Delirium

KEYPOINTS

  • Delirium (with or without hallucinations) is commonly experienced by patients with advanced illnesses
  • Possible causes are many, may be multifactorial and difficult to determine in about 50% of cases
  • Delirium or confusion can be caused by the opioids themselves, and/or the accumulation of opioid neurotoxic metabolites
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  • There are many causes of delirium and hallucinations in children
  • May be due to fatigue only

ASSESSMENT

(see Foreword)

  • Non opioid causes include:
    • Dehydration
    • Hepatic and renal failure
    • Urinary retention
    • Infection e.g. urine infection
    • Constipation
    • Brain metastasis
    • Biochemical imbalances, i.e. hypercalcaemia, hyponatraemia
    • Medications, i.e. tricyclics, corticosteroids, benzodiazepines
    • Hypoxia

MANAGEMENT

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Consider if cause of delirium identifiable and if patient well enough for intervention
  • Discontinue drugs that may be causing the delirium (such as anticholinergics, etc.)
  • A trial of hydration if the patient’s condition would tolerate this. May help correct electrolyte disturbances and may diminish opioid toxic metabolite accumulation
  • Correct electrolyte imbalance; hypercalcemia may respond to hydration and/or to bisphosphonates such as pamidronate 60-90 mg (single dose) IV

Pharmacological Management

If symptoms persist, pharmacological management includes:

Neuroleptics

Benzodiazepines

  • Lorazepam or midazolam can also be used in situations where there is considerable agitation. It should be noted however that benzodiazepines can sometimes make confusion worse and should not be used alone for the treatment of delirium
    • Lorazepam 0.5-2 mg bid to qid + q1h prn PO/SC/IV/PR
    • Midazolam 5-60 mg/24h via infusion SC/IV

Opioid Rotation (if alternative opioids available)

  • Opioid rotation (switching from one opioid to another) can be helpful for some patients who do not respond to the addition of neuroleptics or benzodiazepines. This is especially so in patients who may have renal failure in whom metabolites from morphine can accumulate. If an opioid rotation is done, establish the equianalgesic dose from an equianalgesic table, and start the new opioid at 25-50% of the equianalgesic dose (see Equianalgesic Tables). This is to take into account that there is a large variability between individuals in response to various opioids.
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  • Try to prevent delirium by ensuring regular sleep
  • Use familiar stories and music etc.
  • Haloperidol
    • 0.05-0.15 mg/kg/24hrs as continuous infusion or in divided doses bid or tid PO/SC/IV
  • If agitated delirium consider addition of:
  • Lorazepam 25-50 mcg/kg (max 1 mg) as single dose or q4-8h PO/SL/SC
  • Midazolam
    • 500 mcg/kg (max 10 mg) SL as single dose
    • 100 mcg/kg SC as a single dose
    • 300-700 mcg/kg over 24 hours as continuous infusion

PITFALLS/CONCERNS

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  • Antihistamines may cause paradoxical agitation and confusion
  • Benzodiazepines can be useful in children in controlling agitation but at higher doses may worsen delirium in some children

PALLIATIVE TIPS

  • If opioids are suspected as the cause of delirium, it is important to realize the symptoms may disappear after a few days of stable dosing of the opioid. Thus, unless the symptoms are severe, it is recommended to treat them pharmacologically (e.g. as with a neuroleptic) initially, prior to deciding on changing the opioid
  • The newer atypical antipsychotics such as risperidone and olanzapine can also be used effectively and offer the advantage of less antiparkinsonian/anticholinergic side effects
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  • Adequate lighting, keep noise to low level and keep family present

SOURCES/REFERENCES

  1. Bruera E, Neumann CM. Role of methadone in the management of pain in cancer patients. Oncology 1999;13(9):1275-1282 http://www.ncbi.nlm.nih.gov/pubmed/10509323
  2. Cherny N, Ripamonti C, Pereira J, Davis C, Fallon M, McQuay H et al. Strategies to manage the adverse effects of oral morphine: an evidence-based report. J Clin Oncol 2001;19(9):2542-2554. http://www.ncbi.nlm.nih.gov/pubmed/11331334
  3. Mercadante S. Opioid rotation for cancer patients - rationale and clinical aspects. Cancer 1999;86(9):1856-1866 http://www.ncbi.nlm.nih.gov/pubmed/10547561
  4. Mercadante S, Portenoy R. Opioid poorly-responsive cancer pain, part 3. Clinical strategies to improve opioid responsiveness. J Pain Symptom Manage 2001;21(4):338-354. http://www.ncbi.nlm.nih.gov/pubmed/11312049
  5. Smith MT. Neuroexcitatory effects of morphine and hydromorphone: evidence implicating the 3-glucuronide metabolites. Clin Exp Pharmacol Physiol 2000;27(7):524-528. http://www.ncbi.nlm.nih.gov/pubmed/10874511

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