title: Dose response to nitric oxide in adult cardiac surgery patients.
abstract: OBJECTIVE
  To determine the dose responsiveness to nitric oxide in adult cardiac surgery patients, especially in those patients with pulmonary hypertension.
  
  
  METHODS
  Prospective, randomized, nonblinded study.
  
  
  METHODS
  University teaching hospital.
  
  
  METHODS
  62 consecutive cardiac surgery patients demonstrating pulmonary hypertension immediately before induction of anesthesia.
  
  
  METHODS
  Subjects were assigned by random number allocation to receive one of five doses of inhaled nitric oxide on termination of cardiopulmonary bypass (CBP; i.e., restitution of pulmonary artery flow). Subjects in Group 1 (n = 11) received 10 ppm of inhaled nitric oxide, Group 2 subjects (n = 12) received 20 ppm, Group 3 subjects (n = 12) received 30 ppm, and Group 4 subjects (n = 12) received 40 ppm. The fifth group (n = 15) received no nitric oxide. This fifth group served as a control and was treated with milrinone only. Those patients who were randomized to the milrinone group, had milrinone initiated by bolus administration (50 microg/kg) 15 min before separation from CPB. Milrinone was maintained at 0.5 microg/kg/min in the operating room thereafter. The conduct of anesthesia, surgery, and CBP were controlled. A therapeutic algorithm dictated the use of vasoactive substances for all patients.
  
  
  METHODS
  Heart rate, mean arterial pressure, pulmonary vascular resistance (PVR), peripheral vascular resistance, cardiac index, and right ventricular ejection fraction were monitored throughout the operative experience.
  
  
  RESULTS
  There were no significant differences found in demographic data, baseline hemodynamic data, surgical treatment, conduct of CBP, or the use of inotropic or vasoactive drugs among the five treatment groups. The percentage decrease in PVR on treatment with nitric oxide as compared to baseline values was not significantly different among the groups (10 ppm = 38%, 20 ppm = 50%, 30 ppm = 44%, 40 ppm = 36%, milrinone = 58%, p = 0.86).
  
  
  CONCLUSIONS
  Treatment with nitric oxide was associated with significant reductions in PVR in all groups. Dosages higher than 10 ppm were not associated with greater reductions in pulmonary vascular tone. In view of the fact that nitric oxide-related toxicity is dose-related, doses greater than 10 ppm do not appear to be justified in this patient population.
authors: Department of Anesthesiology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ, USA. solinaal@umdnj.edu
authors: A R
authors: AR
authors: Solina
authors: S H
authors: SH
authors: Ginsberg
authors: D
authors: D
authors: Papp
authors: W R
authors: WR
authors: Grubb
authors: P M
authors: PM
authors: Scholz
authors: E J
authors: EJ
authors: Pantin
authors: R P
authors: RP
authors: Cody
authors: T J
authors: TJ
authors: Krause
mesh_terms: D000280:Administration, Inhalation; D000368:Aged; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016343:Monitoring, Intraoperative; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D009569:Nitric Oxide