Delirium...what's going on?

A 29-year-old male with moderate traumatic brain injury (TBI) remains intubated in the surgical ICU (SICU) due to agitation/ delirium during daily spontaneous awakening and breathing trials (SAT/ SBT).

What are the clinical priorities?

Rule out acute processes that can cause agitation and delirium, such as anemia, acidosis, hypoxemia, infection, intra-cranial process, fever, and an adverse drug reaction.

Other potential causes?

• Immobility, "lines and tubes."

• Isolation, disorientation, lack of normal sleep-wake patterns

• Endocrine or metabolic derangements

• Organ dysfunction (renal disease, liver disease, etc)

• Withdrawal from chronic home medications (benzodiazepines, alcohol, psychiatric medication, etc.).

What are the treatment principles for agitation and delirium?

• Treat organic reversible causes (treat infection, minimize unnecessary medication, etc.)

• Implement non-pharmacology therapy (sleep-wake cycles, lights and stimulation during the day and darkness at night)

• Pharmacologic agents can be used once reversible causes are remedied and non-pharmacologic therapy has been instituted.

After the optimization of non-pharmacologic therapy, the patient was successfully extubated. A few days later on rounds, the patient was sitting up in bed. During our conversation, I noticed that he was drinking a Mountain Dew. His mom told us that he drinks multiple Mountain Dews every day (read- 6 or more). I told her that I suspect this had a significant role in his altered mental status during attempts at ventilator liberation.

Management of Agitation and Delirium

Definition

• Agitation is a psychomotor disturbance characterized by excessive motor activity and a feeling of “inner tension”.

• Delirium is an altered consciousness with reduced focus/ cognitive function. It is abrupt in onset and can have a fluctuating presentation. High prevelance, often misdiagnosed. Classified as hypoactive (most common, worse prognosis, difficult to diagnose), hyperactive (better prognosis) or mixed.

Etiologies

• Acute illness- sepsis, electrolyte/ metabolism disorders, hyperthermia, hypoxia, hypotension, EtOH withdrawal, organ dysfunction, polytrauma, emergency surgery

• Patient factors- elderly, history of depression/ stroke/ dementia, history of EtOH abuse, tobacco use. Hearing or vision impairment.

• Iatrogenic- noise, discomfort, pain, sedative/ analgesics, ventilator dyssynchrony.

• Exacerbated by pain, anxiety, discomfort.

Diagnosis [see charts below]

• Assess consciousness with Richmond Agitation-Sedation Scale (RASS). 10 point scale, ranging from combative to unarousable.

• Assess for delirium with Confusion Assessment Method for the ICU (CAM-ICU). 1-2 min test, 98% accurate in diagnosing delirium.

• Assess over 24 hrs to capture nocturnal symptoms.

Non-Pharmacologic Treatment of Delirium

• Diagnose and manage underlying acute illness

           - Treat sepsis as appropriate- antibiotics, source control, etc.

           - Correct hypoxia, metabolic disturbances, dehydration, hyperthermia

• Non-pharmacologic interventions for anxiety/ discomfort[1]

  • Periodic reorientation and reassurance from nursing staff

  • Cognitive stimulation

  • Correction of sensory deficits

  • Management of environment (reassess need for invasive devices)

  • Normalize sleep/wake cycles

• Minimize iatrogenic factors (sedation)

Pharmacologic Therapy for Delirium

• Typical anti-psychotic- Haloperidol.

  • MIND and HOPE-ICU trial- no difference in duration of delirium.[2,3]

  • AID-ICU trial- no difference in mortality.[4]

• Atypical anti-psychotic- Quetiapine, Ziprasidone

  • MIND-USA trial- no difference in delirium duration with either agent [5]

• Dexmedetomidine

  • MENDS and SEDCOM trials- ↓ mechanical ventilation and ↓ delirium vs benzos [6,7]

  • MIDEX and Prodex trial- non-inferior compared to benzos/ Propofol [8]

  • DahLIA trial- quicker and more sustained resolution of delirium vs placebo [9]

  • SPICE III Trial- similar mortality and similar number of delirium-free days [10]

  • MENDS II Trial- similar number of delirium-free days vs Propofol.[11]

• Melatonin

  • Pro-MEDIC Trial- prophylactic melatonin didn't decrease delirium prevalence[12]

Assessment for Caffeine Withdrawal

     Obtaining a detailed patient history, or even a focused history of the most pertinent diagnoses or medication (blood thinners, cardiac disease) is often challenging in traumatically injured parents who may have decreased mental status due to injury or intoxication. Documenting daily caffeine intake is not typically a key component in a surgical history. However, caffeine is readily available and is the most commonly used drug in the world.[13] Unfortunately, it has significant systemic effects. Along with nicotine, it is gaining more attention as a potential etiology of altered mental status or other symptoms that would typically prompt extensive work-up. If a patient has persistent altered mental status after evaluating typical causes, consider the possibility that the patient could be missing their usual caffeine fix. 

     "Withdrawal symptoms caused by people abruptly stopping smoking or drinking tea and coffee can include nausea, vomiting, headaches, and delirium and can last for up to two weeks."[14]

References

1. Faustino TN et al. Effectiveness of combined non-pharmacological interventions in the prevention of delirium in critically ill patients: A randomized clinical trial. J Crit Care. 2022;68:114-120.

2. MIND Trial. Girard TD et al. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: The MIND randomized, placebo-controlled trial. Crit Care Med. 2010;38(2):428-437.

3. HOPE-ICU Trial. Page VJ et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. Lancet Resp Med. 2013;1(7):515-523.

4. AID-ICU Trial. Andersen-Ranberg NC et al. Haloperidol for the Treatment of Delirium in ICU Patients. N Engl J Med. Published online October 26, 2022.

5. MIND-USA Trial. Girard TD et al. Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness. N Engl J Med. 2018;379(26):2506-2516.

6. MENDS Trial. Hughes CG et al. Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis. N Engl J Med. 2021;384(15):1424-1436. 

7. SEDCOM Trial. Riker RR et al. Dexmedetomidine vs Midazolam for Sedation of Critically Ill Patients: A Randomized Trial. JAMA. 2009;301(5):489.

8. MIDEX and PRODEX Trials. Jakob SM et al. Dexmedetomidine vs Midazolam or Propofol for Sedation During Prolonged Mechanical Ventilation: Two Randomized Controlled Trials. JAMA. 2012;307(11):1151.

9. DahLIA Trial. Reade MC et al. Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated Delirium: A Randomized Clinical Trial. JAMA. 2016;315(14):1460.

10. SPICE III Trial. Shehabi Y et al. Early Sedation with Dexmedetomidine in Critically Ill Patients. N Engl J Med. 2019;380(26):2506-2517.

11. MENDS II Trial. Hughes CG et al. Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis. N Engl J Med. 2021;384(15):1424-1436. 

12. Pro-MEDIC Trial. Wibrow B et al. Prophylactic melatonin for delirium in intensive care (Pro-MEDIC): a randomized controlled trial. Intensive Care Med. 2022;48(4):414-425.

13. Caffeine: The chemistry behind the world’s most popular drug

14. Stephenson J. Nicotine and caffeine withdrawal may affect ICU patients. Nursing Times. June 2019.

RASS for Agitation Assessment

CAM-ICU For Delirium Assessment