title: Comparing anesthesia with isoflurane and fentanyl/fluanisone/midazolam in a rat model of cardiac arrest.
abstract: Only one in ten patients survives cardiac arrest (CA), underscoring the need to improve CA management. Isoflurane has shown cardio- and neuroprotective effects in animal models of ischemia-reperfusion injury. Therefore, the beneficial effect of isoflurane should be tested in an experimental CA model. We hypothesize that isoflurane anesthesia improves short-term outcome following resuscitation from CA compared with a subcutaneous fentanyl/fluanisone/midazolam anesthesia. Male Sprague-Dawley rats were randomized to anesthesia with isoflurane (n= 11) or fentanyl/fluanisone/midazolam (n= 11). After 10 min of asphyxial CA, animals were resuscitated by mechanical chest compressions, ventilations, and epinephrine and observed for 30 min. Hemodynamics, including coronary perfusion pressure, systemic O2consumption, and arterial blood gases, were recorded throughout the study. Plasma samples for endothelin-1 and cathecolamines were drawn before and after CA. Compared with fentanyl/fluanisone/midazolam anesthesia, isoflurane resulted in a shorter time to return of spontaneous circulation (ROSC), less use of epinephrine, increased coronary perfusion pressure during cardiopulmonary resusitation, higher mean arterial pressure post-ROSC, increased plasma levels of endothelin-1, and decreased levels of epinephrine. The choice of anesthesia did not affect ROSC rate or systemic O2consumption. Isoflurane reduces time to ROSC, increases coronary perfusion pressure, and improves hemodynamic function, all of which are important parameters in CA models.NEW & NOTEWORTHYThe preconditioning effect of volatile anesthetics in studies of ischemia-reperfusion injury has been demonstrated in several studies. This study shows the importance of anesthesia in experimental cardiac arrest studies as isoflurane raised coronary perfusion pressure during resuscitation, reduced time to return of spontaneous circulation, and increased arterial blood pressure in the post-cardiac arrest period. These effects on key outcome measures in cardiac arrest research are important in the interpretation of results from animal studies.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark; niels.secher@me.com.
authors.forename: Niels
authors.identifier: http://orcid.org/0000-0002-5207-9932
authors.initials: N
authors.lastname: Secher
authors.affiliation: Department of Bioscience, Section for Zoophysiology, Aarhus University, Aarhus, Denmark; and.
authors.forename: Christian Lind
authors.initials: CL
authors.lastname: Malte
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Else
authors.initials: E
authors.lastname: Tønnesen
authors.affiliation: Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark.
authors.forename: Leif
authors.initials: L
authors.lastname: Østergaard
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Asger
authors.initials: A
authors.lastname: Granfeldt
mesh_terms: D000758:Anesthesia; D000818:Animals; D002090:Butyrophenones / Q000494:pharmacology*; D016887:Cardiopulmonary Resuscitation; D002395:Catecholamines / Q000097:blood; D019332:Endothelin-1 / Q000097:blood; D004837:Epinephrine / Q000494:pharmacology; D005283:Fentanyl / Q000494:pharmacology*; D006323:Heart Arrest / Q000628:therapy*; D006439:Hemodynamics; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D010101:Oxygen Consumption; D017207:Rats, Sprague-Dawley
chemical_list: D002090:Butyrophenones; D002395:Catecholamines; D019332:Endothelin-1; C005014:fluanisone; D007530:Isoflurane; D008874:Midazolam; D005283:Fentanyl; D004837:Epinephrine
keywords: anesthesia; cardiac arrest; catecholamines; fentanyl; isoflurane; oxygen consumption