Managing Delirium

Image by Tadeu Jnr via Unsplash.comContributed by:

Lesley Charles, MBChB, CCFP(COE)
(Click for bio)

Case

Ms. Jones is 78 and presenting with a two-week history of fluctuating confusion with hallucinations. Her past medical history includes hypertension; dyslipidemia; coronary artery disease; osteoporosis; hypothyroidism; and insomnia. Current medications include amlodipine 5 mg daily; atorvastatin 20 mg daily; ECASA 81 mg daily; vitamin D 1000 units daily; calcium 500 mg daily; risedronate 35 mg weekly; levothyroxine 75 mcg daily; and zopiclone. 

Issue

Delirium is a medical emergency with varying presentation and cause. It has severe adverse outcomes. Optimal management of delirium may help alleviate some adverse outcomes but frequently remains unrecognized. 

Background

Delirium is defined by DSM V as an acute change in mental state with fluctuating course, inattention, disturbance of consciousness and disorganized thinking.1 The commonly used Confusion Assessment Method (CAM) is based upon it.2 Delirium results in loss of function, increased morbidity and mortality, and higher health care costs.3-8

Evidence

The prevalence of delirium varies widely by setting being lowest in outpatient settings (2%) and highest in acute care (80%). It also varies in acute care by service being highest in surgical ICU, geriatric and palliative units.6,8 Delirium is commonly seen in patients with an undiagnosed dementia.9 Other risk factors are age, comorbidities, sensory loss, immobility, insomnia, dehydration and malnutrtion.10 By paying attention to risk factors, it is thought that 30-40% of cases of delirium can be prevented.11 Preoperative geriatric consultation and the Modified Hospital Elder Life program have both shown to lower the incidence of delirium. It is important to prevent delirium as serious adverse outcomes are associated with it. Delirium is associated with increased mortality: there is 2-4-fold increased risk of death in ICU and 1.5-fold increased risk in the year following hospitalization for those on medical or geriatric units.12,13

Following identification of delirium, an organic cause should be sought. The most common causes are infection and medications, though consideration needs to also be given to alcohol withdrawal, metabolic disturbance, hypoxia and CNS lesions. Pain, urinary retention and constipation may all precipitate or perpetuate delirium. Delirium is often multifactorial with predisposing, precipitating and perpetuating factors at play.14 

A typical work up should be directed by history and physical examination but may include: laboratory tests (CBC&D; electrolytes; calcium; glucose; renal function; liver function; thyroid function; troponin I; urinalysis; cultures of urine; blood and sputum; drug levels; toxicology screen; ammonia; vitamin B12; and cortisol), arterial blood gas; electrocardiography; chest X-ray; lumbar puncture (reserved for evaluation of fever with headache, and meningeal signs, or suspicion of encephalitis); and CT scan (in selected patients).15 Medications should be reviewed for common culprits in precipitating delirium especially psychoactive medications. 

Table 1

Common medications that cause delirium16

Drug Class

Example Medications

Anticholinergics

Diphenhydramine, promethazine, oxybutynin, solifenacin, fesoterodine

Antidopaminergics

Metocloperamide, chlorpromazine, bupropion

Sedative/hypnotics

Benzodiazepines: diazepam, clonazepam

Barbiturates: secobarbital, phenobarbital

Hypnotics: zolpidem, zaleplon, ramelteon

Antipsychotics

Haloperidol, quetiapine, olanzapine, ziprasidone

Opioids

Hydrocodone, oxycodone, morphine

Other centrally acting agents

Relaxants: tizanidine, cyclobenzaprine, baclofen

Dopaminergic: carbidopa/levodopa, selegiline

Stimulants: amphetamine, methylphenidate

It is important to rule out dementia behaviors versus a delirium. Typically, dementia will be more chronic, though in Lewy body dementia the overlap of fluctuations and inattention can confuse the clinician. 

Treatment of delirium should be directed at the underlying cause. Additional treatment is non-pharmacological with re-orientation by staff or family.17 Avoid restraints and ambulate the patient three times per day. Normalize the sleep-wake cycle. Ensure that the patient has their glasses, hearing aids and dentures. 

Pharmacological treatments should be reserved for cases resistant to non-pharmacological measures and when the patients or others are at risk.18 Haldol remains the mainstay treatment in delirium despite warnings of its efficacy.18 Newer second-generation antipsychotics such as quetiapine, risperidone and olanzapine have been used for short-term treatment. They lower the incidence of delirium but often don’t affect long-term outcomes such as length of stay and mortality. Melatonin, but not cholinesterase inhibitors, has also shown promise.15 There is much heterogeneity with systematic review. Antipsychotics are not supported by current evidence for prevention or treatment of delirium and additional methodologically rigorous studies using standardized outcome measures are needed.19

Recommendation

The patient is assessed in the emergency department with work up revealing a urinary tract infection and suboptimal treatment of her hypothyroidism with a raised TSH. She was treated with cefixime and her levothyroxine was increased. She was admitted to hospital where re-orientation techniques were utilized. During her stay she was started on melatonin and her zopiclone was slowly weaned. 

References

  1. American Psychiatric Association Diagnostic and statistical manual of mental disorders (5th edition), American Psychiatric Association, Washington (DC) (2013).
  2. Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med. 1990 Dec 15; 113(12):941-8.
  3. Inouye SK , Rushing JT, Foreman MD, et al. Does delirium contribute to poor hospital outcomes? a three-site epidemiologic study. J Gen Intern Med, 13 (1998), pp. 234-242.
  4. Murray AM, Levkoff SE, Wetle TT, et al. Acute delirium and functional decline in the hospitalized elderly patient. J Gerontol, 48 (1993), pp. M181-M186.
  5. Pompei P, Foreman M, Rudberg MA , et al. Delirium in hospitalized older persons: outcome and predictors. J Am Geriatr Soc, 42 (1994), pp. 809-815.
  6. Siddiqui N, House AO, Holmes JD. Occurrence and outcome of delirium in medical in-patients: a systemic literature review. Age Ageing, 35 (2006), pp. 350-364.
  7. Brummel NE, Jackson JCP, Pandharipande PP, et al. Delirium in the ICU and subsequent long-term disability among survivors of mechanical ventilation. Crit Care Med, 42 (2) (2014), pp. 369-377.
  8. Leslie DL, Marcantionio ER, Zhang Y, et al. One-year health care costs associated with delirium in the elderly population. Arch Intern Med, 168 (1) (2008), pp. 27-32.
  9. Han JH, Shintani A, Eden S, et al. Delirium in the emergency department: an independent predictor of death within 6 months. Ann Emerg Med, 56 (2010), pp. 244-252.
  10. Flaherty JH, Gonzales JP, Dong B, Antipsychotics in the treatment of delirium in older hospitalized adults: a systemic review. J Am Geriatr Soc, 59 (Suppl 2) (2011), pp. S269-S276.
  11. Inouye SK, Bogardus ST Jr, Charpentier PA, Leo-Summers L, Acampora D, Holford TR, et al. A multicomponent intervention to prevent delirium in hospitalized older patients. N Engl J Med. 1999 Mar 4; 340(9):669–76.
  12. Veiga D, Luis C, Parente D, Fernandes V, Botelho M, Santos P, et al. Postoperative delirium in intensive care patients: risk factors and outcome. Rev Bras Anestesiol. 2012 Jul; 62(4):469–83.
  13.  Leslie DL, Zhang Y, Holford TR, Bogardus ST, Leo-Summers LS, Inouye SK. Premature death associated with delirium at 1-year follow-up. Arch Intern Med. 2005 Jul 25; 165(14):1657–62.
  14.  Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA. 1996 Mar 20; 275(11): 852–7.
  15. Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014 Mar 8;383(9920):911-22. doi: 10.1016/S0140-6736(13)60688-1. Epub 2013 Aug 28.
  16. Setters B, Solberg LM. Delirium. Prim Care. 2017 Sep;44(3):541-559. doi: 10.1016/j.pop.2017.04.010.
  17. Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically ill patients: validation of the confusion assessment method for the intensive care unit (CAM-ICU). Crit Care Med, 29 (2011), pp. 1370-1379.
  18. Vasilevskis EE, Ely EW. 2013: updates in delirium. Neurohospitalist, 4 (2) (2014), pp. 58-60.
  19. Neufeld KJ, Yue J, Robinson TN, Inouye SK, Needham DM. Antipsychotic Medication for Prevention and Treatment of Delirium in Hospitalized Adults: A Systematic Review and Meta-Analysis. J Am Geriatr Soc. 2016 Apr;64(4):705-14. doi: 10.1111/jgs.14076. Epub 2016 Mar 23.

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