Is Nitric Oxide the Solution to Ventilator Associated Pneumonia?


[box] Suborno Ghosh reports on a potentially promising technique for preventing ventilator associated pneumonia [/box]


A UK study is currently being undertaken to discover if the delivery of nitric oxide helps to reduce the occurrence of ventilator-associated pneumonia in intubated patients.

In a phase I dose-finding study researchers are using a liquid system to generate and deliver NOx (the collective term for other nitrogen oxides) to the stomach and oral cavity of mechanically ventilated patients (‘A Nitric Oxide (NOx) generating solution for the prevention of VAP’, UKCRN ID – 15334). Essentially this solution is being used to restore NO back to physiological levels. It is hypothesised that this solution could be used to decontaminate the mouth, upper throat and stomach therefore reducing the incidence of VAP in mechanically ventilated patients.

In UK intensive care units (ICUs) it has been estimated that over 60,000 patients are mechanically ventilated every year with an average stay of 5 days. This equates to a cost of approximately £500 million per annum. In 1997, a study by McKnight et al. found that iIn critically ill patients in ICUs a markedly reduced production of NO in the digestive tract is noticeable within hours of mechanical ventilation. Deficiency of NO predisposes to overgrowth of bacteria in the stomach and oral cavity, with consequent development of VAP following unwanted inhalation of infected secretions. Even with the introduction of specialist care bundles, the incidence of ventilator-associated pneumonia (VAP) remains high, reports varying between 10 and over 30%. The team of researchers based at QMUL, in partnership with EdixoMed Ltd, Edinburgh, are therefore investigating the potential benefits of exogenous NOx delivery in this particular setting.

Nitric oxide (NO) is a key molecule inside the body as it has roles in numerous critical signalling pathways. For example NO is an important regulator of vascular tone, inhibits platelet aggregation, aids the regulation of the immune response and has potent anti-microbial activity. Indeed in many disease states, dysfunction of the main enzymatic pathway that generates NO is a key aetiological event. Strategies that aim to remedy the situation have potential therapeutic utility. Numerous strategies have evolved to try and alleviate disease including administration of substrates that are required for NO production and replenishment of NO levels through the diet. However, an alternative strategy that aims to utilise a solution that can deliver exogenous NO, as well as other oxides of nitrogen, is gaining significant attention. This particular approach is being used in the prevention of VAP.

Confirmation of safety and tolerability of the NOx generating solution in phase I and II trials will pave the way for phase III efficacy trials. Thus there is hope to harness the potential of this simple solution as an easy-to-use bedside delivery system in every mechanically ventilated patient.

Suborno Ghosh

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