title: Controlled pauses at the initiation of sodium nitroprusside-enhanced cardiopulmonary resuscitation facilitate neurological and cardiac recovery after 15 mins of untreated ventricular fibrillation.
abstract: OBJECTIVE
  A multipronged approach to improve vital organ perfusion during cardiopulmonary resuscitation that includes sodium nitroprusside, active compression-decompression cardiopulmonary resuscitation, an impedance threshold device, and abdominal pressure (sodium nitroprusside-enhanced cardiopulmonary resuscitation) has been recently shown to increase coronary and cerebral perfusion pressures and higher rates of return of spontaneous circulation vs. standard cardiopulmonary resuscitation. To further reduce reperfusion injury during sodium nitroprusside-enhanced cardiopulmonary resuscitation, we investigated the addition of adenosine and four 20-sec controlled pauses spread throughout the first 3 mins of sodium nitroprusside-enhanced cardiopulmonary resuscitation. The primary study end point was 24-hr survival with favorable neurologic function after 15 mins of untreated ventricular fibrillation.
  
  
  METHODS
  Randomized, prospective, blinded animal investigation.
  
  
  METHODS
  Preclinical animal laboratory.
  
  
  METHODS
  Thirty-two female pigs (four groups of eight) 32±2 kg.
  
  
  METHODS
  After 15 mins of untreated ventricular fibrillation, isoflurane-anesthetized pigs received 5 mins of either standard cardiopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation+adenosine, or controlled pauses-sodium nitroprusside-enhanced cardiopulmonary resuscitation+adenosine. After 4 mins of cardiopulmonary resuscitation, all animals received epinephrine (0.5 mg) and a defibrillation shock 1 min later. Sodium nitroprusside-enhanced cardiopulmonary resuscitation-treated animals received sodium nitroprusside (2 mg) after 1 min of cardiopulmonary resuscitation and 1 mg after 3 mins of cardiopulmonary resuscitation. After 1 min of sodium nitroprusside-enhanced cardiopulmonary resuscitation, adenosine (24 mg) was administered in two groups.
  
  
  RESULTS
  A veterinarian blinded to the treatment assigned a cerebral performance category score of 1-5 (normal, slightly disabled, severely disabled but conscious, vegetative state, or dead, respectively) 24 hrs after return of spontaneous circulation. Sodium nitroprusside-enhanced cardiopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation+adenosine, and controlled pauses-sodium nitroprusside-enhanced cardiopulmonary resuscitation+adenosine resulted in a significantly higher 24-hr survival rate compared to standard cardiopulmonary resuscitation (7 of 8, 8 of 8, and 8 of 8 vs. 2 of 8, respectively p<.05). The mean cerebral performance category scores for standard cardiopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation, sodium nitroprusside-enhanced cardiopulmonary resuscitation+adenosine, or controlled pauses-sodium nitroprusside-enhanced cardiopulmonary resuscitation+adenosine were 4.6±0.7, 3±1.3, 2.5±0.9, and 1.5±0.9, respectively (p<.01 for controlled pauses-sodium nitroprusside-enhanced cardiopulmonary resuscitation+adenosine compared to all other groups).
  
  
  CONCLUSIONS
  Reducing reperfusion injury and maximizing circulation during cardiopulmonary resuscitation significantly improved functional neurologic recovery after 15 mins of untreated ventricular fibrillation. These results suggest that brain resuscitation after prolonged cardiac arrest is possible with novel, noninvasive approaches focused on reversing the mechanisms of tissue injury.
authors.affiliation: Cardiovascular Division, Department of Emergency Medicine, University of Minnesota, Minneapolis, MN, USA. yanno001@umn.edu
authors.forename: Demetris
authors.initials: D
authors.lastname: Yannopoulos
authors.forename: Nicolas
authors.initials: N
authors.lastname: Segal
authors.forename: Scott
authors.initials: S
authors.lastname: McKnite
authors.forename: Tom P
authors.initials: TP
authors.lastname: Aufderheide
authors.forename: Keith G
authors.initials: KG
authors.lastname: Lurie
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000503:physiopathology; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004452:Echocardiography; D005260:Female; D006321:Heart / Q000503:physiopathology; D009599:Nitroprusside / Q000008:administration & dosage / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000517:prevention & control; D013552:Swine; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000628:therapy*; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; D000241:Adenosine