Critical Care Fellows' Boot Camp

Delirium in the ICU

Recognition, prevention, and evidence-based management of acute brain dysfunction in critical illness.

Anirban Bhattacharyya, MD, MS, MPH
Consultant, Critical Care Medicine · Mayo Clinic
July 7, 2026
Roadmap

What we'll cover

What delirium is

Definition

A disturbance of consciousness with inattention, accompanied by a change in cognition or perceptual disturbance, that develops over hours to days and fluctuates over time.

1

Acute onset & fluctuating course

Develops over hours–days; waxes and wanes

2

Inattention

The cardinal feature — cannot sustain or shift focus

3

Disorganized thinking

Rambling, illogical, incoherent stream

4

Altered level of consciousness

Anything other than alert & calm

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR), 2022.
Scale of the problem

Epidemiology & burden

Reported ICU prevalence spans 20–80%

↑Independent predictor of 6-month mortality
↑Longer ICU & hospital length of stay
↑Higher healthcare costs & caregiver burden
Ely et al., JAMA 2001; 2004. · Salluh et al., BMJ 2015 (meta-analysis).
It doesn't end at ICU discharge

Long-term effects of delirium

Time after ICU discharge Global cognition 3 mo12 mo shorter delirium longer delirium
  • ▸ Long-term cognitive impairment at 3 & 12 months — resembling mild Alzheimer's / TBI (BRAIN-ICU)
  • ▸ Longer delirium = worse cognition (dose-dependent)
  • ▸ Functional decline, loss of independence, institutionalization
  • ▸ Part of post-intensive care syndrome (PICS) — cognitive, physical, psychological
  • ▸ Increased mortality; heavy caregiver burden
Pandharipande PP, et al. Long-term cognitive impairment after critical illness (BRAIN-ICU). N Engl J Med 2013.
What it looks like

Clinical features & motor subtypes

Core features
  • ▸ Acute onset & fluctuating course
  • ▸ Inattention & disorganized thinking
  • ▸ Altered level of consciousness
  • ▸ Perceptual disturbances (hallucinations, delusions)
  • ▸ Psychomotor disturbance (agitation ↔ hypoactivity)
  • ▸ Sleep–wake cycle disruption
Motor subtypes
Hypoactive — commonest, often missed, worst prognosis
Hyperactive — agitation, easiest to spot
Mixed — fluctuates between the two
Hypoactive delirium predominates in the ICU and carries the worst prognosis — screening, not observation, catches it.
Assessment

Delirium assessment — the CAM-ICU

1 · Acute onset OR fluctuating course Change from baseline mental status that comes and goes 2 · Inattention Letters ("SAVEAHAART") or pictures — the cardinal, required feature 3 · Altered LOC RASS ≠ 0 (anything butalert & calm) OR 4 · Disorganized thinking Yes/no questions +simple commands CAM-ICU POSITIVE = DELIRIUM Features 1 AND 2, plus 3 OR 4
~80%Sensitivity
~96%Specificity
  • ▸ Validated for bedside use by nurses & physicians
  • ▸ Anchored to a RASS sedation assessment first
  • ▸ ICDSC is a validated alternative
  • ▸ Screen each shift — hypoactive delirium is invisible otherwise
Ely EW, et al. JAMA 2001 (validation). Pooled sensitivity ~80%, specificity ~96% (Gusmao-Flores meta-analysis, Crit Care 2012). · icudelirium.org
Recognize · two traps

Special forms — check sedation first

Rapidly reversible

Delirium that clears soon after lightening sedation is not the same as delirium that persists.

10.5×more CAM-ICU⁺ before vs after sedation interruption
↔rapidly reversible: no rise in 1-yr mortality

Only persistent delirium carried the poor prognosis.

Subsyndromal

Some — but not all — features. Outcomes sit between no delirium and full delirium.

  • ▸ Common — ~36% vs ~20% full delirium in one ICU cohort
  • ▸ ICDSC is more sensitive to it than CAM-ICU
  • ▸ A signal to intensify prevention, not to start drugs

Pair the CAM-ICU with the daily awakening trial.

Patel SB, et al. Rapidly reversible, sedation-related delirium. Am J Respir Crit Care Med 2014. · Burry LD, et al. Chest 2025.
Why it happens

Pathophysiology — a multifactorial final common pathway

Acute brain dysfunction Neuroinflammationcytokines, BBB disruption Neurotransmitter imbalance↓ acetylcholine, ↑ dopamine Oxidative stressmetabolic / energy failure Circadian disruptionsleep–wake breakdown Network disconnectivity Impaired neuroplasticity
Maldonado JR. Delirium pathophysiology: a systems-integration hypothesis. Int J Geriatr Psychiatry 2018.
Who is vulnerable

Risk factors — vulnerability meets insult

High baseline vulnerability
large predisposing loadsmall insult → delirium
Low baseline vulnerability
little predispositionneeds a large insult

The more predisposed the patient, the smaller the precipitant needed to tip into delirium.

Predisposing · baseline
  • ▸ Advanced age
  • ▸ Pre-existing cognitive impairment / dementia
  • ▸ Sensory deficits (vision, hearing)
  • ▸ Multimorbidity, frailty, functional dependence
Precipitating · acute
  • ▸ Acute illness / sepsis, hypoxia, shock
  • ▸ Deliriogenic drugs (benzodiazepines, anticholinergics)
  • ▸ Metabolic derangement; immobility & restraints
  • ▸ Sleep deprivation; the ICU environment itself
Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet 2014.
The organizing framework

The ABCDEF bundle

An integrated, evidence-based approach applied together, every day — not an à-la-carte menu.
How we got here

Development of the bundle

20002008201220132018–19
Daily sedation interruptionKress, NEJM — fewer ventilator days
ABC trial (paired SAT+SBT)Girard, Lancet — survival benefit
Protocolized light sedationSLEAP, Mehta, JAMA
PAD guidelinesBarr, Crit Care Med — codify ABCDE
PADIS + ICU LiberationDevlin; Pun — “F” added
Kress NEJM 2000 · Girard Lancet 2008 · Mehta (SLEAP) JAMA 2012 · Barr (PAD) Crit Care Med 2013 · Devlin (PADIS) 2018 · Pun 2019.
Evidence · the "B" of the bundle

Paired SAT + SBT: the Wake Up and Breathe trial

1-year survival 100755025 090180270360 Days after randomization Patients alive (%) ~53% ~40%
SAT + SBT (intervention) Usual care + SBT
+3.1more ventilator-free days (14.7 vs 11.6)
0.681-yr mortality HR (95% CI 0.50–0.92)
7NNT to save one life at 1 year

Earlier extubation and ICU/hospital discharge, with no increase in adverse outcomes.

Girard TD, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol (Awakening and Breathing Controlled trial). Lancet 2008.
Evidence · the bundle as a whole

More bundle, better outcomes — a dose-response

Proportional bundle performance → Likelihood of good outcome low··complete

ICU Liberation Collaborative: 15,226 patients across 68 ICUs.

  • ▸ Each increment of bundle performance → dose-dependent improvement in survival
  • ▸ More delirium/coma-free days
  • ▸ Less mechanical ventilation, restraint use, ICU readmission
Partial performance still helped — but complete performance helped most

Caveat: this is observational. The first pragmatic RCT of the bundle (Sosnowski 2026) found no delirium reduction — the bundle's clearest wins are liberation & function.

Pun BT, et al. ICU Liberation Collaborative. Crit Care Med 2019. · Sosnowski KJ, et al. ABCDEF bundle pragmatic RCT. Crit Care Med 2026.
Prevention — the highest-yield intervention

Multicomponent non-pharmacologic prevention

Reorientation & cognition
Early mobilization
Sleep promotion
Prevent deliriumHELP-derived
Avoid deliriogenic drugs
Hydration & nutrition
Vision / hearing aids
~44% relative reduction in delirium incidence with multicomponent programs

The strongest evidence in delirium is for prevention, not treatment — and it's overwhelmingly non-pharmacologic. These map directly onto the bundle's D–E–F.

Hshieh TT, et al. Effectiveness of multicomponent nonpharmacological delirium interventions (meta-analysis). JAMA Intern Med 2015. · Devlin JW, et al. PADIS guidelines, Crit Care Med 2018.
Prevent & manage · at the bedside

Approach to the delirious patient

1

Detect — screen every shift

CAM-ICU / ICDSC anchored to RASS

2

Check sedation depth first

Lighten & reassess before calling it delirium

3

Find & treat the cause

Work through DELIRIUMS →

4

Non-pharmacologic bundle

Reorient, mobilize, sleep, glasses/hearing, family

5

Optimize sedation

Light (RASS 0 to −2); avoid benzodiazepines

6

Drugs only for distress

Brief antipsychotic for dangerous agitation — then stop

DELIRIUMS — screen for causes
  • Drugs (benzodiazepines, anticholinergics)
  • Electrolytes / metabolic (Na, glucose, uremia)
  • Lack of drugs — withdrawal
  • Infection / sepsis
  • Respiratory — hypoxia, hypercapnia
  • Intracranial — stroke, seizure, Wernicke
  • Urinary / stool retention
  • Myocardial / shock / hypoperfusion
  • Sleep deprivation & sensory deficits
No drug treats delirium — treat the cause. Stollings JL, et al. Intensive Care Med 2021. · Devlin JW, et al. PADIS, Crit Care Med 2018.
When drugs are considered

Pharmacologic management

Do first
  • ✓ Treat the underlying cause & precipitating factors
  • ✓ Minimize sedation; target light sedation (RASS 0 to −2)
  • ✓ Non-pharmacologic bundle first, every time
  • ✓ Dexmedetomidine when a sedative is needed in agitated, ventilated patients
  • ✓ Melatonin/ramelteon considered for sleep–wake disruption
Use with caution
  • ✕ Benzodiazepines — deliriogenic; avoid except for specific indications (alcohol/benzo withdrawal, seizures)
  • △ Antipsychotics (haloperidol, olanzapine, quetiapine) — reserve for severe agitation / distressing psychosis, not routine prevention or treatment
  • ! Watch QTc, extrapyramidal effects; stop when no longer needed
Devlin JW, et al. PADIS guidelines, Crit Care Med 2018 — no drug is recommended to routinely prevent or treat delirium.
Evidence · antipsychotics put to the test

MIND-USA: antipsychotics did not help

Days alive without delirium or coma (adjusted median, 95% CI) 4681012 Days (higher = better) Placebo Haloperidol Ziprasidone CIs overlap

Placebo-controlled RCT of haloperidol and ziprasidone for ICU delirium (89% hypoactive).

No differencein days alive without delirium or coma, duration of delirium, or 90-day survival

The practice-changer: routine antipsychotics do not treat ICU delirium. Reserve them for the symptom — distressing agitation — not the diagnosis.

Girard TD, Ely EW, et al. Haloperidol and ziprasidone for treatment of delirium in critical illness (MIND-USA). N Engl J Med 2018.
Why this stays hard

Challenges in delirium management

◆

Fluctuating & under-recognized

Symptoms wax and wane; hypoactive delirium is easily missed without formal screening

◆

Diagnostic overlap

Hard to distinguish from dementia, depression, and primary psychiatric illness

◆

Inconsistent screening

Protocols and compliance vary widely between units and shifts

◆

Incomplete mechanism

Pathophysiology is multifactorial and still only partly understood

◆

Limited drug options

No agent reliably prevents or treats it; antipsychotics carry real harms

◆

Implementation barriers

Bundle adherence demands staffing, culture change, and sustained resources

The field since the landmarks

Recent major evidence (2019–2026)

SPICE III · 2019

sedation

Early dexmedetomidine — no mortality benefit.

MENDS2 · 2021

sedation

Dexmedetomidine ≈ propofol on delirium/coma-free days.

AID-ICU · 2022

antipsychotic

Haloperidol ≈ placebo — echoing MIND-USA.

TEAM · 2022

caution

High-intensity early mobility: no gain, more harm.

Pro-MEDIC · 2022

negative

Nightly melatonin did not reduce delirium.

PADIS update · 2025

guideline

Light, benzo-sparing sedation; dexmedetomidine over propofol.

The landmarks still stand. Newer trials refine how we sedate — while confirming no drug reliably prevents or treats delirium.

Full citations on the linked literature page (📚 / press L).
The bottom line

Conclusion

  • ▸ Delirium is common, serious, and under-recognized in the ICU
  • ▸ Screen every shift (CAM-ICU) — you cannot manage what you don't measure
  • ▸ Prevention via the multicomponent bundle is the highest-yield action
  • ▸ Light sedation, avoid benzodiazepines; no drug reliably treats delirium
  • ▸ It's a whole-team effort with consequences that outlast the ICU stay
ABCDEF applied together, daily ABC DEF
Assess pain · Both SAT/SBT · Choice of sedation · Delirium monitoring · Early mobility · Family engagement.
Delirium in the ICU · Boot Camp

Thank you

delirium-icu.pages.dev

Scan to keep these slides & the linked literature.

1 / 20 ← → to navigate