Intravenous S-ketamine does not inhibit alveolar fluid clearance in a septic rat model.
We previously demonstrated that intratracheally administered S-ketamine inhibits alveolar fluid clearance (AFC), whereas an intravenous (i.v.) bolus injection had no effect. The aim of the present study was to characterize whether continuous i.v. infusion of S-ketamine, yielding clinically relevant plasma concentrations, inhibits AFC and whether its effect is enhanced in acute lung injury (ALI) which might favor the appearance of i.v. S-ketamine at the alveolar surface. AFC was measured in fluid-instilled rat lungs. S-ketamine was administered i.v. over 6 h (loading dose: 20 mg/kg, followed by 20 mg/kg/h), or intratracheally by addition to the instillate (75 µg/ml). ALI was induced by i.v. lipopolysaccharide (LPS; 7 mg/kg). Interleukin (IL)-6 and cytokine-induced neutrophil chemoattractant (CINC)-3 were measured by ELISA in plasma and bronchoalveolar lavage fluid. Isolated rat alveolar type-II cells were exposed to S-ketamine (75 µg/ml) and/or LPS (1 mg/ml) for 6 h, and transepithelial ion transport was measured as short circuit current (ISC). AFC was 27±5% (mean±SD) over 60 min in control rats and was unaffected by i.v. S-ketamine. Tracheal S-ketamine reduced AFC to 18±9%. In LPS-treated rats, AFC decreased to 16±6%. This effect was not enhanced by i.v. S-ketamine. LPS increased IL-6 and CINC-3 in plasma and bronchoalveolar lavage fluid. In alveolar type-II cells, S-ketamine reduced ISC by 37% via a decrease in amiloride-inhibitable sodium transport. Continuous administration of i.v. S-ketamine does not affect rat AFC even in endotoxin-induced ALI. Tracheal application with direct exposure of alveolar epithelial cells to S-ketamine decreases AFC by inhibition of amiloride-inhibitable sodium transport.
Department of Anesthesiology, University Hospital, Heidelberg, Germany; Medical Clinic VII, Sports Medicine, University Hospital, Heidelberg, Germany.
Christian
C
Fastner
Medical Clinic VII, Sports Medicine, University Hospital, Heidelberg, Germany.
Heimo
H
Mairbäurl
Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam (AMC), Amsterdam, The Netherlands.
Nina C
NC
Weber
Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam (AMC), Amsterdam, The Netherlands.
Koen
K
van der Sluijs
Department of Anesthesiology, Critical Care and Pain Medicine, Salzburg General Hospital, Paracelsus Medical University, Salzburg, Austria.
Florian
F
Hackl
Department of Anesthesiology, University Hospital, Heidelberg, Germany; Department of Anesthesiology, Critical Care and Pain Medicine, Salzburg General Hospital, Paracelsus Medical University, Salzburg, Austria.
Lorenz
L
Hotz
Department of Anesthesiology, University Medical Center, Leiden, The Netherlands.
Albert
A
Dahan
Department of Anesthesiology, University of Amsterdam (AMC), Amsterdam, The Netherlands.
Markus W
MW
Hollmann
Department of Anesthesiology, University Hospital, Heidelberg, Germany; Department of Anesthesiology, Critical Care and Pain Medicine, Salzburg General Hospital, Paracelsus Medical University, Salzburg, Austria.
Marc M
MM
Berger
D061605:Administration, Intravenous; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid; D007649:Ketamine / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D008297:Male; D011650:Pulmonary Alveoli / Q000473:pathology*; D011654:Pulmonary Edema / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism
D007649:Ketamine; D012964:Sodium