ICU Delirium

   MCC ICU Topic Deep Dive: ICU Delirium

Definition: A sudden state of confusion or altered mentation that develops in ICU patients 

Risk Factors: Benzodiazapine use, blood transfusions, advanced age, underlying dementia, prior coma, pre-ICU emergent surgery or trauma, and elevated APACHE score 

Symptoms: Confused thoughts, agitation, inability to pay attention, hallucinations, sleep pattern alteration, memory issues, repetitive movements (Pulling at clothes, lines, wires, repeated attempts to get out of bed) 

Pharmacologic Treatment: There are NO FDA approved medications for ICU delirium. 

Nonpharmacologic: Use simple language, reorientation, ensure glasses or hearing aids are in place, encourage family to visit, keep familiar items from home in the room, encourage normal sleep/wake cycle, cognitive stimulation when alert.

Guidelines: Society of Critical Care (2018) 

• Delirium can be predicted (Pre-Deliric model or E-Pre-Deliric models, Cam-ICU)
• Delirium should be screened for; Admittedly there is no evidence to support this as changing outcomes. 
• Level of arousal may influence delirium (As measured by RASS scoring). Low level of evidence available, but there is some data to suggest patients maintained at a RASS -2 were more likely to develop ICU delirium than patients maintained at a RASS -1 to 0 
• ICU delirium may be associated with a longer hospital stay 
• ICU delirium has NOT been shown to be associated with PTSD 
• ICU delirium has NOT been shown to be associated with long ICU length of stay 
• Rapidly reversed delirium is associated with outcomes similar to patients without delirium
• Pharmacologic agents SHOULD NOT be used to prevent ICU delirium 
• Pharmocologic agents SHOULD NOT be used for patients with subsyndromal delirium 
• Haldol, atypical antipsychotics, statins SHOULD NOT be routinely used to treat delirium. These agents were not associated with shorter duration of delirium, reduced mechanical ventilation, reduced ICU length of stay, or decreased mortality. 
• Short term use of the above agents for patients to treat anxiety, fearfulness, hallucinations, delusions, agitation, or to prevent physical harm to themselves or others. Continued use of antipsychotic medications can result in significant mortality and financial cost. 
• Dexmedetomidine IS recommended for delirium in mechanically ventilated patients where agitation is precluding weaning/extubation. 
• Bright light therapy should not be used as a solo agent to treat ICU delirium 
• A multicomponent nonpharmacological strategy IS recommended to treat ICU delirium. This included optimizing sleep, reorientation, cognitive stimulation, reducing sedation, early mobilization, reducing visual/hearing impairment (glasses, hearing aids) 
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So, the above gives us a reasonable guideline for ICU delirium, but even SCCM admits that much of this is low evidence and not studied very well. We use pharmacological interventions all of the time in the ICU, but be mindful that you are not actually treating delirium. You are treating some of the agitation/irritability that the delirium causes by basically sedating the patient. 

                     Pharmacological options (All off label for delirium): 

Antipsychotics: 

Quetiapine (Seroquel): PO route only, 25-50 mg. Half life 6 hours. Keep in mind a therapeutic dose for true psychiatric disorder is up to 800 mg per day in divided doses. Monitor QT, metabolized in the liver. 

Haloperidol (Haldol): IV/IM/PO routes all available. 2.5-5 mg starting dose (IM/IV).Variable half life between 8.5 hours to 48 hours. Quick acting (~15 min) and do not need PO access, but prolonged half life potential make this less preferred.  Monitor QT, metabolized in the liver. 

Ziprasidone (Geodon): PO or IM routes. Half life 7-10 hours. Typically, 10 mg IM for agitation in a patient without IV or PO access. Monitor QT, metabolized in liver 

Olanzapine (Zyprexa): PO route only, 5-10 mg. Prolonged half life 24-36 hours, generally avoided for this reason. Monitor QT, metabolized in liver

Risperidone (Risperdal): PO route only, 2-4 mg nightly. Prolonged half life of 20 hours. Monitor QT, metabolized in the liver. 

Acetamides: 

Melatonin: PO route only, 3-10 mg po to promote sleep. Half life 20-40 minutes. 

Alpha 2 Adrenergic Agonists:

Dexmedetomide (Precedex): IV route only, 0.1-1.5 mcg/kg/min per hour. Short half life (6 minutes) and requires constant infusion. Metabolized in the liver. There is some low level evidence that this could reduce the incidence of delirium in the ICU. 

Serotonin Receptor Antagonists and Reuptake Inhibitor (SARIs) 

Trazadone: PO route only, 25-50 mg nightly to promote sleep. Half life 5-10 hours.  Monitor QT, metabolized in the liver. 

Medications to avoid: 

Benzodiazepines, antihistamines, opiates (unless pain is present), sedatives, hypnotics, barbiturates (unless alcohol withdrawal present)   

Random Dan Advice: 

• Be careful what you read. There are a lot of low powered studies out there suggesting that different medications are effective for delirium. To date, there is no proven magic bullet. Your goal is to keep your patient and nursing staff safe while the delirium runs its course. 
• Not all delirium is hyperactive. Your patient that is constantly asleep or goes back and forth from unresponsive and agitated (mixed) is also delirious.  
• Delirium is common (50-70% of high risk ICU patients depending on what you read). Don’t get in the habit of just calling everything delirium. Seizure, withdrawal, paradoxical reactions, pain, intoxication, to name a few, can all look like delirium and should be treated appropriately.  
• For agitated delirium, your restraints and sedation may be prolonging the problem. Keeping someone sedated just passes the problem on to the next day. Take reasonable chances to wake your patient up and see how they are mentating. A patient that is yelling is annoying….but not dangerous. ICU delirium usually lasts in the 3-5 day range, sometimes as long as 7 days. 

Recent evidence for/against some of the above with a significant (>400) patient mix: 

Pro-Medic Trial: 2017 randomized double blind placebo trial in Australia. 419 patients given melatonin and 422 given placebo. Results: No difference in ICU LOS, hospital LOS, mortality, quantity or quality of sleep. 

Prophylactic Melatonin for Delirium in Critically Ill Patients: A Symptomatic Review and Meta-Analysis with Trial Sequential Analysis: 2022 Cochrane review of 12 trials and 2538 patients receiving early administration of melatonin. Results: Sensitivity analysis of high quality studies do not support the use of melatonin to prevent ICU delirium. 

Haloperidol for the Treatment of Delirium in ICU patients: 2022 New England Journal study of 1000 patients with delirium randomized to placebo or haldol 2.5 mg TID + prn doses up to 20 mg daily. No difference in total of days in the hospital or alive after 90 day review. 

The Impact of Nursing Delirium Preventitive Interventions in the ICU: A Multicenter Cluster-randomized Controlled Clinical Trial: 2021 American Journal of Critical Care and Respiratory Medicine study of 1749 patients. Nursing staff was educated to delirium interventions and modifiable risk factors and implemented after a control period was conducted. There was no difference in the number of delirium-free or coma free days alive at 28 days. 

REDUCE Randomized Clinical Trial: 2018 Journal of American Medical Association trial of 1789 critically ill adults with high risk of delirium randomized to prophylactic haloperidol 1 mg TID (n = 350) or 2 mg (n = 732) or haloperidol or placebo (n = 707). There was no difference in survival at 28 days.