Which is better for neuro-cognitive recovery after anaesthesia: propofol or sevoflurane?

Propofol compared with sevoflurane general anaesthesia is associated with decreased delayed neurocognitive recovery in older adults. Zhang et al

Of all the things I’ve lost, I miss my mind the most – Ozzy Osbourne

Background

The incidence of Post Operative Cognitive Dysfunction (POCD) is 25.8% at 1 week, 9.9% at three months and 1% at 1-2years. The condition has both short and long term bio-psycho-social implications.

Previous studies have failed to demonstrate as clearly that one anaesthetic technique is superior to another, however previous studies have failed to include control groups and there was significant variation in how they assessed cognition

Aim

The aim of the current study was to compare the effect of propofol vs sevoflurane on the incidence of delayed neurocognitive recovery in older adults undergoing major cancer surgery, with age- and education-matched non-surgical controls included to factor in learning effects from repeated neurocognitive tests

The primary endpoint was the incidence of delayed neurocognitive recovery at 1 week after surgery

Methods

Single centre trial at Peking University First  between 1st April 2015- 15th October 2016.

Aged between 65 and 90 yrs; Primary cancer without any radio- or chemotherapy before surgery and scheduled to undergo surgery for cancer with an expected duration of 2 hours under general anaesthesia

Patients were randomised to receive either sevoflurane or propofol maintenance and they underwent cognitive assessment pre and post operatively and function assessment preoperatively

A large amount of data was collected concurrently including drugs given, co-mordities, admission to ITU, mortality.

The control group was recruited from friends and family of patients, of similar age and educational level, who also underwent cognitive assessments at the same intervals

Results

When compared with control subjects, the incidence of cognitive decline at 1-week follow-up was higher in subjects [19.0% (72/379) vs 6.8% (4/59) in control subjects, P=0.02]

The incidence of delayed neurocognitive recovery at one week was significantly lower in the propofol group than in the sevoflurane group [14.8% (28/189) with propofol vs 23.2% (44/190) with sevoflurane; odds ratio (OR) 0.577, 95% CI 0.342-0.975; P=0.038).

The propofol group also reported statistically significant lower pain scores,  had lower BIS values, and fewer episodes of tachycardia intraoperatively.

Discussion

Suggested mechanisms for the published results were; neurotoxic effects of volatiles leading to accumulation of products such as amyloid plaques; neuroinflammatory seen with volatiles or the reduction in pain scores noted with propofol.

Taking all the evidence together, whether or not anaesthetic agents may contribute to the development of delayed neurocognitive recovery remains controversial.  Furthermore, the potential confounding effects of opioids cannot be ignored.

Analysis

Good points:

  • The neuropsychological test battery chosen according to the consensus on assessment of postoperative neurobehavioral outcomes, and covers the cognitive domains that are frequently affected after surgery.
  • A group of control subjects was enrolled and was well matched with patients.
  • Delayed neurocognitive recovery was diagnosed according to the definition of the ISPOCD1 study, which is widely accepted as a valid

Limitations:

  • Recruited in only one centre, therefore the generalisability of results can legitimately be questioned.
  • ‘Detrimental’ effects of sevoflurane may be underestimated because propofol was also used during induction
  • BIS monitoring was used to guide anaesthetic maintenance in the present study, and mean BIS values differed between the two group
  • Many different surgeries were included in this study
  • Delirium and delayed neurocognitive recovery might represent distinct or overlapping clinical entities
  • No discussion or allowance for sleep deprivation experienced perioperatively as compared to control group
  • The sample size was calculated to detect the difference of delayed neurocognitive recovery at 1 week after surgery
  • No comment of the greater deviation from study protocol in inhalation group

Will this change my practice?

It is currently unlikely that the results of this study will change my practice. Most importantly it is unclear whether a statistical difference in cognitive function at one week post operatively between those receiving propofol or volatile maintenance, translates to a clinical, or bio-psyco-social, difference long term.

I also have some issues with the methodology: there was no information given about the TCI model used and in this group of patients I feel that BIS may not be the most appropriate method to “standardise” between the two arms, considering the effect physiological and pathological changes can have on the reading, especially for example differences seen in relation to dementia.

Finally, and perhaps most importantly, a recent Cochrane review stated:

“We are uncertain whether maintenance with propofol-based TIVA or with inhalational agents affect incidences of postoperative delirium, mortality, or length of hospital stay because certainty of the evidence was very low. We found low-certainty evidence that maintenance with propofol-based TIVA may reduce POCD. We were unable to perform meta-analysis for intraoperative hypotension or length of stay in the PACU because of heterogeneity between studies. We identified 11 ongoing studies from clinical trials register searches; inclusion of these studies in future review updates may provide more certainty for the review outcomes.”

Conclusion

With an ageing population POCD is an issue that is vital that as anaesthetists we engage in as it results in significant social, economic and health implications in the short and long term. Given the recent Cochrane Review, at present there is not substantial evidence to suggest any one technique for anaesthetising this complex patient group is superior but we await outcomes from ongoing trials and subsequent reviews. In the interim we should focus on employing strategies to optimise modifiable risk factors which have a significant effect on overall cognition, for example nutrition, physical exercise, cognitive training, management of vascular and metabolic risk factors, and stimulation of social engagement

Summary by Dr Maddie Wells

 

 

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