Effects of levosimendan on right ventricular afterload in patients with acute respiratory distress syndrome: a pilot study.
OBJECTIVE
Acute respiratory distress syndrome (ARDS) is frequently associated with increased pulmonary vascular resistance and thus with systolic load of the right ventricle. We hypothesized that levosimendan, a new calcium sensitizer with potential pulmonary vasodilator properties, improves hemodynamics by unloading the right ventricle in patients with ARDS.


METHODS
Prospective, randomized, placebo-controlled, pilot study.


METHODS
Twenty-two-bed multidisciplinary intensive care unit of a university hospital.


METHODS
Thirty-five patients with ARDS in association with septic shock.


METHODS
Patients were randomly allocated to receive a 24-hr infusion of either levosimendan 0.2 microg/kg/min (n = 18) or placebo (n = 17). Data from right heart catheterization, cardiac magnetic resonance, arterial and mixed venous oxygen tensions and saturations, and carbon dioxide tensions were obtained before and 24 hrs after drug infusion.


RESULTS
At a mean arterial pressure between 70 and 80 mm Hg (sustained with norepinephrine infusion), levosimendan increased cardiac index (from 3.8 +/- 1.1 to 4.2 +/- 1.0 L/min/m) and decreased mean pulmonary artery pressure (from 29 +/- 3 to 25 +/- 3 mm Hg) and pulmonary vascular resistance index (from 290 +/- 77 to 213 +/- 50 dynes/s/cm(5)/m(2); each p < .05). Levosimendan also decreased right ventricular end-systolic volume and increased right ventricular ejection fraction (p < .05). In addition, levosimendan increased mixed venous oxygen saturation (from 63 +/- 8 to 70 +/- 8%; p < .01).


CONCLUSIONS
This study provides evidence that levosimendan improves right ventricular performance through pulmonary vasodilator effects in septic patients with ARDS. A large multiple-center trial is needed to investigate whether levosimendan is able to improve the overall prognosis of patients with sepsis and ARDS.
Morelli
Andrea
A
Department of Anesthesiology and Intensive Care, University of Rome La Sapienza, Italy.
Teboul
Jean-Louis
JL
Maggiore
Salvatore Maurizio
SM
Vieillard-Baron
Antoine
A
Rocco
Monica
M
Conti
Giorgio
G
De Gaetano
Andrea
A
Picchini
Umberto
U
Orecchioni
Alessandra
A
Carbone
Iacopo
I
Tritapepe
Luigi
L
Pietropaoli
Paolo
P
Westphal
Martin
M
D000368:Aged; D005260:Female; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D010100:Oxygen / Q000097:blood; D010865:Pilot Projects; D011446:Prospective Studies; D011724:Pyridazines / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D012772:Shock, Septic / Q000188:drug therapy / Q000503:physiopathology; D000077464:Simendan; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D013599:Systole / Q000187:drug effects* / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000627:therapeutic use*; D018497:Ventricular Dysfunction, Right / Q000188:drug therapy* / Q000503:physiopathology
D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan; D010100:Oxygen