Delirium – Help From Dr. Farkas’ Internet Book Of Critical Care

This post contains links to and excerpts from IBCC chapter & cast: Delirium
[Link is to the podcast] November 7, 2018 by Dr. Josh Farkas MD, author of The Internet Book Of Critical Care [Link is to the Table of Contents].

And here is the link to the outstanding show notes.

Here are the direct links from the show notes to the various sections of the post.


And here are some excerpts from the post:

  • Delirium is acute, generalized brain dysfunction (“cerebral insufficiency”).  Key features:
    • acute (e.g. not dementia)
    • causes inattention (e.g. disorientation, inability to perform complex tasks)
    • tends to wax and wane:  may have periods of lucidity in between periods of confusion.
  • Diagnosis is made clinically, based on examination and history.
common features
  • Commonly classified as follows:
    • Hyperactive delirium: agitation
    • Hypoactive delirium: patient is withdrawn, mute, drowsy.  This can often fly under the radar because it’s not overtly problematic.
    • Mixed delirium:  periods of hyperactive delirium & hypoactive delirium
  • Features can involve:
    • Psychotic symptoms (hallucinations, delusions, paranoia).
    • Emotional symptoms (fear, anxiety, irritability, anger).
    • Day-night reversal with hyperactivity at night (“sundowning”).
    • Increased sympathetic activity (hypertension, tachycardia).

Delirium can reflect a broad range of neurologic or systemic aberrations.  In elderly patients, delirium can be the manifestation of systemic illness (e.g. sepsis or respiratory failure).  All contributory factors should be sought out and managed.   Common causes are listed here, but this list isn’t exhaustive.

  • CVA
    • Hemorrhage (e.g., parenchymal hemorrhage, subdural hematoma)
    • Ischemic stroke
  • Infection
    • Meningitis, encephalitis
    • Sepsis arising from any focus of infection (e.g. urinary tract infection, pneumonia)
  • Medications:  The biggest offenders are listed here, but dozens can cause confusion.  Review the entire medication list carefully, focusing on new medications and medications acting on the nervous system.  Use an application such as Epocrates to look for drug-drug interactions and search for medications that cause delirium.
    • GABAergics (benzodiazepines,3 muscle relaxants)
    • Antihistamines (e.g. diphenhydramine, promethazine)
    • Opioids
    • Antimicrobials (esp fluoroquinolones, cefepime)
    • Anticonvulsants (carbamazepine, phenytoin, valproate)
    • Parkinson’s medications
    • Metoclopramide
    • Zolpidem and related sleep medications
    • Steroid
  • Metabolic
  • Organ failure
    • Cardiovascular:  shock, hypertensive encephalopathy
    • Pulmonary:  hypoxemia, hypercapnia
    • Liver:  Hepatic encephalopathy
    • Renal:  Uremia
    • Endocrine:  Thyroid storm/myxedema coma
    • Heme:  Thrombotic thrombocytopenia purpura (TTP)
  • Seizure
  • Toxicologic
    • Withdrawal from EtOH, benzodiazepines, gabapentin, baclofen, opioid, serotonin-norepinephrine receptor inhibitors
    • Intoxication/poisoning (e.g. carbon monoxide, lithium, digoxin)
  • Sleep deprivation
    • Noisy ICU environment
    • Frequent blood pressure or neurologic checks
    • Uncontrolled pain

This is tricky. Delirium can be due to life-threatening conditions, so a thorough evaluation is required for a patient with new-onset delirium.

exam, with focus on:
  • Vital sign abnormalities (may reflect shock or respiratory insufficiency)
  • Neurologic exam (evaluate for any focal neurologic findings)
  • Foci of infection (e.g. site of any invasive lines/tubes)
  • Basics
    • Fingerstick glucose (STAT)
    • Electrolytes, including Ca/Mg/Phos
    • CBC with differential
  • Consider, depending on context:
    • LFTs
    • Ammonia
      • See my post “What is the utility of measuring the serum ammonia level in patients with altered mental status” – Help From The Cleveland Clinic
        Posted on July 22, 2019 by Tom Wade MD
    • TSH
    • ABG/VBG if patient somnolent and hypercarbia suspected
    • Infectious workup (e.g. urinalysis, blood cultures)
    • Pertinent drug levels (e.g. digoxin, lithium, theophylline)
    • Additional toxicologic workup, depending on context (e.g. carboxyhemoglobin level for community-onset delirium during winter).
  • Nonenhanced CT head may be considered for:
    • Patients presenting with delirium, especially if history is unclear
    • CNS trauma
    • Significant anticoagulation
    • Neurologic exam showing focal signs (note though that subdural hematoma can depress mental status without focal findings)
    • Substantially reduced level of consciousness
  • MRI may provide additional information about a variety of conditions (especially CVA).
lumbar puncture
  • Primarily useful for patients presenting to the hospital with delirium.
  • In the absence of a specific precipitating factor (e.g. neurosurgery, endocarditis), it’s uncommon for a patient to develop meningitis de novo within the hospital.  Thus, lumbar puncture is generally low-yield for someone who develops delirium while in the ICU.
  • Indicated if there is a suspicion for seizure or nonconvulsive status epilepticus:
    • Seizure history
    • Unusual facial twitching or automatisms (e.g. chewing or lip-smacking movements)
    • Nystagmoid eye movements or hippus (spontaneous pupillary fluctuations; video below)
Treatment Overview

Treatment begins with basic anti-delirium strategies listed in the last section on delirium prevention.

  • Evaluate for and treat any specific cause(s).
  • Exclude hypoglycemia and fix electrolyte abnormalities (especially hypernatremia).
  • Treat fever if that may be contributing.
  • Give thiamine if Wernicke’s encephalopathy is possible (a treatment dose for Wernicke’s encephalopathy is high, e.g. 500 mg IV q8hr).
  • Review the medication list and discontinue drugs that may be aggravating delirium.
  • Treat pain adequately and relieve other sources of discomfort (e.g. constipation, unnecessary invasive devices).
  • Provide patient’s eyeglasses and hearing aids.
philosophy of medication therapy for delirium
  • Medications don’t really fix delirium (the only thing that seems to do that is sleep).
  • The goals of medication are:
    • (a) Render the patient safe and manageable (if severely agitated).
    • (b) Promote sleep and normal circadian cycle.
entrainment of circadian rhythm
  • Delirious patients often lose their normal day-night cycle.  They may benefit from efforts to promote sleep at night.
  • Simple measures may be effective:
    • During the day:  Open the curtains, use aggressive physical therapy, stimulate patient.
    • At night:  Use ear plugs, avoid frequent blood pressure measurement, turn off the television, and limit stimulation.
  • Medications can help promote sleep at night, particularly QHS melatonin or ramelteon (a synthetic melatonin agonist).  Some evidence suggests that these agents may prevent or treat delirium.
  • For patients who are frequently requiring antipsychotics, it may be helpful to schedule these before sleep (e.g. quetiapine 50 mg QHS).  Scheduling antipsychotics at ~9 PM before sleep may avoid the patient’s getting PRN doses at 3-5 AM, which causes the patient to sleep all day and then be agitated the following night.
  • Emerging as a useful and extremely safe therapy for agitated delirium.  Advantages include lack of respiratory depression and ability to titrate.
  • Great choice for dealing with nocturnal agitation (sundowning).  Titratability allows this drug to be used to re-entrain a circadian rhythm:
    • During night:  titrate dexmedetomidine to promote sleep.
    • During day:  aggressively titrate dexmedetomidine OFF, promoting wakefulness during the day.
  • The short half-life of dexmedetomidine avoids the sundowning cycle wherein patient gets tons of medications for sundowning around 2 AM, sleeps for ~18 hours, and then wakes up and gets agitated the following evening.
  • Main complication is bradycardia.  If dexmedetomidine is truly needed, this may be managed with a very low-dose infusion of peripheral epinephrine (e.g. 0-4 mcg/min).
role of antipsychotics in treatment of delirium?
  • (1) Treatment of agitation:  May avoid inadvertant tube removal and facilitate cooperation with care.
  • (2) Treatment of insomnia.
  • Antipsychotics are not beneficial in patients with hypoactive delirium.4
  • Antipsychotics are contraindicated in patients with Parkinson’s disease or Lewy Body Dementia, as these patients will be at increased risk for extrapyramidal side-effects.

For much more on antipsychotic use in delirium please see antipsychotics in the show notes.

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