α-agonist, exhibited deleterious effects on systolodiastolic function and ventriculoarterial coupling. Conductance catheter and positron emission tomography yielded identical results with regard to myocardial function evolution under vasopressor treatment.
  
  
  CONCLUSIONS
  Phenylephrine, a drug without β-1 effects, was associated with decreased ventricular performance and ventriculoarterial uncoupling, whereas epinephrine and norepinephrine improved global hemodynamics and myocardial function in severely hypokinetic and hypotensive experimental septic shock. Nevertheless, epinephrine was associated with increased myocardial oxygen consumption. Thus, norepinephrine appears to be a more reliable and safer strategy as a first-line therapy in this particular setting.
authors.affiliation: Groupe Choc Contrat Avenir Inserm, U961, Faculte de Medecine, Nancy Universite, Nancy, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ducrocq
authors.forename: Antoine
authors.initials: A
authors.lastname: Kimmoun
authors.forename: Anna
authors.initials: A
authors.lastname: Furmaniuk
authors.forename: Zerin
authors.initials: Z
authors.lastname: Hekalo
authors.forename: Fatiha
authors.initials: F
authors.lastname: Maskali
authors.forename: Sylvain
authors.initials: S
authors.lastname: Poussier
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Marie
authors.forename: Bruno
authors.initials: B
authors.lastname: Levy
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology; D001794:Blood Pressure / Q000502:physiology; D002302:Cardiac Output / Q000502:physiology; D002404:Catheterization; D002432:Cecum / Q000293:injuries; D004837:Epinephrine / Q000008:administration & dosage* / Q000627:therapeutic use*; D006331:Heart Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D019344:Lactic Acid / Q000378:metabolism; D008026:Ligation; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009638:Norepinephrine / Q000008:administration & dosage* / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000502:physiology; D010538:Peritonitis / Q000150:complications; D010656:Phenylephrine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D013318:Stroke Volume / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000627:therapeutic use*
chemical_list: D000227:Adenine Nucleotides; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019344:Lactic Acid; D009638:Norepinephrine; D004837:Epinephrine