Welcome back to the tasty morsels of critical care podcast.

In a further scandalous departure from Oh’s Manual today we’re going to look at a chapter of verified Irish Critical Care legend, Martin Tobin’s huge mechanical ventilation textbook. I have made it through about 5 chapters of this beast and it is undoubtedly comprehensive.

Anyhow, today will be nitric oxide, covering Tobin’s Chapter 61.

Nitric oxide is a colourless, odourless gas that exists in the atmosphere at anywhere between 10 and 500 parts per billion (emphasis on the billion here). Oddly it exists in quite high concentration in the nasal sinuses where it has been found at concentrations up to 30ppm which is in the therapeutic range. It seems that it has some kind of antimicrobial role here in the snot factory. NO is generated by the enzymatic actions of the practically named nitric oxide synthase enzyme.

How does it work in the lungs? Well the basic principle is that when NO reaches an alveolus it encourages more blood to flow past it. Thus it improves matching of ventilation with perfusion otherwise termed as improving V/Q matching. The hope is that in doing so it will also divert blood away from non ventilated alveoli reducing shunt. In a wonderfully patient oriented mechanism it becomes inert as it traverses the alveolar-blood membrane thus taking care of its own clearance and preventing systemic side effects.

There are a few potential indications for nitric

Persistent pulmonary hypertenison of the newborn where it seems to substantially reduce the need for ECMO.
RV dysfunction, particularly surrounding cardiac surgery or for primary graft dysfunction in lung transplant
- it has been definitively shown to reduce pulmonary artery pressures but not mortality
- in this scenario it can be used at a much higher dose than ARDS at up to 100ppm
ARDS
- usually at a fixed dose of 20ppm
- better in primary pulmonary ARDS (eg pneumonia, aspiration) rather than secondary causes (such as pancreatitis)
- no study has found definitive benefit
- it can be used as a brief trial at 20ppm in refractory hypoxaemia and you’re looking for a ~20% increase in the PaO2. Only about 50% respond.

Beyond the hassle of setting it up and getting all the plumbing on the vent right, are there any issues with giving it? Well, glad you asked there are indeed a few concerns.

Nitric Dioxide (NO2) is the evil cousin of NO that can cause pulmonary oedema and haemorrahge. Can be formed with high concentrations of NO and O2 together and the machine monitors for it
there is often rebound hypoxaemia after withdrawal probably related to suppression of native NO synthase. Sometimes it can feel like you’re stuck on homeopathic doses of NO trying to wean it off safely.
MetHb can be an issue as a byproduct of NO binding to Hb at the alveolar membrane. This is mentioned but is not something I have seen in real life.
it is thought to impair platelet aggregation, however clinically a variety of anti and pro coagulant effects have been noted
there is a definite association between AKI and NO in the ARDS trials of unclear mechanism

References

Tobin’s Principles and Practice of Mechanical Ventilation

LITFL

Mailbag: Who’s getting relegated from the Premier League this season?

Football Ramble

Forest's European distraction risk

The AI-powered Podcast Player