The international ENIGMA II substudy on postoperative cognitive disorders

Information about yourself

I am currently an Assistant Professor at the Department of Acute Care Medicine - Anaesthesia - University of Geneva (Switzerland) and a member of the Committee for Quality and Data management at the Swiss Society of Anaesthesia. My research interests focus on quality and safety in anaesthesia.

Tell us a little about the background and methods of your research

Nitrous oxide (N₂O) is an anaesthetic gas used on a regular basis since the middle of the 19th century for sedation or general anaesthesia. For the latter, because it has weak anesthetic properties, it is used only as an adjuvant that enables dose reduction of other anesthetic drugs and limits their side effects. Considered for decades as innocuous, there is emerging evidence that N₂O carries a number of potential side effects. It enlarges natural air spaces (bowels, lungs, tympanic cavity). It can cause transitory leucopenia, postoperative nausea, and vomiting.N₂O also increases plasma homocysteine for up to a week after surgery. Elevation of plasma homocysteine causes endothelial dysfunction and mismatches between cerebral metabolism and blood flow. As a result, N₂O may also lead to cerebrovascular dysfunction resulting in delirium, delayed neurocognitive recovery, or persisting neuro cognitive disorders. However, existing evidence on the true impact of N₂O on postoperative cognitive performance and recovery is controversial. Whilst some studies attribute postoperative learning difficulties, loss of memory, disorientation, and reduced psychomotor performance to N₂O, others including randomized trials, fail to identify any detrimental effect of N₂O on cognitive performance. Thus, the role of N₂O in the development of delayed neurocognitive recovery remains to be determined. We therefore performed a multicentric trial to assess neurocognitive function change after anaesthesia in patients undergoing major non-cardiac surgery.

We used five computerized neuropsychological tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB):

• Motor Screening Task (MOT)
• Paired Associates Learning (PAL)
• Pattern Recognition Memory (PRM)
• Reaction time (RTI)
• One Touch Stocking of Cambridge (OTS) 

We compared postoperative neurocognitive recovery of patients receiving N₂O in the anesthetic gas mixture administered during surgery with patients receiving N₂O free anesthesia.

What were your key findings and implications of your study?

We compared recovery scores with CANTAB outcomes including episodic memory, decision making/processing speed, and executive functioning. At the first interim analysis, we found no change in episodic memory and decision making/processing speed scores pre and post-surgery. But executive functioning differences were found at seven days with an improved recovery for patients receiving N₂O compared with patients receiving Air/Oxygen in their anesthetic gas mixture. This suggests that nitrous oxide may have a neuroprotective effect on the brain. However, these are preliminary results from an interim analysis study and further assessment is required to confirm these findings.

Why did you choose CANTAB for your study?

As the trial took place in several countries with several different languages used, we chose the CANTAB test battery because it is language-independent, culturally neutral, and has been validated for the diagnosis of a wide range of cognitive disorders and syndromes. 

Are there any future areas of investigation that could follow your research?

Other areas of research will include cognitive recovery following other anaesthetic drugs administered.

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