perioperative delirium

Dr. Tou Weng Ieong

1. Perioperative Delirium Tutor: Dr. Choi Nim IC: Tou Weng Ieong (Psychiatry ) Date: 2022/04/22

2. Content Case share Brief Introduction Diagnosis Pathophysiology Risk factor Assessment Prevention and management Summary

3. Short case sharing 37-year-old man A government-employed, active police No family history of dementia. History of alcoholism Acute onset right upper abdominal pain after dinner High fever, PE: RUQ tender and murphy sign (+) Lab: Leukocytosis, mild elevated ALP and total bil . CT: multiple gallbladder stone with CBD dilatation Impression: A cute calculous cholecystitis

4. Short case sharing Lap cholecystectomy : uneventfully, minimal blood loss. POD 1: Present with acute onset of inattention and fluctuating course of agitation and drowsy Lab and head CT: unremarkable. The CAM Diagnostic Algorithm: Suspected delirium DSM-5 Diagnosis: Hyperactive perioperative delirium DSM-5: The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition delirium CAM: The Confusion Assessment Method

5. Short case sharing Hyperactive perioperative delirium And history of alcoholism ECG: sinus rhythm Haloperidol 0.5 mg IV once ECG: sinus rhythm, no sign of QT prolongation Haloperidol 1 mg IV once 30 minutes later then regular at Q12H

6. Short case sharing POD 2: No more agitation nor inattention Change Haloperidol IV to oral 1mg morning and 1mg at night POD 3: No sign of delirium Discharge and early psychiatry OPD.

7. Definitions Delirium is defined as a transient, usually reversible, cause of mental dysfunction and manifests clinically with a wide range of neuropsychiatric abnormalities Any delirium that occurs before or after surgery may be called perioperative delirium The condition is a medical emergency associated with increased morbidity and mortality rates. JAMA, July 4, 2012— Vol 308, No. 1

8. Hospitalized elderly: prevalence of delirium Prevalent delirium among older patients at hospital admission ranges from 14-24% The incidence of delirium among older patients arising during admission ranges from 6% to 56% in general hospital populations Arch Intern Med. 2002 Feb 25;162(4):457-63 . Am J Psychiatry. 1999 May;156(5 Suppl ):1-20 . Am Heart J. 2015 Jul;170(1):79-86, 86.e1

9. Predisposing factors for delirium Clin Geriatr Med. 2020 May;36(2):183-199. doi : 10.1016/j.cger.2019.11.001.

10. Prevalence of perioperative delirium based on hospital setting Setting Incidence of delirium References Abdominal Aortic anyeurism surgery 33-54% Mercantonio et al 1994 Abdominal surgery 5-51% Mann et al 2000 Cataract surgery 4% Milstein et al 2002 Coronary artery bypass graft surgery 37-52% Dyer et al 1995 Elective orthopedic surgery 9-15% Mercantonio et al 1994 Head and Neck Surgery 17% Weed et al 1995 Hip Fracture surgery 35-65% Gustafson et al 1988 Peripheral vascular surgery 30-48% Schneider et al 2002 Urologic surgery 4-7% Dyer et al 1995 Non-intubated ICU patients 30-50% Pun et al 2007 Intubated ICU patients 80% Pun et al 2007 General medical inpatients 15-31% Inouye et al 2007

11. High mortality rate Patient admitted with delirium have a mortality of 11-26%. Patients who develop delirium during their admission have a mortality ranging between 22-76%. V.S.: Septic shock mortality rate: 10-56% Arch Intern Med. 2002 Feb 25;162(4):457-63 . Am J Psychiatry. 1999 May;156(5 Suppl ):1-20 . Am Heart J. 2015 Jul;170(1):79-86, 86.e1

12. Negative consequences during hospitalization Increased hospital length of stay Increased incidence of falls Increased incidence of aspiration Poor recovery from acute medical condition or surgery Behavior concerns leading to need for increased surveillance Potential self harm Arch Intern Med. 2002 Feb 25;162(4):457-63 . Am J Psychiatry. 1999 May;156(5 Suppl ):1-20 . Am Heart J. 2015 Jul;170(1):79-86, 86.e1

13. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) Acute Process Affecting consciousness (alertness/awareness ) Affecting cognition (executive skills) There is evidence that the disturbance is caused by a medical condition, substance intoxication or withdrawal, or medication side effect No better explained by an alternative diagnosis. American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing. pp. 5–25. ISBN 978-0-89042-555-8.

14. DSM-V additional features Psychomotor behavioral disturbances such as hypoactivity , hyperactivity, (or mixed) with increased sympathetic activity, and impairment in sleep duration and architecture Variable emotional disturbances, may include: Fear Depression Euphoria Perplexity Agitation American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing. pp. 5–25. ISBN 978-0-89042-555-8. Hyperactive Hypoactive Mixed

15. Prodromal Phase ( Subsyndromal delirium) Prodromal features includes: Complaints of fatigue Sleep disturbance (excessive daytime somnolence or insomnia) Depression Anxiety Restlessness Irritability Hypersensitivity to light or sound

16. Subsyndromal delirium International Journal of Geriatric Psychiatry 2013; 28:771–780 A state in which patient only have a few criteria for delirium; do not meet full criteria May precede delirium by a few hours or days At very high risk for developing “ full blown “ delirium Associated with negative outcomes intermediate to “ full blown” delirium Figure 3. Individual and Combined Odds Ratio (OR) (and 95% Confidence Intervals (95% CI)) in Studies of Outcomes of Subsyndromal Delirium.

17. Development is Multifactorial Older Age Multiple comorbid medical conditions Hx of delirium Pre-morbid cognitive impariment Hx of psychiatric disease Malnutrition Dehydration Sensory deficits An Acute medical problem Disruption of normal sleep/wake cycle Lack of cognitive stimulation Indwelling urinary catheter Medicines that cause delirium Immobilization DELIRIUM + NON-MODIFIABLE MODIFIABLE + =

18. Chemical – Hormonal Hypothesis Cholinergic Deficiency hypothesis Dopaminergic Excess hypothesis Contribution of other neuro -transmitter function perturbation: Norepinephrine Serotonin GABA Glutamate Melatonin Cytokines J Gerontol A Biol Sci Med Sci. 1999 Jun;54(6):B239-46. doi : 10.1093/ gerona /54.6.b239.

19. Mainstream theory in peri operative delirium: TNF-alpha during surgery and anaesthesia in mice Proc Natl Acad Sci U S A 2 010 Nov 23;107(47):20518-22. doi: 10.1073/pnas.1014557107 . Fig. 1. TNF- α and HMGB-1 measured by ELISA were increased following tibial surgery. (A) Plasma levels of TNF- α were significantly increased after 30 min from skin incision; (B) HMGB-1 was up-regulated after 1 h, peaking at 6 h, and returning to baseline thereafter. Plasma levels of both TNF- α ( C) and HMGB-1 (Results are expressed as mean ± SEM (n = 6). *, P < 0.05; **, P < 0.001 versus naive by one-way ANOVA followed by Student-Newman- Keuls test. ND, not determined Tibial surgery Anaesthesia

20. Neurofilament light (NFL) Surgery -> peripheral inflammation + leaky BBB -> Neuronal damage – release of NFL and tau -> Delirium NFL is a component of the axonal cytoskeleton tissue Plasma levels of NFL are sensitive marker of TBI in contact sports. Brain. 2020 Jan 1;143(1):47-54. doi : 10.1093/brain/awz354 .

21. JAMA, July 4, 2012— Vol 308, No. 1

22. Cerebral Perfusion Changes in Delirious Patients Cerebral Perfusion Changes in Older Delirious Patients Using 99mTc HMPAO SPECT

23. Brain Gray Matter is reduced following an episode of delirium Crit Care Med. 2012 Jul;40(7):2022-32. doi : 10.1097/CCM.0b013e318250acc0.

24. Persistent Cognitive Dysfunction Signs of delirium may persist for 12 months or longer , particularly in those with underlying dementia One long-term follow-up study found that after two years, only one-third of patients who had experienced delirium still lived independently in the community. J Gen Intern Med. 2003 Sep;18(9):696-704 . J Am Geriatr Soc. 1992 Jun;40(6):601-6.

25. Short-term and long-term relationship between delirium and cognitive trajectory Alzheimers Dement. 2016 Jul;12(7):766-75. doi : 10.1016/j.jalz.2016.03.005. Epub 2016 Apr 18.

26. Who is at Risk in perioperative delirium? Elderly Dementia Dementia is an underlying issue in 25-50% of delirium cases CVA Parkinson’s disease

27. Pre-operative screening tool Screening tools MoCA , MiniCog , Clock Drawing test Subjective assessment MCI Sensitivity Specificity MMSE 66% 90% MoCA 94% 40% Mild cognitive impairment (MCI) Montreal Cognitive Assessment ( MoCA ) Mini-mental state examination (MMSE)

28. Precipitants of Perioperative Delirium Drugs/Toxins – 30% of delirium Specially drug with anticholinergic effect Infection Metabolic Systems organ diseases Brain specific issues Physical disorders

29. Delirium Screening Confusion Assessment Method (CAM): Presence of 1 and 2 Acute onset and fluctuating course Inattention Presence of at least one item from 3 and 4 Disorganized thinking Altered level of consciousness Inouye et al. Ann int Med (1990)

30. Delirium Screening Confusion Assessment Method (CAM) 3 minutes Confusion Assessment Method (3DCAM ) Ultra-Brief CAM -Months of the Year Backwards, and what is the day of the week? Inouye et al. Ann int Med (1990)

31. The Work Up First: Evaluate medications 30% of delirium cases are due to medication issues Anticholinergic/opioid/benzodiazepines/levodopa/H2 blocker/antibiotic/ anticovulsants / hypoglcemic agent. Over the counter medications should NOT be overlooked as a cause Elderly do NOT have to have a TOXIC LEVEL to be in fact: TOXIFIED

32. Lab testing CBC: To diagnose infection / anemia Glucose: To diagnose hypoglycemia, DKA, HHS Thyroid function: Hypothyroidism Urine/blood drug screening: toxicological causes Culture/viral test: to diagnose infection Electrolyte: to diagnose imbalance Renal and liver function: liver or renal failure Thiamine and vitamin B-12 levels: deficiency states of these vitamins

33. Neuro i maging and EEG Neuroimaging: Perform CT scan of the head MRI of the head may be helpful in the diagnosis of stroke, hemorrhage, and structural lesions EEG to differentiate other disease: General medical condition > Posterior dominant rhythm and increased generalized slow-wave activity alcohol/sedative withdrawal > fast-wave activity hepatic encephalopathy > diffuse EEG slowing occurs toxicity/metabolic derangement > Triphasic waves

34. Prevention/Treatment Multi-Component Treatment Orientation protocol Provision of clocks, calendars, windows with outside views, and verbally re-orienting patients Cognitive stimulation and mobilization Patients with cognitive impairment, in particular, may benefit from activity such as regular visits from family and friends Facilitation of physiology sleep Night-time noise should be reduced Ear plugs and melatonin were found to be effective Managing pain : pain may be a significant risk factor for delirium

35. Antipsychotics as treatment If potential patient harm is at risk, then trial of antipsychotics is warranted Haldol (1 st ) and 2 nd generation antipsychotics seems to be equally effective 2 nd generation have less side effects CAVEAT: Haldol IV has a black box warning regarding prolonged QT – DO NOT GIVE if you don’t know the baseline QT.

36. Antipsychotic agents xxx

37. E ffect of antipsychotics on the incidence of adverse effects Ann Intern Med. 2019 Oct 1;171(7):485-495. doi: 10.7326/M19-1860. Epub 2019 Sep 3. Figure 2. Meta-analysis of trials evaluating the effect of antipsychotics on the incidence of adverse effects

38. Anti-Psychotics as prophylaxis? Prophylactic Antipsychotic Use for Postoperative Delirium: A Systematic Review and Meta-Analysis Antipsychotics for the Prevention and Treatment of Delirium. Comparative Effectiveness Review Number 219

39. Discharge planning Discharge destination planning Involve caregivers and family Do not discharge with delirium (10% hypoactive delirium were discharged in real world data) Prevent long-term cognitive impairment.

40. Summary Perioperative delirium is common POD has serious short and long-term poor outcomes Preoperative screening is critical Perioperative monitoring and management is essential Biomarkers suggest inflammatory and neuronal injury may play a role Multi-component interventions may reduce/prevent delirium 2 nd generation antipsychotic as prophylaxis Haloperidol for hyperactive delirium Discharge destination planning for hypoactive delirium

41. Reference Cochrane Database Syst Rev. 2018 Jun; 2018(6): CD005594 . JAMA , July 4, 2012— Vol 308, No. 1 Arch Intern Med. 2002 Feb 25;162(4):457-63. Am J Psychiatry. 1999 May;156(5 Suppl ):1-20. Am Heart J. 2015 Jul;170(1):79-86, 86.e1 Clin Geriatr Med. 2020 May;36(2):183-199. Alzheimers Dement. 2016 Jul;12(7):766-75. Epub 2016 Apr 18. Arlington , VA: American Psychiatric Publishing. pp. 5–25. ISBN 978-0-89042-555-8. International Journal of Geriatric Psychiatry 2013; 28:771–780 J Gerontol A Biol Sci Med Sci. 1999 Jun;54(6):B239-46. Proc Natl Acad Sci U S A 2010 Nov 23;107(47):20518-22. Brain. 2020 Jan 1;143(1):47-54. J Gerontol A Biol Sci Med Sci. 2006 Dec;61(12):1294-9. Crit Care Med. 2012 Jul;40(7):2022-32. Inouye et al. Ann int Med (1990) Ann Intern Med. 2019 Oct 1;171(7):485-495. Epub 2019 Sep 3. Antipsychotics for the Prevention and Treatment of Delirium. Comparative Effectiveness Review Number 219

42. A typical antipsychotic versus typical antipsychotic. Antipsychotics to treat delirium in hospitalised patients, not including those in intensive care units. Cochrane Database Syst Rev. 2018 Jun; 2018(6): CD005594.