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Lars I. Eriksson, MD, PhD, FRCA
Professor, Academic Chairman Dept of Anesthesiology and Intensive Care Medicine
Function Perioperative Medicine and Intensive Care Karolinska Institutet and
Karolinska University Hospital Stockholm, Sweden [email protected]
SwERAS, World Trade Centre, Stockholm Nov 21-22, 2019
Neuroprotection - the Human Brain after Anesthesia and Surgery
Globally increased focus on postoperative neurocognitive outcomes
M Leslie, Science Magazine June 2, 2017 American Soc Anesthesiologists website
Time course of brain dysfunction after surgery
Hours/days Week/Month Permanent
DSM-code DSM alignment DSM-code with new nomenclature
Delirium Postoperative cognitive decline
Dementia
Postoperative delirium POD
Acute onset of change in mental status inattention, desorganised thinking, altered consciouness Usually within 72 hours postop Hyperactive delirium (most common) agitation, confusion, combativeness Hypoactive delirium (less common) drowsiness, lethargy, slow speech, inattention
Definition and types of POD
POD is associated with - increased burden of postop care, - longterm cognitive decline and dementia - increased postoperative mortality
Patients developing POD cost on averege 2.5 times the care for patients without POD
Overall incidence of POD at 35 % (n=1823 patients) Range 10 – 60 % in older patients
Incidence of POD in the adult
Guenther et al Curr Op Anesthesiol 2011, Allen et al N Am Surg Clin 2013 Rudolph et al Anesth Analg 2011, Leslie et al Arch Intern Med 2008
Risk factors for postoperative delirium Major preexisting risk factors - age > 65 y - preop cognitive impairment or dementia - poor vision or hearing - severe illness, malnutrition, frailty - Infection
Additional factor: sleep deprivation, poor functional status, metabolic derangements, polypharmacy, poorly controlled pain, dehydration, neuropsychiatric conditions, alcohol or drug abuse
ESA Guideline for POD, 2017 Am J Surg. 2010, Expert Panel on Postop delirium Journal of the American Geriatrics Society 2015
Risk factors for postoperative delirium Precipitating risk factors and drugs at-risk - urgency, i.e. acute > elective - anticholinergics - long duration and invasiveness - opioids - need admission to the ICU - benzodiazepines - postop infection - dopaminergics - postop vascular adverse events - metoclopramide
- barbiturates
ESA Guideline for POD, 2017 Am J Surg. 2010, Expert Panel on Postop delirium Journal of the American Geriatrics Society 2015
Well-established diagnos within DSM V system POD is typically studied with neuropsychological bedside tests CAM (Confusion Assessment Method) DRS (Delirium Rating Scale)
Assessment of POD
Strom, Lancet 2010, Guenther,l Curr Op Anesthesiol 2011, Barnes-Daly CCM 2017, Hishieh JAMA Intern Med 2015, ESA Guidelines on POD 2017, Mahanna-Gabrielli Br J Anaesth 2019
Prevention and Treatment of POD Non-pharmacological care process approach ! ERAS concept (provide clock, visual/hearing aids, day/
night rythm, no indwelling catheters or IV lines, early mobilization and nutrition
Perioperative management still under debate ! Raw EEG to avoid burst suppression - promising but still unclear ! Processed EEG - conflicting impact on outcome ! NIRS-guided anesthesia, small size studies, methodological issues ! Dexmedetomidine perioperatively may reduce POD but not POCD
! Sedation at BIS > 80 vs < 50 during regional anesthesia
! Melatonin show conflicting results - unclear evidence
Adapted from Mahanna-Gabrielli Br J Anaesth 2019
Gaps and needs to be explored How should dexmedetomidine be administered perioperatively to reduce POD and prevent cognitive decline? Does EEG-guided anesthesia reduce the incidence or severity of postoperative postoperative delirium or cognitive decline ? Does NIRS-guided anesthesia/ optimization of cerebral perfusion reduce the incidence or severity of postoperative delirium or cognitive decline ? Can maintenance of intraoperative blood pressure above an individual’s cerebral pressure autoregulatory threshold reduce the incidence or severity of postoperative delirium (or cognitive decline) ?
Postoperative cognitive dysfunction
! Incidence is 20-40 % at 1 week and 10-15 % at 3 months Möller et al, Lancet 1998, Monk et al Anesthesiology 2008
! No or minimal difference in longterm impact by general anesthesia
v.s. regional techniques ! Rasmussen et al acta Anesthesiol Scand 2002 ! No or minimal difference between IV versus inhaled anesthetics
Shoen et al, Br J Anaesth 2011, Royse et al, Anaesthesia 2011, Qiao Anesthesiology 2015
Cognitive decline after non-cardiac surgery
Patient and Perioperative factors
Perioperative protocols impact early cognitive decline in orthopedics
Incidence of POCD 1 week 3 months n= 220, TKA or THA 9.1 % 8.0 % Ortho part ISPOCD and others 20-40 % 6-15 %
Krenk et al, Anesth Analg 2014
Silbert, Evered, Scott et al Anesthesiology 2015
Is preop cognitive impairment a risk factor?
Preoperative cognitive
screening - the Clock-in-a-box test
Culley et al Anesthesiology 2017
MMSE Mini-COG
Test batteries
Evered et al Anesthesiology 2016
• 57 patients undergoing orthopedic surgery with preop CSF sampling.
• 27.3 % of patients with AD biomarker (a-beta amyloid) had POCD • Only 4.3 % patients with no AD biomarker had POCD
Patients with preop AD biomarkers have > risk for POCD
Is preop Alzheimer biomarkers in CSF a risk factor for cognitive decline ?
Evered et al JAMA Neurol 2018
30 patients older than 60 years, 73 % joint arthroplasty. Transient increase in plasma NFL and Tau levels during the first 48 hours postsurgery
Plasma Tau Plasma Neurofilament light
Nation-wide large scale outcome study in > 20.000 swedish twins Focus on hospitalization and risk of later dementia Twins aged <65 years at start of follow-up with up to 33 years of follow-up - mean 23.9 years Critical care > non-surgical care > routine surgery are all associated with slightly increased risk for later dementia Eriksson, Lundholm, Narisimhalu, Sandin, Jin, Gatz, Pedersen, Alzheimer and Dementia 2019
The impact of surgery or nonsurgical care disapperad in identical twins – risk for dementia is dependent on genetic predisposition
What we need ! Identify patients at-risk prior to surgery ! Introduce preop cognitive screening
! Introduce standardized neurological outcome measures –Part of global perioperative outcome measures initiative by P Myles 2016
! Find biomarker(s) that can identify the development of cognitive decline in postop patients
! Individualized perioperative care process and follow-up for high risk patients
What we need to know ! Is there a link between delirium and dementia
! Do anesthetic compounds have a built-in property to accelerate a dementia trajectory
! Are there imaging techniques, biomarkers or combinations of them to indicate such risks
! Are there an immune and/or inflammatory signaling pattern in humans that associates with cognitive decline
! Can we find (blood) biomarkers either pre- or postoperatively that can detect those patients
The Research Group
Karolinska Institutet Helena Harris Bob Harris Jinming Han Fredrik Granath Nancy Pedersen Lars Farde Andrea Varrone Anton Forsberg Ulrica Nilsson Nippon Medical School, Japan Shinhiro Takeda Chol Kim Gothenburg University, Sweden Sven-Erik Ricksten Mattias Danielsson Kai Blennow Henrik Zetterberg Bengt Nellgård
University of Pennsylvania Rod Eckenhoff Copenhagen University, Denmark Lars Rasmussen Tokyo Shinhiro Takeda Utrecht MC, The Netherlands Cor Kalkman Monash University, Australia Paul Myles Jennifer Reilly Pasteur Institute, France Jean-Pierre Changeux Uwe Maskos
Marta Gomez, PhD, Malin J Fagerlund, MD, PhD Jessica Kåhlin, MD PhD Andreas Wiklund, MD, PhD Anette Ebberyd, Lab manager Souren.Mkrtchian, PhD Anna Granström, CRNA-research Anna Schening, CRNA-reasearch Malin Hildenborg,MD, PhD-student Pia Glatz, MD, PhD-student Eva Christensson, MD, PhD-student Max Kynning, student Lars I Eriksson, MD PhD, FRCA, Professor, Academic Chair, Research Group Leader
Collaborators