title: Epinephrine, compared with arginine vasopressin, is associated with similar haemodynamic effects but significantly improved brain oxygenation in the early phase of anaphylactic shock in rats: An experimental study.
abstract: BACKGROUND
  In contrast to other types of shock, anaphylactic shock decreases cerebral blood flow more than would be expected from severe arterial hypotension, thus potentially affecting survival through brain ischaemia/hypoxia. We hypothesised that epinephrine (EPI) used as a first-line treatment of anaphylactic shock and arginine vasopressin (AVP) proposed in case of EPI refractoriness may have different effects on brain oxygenation.
  
  
  OBJECTIVE
  To compare the effect of EPI and AVP on brain oxygenation under similar macro-haemodynamic target values in an anaphylactic shock model.
  
  
  METHODS
  Prospective laboratory study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Male brown Norway rats (n = 27).
  
  
  METHODS
  Twenty-seven rats were sensitised with ovalbumin (OVA). Twenty rats had anaphylactic shock induced with OVA and were resuscitated with either 0.9% saline (OVA group), EPI (EPI group) or AVP (AVP group). Sensitised control rats received only 0.9% saline and no OVA (CON group).
  
  
  METHODS
  Mean arterial pressure (MAP), carotid artery blood flow (CaBF), cerebral cortical blood flow (CBF) and hippocampal oxygen partial pressure (PtiO2) were recorded.
  
  
  RESULTS
  All rats in the OVA group died within 15 min. EPI and AVP restored comparable levels of MAP, carotid artery blood flow and CBF, and extended survival time. EPI was associated with biologically relevant and significantly (P < 0.05) higher PtiO2 values (nadir values at 20 min: 25.0 ± 2.2 mmHg) compared with the AVP group (14.9 ± 2.0 mmHg). The slopes of the correlations of MAP vs. PtiO2 and CBF were significantly steeper with AVP (more pressure dependence) compared with EPI. By the end of the experiment, hippocampal PtiO2 values between the EPI (24.1 ± 2.1 mmHg) and the AVP (20.8 ± 2.0 mmHg) groups were similar.
  
  
  CONCLUSIONS
  At early, but not at late time points, resuscitation of anaphylactic shock with EPI or AVP to similar MAP and CBF endpoints resulted in hippocampal PtiO2 being significantly higher after EPI. In addition, the PtiO2 after EPI always remained above the threshold for brain hypoxia, whereas PtiO2 after AVP was below the hypoxic threshold most of the time. Because of this early brain hypoxia, AVP may not be the drug of first choice for resuscitation of anaphylactic shock.
authors.affiliation: From the Groupe Choc, Contrat AVENIR INSERM U1116, Faculté de Médecine, Université de Lorraine, Vandœuvre-lès-Nancy, France (FZ, GB, BL, GA, J-MM, P-MM), Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China (FZ), Pôle Anesthésie, Réanimations Chirurgicales, SAMU, Hôpitaux Universitaires de Strasbourg, and Laboratoire EA 3072: « Mitochondries, stress oxydant et protection musculaire », Institut de Physiologie, Faculté de Médecine, Université de Strasbourg, Strasbourg (FZ, OC, WO, P-MM), Pôle Urgences Réanimation Anesthésie Douleur, Hôpital Maison Blanche, CHU de Reims, Reims (JD, J-MM), Département d'Anesthésie-Réanimation Chirurgicale, Centre Hospitalier Universitaire (CHU) Central, Nancy (GB, GA), Laboratoire U961, Faculté de Médecine, Université de Lorraine, Vandœuvre-lès-Nancy (SNT), Département d'Anesthésie-Réanimation Chirurgicale, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, and Unité INSERM U1148, Laboratory for Vascular Translational Science (LVTS), Université Paris Diderot, Sorbonne Paris Cité, Paris (DL), Service de Réanimation Médicale Brabois, CHU de Nancy, Vandœuvre-lès-Nancy, France (BL).
authors.forename: Feng
authors.initials: F
authors.lastname: Zheng
authors.forename: Olivier
authors.initials: O
authors.lastname: Collange
authors.forename: Julien
authors.initials: J
authors.lastname: Davidson
authors.forename: Grégoire
authors.initials: G
authors.lastname: Barthel
authors.forename: Walid
authors.initials: W
authors.lastname: Oulehri
authors.forename: Simon N
authors.initials: SN
authors.lastname: Thornton
authors.forename: Dan
authors.initials: D
authors.lastname: Longrois
authors.forename: Bruno
authors.initials: B
authors.lastname: Levy
authors.forename: Gérard
authors.initials: G
authors.lastname: Audibert
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Malinovsky
authors.forename: Paul-Michel
authors.initials: PM
authors.lastname: Mertes
mesh_terms: D000707:Anaphylaxis / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D011446:Prospective Studies; D051381:Rats; D011914:Rats, Inbred BN
chemical_list: D001127:Arginine Vasopressin; D010100:Oxygen; D004837:Epinephrine