Can dexmedetomidine help prevent cognitive decline after surgery?

A multicentre randomised control trial of the effect of intra-operative dexmedetomdine on cognitive decline after surgery. X.-Q. Cheng et al. Anaesthesia (2019), 74(6), 741-750.

Background

·     Post-operative cognitive decline is thought to affect 30% of patients over 60 after non-cardiac surgery.  It is associated with prolonged hospital stay, increased mortality and worse short-term quality of life.

·     Recent studies have shown a reduction in cognitive decline when using dexmedetomidine. 

·     A reduction in brain derived neurotrophic factor has been associated with post-operative cognitive decline.

Aim

1)     Does intra-operative infusion of dexmedetomidine have an effect on cognition up to six months post-operatively?

2)     Evaluate the association of dexmedetomidine infusion with changes in brain- derived neurotrophic factor (BDNF).

Method

·     Multi-centre, prospective, randomised control trial in China involving 10 different sites.

·     Performed between October 2014 to February 2017.

·     Patients were all over 65 years old and undergoing elective gastro-intestinal laparotomy.

·     Patients were randomised to dexmedetomidine and placebo (1:1 ratio) and allocations kept in envelopes at the investigating site.

·     Pharmacy prepared and dispensed the drugs (either dexmedetomidine or saline).

·     A standardised induction with propofol and sufentanil was given to all patients and maintenance of anaesthesia with propofol infusion. 

·     Each patient received a bolus of either dexmedetomidine or saline prior to induction and an intraoperative infusion, all dosed according to weight.

·     BDNF serum levels were taken 1 day before surgery and then at 3 and 7 days post-operatively. 

·     Cognitive assessments were carried out the day before surgery, 3 and 7 days post-operatively and at 1, 3 and 6 months. 

Results

·     Patient numbers were; Dexmedetomidine = 269, Placebo = 266. 

·     Reduced occurrence of delirium post-operatively in recovery with dexmedetomidine (5% vs 10%; p value = 0.03).

·     Reduced rates of post-operative cognitive decline at 3 and 7 days and 1 month with dexmedetomidine (3 days = 15% vs 24%, p value = 0.006; 7 days = 12% vs 18%, p value 0.03; 1 month = 17% vs 25%, p value 0.04).

·     No improvement noted at 3 months and in length of stay or mortality.

·     A linear reduction in BDNF levels were noted at 3 and 7 days but this reduction was lower in the dexmedetomidine group.

Discussion

Strengths

·     10 sites all conforming to the same practice- both groups were treated equally.

·     The two experimental groups were well matched.

·     Good method for blinding as the pharmacy would prepare the drugs with appropriate dosing.

Weaknesses

·     Drop-out of participants may have induced bias- one fifth of participants were lost to follow up.

·     Blinding of the anaesthetist may have been unsuccessful as the pre-operative bolus may have caused an obvious change in the patient’s observations.

·     No information was provided as to many intraoperative variables including experience of anaesthetist, use of invasive monitors and ionotropes/vasopressors.

·     Unable to control confounding variables once patients left hospital, possibly affecting the outcomes at 1, 3 and 6 months

·     Results from cognitive testing once the patients were at home may have been inaccurate due to difficulties with communication over the phone.

·     The results of the cognitive assessments showed that dexmedetomidine mainly limited the impairment in attention and not the decline in other areas of cognition.

Conclusion

Overall this study had a good method and made a good effort to keep all parties blinded.

However, there were intraoperative details missing which could have had a big impact on the outcome of the patients and too many confounding variables to consider once the patients were discharged from hospital. 

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s