Aerosolized prostacyclin and inhaled nitric oxide in septic shock--different effects on splanchnic oxygenation?
OBJECTIVE
To compare the effects of inhaled nitric oxide and aerosolized prostacyclin (PGI2) on hemodynamics and gas exchange as well as on the indocyanine-green plasma disappearance rate and gastric intramucosal pH in patients with septic shock.


METHODS
Prospective, randomized, interventional clinical study.


METHODS
Intensive care unit in a university hospital.


METHODS
Sixteen patients with pulmonary hypertension and septic shock according to the criteria of the ACCP/SCCM consensus conference all requiring norepinephrine and/or epinephrine to maintain mean arterial blood pressure above 65 mmHg.


METHODS
Patients were randomly assigned to receive either nitric oxide or aerosolized prostacyclin. Nitric oxide was inhaled using a commercially available delivery system, prostacyclin was administered with a modified ultrasound nebulizer. Both nitric oxide and prostacyclin were incrementally adjusted to obtain a 15% decrease of mean pulmonary artery pressure. Hemodynamics and gas exchange as well as indocyanine-green plasma disappearance rate and gastric intramucosal pH were determined at baseline after 90 min in steady state, after 90 min of nitric oxide inhalation or prostacyclin aerosol administration had elapsed in stable conditions, and after 90 min in stable conditions after nitric oxide or prostacyclin withdrawal.


RESULTS
Both inhaled nitric oxide and aerosolized prostacyclin selectively reduced the mean pulmonary artery pressure from 35 +/- 4, 30 +/- 4 mmHg (p < 0.05) and 34 +/- 4 to 30 +/- 3 mmHg (p < 0.05) respectively; after removal of nitric oxide and prostacyclin, the mean pulmonary artery pressure returned to the baseline values. Systemic hemodynamics remained unaltered during the vasodilator treatment. While the mean PaO2 was not significantly influenced, it increased in 4/8 of the NO- and 3/8 of the PGI2-treated patients. Neither of the drugs influenced indocyanine-green plasma disappearance rate, but prostacyclin--unlike nitric oxide--significantly increased gastric intramucosal pH (from 7.26 +/- 0.07 to 7.30 +/- 0.05, p < 0.05) which remained elevated in four of these patients after prostacyclin removal, and decreased the arterial-gastric mucosal pressure of carbon dioxide gap from 19 +/- 6 to 15 +/- 4 mmHg (p < 0.05).


CONCLUSIONS
Our data suggest that aerosolized prostacyclin--unlike nitric oxide--has similar beneficial effects on splanchnic perfusion and oxygenation as intravenous prostacyclin without detrimental effects on systemic hemodynamics. The different effects of prostacyclin and nitric oxide might be explained by the longer half-life of prostacyclin associated with a certain spillover into the systemic circulation.
Klinik für Anästhesiologie und Intensivmedizin, Universität Ulm, Germany.
O
O
Eichelbrönner
H
H
Reinelt
H
H
Wiedeck
M
M
Mezödy
R
R
Rossaint
M
M
Georgieff
P
P
Radermacher
D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D011464:Epoprostenol / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000187:drug effects*; D011446:Prospective Studies; D012772:Shock, Septic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D013152:Splanchnic Circulation / Q000187:drug effects*
D000336:Aerosols; D000959:Antihypertensive Agents; D009569:Nitric Oxide; D011464:Epoprostenol