Ketamine Inhibits Lung Fluid Clearance through Reducing Alveolar Sodium Transport

Abstract

Ketamine is a broadly used anaesthetic for analgosedation. Accumulating clinical evidence shows that ketamine causes pulmonary edema with unknown mechanisms. We measured the effects of ketamine on alveolar fluid clearance in human lung lobes ex vivo. Our results showed that intratracheal instillation of ketamine markedly decreased the reabsorption of 5% bovine serum albumin instillate. In the presence of amiloride (a specific ENaC blocker), fluid resolution was not further decreased, suggesting that ketamine could decrease amiloride-sensitive fraction of AFC associated with ENaC. Moreover, we measured the regulation of amiloride-sensitive currents by ketamine in A549 cells using whole-cell patch clamp mode. Our results suggested that ketamine decreased amiloride-sensitive Na+ currents (ENaC activity) in a dose-dependent fashion. These data demonstrate that reduction in lung ENaC activity and lung fluid clearance following administration of ketamine may be the crucial step of the pathogenesis of resultant pulmonary edema.

Differential Intraocular Pressure Measurements by Tonometry and Direct Cannulation After Treatment with Soluble Adenylyl Cyclase Inhibitors

“…This effect may disguise the effect DMSO would have on corneal thickness in the KXA group. Previous literature has shown that ketamine may be involved in pulmonary edema, 30,31 lending support to this hypothesis.…”

Intravenous S-Ketamine Does Not Inhibit Alveolar Fluid Clearance in a Septic Rat Model

“…The results further show that in S-ketamine treated cells, the amiloride-inhibitable portion of ISC was significantly reduced. This finding suggests, that S-ketamine partially inhibited ENaC, which might explain the inhibition of reabsorption upon alveolar application, which is in line with previous observations [16] , [29] .…”

“…Due to the many between-species variations in the properties of the ENaC, our findings do not exclude the possibility that IV S-ketamine might reduce ENaC activity – and thus AFC – in humans, but not in rats, as suggestedpreviously [29] , [36] .…”

“…The first studies documenting that S-ketamine in the rat alveolar space impairs AFC [16] , [29] raised the question whether S-ketamine might be disadvantegous as analgosedative drug in patients with ALI. The present study does not support this concern.…”