Cerebral side effects of general anesthesia Postoperative cognitive dysfunction and delirium Underlying mechanisms and preventive measures

Transcription

1 Cerebral side effects of general anesthesia Postoperative cognitive dysfunction and delirium Underlying mechanisms and preventive measures Gerhard Schneider Department of Anaesthesiology Witten/Herdecke University HELIOS Clinic Wuppertal

2 I was lying on my back. I could not move nor speak. It seemed I was in a highly advanced civilized culture and - for some purpose - robots were taking care of me. (a physician's experience in the ICU) Anonymous: Anaesthesist 2003; 52:815-7

3 Postoperative Cognitive Decline Postoperative delirium: POD Postoperative cognitive dysfunction: POCD

4 Overlap POD POCD Impairment of cognitive and executive function h POD POCD

5 Neuropsychology cognitive function: e.g. memory, attention (orientation, verbal communication, visual perception, spatial perception, constructive capabilities, arithmetics, praxia) executive function: e.g. impulse, impulse control, planning, thinking personality, mood, affect, social behaviour

6 Definition POCD Impairment of cognition and memory No ICD-10 diagnosis Diagnosis on basis of psychometric (non-pocd validated) Tests

7 POCD early onset: 1 week postop intermediate onset: 3 months postop longterm onset: 1-2 years postop

8 Diagnosis: Roach-Criteria Type I: focal symptoms stupor, coma at discharge Type II: decline in cognitive function memory impairment seizures

9 Assessment: Neuropsychologic Tests Mini Mental State Exam Delirium Rating Scale / Confusion Assessment Method Visual Verbal Learning Test (word learning / recall) Trail Making Test / Concept Shifting Test (cognitive flexibility) Stroop Colour Word Interference Test (distractibility) Paper And Pencil Memory Scanning Test Letter-digit coding / Wechsler adult intelligence scale (working memory) Four boxes test Moller JT et al. ISPOCD1 study. Lancet 1998; 351 Johnson T et al. ISPOCD2 study. Anesthesiology 2002; 96 Monk TG et al. Anesthesiology 2008; 108

10 Trail Making Test

11 Trail Making Test

12 Criteria: Diagnosis POCD Rasmussen LS et al.: Acta Anaesthesiol Scand 2001; 45:

13 Diagnosis: Neuropsychologic Tests Variable definition of deficit Test batteries may not be sensitive for minor changes Rasmussen LS et al. Acta Anaesthesiol Scand 2001; 45 Deiner S, Silverstein JH. BJA 2009; 103 Newman S et al. Anesthesiology 2007; 106

14 Long-term postoperative cognitive dysfunction in the elderly: ISPOCD patients 60 years and older major non-cardiac surgery NIBP, SpO 2 (+3 d) Follow Up: 1 week, 3 months neuropsychological tests Moller JT et al.: Lancet 1998; 351:

15 Long-term postoperative cognitive dysfunction in the elderly: ISPOCD1 25 % POCD 1 week postop 10 % POCD 3 months postop risk factors early onset: age duration of surgery level of education revision, infection, respiratory complications risk factors late onset: age no risk factors: hypoxaemia, hypotension Moller JT et al.: Lancet 1998; 351:

16 Postoperative cognitive dysfunction in middleaged patients (ISPOCD2) 580 patients y major non-caridac surgery compared to age-matched control follow up: 1 week, 3 months neuropsychologic tests cognitive function, depression, daily life activity Johnson T et al.: Anesthesiology 2002; 96:

17 Postoperative cognitive dysfunction in middleaged patients (ISPOCD2) 19 % early POCD no late POCD risk factors: center effect epidural anaesthesia alcohol abstinent Johnson T et al.: Anesthesiology 2002; 96:

18 The Octopus Study: Rationale and Design of Two Randomized Trials on Medical Effectiveness, Safety, and Cost-Effectiveness of Bypass Surgery on the Beating Heart 120 patients off / on bypass ACVB psychomotor tests prae- and postop (103 d) Jensen BO et al.: Circulation 2006; 113:

19 Incidence of POCD after coronary artery bypass grafting Incidence POCD: 31% (vs. 26.8%)

20 The incidence of cognitive decline after (not) undergoing coronary artery bypass grafting: the impact of a controlled definition 112 healthy volunteers neurocognitive tests, follow up 3 months 14-28% POCD in healthy volunteers Keizer AJ et al.: Acta Anaesthesiol Scand 2005; 49:

21 "Reliable Change" Concept RC = ((X1-X2) - training effect) / SD (difference) X1: praeop. score X2: postop. score SD (differece): variability of scores without underlying pathology RC > 1.96 unlikely without neurological change (p<0.05) neuropsychologic batteries overestimate incidence of POCD Rasmussen LS et al.: Acta Anaesthesiol Scand 2001; 45:

22 "Reliable Change" Calculation of RC for: Octopus trial: 7.7% POCD (vs. 31%) healthy volunteers : 4.6% (26.8%) after 3 months Keizer AJ et al.: Acta Anaesthesiol Scand 2005; 49

23 DSM V: Diagnosis Delirium Alteration of consciousness Bewusstseinsstörung mit gestörter Aufmerksamkeit Veränderung der kognitiven Fähigkeiten Wahrnehmungsstörung Entwicklung Symptoms: innerhalb hours von Stunden - days Ausprägung fluktuiert im Tagesverlauf Tritt in der Regel 1-4 Tage postoperativ auf dauert 1-4 Tage Impairment of cognitive functions fluctuations during day Physical consequence of a medical condition

24 Delirium Incidence patients in hospital % geriatric patients % fracture of femur % cardiac surgery % elektive orthopaedic surgery % Rudolph JL, Marcantonio ER.: Anesth Analg 2011; 112;

25 Postoperative Delirium Incidence overall: 5-15% patients at risk: 10-60% (35%) Long term sequelae long term: 40% persistence of symptoms usually 6 months Bekkar AY, Weeks EJ. Best Prac Res Clin Anaesthesiol 2003; 17 Bitsch M et al. Acta Orthop Scand 2004; 75 Pompei P et al. J Am Geriatr Soc 1994; 42 Levkoff SE et al. Arch Intern Med 1992; 152 Murray AM et al. J Gerontol 1993; 48

26 Delirium - ICU all patients % depends on: subgroup of patients diagnostic tool increased incidence: geriatric patients sepsis Van Eijk et al.: Am J Resp Crit Care Med 2011; 184:340-4.

27 Deiner S, Silverstein JH.: Br J Anaesth 2009; 103 S1: i41-46

28 Risk Factors praeop cognit impairment age > 80 age > 65 impaired vision > 3 comorbidities > 3 drugs > 7 drugs source:

29 Steiner L.: Eur J Anaesthesiol 2011; 28: Delirium - Development

30 Delirium - Trigger surgical / multiple (diagnost.) procedures comorbidities infection, complications, severe acute illness, metabolic imbalance, fever/hypothermia, shock, hypoxia, anaemia, dehydration, hypalbuminaemia, malnutrition neurologic disease stroke, ICB, meningitis, encephalitis drugs sedatives, hypnotics, benzodiazepines, opioids, anticholinergics, multiple medication, alcohol / drug withdrawal Inouye SK.: N Engl J Med 2006; 354:

31 Delir - Trigger pain ICU physical restraints urinary catheter emotional stress sleep deprivation Inouye SK.: N Engl J Med 2006; 354:

32 Hyperactive 15-20% good prognosis Hypoactive 20-70% poor prognosis Mixed 40-70% poor prognosis Delir - Subtypes Yang FM et al.: Psychosomatics 2009; 50:248

33 Bewusstseinsstörung mit gestörter Aufmerksamkeit Veränderung der kognitiven Fähigkeiten Wahrnehmungsstörung Entwicklung innerhalb von Stunden Ausprägung fluktuiert im Tagesverlauf Tritt in der Regel 1-4 Tage postoperativ auf dauert 1-4 Tage

34 POD Diagnostic Approach 1. Sedation - Richmond Agitation and Sedation Scale 2. Delirium - Confusion Assessment Method (CAM) / DSM IV 3. Follow up / Treatment: Delirium Rating Scale

35 CAM Rudolph JL, Marcantonio ER.: Anesth Analg 2011; 112;

36 Bewusstseinsstörung mit gestörter Aufmerksamkeit Veränderung der kognitiven Fähigkeiten Wahrnehmungsstörung Entwicklung innerhalb von Stunden Ausprägung fluktuiert im Tagesverlauf Tritt in der Regel 1-4 Tage postoperativ auf dauert 1-4 Tage

37 CAM - ICU Comparison: CAM-ICU - Diagnosis Van Eijk et al.: Am J Resp Crit Care Med 2011; 184:340-4.

38 CAM - ICU Sensitivity 47% (CI: 35% - 58%) Specificity 98% (CI: 93% -100%) "CAM-ICU = SCAM-ICU" J. Takkala, ISICEM 2010 Van Eijk et al.: Am J Resp Crit Care Med 2011; 184:340-4.

39 Bewusstseinsstörung mit gestörter Aufmerksamkeit Veränderung der kognitiven Fähigkeiten Wahrnehmungsstörung Entwicklung innerhalb von Stunden Ausprägung fluktuiert im Tagesverlauf Tritt in der Regel 1-4 Tage postoperativ auf dauert 1-4 Tage

40 Preexisting Cognitive Impairment Evered LA et al.: Anesthesiology 2011; 114:

41 Cognitive Reserve "The greater the reserve, the more severe the pathology must be to cause functional impairment" Richards et al.: Ann Neurology 2005

42 Cognitive Reserve Jankowski CJ et al.: Anesth Analg 2011; 112:

43 POCD: Genotype Alterations ApolipoproteinE Allel ε4 Lynch JR et al. J Biol Chem 2003; 278 Heyer EJ et al. Neurology 2005;65 Abildstrom H et al. Anesthesiology 2004; 101 Leung JM et al. Anesthesiology 2007; 107

44 (Neuro)Inflammation Buvanendran A et al. Anesthesiology 2006;104 Adamis D et al. Age and Ageing 2009; 38 Wan Y et al. Anesthesiology 2007; 106 Zhu J et al. Eur J Anaesthesiol 2009; 26 Liu M et al. J Am Soc Nephrol 2008; 19 Sanders RD, Maze M. Eur J Anaesthesiol 2010; 27

45 Hughes CG et al.: Curr Opin Crit Care 2012; 18:518-26

46 Dilger RN et al.: J Leucocyte Biol 2008; 84:932 Cerejeira J et al.: Acta Neuropathol 2010; 119:737 Neuroinflammation

47 Terrando N et al.: PNAS 2010; 107: TNF - a

48 Mechanisms Hughes CG et al.: Curr Opin Crit Care 2012; 18:518-26

49 Hughes CG et al.: Anesthesiology 2013; 118:631-9 Endothelial Dysfunction

50 Hughes CG et al.: Anesthesiology 2013; 118:631-9 Mechanisms

51 Hughes CG et al.: Anesthesiology 2013; 118:631-9 Endothelial Dysfunction

52 Hughes CG et al.: Anesthesiology 2013; 118:631-9 Endothelial Dysfunction

53 Lorazepam is an Independent Risc Factor for ICU Delirium 198 ventilated patients transition to delirium Pandharipande P et al.: Anesthesiology 2006; 104:21-6

54 Lorazepam is an Independent Risc Factor for ICU Delirium Pandharipande P et al.: Anesthesiology 2006; 104:21-6

55 Lorazepam is an Independent Risc Factor for ICU Delirium Pandharipande P et al.: Anesthesiology 2006; 104:21-6

56 Lorazepam is an Independent Risc Factor for ICU Delirium Pandharipande P et al.: Anesthesiology 2006; 104:21-6

57 Delirium - Sleep Pathway Sanders RD, Maze M.: Can J Anaesth 2011; 58:149

58 Delirium - Sleep Pathway Sanders RD, Maze M.: Can J Anaesth 2011; 58:149

59 Van Rompaey B.: Critical Care 2009; 13:R77 Delirium - Factors

60 Delirium Duration, White Matter Integrity, and Cognitive Impairment 47 patients CAM-ICU MRI: diffusion tensor imaging 3 mo / 12 mo follow up Morandi A et al.: Crit Care Med 2012; 40:2182-9

61 Delirium Duration, White Matter Integrity, and Cognitive Impairment Morandi A et al.: Crit Care Med 2012; 40:2182-9

62 Review proactive 1966 geriatric : visits 6 Studien, (hip fractures) 833 chirurgische Patienten inkomplette Studiendaten low Outcome-Studien; dose haloperidol keine (reduced Untersuchung duration) von: Tod, Lebensqualität, Aktivitäten des täglichen Lebens, Verwendung psychotroper Medikamente Follow-up nur bis zur Entlassung Siddiqi N et al.: Cochrane Database Syst Rev Apr 18;(2):CD

63 Multicomponent Intervention Oxygen delivery Fluid and electrolyte balance Pain management Reduced usage of psychoactive and anticholinergic drugs Regulation of bowel and bladder function Nutrition Early mobilisation Early detection of postoperative complications Environmental stimulation (glasses, hearing aids) Day-night cycle

64 177 patients at increased risk 1mg Haloperidol / 8h van den Boogaard M et al.: Crit Care 2013; 17:R9

65 van den Boogaard M et al.: Crit Care 2013; 17:R9

66 van den Boogaard M et al.: Crit Care 2013; 17:R9

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