· 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.
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).
· 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.
· 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.
· 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.
· 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.
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.