Prevention is difficult to demonstrate but treatment usually is easier and high dosage for few days is possible. Look at this study plan below. Could it be used for PBT2 ? There is also other clinical possibilities as depression in old people which could be corresponding clinical diagnosis to treat with PBT2 but IMO postoperative delirium treatment with 600mg of PBT2 for 5 days could be interesting. This paper is only a study plan but it is an Australian group and Prana could only make a deal that they continue with PBT2 after they have done their study first.
See comment in PubMed Commons below
Trials. 2016 Aug 9;17:395. doi: 10.1186/s13063-016-1529-4.
The Post-Anaesthesia N-acetylcysteine Cognitive Evaluation (PANACEA) trial: study protocol for a randomised controlled trial.
Skvarc DR1,2,3,
Dean OM2,3,
Byrne LK1,
Gray LJ3,
Ives K4,
Lane SE3,5,
Lewis M6,
Osborne C4,
Page R3,7,
Stupart D8,
Turner A2,3,
Berk M2,3,
Marriott AJ9,10,11.
Author information
- 1School of Psychology, Deakin University, 221 Burwood Highway, Burwood, 3215, VIC, Australia.
- 2Innovations in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, Deakin University/Barwon Health Clinical School, Pigdons Road, Waurn Ponds, 3216, VIC, Australia.
- 3School of Medicine, Deakin University, Pigdons Road, Waurn Ponds, 3216, VIC, Australia.
- 4Department of Anaesthesia, Perioperative Medicine and Pain Management, Barwon Health, Bellarine Street, Geelong, 3220, VIC, Australia.
- 5Biostatistics Unit, Barwon Health, Bellarine Street, Geelong, 3220, VIC, Australia.
- 6Aged Psychiatry Service, Caulfield Hospital, Alfred Health, 260 Kooyong Road, Caulfield, 3162, Victoria, Australia.
- 7Barwon Orthopaedic Research Unit, Bellarine Street, Geelong, 3220, VIC, Australia.
- 8Department of General Surgery, Barwon Health, Bellarine Street, Geelong, 3220, VIC, Australia.
- 9Department of Anaesthesia, Perioperative Medicine and Pain Management, Barwon Health, Bellarine Street, Geelong, 3220, VIC, Australia. [email protected].
- 10Innovations in Mental and Physical Health and Clinical Treatment (IMPACT) Strategic Research Centre, Deakin University/Barwon Health Clinical School, Pigdons Road, Waurn Ponds, 3216, VIC, Australia. [email protected].
- 11School of Medicine, Deakin University, Pigdons Road, Waurn Ponds, 3216, VIC, Australia. [email protected].
Abstract
BACKGROUND:
Some degree of cognitive decline after surgery occurs in as many as one quarter of elderly surgical patients, and this decline is associated with increased morbidity and mortality. Cognition may be affected across a range of domains, including memory, psychomotor skills, and executive function. Whilst the exact mechanisms of cognitive change after surgery are not precisely known, oxidative stress and subsequent neuroinflammation have been implicated. N-acetylcysteine (NAC) acts via multiple interrelated mechanisms to influence oxidative homeostasis, neuronal transmission, and inflammation. NAC has been shown to reduce oxidative stress and inflammation in both human and animal models. There is clinical evidence to suggest that NAC may be beneficial in preventing the cognitive decline associated with both acute physiological insults and dementia-related disorders. To date, no trials have examined perioperative NAC as a potential moderator of postoperative cognitive changes in the noncardiac surgery setting.
METHODS AND DESIGN:
This is a single-centre, randomised, double-blind, placebo-controlled clinical trial, with a between-group, repeated-measures, longitudinal design. The study will recruit 370 noncardiac surgical patients at the University Hospital Geelong, aged 60 years or older. Participants are randomly assigned to receive either NAC or placebo (1:1 ratio), and groups are stratified by age and surgery type. Participants undergo a series of neuropsychological tests prior to surgery, 7 days, 3 months, and 12 months post surgery. It is hypothesised that the perioperative administration of NAC will reduce the degree of postoperative cognitive changes at early and long-term follow-up, as measured by changes on individual measures of the neurocognitive battery, when compared with placebo. Serum samples are taken on the day of surgery and on day 2 post surgery to quantitate any changes in levels of biomarkers of inflammation and oxidative stress.
DISCUSSION:
The PANACEA trial aims to examine the potential efficacy of perioperative NAC to reduce the severity of postoperative cognitive dysfunction in an elderly, noncardiac surgery population. This is an entirely novel approach to the prevention of postoperative cognitive dysfunction and will have high impact and translatable outcomes if NAC is found to be beneficial
(20min delay)