title: Acute effect of sildenafil on central hemodynamics in mechanically ventilated patients with WHO group III pulmonary hypertension and right ventricular failure necessitating administration of dobutamine.
abstract: OBJECTIVE
  Sildenafil decreases pulmonary vascular resistance index (PVRI), in patients with pulmonary hypertension (PH). We investigated sildenafil's effects on central hemodynamics of mechanically ventilated patients with WHO group-III PH and RV failure necessitating dobutamine administration.
  
  
  METHODS
  Prospective non-controlled study involving 12 (9 males, 59 ± 4 years old), patients with the above characteristics. All patients in phase-1 (days 1-2) received dobutamine (5 μg/kg/min IV). During phase-2 (days 3-6), sildenafil was started via nasogastric tube (80 mg/day) and dobutamine discontinuation was attempted. Patients were designated responders or non-responders based on whether dobutamine could be stopped or not. Phase-3 lasted from day 7 to day of weaning from mechanical ventilation; or if weaning failed, until day 20 following admission (end-of-study). Invasive and echocardiographic parameters were repeatedly recorded throughout the study.
  
  
  RESULTS
  Significantly changed parameters (P<0.025) from baseline to phase-1, -2 and -3 (%change of mean ratios), in responders (n=7) included among others PVRI (-40%, -51%, -42%), RV stroke work index (RVSWI: 43%, 79%, 41%) and cardiac index (49%, 54%, 48%), which also differed significantly from non-responders (N=5). In phases-1 and -3 non-responders had not significant changes, in phase-2 PVRI (27%) and RVSWI (-22%) changed significantly. In contrast to non-responders, all responders were weaned from mechanical ventilation until the end-of-study (P<0.025).
  
  
  CONCLUSIONS
  Sildenafil may improve central hemodynamics and RV function indices in ventilated patients with WHO group-III PH and RV failure requiring dobutamine infusion, when they respond favorably to the latter. Accordingly, an adequate RV systolic reserve may be mandatory for sildenafil to exert its actions.
authors.affiliation: Intensive Care Unit, General State Hospital of Athens, Athens, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karakitsos
authors.forename: John
authors.initials: J
authors.lastname: Papanikolaou
authors.forename: Andreas
authors.initials: A
authors.lastname: Karabinis
authors.forename: Raed
authors.initials: R
authors.lastname: Alalawi
authors.forename: Mitchell
authors.initials: M
authors.lastname: Wachtel
authors.forename: Cynthia
authors.initials: C
authors.lastname: Jumper
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Alexopoulos
authors.forename: Periklis
authors.initials: P
authors.lastname: Davlouros
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists; D004280:Dobutamine / Q000008:administration & dosage*; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage*; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D011687:Purines / Q000008:administration & dosage; D012121:Respiration, Artificial / Q000379:methods; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D018497:Ventricular Dysfunction, Right / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D004280:Dobutamine; D000068677:Sildenafil Citrate