The Lancet; The Safety of Addition of Nitrous Oxide to General Anaesthesia in At-Risk Having Major Non-Cardiac Surgery
What's It About?
So What've They Done?
Patients who had cardiovascular risk factors (e.g. known IHD or cerebrovascular disease), and were undergoing non cardiac surgery of longer than 2 hours were elligile. They were randomised to receive either 70% nitrous oxide with 30% O2 or an air-oxygen mix with 30% O2. The anaesthetist was aware of the allocation but no-one else in the process was (patient, surgical team, research team). The patients had close follow up whilst in hospital, including specifically timed ECG and troponin investigations, and telephone follow up at 30 days. The primary outcome was a composite of death and cardiovascular event, with a number of secondary and tertiary outcomes, including surgical site infection, post-op nausea and vomiting (PONV), all-cause mortality, and ICU admission.
What Did They Find?
Is It Any Good?
With regards to measurement and observation, they have been clear in their definitions of the outcomes they are looking at; a potential hazard when describing myocardial ischaemia/infarction. The data showing the different outcomes and other variables of the two groups (ASA status, baseline meds, types of operation, anaesthetic drugs used, etc.) are clearly presented and similar between the groups, as would be expected from randomisation.
Where do they fall down then? To be honest the criticisms of the study are more nit-picking in nature than strongly questioning the validity of the study’s conclusions. I suppose the first question that came to my mind was that they have been selective about the population they wanted to look at; namely the patients with the higher cardiovascular risk. This is done with the reasoning that it would make it easier to detect the desired outcome in this population, because these are the ones that are most at risk of post-operative events. But this is assuming that these will also be the patients that are most at risk from nitrous’ side effects, and that we can then extrapolate the results back to the lower risk population. Not an unreasonable preposition but still involves some extrapolation of the results. Secondly, they lose some marks for the absence of double-blinding. It is certainly impractical and probably impossible to safely blind anaesthetists to the gas mixture they are given, but it does bring in the risk that the anaesthetist knowing which gas mixture they are giving might affect the other aspects of the anaesthetic they give. The authors have approached this problem by looking at the drugs given and intraoperative variables, noting a few small differences like the incidence of antiemetic prophylaxis being given, but there is always the potential to miss things and hence why double blinding is the ideal scenario.
Ultimately, I think this study does a lot for nitrous’ safety profile. As has been commented in some of the reviews in the past, nitrous has a long long history, and you don’t usually hang around that long if you’re a bit of a killer. It is a drug, it has side effects and it has desired effects. The side effects here are probably less worrying than we had been starting to think, so we are left to balance them against the plus points to provide the best anaesthetic for our patients. I can see scenarios where I would choose to use nitrous and others where I would like to avoid it. Now I can have more confidence that I am not dishing out myocardial infarctions when I do turn it on. I just might need to grab some extra ondansetron though.
Once again thanks for reading, and please let me know your thoughts on the subject. What role does nitrous play in your anaesthetics and has ENIGMA II changed this at all?
- The Lancet; The Safety of Addition of Nitrous Oxide to General Anaesthesia in At-Risk Having Major Non-Cardiac Surgery. 2014
- Anesthesiology: Avoidance of Nitrous Oxide for Patients Undergoing Major Surgery: A Randomized Controlled Trial. 2008
- Anesthesia & Analgesia: Nitrous oxide and long-term morbidity and mortality in the ENIGMA trial. 2011
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