Ketamine Inhibits Lung Fluid Clearance through Reducing Alveolar Sodium Transport

Yong Cui,Lei Chen,Junke Wang,Lin Zhang,Honglong Ji,Hongguang Nie,Hong Ma

doi:10.1155/2011/460596

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.

Highlights

Ketamine is a broadly used anaesthetic for analgosedation, especially during sepsis and cardiovascular instability
Ketamine can only alter Alveolar fluid clearance (AFC) fractions contributed by non-epithelial Na+ channels (ENaC) pathways
These data suggest that ketamine could almost completely decrease amiloride-sensitive fraction of AFC associated with ENaC (Figure 1(b))

Summary

Introduction

Ketamine is a broadly used anaesthetic for analgosedation, especially during sepsis and cardiovascular instability. Pulmonary edema is the abnormal fluid accumulation in the interstitial or alveolar spaces of the lung. Traditional teaching is that pulmonary edema occurring in patients tends to be cardiac in aetiology, usually with left heart dysfunction which caused back pressure across the pulmonary system, and led to extravasation of fluid into the alveolar space. Impairment of AFC is often related with worsened survival in ALI and ARDS patients [11, 12], which leads to the development of pulmonary edema [13]. We Journal of Biomedicine and Biotechnology evaluated whether AFC of fluid-instilled human lung lobes is impaired when ketamine is administered into the alveolar space ex vivo, aiming to find the role of ketamine in lung epithelial fluid transport

Methods

Results

Conclusion