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Delirium: How ER Physicians Can Impact Course Emergency Medicine Palliative Care Series

Delirium: How ER Physicians Can Impact Course Emergency Medicine Palliative Care Series Alan Bates, MD, PhD, FRCPC Provincial Practice Leader for Psychiatry BC Cancer Agency. In 1959…. Engel and Romano

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Delirium: How ER Physicians Can Impact Course Emergency Medicine Palliative Care Series

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  1. Delirium: How ER Physicians Can Impact Course Emergency Medicine Palliative Care Series Alan Bates, MD, PhD, FRCPC Provincial Practice Leader for Psychiatry BC Cancer Agency

  2. In 1959… • Engel and Romano • “…while most physicians have a strong bias toward an organic etiology of mental disturbances, … they seem to have little interest in … the one mental disorder presently known to be based on derangement of cerebral metabolism.” • “… deficiencies in the education of many physicians ill equip them to recognize any but the most flagrant examples of delirium…”

  3. In 1959… • Engel and Romano continued • “Only … a management problem on a medical or surgical service is likely to result in a psychiatric consultation.” • “[The psychiatrist] … seeing the patient in the home territory of the “organic” specialists … is less likely or able to pursue an understanding of the underlying physiologic derangements, which are generally conceived to be the proper domain of the internist.”

  4. In 1959… • Engel and Romano continued • “Unhappily, the unfortunate patient’s malfunctioning brain rests in limbo, an object of attention and interest neither to the medical man nor to the psychiatrist.” • “Not only does the presence of delirium often complicate and render more difficult the treatment of a serious illness, but also it carries the serious possibility of permanent irreversible brain damage.”

  5. In 1959… • Engel and Romano continued • “With increasing life expectancy … we are now beginning to see an increasing incidence of so-called senile and arteriosclerotic dementias.” • “The physician who is greatly concerned to protect the functional integrity of the heart, liver, and kidneys … has not yet learned to have similar regard for the functional integrity of the brain.”

  6. From Cresswell III et al.

  7. DSM-5 Criteria • Disturbance in attention and awareness • Develops over short time, change from baseline, fluctuates in severity over course of a day • An additional cognitive disturbance (e.g. memory, orientation, language, visuospatial, perception) • Not another neurocognitive disorder, not coma • Direct consequence of another medical condition

  8. Meagher et al., 2007 • 100 palliative care patients • Attention – 97% (e.g. distractibility, digit span) • Sleep-wake cycle – 97% (?cause of fluctuation, early) • Long-term memory – 89% • Short-term memory – 88% • Orientation – 76% (misses ¼) • Visuospatial ability – 87% • Motor agitation – 62% (early) • Motor retardation – 62% (early) • Language – 57% • Perceptual – 50% (motor agitation = retardation)

  9. Incidence • Hospitalized elderly patients – 25% (van Blanken et al., 2005) • ICU – 70% at some point (McNicoll et al., 2003) • 30% of critically ill children (Smith et al., 2013) • Post-operative delirium in patients over 60 after cardiac surgery – 52% (Rudolph et al., 2009) • Terminal illness – 88% (Massie etl al., 1983; Lawlor et al., 2000)

  10. Incidence and detection - ER • Elie et al., 2000 • 10% of 447 ER patients over 65 delirious • Detection by ED physician • Sensitivity: 35%, Specificity: 99% • Han et al., 2014 • 12% of 406 ER patients over 65 delirious • Detection by ED physician using CAM-ICU • Sensitivity: 72% (better than RAs) • Specificity: 99% • Han et al., 2014 • CC of “altered mental status”: 38% sensitivity, 99% specificity (when not coma, non-verbal etc.)

  11. Impact (reviewed by Maldonado et al., 2009) • Clear immediate increase in suffering of patient and family • Increased morbidity and mortality • Prolonged hospital stays • Increased cost of care • Increased hospital-acquired complications • Poor functional and cognitive recovery • Decreased quality of life • Increased placement in intermediate- and long-term care facilities

  12. Impact – ER specific • Han et al., 2010 / 2011 • 628 ER patients over age 65 • 17% delirious • 6-month mortality: • 37% in delirious group • 14% in non-delirious group • Median length of stay: • 2 days for delirious • 1 day for non-delirious

  13. Distress • Rate of diagnosable PTSD was 9.2% at 3 months post-ICU in 238 post-ventilated patients with a strong association between PTSD and recall of delusional memories (Jones et al., 2007) • Delirium is even more distressing for spouses than for patients (Breitbart et al., 2002)

  14. Milbrandt et al., 2004 • 224 consecutive mechanically ventilated ICU patients (after excluding 51 with coma leading to death) • 82% developed delirium, mean duration 2 days

  15. Barrough, 1601 • “It commeth to passe also that the soporiferous diseases being ended, there ensuethforgetfulnesse: which when it chanceth then a cold distempure is the cause that the memorie is perished or grievously hurt.”

  16. Witlox et al., 2010 • Meta-analysis of elderly patients with delirium • Delirium associated with increased risk of death (38% vs. 28% in controls at average follow-up of 23 months) • Delirium associated with increased risk of institutionalization (33% vs. 11% in controls at average follow-up of 15 months) • Delirium associated with increased risk of dementia (63% vs. 8% in controls at average follow-up of 4 years) • Above results are independent of age, sex, comorbid illness, illness severity, and baseline dementia

  17. Risk factors • Infection • Withdrawal • Acute metabolic • Trauma • CNS (structural) • Hypoxia • Deficiency of vitamins • Endocrine • Acute vascular • Toxins/Medications (Lexicomp is your friend) • Heavy metals

  18. Deleriogenic Medications • Anticholinergic • e.g. diphenhydramine, hydroxyzine, atropine, amitriptyline, imipramine, paroxetine, doxepin, furosemide, prochlorperazine • Benzodiazepines • Barbiturates • Opiates • Especially meperidine • ? Morphine > Hydromorphone > Oxycodone (rotation can help) • Incontinence meds • e.g. oxybutynin • Cardiac meds • e.g. digitalis, quinidine, procainamide, lidocaine, beta-blockers • GI meds • H2-blockers (e.g. cimetidine, ranitidine), PPIs, metoclopramide • Many others: e.g. phenytoin, steroids

  19. Sockalingam et al. 2005

  20. van der Mast et al., 1996 • “Of all the reported differences in the studies, only year of publication is significantly related to the incidence of delirium after cardiac surgery, the later publications showing a tendency towards a lower incidence.” • “… a cautious conclusion may be drawn that no strong risk factor has been identified…”

  21. Pathophysiology: Neurotransmitters (Reviewed by Trzepacz, 1994) • Acetylcholine • Anticholinergic drugs induce delirium • Correlation between poor cognitive function and serum anticholinergic level • Serum anticholinergic levels decrease as delirium resolves • Reversal of anticholinergic delirium with physostigmine

  22. Pathophysiology: Neurotransmitters (Reviewed by Trzepacz, 1994) • Dopamine • Effective treatment with dopamine receptor blockers like loxapine or haloperidol • Norepinephrine • Glutamate • Serotonin • GABA • Histamine

  23. Pathophysiology (Maldonado, 2008)

  24. Pathophysiology

  25. Wrist actigraphy Osse et al. (2009): motor activity at the wrist over five 24hr cycles after elective cardiac surgery

  26. Definitive treatment: • Find the underlying cause or causes and treat it/them

  27. Non-pharmacological interventions (Inouye et al., 1999) • In a study of 852 elderly patients admitted to a general medical service, Inouye et al. reduced the incidence of delirium from 15% to 9% with a number of non-pharmacological interventions including promotion of sleep with sleep inducing stimuli (e.g. relaxation tapes, warm milk) and a sleep promoting environment (e.g. through noise reduction)

  28. Patel et al., 2014 • Screened for ICU delirium before (n=167) and after (n=171) implementing measures to promote sleep • Noise and light reduction at night, minimize care that interrupts sleep at night, reduce daytime sedation when possible, address pain early, early mobilization • Found reduced incidence (14% vs. 33%) and duration (1.2 vs. 3.4 days) of delirium

  29. Melatonin • Al-Aama et al. (2011) demonstrated decreased incidence of delirium in older adult patients on a general medicine unit who received 0.5mg of melatonin nightly • Evidence that melatonin could actually aid in treating ongoing delirium is mostly limited to case studies (e.g. Hanania and Kitain, 2002) • Other findings suggest melatonin isn’t helpful (e.g. Ibrahim et al., 2006)

  30. Haloperidol • Standard treatment in most places • Relatively little anticholinergic effect • Little effect on orthostatic hypotension • Less sedation good for hypoactive delirium • Risk of QT prolongation • Relatively high risk of extrapyramidal effects • No difference between IV and PO • Menza et al. (1987) and Maldonado (2000) both seriously flawed • Are reports of EPS with IV (Blitzstein & Brandt, 1997) • Small doses (e.g. 0.5mg IV BID or 1mg IV QHS)

  31. Methotrimeprazine • Also sedating and can be given SC or IV • Significant analgesic effect • Need to be cautious of hypotension • e.g. 5 - 10mg Q1H PRN for agitation • Can go as high as 50mg Q4H

  32. Quetiapine • When we use low dose quetiapine at night, it’s primarily acting as an antihistamine • Maneenton et al. (2013) found no difference between 25-100mg/day of quetiapine HS and 0.5-2mg/day of haloperidol HS in a double-blind, randomized trial of delirious patients eliciting CL consult • e.g. quetiapine 25mg PO QHS • e.g. quetiapine 50mg PO QHS • Caution re orthostatic hypotension

  33. Olanzapine • A number of studies also support use of olanzapine (e.g. Breitbart et al., 2002; Skrobik et al., 2004; Grover et al., 2011) • e.g. Olanzapine oral dissolving 2.5mg QHS • e.g. Olanzapine oral dissolving 5mg QHS • Promotes appetite • Reduces nausea • Promotes sleep • Pro-cholinergic at lower doses, but becomes anticholinergic at larger doses

  34. Loxapine (Bates et al., submitted) • In 31 patients over 55 with post-operative delirium referred to the CL service, loxapine was associated with a mean decrease of 8.48 on the DRS-98-R over the first 2 days of treatment • Only 3 participants had a worsening of delirium, and each of those 3 showed improvement from day 2 to day 4 • Mean number of days to resolution of delirum (DRS < 10) was 3.2 • There was not a significant increase in QTc

  35. Loxapine (Bates et al., submitted)

  36. Terminal Illness • Delirium interferes with identification of sources of distress like pain • How much should one investigate? • Definitive etiology discovered in less than 50%, and often irreversible when found (Bruera et al. 1992) • However, Tuma and DeAngelis (1992) report 68% can be improved even when 30-day mortality is 31% • Lawlor et al. (2000): • 49% reversibility in advanced cancer patients admitted to palliative care • Reversibility associated with opioids, other meds, and dehydration being primary causes

  37. Terminal Illness • Some view delirium as natural part of dying process • Some worry that antipsychotic will make patient more delirious • Evidence is that antipsychotic generally safe and effective at reducing distress • “Unfortunately, the hallucinations in delirium are rarely sugarplum fairies.”

  38. Jacobson et al., 2008 • Elderly delirious postoperative patients: • Fewer nighttime minutes resting • Fewer minutes resting over 24hrs • Greater mean activity at night • Smaller change in activity from day to night • Delirium may be simultaneous wakefulness and sleep • REM intrusion into wakefulness might cause visual hallucinations

  39. Slatore et al., 2012 • Assessed sleep quality and screened for delirium in veterans referred to hospice (55% had cancer) using the Pittsburgh Sleep Quality Index (PSQI) and the Confusion Assessment Method (CAM) • Sleep quality was significantly worse in 33 participants who became delirious than in 42 who did not • Hazard ratio for developing delirium of 2.37 for every point of worse sleep on the PSQI (where 1 = very good; 4 = very bad)

  40. Glymphatic system Xie et al. (2013) demonstrated that sleep is associated with a 60% increase in the interstitial space causing striking increase in exchange between CSF and interstitial fluid Increased rate of β–amyloid clearance

  41. Maldonado et al., 2009 (From Aantaa & Jalonen, 2006) 90 patients who underwent valve procedures randomly assigned to post-op sedation with dexmedetomidine, propofol, or midazolam

  42. Maldonado et al., 2009 Incidence of delirium was 50% for both propofol and midazolam groups and only 3% for dexmedetomidine group Possible benefits of dexmedetomidine: not GABAergic, not anticholinergic, sedating, promotes physiologic sleep pattern without significant respiratory depression, lowers opioid requirements

  43. Chlorpromazine • The double-blind randomized trial by Breitbart et al. (1996) is frequently cited as evidence haloperidol should be chosen over other antipsychotics • However, the findings showed the superiority of both haloperidol and chlorpromazine (a sedating low-potency antipsychotic) over lorazepam while showing equal effectiveness between the two antipsychotics • Sedating antipsychotic with IV option • An example of dosing: chlorpromazine 25mg IV Q6H standing (give over 30min; hold for SBP < 90; hold for sedation)

  44. Maclullich et al., 2009 • Reviewed 9 recent studies with total of 2025 patients • 8/9 studies found a significant association between delirium and cognitive impairment • What is the relationship? • CNS insult causes both in parrallel? • Premorbiddementing process unmasked in form of delirium by stress/insult? • Delirium causes things like dehydration, poor nutrition, suboptimal care etc. and this leads to long-term cognitive impairment? • Delirium is a neurotoxic state? • Delirium management is neurotoxic?

  45. Cardiac Surgery Risk Factors • Giltay et al. (2006): 8139 consecutive patients undergoing CABG and/or valve procedure • Post-op psychotic symptoms associated with age, renal failure, dyspnea, heart failure, and LVH pre-operatively and hypothermia, hypoxemia, low hematocrit, renal failure, high sodium, infection, and stroke perioperatively

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