title: Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study.
abstract: BACKGROUND
  Patients with distributive shock who require high dose vasopressors have a high mortality. Angiotensin II (ATII) may prove useful in patients who remain hypotensive despite catecholamine and vasopressin therapy. The appropriate dose of parenteral angiotensin II for shock is unknown.
  
  
  METHODS
  In total, 20 patients with distributive shock and a cardiovascular Sequential Organ Failure Assessment score of 4 were randomized to either ATII infusion (N =10) or placebo (N =10) plus standard of care. ATII was started at a dose of 20 ng/kg/min, and titrated for a goal of maintaining a mean arterial pressure (MAP) of 65 mmHg. The infusion (either ATII or placebo) was continued for 6 hours then titrated off. The primary endpoint was the effect of ATII on the standing dose of norepinephrine required to maintain a MAP of 65 mmHg.
  
  
  RESULTS
  ATII resulted in marked reduction in norepinephrine dosing in all patients. The mean hour 1 norepinephrine dose for the placebo cohort was 27.6 ± 29.3 mcg/min versus 7.4 ± 12.4 mcg/min for the ATII cohort (P =0.06). The most common adverse event attributable to ATII was hypertension, which occurred in 20% of patients receiving ATII. 30-day mortality for the ATII cohort and the placebo cohort was similar (50% versus 60%, P =1.00).
  
  
  CONCLUSIONS
  Angiotensin II is an effective rescue vasopressor agent in patients with distributive shock requiring multiple vasopressors. The initial dose range of ATII that appears to be appropriate for patients with distributive shock is 2 to 10 ng/kg/min.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01393782. Registered 12 July 2011.
authors.forename: Lakhmir S
authors.initials: LS
authors.lastname: Chawla
authors.forename: Laurence
authors.initials: L
authors.lastname: Busse
authors.forename: Ermira
authors.initials: E
authors.lastname: Brasha-Mitchell
authors.forename: Danielle
authors.initials: D
authors.lastname: Davison
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Honiq
authors.forename: Ziyad
authors.initials: Z
authors.lastname: Alotaibi
authors.forename: Michael G
authors.initials: MG
authors.lastname: Seneff
mesh_terms: D061605:Administration, Intravenous; D000368:Aged; D000804:Angiotensin II / Q000627:therapeutic use*; D001794:Blood Pressure; D002302:Cardiac Output; D002395:Catecholamines / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000627:therapeutic use*; D010865:Pilot Projects; D012772:Shock, Septic / Q000188:drug therapy*; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
chemical_list: D002395:Catecholamines; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009638:Norepinephrine