17.1 Coma, Altered Mental Status & Acute Delirium in the ICU

ABIM Critical Care Medicine Study Guide Exam

Track your progress as you read

Finished sections get a check mark.

1 Chapter 1: Exam Orientation: Format, Blueprint & Study Strategy

1.1 ABIM Critical Care Medicine Exam: Format, Blueprint & Study Strategy

2 Chapter 2: Acute Respiratory Failure & ARDS

2.1 ARDS Definition, Pathophysiology & Phenotypes 2.2 Lung-Protective Mechanical Ventilation 2.3 Refractory ARDS: Prone Positioning, Neuromuscular Blockade & VV-ECMO

3 Chapter 3: Obstructive Airways, Pulmonary Vascular & Pleural Emergencies

3.1 Severe Asthma & COPD Exacerbations in the ICU 3.2 Massive & Submassive Pulmonary Embolism 3.3 Pulmonary Hypertension & Right Ventricular Failure in the ICU 3.4 Massive Hemoptysis, Complex Pleural Effusions & Thoracic Drainage

4 Chapter 4: Airway, Parenchymal & Nonthrombotic Pulmonary Emergencies

4.1 Airway Management, Upper-Airway Obstruction & Artificial-Airway Complications 4.2 Diffuse Alveolar Hemorrhage, Interstitial Lung Disease, Pulmonary Vasculitis & Noncardiogenic Edema 4.3 Severe Community-Acquired & Viral Pneumonia 4.4 Nonthrombotic Embolism (Air, Fat, Amniotic Fluid, Tumor, Septic) & Acute Chest Syndrome

5 Chapter 5: Mechanical Ventilation Modes, Dyssynchrony & Liberation

5.1 Mechanical Ventilator Modes & Advanced Breath Delivery 5.2 Patient-Ventilator Dyssynchrony & Waveform Analysis 5.3 Ventilator Liberation, Spontaneous Breathing Trials & Post-Extubation Support

6 Chapter 6: Shock Syndromes & Hemodynamic Principles

6.1 Shock Classification, Cellular Pathophysiology & Biomarkers 6.2 Hemodynamic Monitoring: Arterial Lines, CVP & Pulmonary Artery Catheter 6.3 Dynamic Assessment of Fluid Responsiveness & Resuscitation Targets

7 Chapter 7: Vasoactive Therapies & Mechanical Circulatory Support

7.1 Vasopressors & Inotropes: Pharmacology & Clinical Titration 7.2 Temporary Mechanical Circulatory Support: IABP, Impella & TandemHeart 7.3 Venoarterial ECMO (VA-ECMO) & Differential Hypoxemia 7.4 Post-Cardiac Arrest Care, Targeted Temperature Management & Neuroprognostication

8 Chapter 8: Acute Kidney Injury & Renal Replacement Therapy

8.1 KDIGO AKI Classification, Etiologies & Diagnostic Evaluation 8.2 Continuous Renal Replacement Therapy (CRRT) vs Intermittent Hemodialysis 8.3 Indications & Timing for RRT in Critical Illness: AKIKI & STARRT-AKI

9 Chapter 9: Electrolyte, Acid-Base & Endocrine Emergencies

9.1 Severe Dysnatremias: Hyponatremia, Hypernatremia & Osmotic Demyelination 9.2 Potassium, Calcium, Magnesium & Phosphate Disorders 9.3 Complex & Mixed Acid-Base Disorders: Boston vs Copenhagen vs Stewart 9.4 Endocrine Crises: DKA, HHS, Thyroid Storm, Myxedema Coma & Adrenal Crisis

10 Chapter 10: Glycemic Control, Hyperammonemia, Pituitary & Adrenal Disorders

10.1 ICU Glycemic Control & Severe Hypoglycemia 10.2 Non-Hepatic Hyperammonemia & Metabolic Encephalopathy 10.3 Pituitary Emergencies, Adrenal Excess & Critical Illness-Related Corticosteroid Insufficiency

11 Chapter 11: Acute Coronary Syndromes & Cardiac Arrhythmias

11.1 Acute Coronary Syndromes & Mechanical Complications of Myocardial Infarction 11.2 Critical Tachyarrhythmias: Atrial Fibrillation with RVR, VT & VF 11.3 Critical Bradyarrhythmias, Conduction Blocks & Temporary Cardiac Pacing

12 Chapter 12: Acute Heart Failure, Valvular & Pericardial Emergencies

12.1 Acute Decompensated Heart Failure & Cardiogenic Pulmonary Edema 12.2 Acute Valvular Regurgitation & Prosthetic Valve Emergencies 12.3 Pericardial Tamponade & Acute Aortic Syndromes

13 Chapter 13: Myocardial Disease, Hypertensive & Cardiac Device Emergencies

13.1 Fulminant Myocarditis, Stress & Peripartum Cardiomyopathy, and Hypertrophic Cardiomyopathy 13.2 Hypertensive Emergencies & Ruptured Abdominal Aortic Aneurysm 13.3 Implanted Cardiac Devices, LVAD Emergencies & Electrical Storm

14 Chapter 14: Sepsis & Systemic Infectious Diseases

14.1 Sepsis-3 Definitions & Surviving Sepsis Campaign 2026 Guidelines 14.2 Refractory Septic Shock & Adjunctive Therapies 14.3 Multidrug-Resistant Pathogens & Antimicrobial Stewardship in the ICU

15 Chapter 15: ICU-Acquired & Severe Focal Infections

15.1 Hospital-Acquired & Ventilator-Associated Pneumonia 15.2 Central Line-Associated Bloodstream Infections & Catheter-Associated UTIs 15.3 Intra-Abdominal Sepsis, Necrotizing Soft Tissue Infections & CNS Infections

16 Chapter 16: Focal, Special-Host & Systemic Infections

16.1 CNS Infections Beyond Bacterial Meningitis: Encephalitis, Brain Abscess & Epidural Abscess 16.2 Infections in the Immunocompromised Host, Tropical & Bioterror Infections 16.3 Infective Endocarditis, Device Infections & Other Focal Cardiovascular Infections 16.4 Antimicrobial Pharmacokinetics, Allergy, Toxicity & Infection Prevention 16.5 Gastrointestinal & Hepatobiliary Infections: Fulminant C. difficile, Typhlitis, CMV Colitis & Abscesses

17 Chapter 17: Neurocritical Care & Coma

17.1 Coma, Altered Mental Status & Acute Delirium in the ICU 17.2 Status Epilepticus & Non-Convulsive Status Epilepticus 17.3 Acute Ischemic Stroke & Intracranial Hemorrhage

18 Chapter 18: Cerebrovascular Syndromes, Encephalopathy & Withdrawal States

18.1 Cerebral Venous Sinus Thrombosis, PRES & Reversible Cerebral Vasoconstriction Syndrome 18.2 Alcohol & Sedative Withdrawal, Wernicke Encephalopathy & Drug-Induced Encephalopathy

19 Chapter 19: Intracranial Hypertension & Neuromuscular Weakness

19.1 Intracranial Pressure Monitoring, Cerebral Perfusion & Tiered ICP Management 19.2 Acute Neuromuscular Respiratory Failure, ICU-Acquired Weakness & Brain Death Determination

20 Chapter 20: Traumatic Brain Injury, Spinal Cord Injury & Toxin-Mediated Paralysis

20.1 Traumatic Brain Injury Management & Paroxysmal Sympathetic Hyperactivity 20.2 Acute Spinal Cord Injury, Neurogenic Shock & Autonomic Dysreflexia 20.3 Toxin-Mediated Paralysis & Neuromuscular Crises: Botulism, Tetanus, Tick Paralysis & Myasthenic Crisis

21 Chapter 21: Gastrointestinal, Hepatic & Abdominal Emergencies

21.1 Acute Upper & Lower Gastrointestinal Bleeding in the ICU 21.2 Acute Liver Failure & Severe Acute Pancreatitis 21.3 Abdominal Compartment Syndrome & Acute Mesenteric Ischemia

22 Chapter 22: Luminal GI Emergencies & Complications of Cirrhosis

22.1 Esophageal, Gastric & Bowel Emergencies: Perforation, Obstruction, Ogilvie Syndrome & Colonic Ischemia 22.2 Complications of Cirrhosis: Alcohol-Associated Hepatitis, Hepatorenal Syndrome & Pulmonary Vascular Syndromes

23 Chapter 23: Trauma, Burns & Perioperative Critical Care

23.1 Polytrauma Resuscitation, Damage Control & Massive Transfusion 23.2 Severe Burn Injury, Inhalation Injury & Environmental Emergencies 23.3 Perioperative Critical Care for High-Risk Surgical Patients

24 Chapter 24: Thoracic Trauma, Environmental Injury & Obstetric Critical Care

24.1 Thoracic Trauma: Flail Chest, Pulmonary Contusion, Great Vessel & Tracheobronchial Injury 24.2 Environmental Injury: Drowning, Diving, Altitude, Heat, Cold, Electrical & Radiation 24.3 Obstetric & Genitourinary Emergencies and the Physiology of Pregnancy

25 Chapter 25: Transplantation, Donor Management & Post-Cardiac Surgery Care

25.1 Solid Organ Transplant Recipients & Deceased Donor Management 25.2 Post-Cardiac Surgery Critical Care: Bleeding, Tamponade, Low Output & Vasoplegia

26 Chapter 26: Hematologic Emergencies, Toxicology, Critical Ultrasound & ICU Liberation

26.1 Hematologic Emergencies in the ICU: HIT, DIC, TMA & Anticoagulant Reversal 26.2 Critical Care Toxicology, Toxidromes & Specific Antidotes 26.3 Critical Care Point-of-Care Ultrasound (POCUS) 26.4 ICU Liberation, Analgosedation, Goals of Care & Critical Care Ethics

27 Chapter 27: Transfusion Medicine, Hematologic & Oncologic Disorders

27.1 Transfusion Medicine: Products, Thresholds, Reactions & Apheresis 27.2 Red and White Cell Disorders, Hemoglobinopathies, Factor Deficiencies & Hypercoagulable States 27.3 Oncologic Emergencies, Hematopoietic Cell Transplant Complications & Cellular Therapy Toxicity

28 Chapter 28: Clinical Pharmacology, Adverse Drug Reactions & Specific Poisonings

28.1 Pharmacokinetic Principles, Dose Adjustment & Drug Interactions in Critical Illness 28.2 Adverse Drug Reactions: Anaphylaxis, Severe Cutaneous Reactions & Hyperthermic Syndromes 28.3 Specific Poisonings: Sodium-Channel Blockers, Lithium, Valproate, Theophylline, Iron, Sulfonylureas & Methemoglobinemia

29 Chapter 29: Ethics, Research Methods, Administration & Abdominal Ultrasound

29.1 Advance Care Planning, Nonbeneficial Treatment, Informed Consent & Confidentiality 29.2 Critical Care Research Methods, Statistics, IRB Oversight & Quality Improvement 29.3 Abdominal, Vascular & Procedural Point-of-Care Ultrasound

17.1 Coma, Altered Mental Status & Acute Delirium in the ICU

Key Takeaways Explain This Topic AI

Coma requires bilateral bihemispheric cortical dysfunction or a focal brainstem lesion disrupting the ascending reticular activating system (ARAS); the FOUR score overcomes Glasgow Coma Scale (GCS) limitations in intubated ICU patients by incorporating brainstem cranial nerve reflexes and respiratory drive.

Pupillary reflex localization is clinically decisive: an acute unilateral dilated, non-reactive pupil indicates uncal herniation compressing the ipsilateral oculomotor nerve (CN III); pinpoint reactive pupils indicate pontine lesions or opioid toxicity; bilateral fixed, dilated pupils signify catastrophic midbrain damage, severe anoxia, or brain death.

ICU delirium is classified into hyperactive, hypoactive, and mixed subtypes; hypoactive delirium is the most prevalent (~50% to 60% of cases), carries the highest mortality and longest duration of mechanical ventilation, and is the most frequently missed.

The CAM-ICU algorithm requires acute onset or fluctuating course (Feature 1) AND inattention (Feature 2) PLUS either an altered level of consciousness (Feature 3) OR disorganized thinking (Feature 4); patients with deep sedation (RASS -4 or -5) cannot be assessed.

The 2018 PADIS guideline supports the ABCDEF bundle, non-pharmacological delirium prevention and light sedation (RASS -1 to 0) with propofol or dexmedetomidine rather than benzodiazepines; the 2025 focused update suggests dexmedetomidine over propofol when light sedation is the goal. Routine antipsychotic prophylaxis is not recommended, and haloperidol or quetiapine requires QTc monitoring.

Last updated: October 2026

Neurobiology of Consciousness and Coma Localization

Consciousness comprises two physiologically distinct components: arousal (wakefulness, the level of consciousness) and awareness (content of consciousness, including cognition, perception, and purposeful interaction with the environment). Arousal is mediated by the ascending reticular activating system (ARAS) —a dense network of interconnected cholinergic, monoaminergic, and glutamatergic nuclei residing within the dorsal brainstem tegmentum (midbrain and upper pons) that projects rostrally to the intralaminar nuclei of the thalamus and diffusely to the cerebral cortex. Awareness, by contrast, depends on the functional integrity of widespread bilateral cerebral cortical networks and reciprocal thalamocortical loops.

From a neuroanatomical standpoint, coma —defined as a state of sustained unarousability, complete unresponsiveness to external stimuli, and absence of awareness—can arise from only two fundamental mechanisms:

Diffuse bilateral cerebral cortical dysfunction : Widespread structural damage or metabolic, toxic, or anoxic disruption affecting both cerebral hemispheres simultaneously (e.g., severe hypoglycemia, global anoxic-ischemic brain injury post-cardiac arrest, severe septic encephalopathy, hepatic coma, profound hypothermia).

Focal brainstem or diencephalic lesions : Direct structural destruction or mechanical compression of the paramedian ARAS within the upper pons, midbrain, or bilateral thalami (e.g., basilar artery occlusion, pontine hemorrhage, central or uncal transtentorial herniation).

Note

A unilateral hemispheric cortical lesion (such as an isolated left middle cerebral artery territory infarction) does not cause coma unless it produces massive mass effect, lateral shift, and secondary compression of the contralateral hemisphere or downward herniation compressing the diencephalon and brainstem ARAS.

• Coma Assessment: Glasgow Coma Scale (GCS) vs. FOUR Score
• Limitations of the Glasgow Coma Scale in the ICU

Devised in 1974 for acute traumatic brain injury triage, the Glasgow Coma Scale (GCS) evaluates three behavioral domains: Eye Opening (1 to 4), Verbal Response (1 to 5), and Best Motor Response (1 to 6), yielding a composite score ranging from 3 to 15. Although deeply entrenched in critical care scoring systems (APACHE, SOFA), the GCS exhibits major clinical deficiencies in the medical and surgical ICU:

Endotracheal intubation invalidates verbal scoring : An intubated patient cannot vocalize; clinicians frequently assign an arbitrary verbal score of 1 (or "1T"), deflating the score artificially and obscuring true neurological status.

Absence of brainstem reflex assessment : The GCS contains no evaluation of pupillary light reflexes, corneal reflexes, or spontaneous respiratory patterns, failing to detect progressive rostral-caudal brainstem compression or impending herniation.

Failure to distinguish locked-in syndrome or vegetative states : A patient with pontine infarction and preserved vertical eye tracking receives a minimal eye score on the GCS, misleading clinicians regarding intact awareness.

The Full Outline of UnResponsiveness (FOUR) Score

To address these limitations, Wijdicks and colleagues at the Mayo Clinic validated the FOUR Score . The FOUR score evaluates four operational domains, each scored on a 0-to-4 scale, yielding a total score from 0 to 16:

Eye Response (E) :

E4 : Eyelids open or opened, tracking or blinking to command.

E3 : Eyelids open but not tracking.

E2 : Eyelids closed but open to loud voice.

E1 : Eyelids closed but open to noxious stimuli.

E0 : Eyelids remain closed despite noxious stimuli.

Motor Response (M) :

M4 : Demonstrates thumbs-up, fist, or peace sign to command.

M3 : Localizing to painful stimulus.

M2 : Flexor posturing (decorticate rigidity; adduction, internal rotation, elbow flexion).

M1 : Extensor posturing (decerebrate rigidity; extension, adduction, pronation of upper extremities).

M0 : No motor response or generalized myoclonic status.

Brainstem Reflexes (B) :

B4 : Both pupillary AND corneal reflexes present.

B3 : One pupil wide and fixed.

B2 : Pupillary OR corneal reflex absent.

B1 : Pupillary AND corneal reflexes absent.

B0 : Pupillary, corneal, AND cough reflexes absent.

Respiration (R) :

R4 : Regular, unassisted breathing (not intubated).

R3 : Cheyne-Stokes breathing pattern (not intubated).

R2 : Irregular breathing pattern (not intubated).

R1 : Intubated, breathing spontaneously above ventilator backup rate.

R0 : Intubated, breathing entirely at ventilator backup rate or completely apneic.

• Assessment Domain Glasgow Coma Scale (GCS) FOUR Score
• Total Score Range 3 to 15 points 0 to 16 points

Intubated Patients Verbal component impossible; assigned arbitrary 1T Fully testable; incorporates ventilator interaction ( R 1 R_1 R 1 ​ vs. R 0 R_0 R 0 ​ )

Brainstem Reflexes None assessed Evaluates pupils, corneal reflexes, and cough reflex

Motor Testing 6 levels (commands, localization, withdrawal, flexion, extension, none) 5 levels (thumbs-up/peace sign, localization, flexion, extension, none/myoclonus)

Locked-in Detection Fails; eye tracking not recognized Recognized via E 4 E_4 E 4 ​ (voluntary tracking/blinking) with M 0 M_0 M 0 ​

Herniation Detection Unreliable until motor posturing occurs Detects evolving herniation early via pupillary asymmetry ( B 3 B_3 B 3 ​ )

Pupillary and Ocular Brainstem Reflexes

Bedside examination of cranial nerve reflexes provides immediate anatomical localization of the level of brainstem injury in the comatose patient.

1. Pupillary Light Reflexes

The pupillary light reflex pathway tests the midbrain. The afferent limb travels via the optic nerve (CN II) to the pretectal nuclei of the midbrain, which project bilaterally to the Edinger-Westphal nuclei. The efferent limb travels through preganglionic parasympathetic fibers within the oculomotor nerve (CN III) to the ciliary ganglion, stimulating the pupillary sphincter muscle to produce conjugate miosis.

Simultaneously, the sympathetic pathway originates in the posterolateral hypothalamus, descends uncrossed through the brainstem tegmentum to the ciliospinal center of Budge ( C 8 − T 2 C_8-T_2 C 8 ​ − T 2 ​ ), ascends through the sympathetic chain to the superior cervical ganglion, and travels along the internal carotid artery to the pupillodilator muscle.

Unilateral Dilated and Fixed Pupil ("Blown Pupil") : Compression of the ipsilateral oculomotor nerve (CN III) against the rigid tentorial incisura by the herniating uncus of the medial temporal lobe ( uncal herniation ). The superficial, parasympathetic pupilloconstrictor fibers on the periphery of CN III are damaged first, leaving sympathetic dilator tone unopposed. This is an acute neurosurgical emergency.

Warning

Uncal herniation classically produces contralateral hemiparesis due to ipsilateral cerebral peduncle compression. However, severe lateral shift can displace the contralateral midbrain against the opposite tentorial edge ( Kernohan's notch phenomenon ), producing an ipsilateral hemiparesis that acts as a false-localizing sign.

Pinpoint Reactive Pupils ( 1 − 2 mm 1-2\text{ mm} 1 − 2 mm ) : Characteristically produced by acute destructive pontine lesions (pontine hemorrhage or basilar artery infarction) due to interruption of descending sympathetic pathways, unmasking unopposed parasympathetic tone. Differentiated from metabolic causes ( opioid toxicity , organophosphate poisoning) by lack of response to naloxone and presence of impaired horizontal eye movements.

Bilateral Fixed and Dilated Pupils ( > 7 mm >7\text{ mm} > 7 mm ) : Reflects catastrophic, bilateral destruction of midbrain pretectal and Edinger-Westphal nuclei, terminal diffuse anoxic-ischemic encephalopathy, or brain death. Non-neurological mimics include high-dose anticholinergic toxicity (atropine, scopolamine) and severe hypothermia.

2. Oculocephalic (Doll's Eyes) and Oculovestibular (Cold Calorics) Reflexes

These reflex arcs evaluate the integrity of the pontomedullary and midbrain connections across cranial nerves VIII, VI, and III coordinated through the medial longitudinal fasciculus (MLF) :

Oculocephalic Reflex : Elicited by rapidly rotating the head horizontally in a patient without cervical spine trauma. A normal (intact) reflex manifests as conjugate movement of the globes in the direction opposite to head rotation (the eyes remain fixed on an imaginary point in space). Bilateral failure of the eyes to move (doll's eyes absent) signifies pontine or midbrain tegmental dysfunction.

Caution

The oculocephalic maneuver is strictly contraindicated in trauma patients until cervical spine clearance is definitively established.

Oculovestibular Reflex (Cold Caloric Testing) : Performed after otoscopic exclusion of tympanic membrane perforation and ear canal obstruction. The patient's head is elevated 30 ∘ 30^\circ 3 0 ∘ above the horizontal to align the horizontal semicircular canal vertically. Instillation of 30 − 50 mL 30-50\text{ mL} 30 − 50 mL of ice-cold water into the external auditory meatus induces convection currents in the endolymph:

Normal Awake Patient : Causes slow conjugate tonic deviation toward the irrigated ear, followed rapidly by corrective, fast saccadic nystagmus toward the opposite ear (mnemonic COWS : Cold Opposite, Warm Same).

Comatose Patient with Intact Brainstem : Cortical fast saccades are abolished; the eyes display sustained, conjugate tonic deviation toward the irrigated ear for 2 to 3 minutes.

Pontomedullary / Brainstem Lesion : Absence of any ocular movement confirms disruption of the vestibular nerve, vestibular nuclei, MLF, or abducens/oculomotor nuclei.

ICU Delirium: Phenotypes and the CAM-ICU Instrument

Delirium is an acute, fluctuating syndrome characterized by impaired attention, disorganized thinking, and an altered level of consciousness resulting from underlying medical illness, critical care interventions, or drug toxicity. In the intensive care unit, delirium affects up to 70-80% of mechanically ventilated patients and is independently associated with increased 6-month mortality, prolonged mechanical ventilation, increased ICU length of stay, and long-term cognitive impairment resembling Alzheimer-type dementia.

Clinical Delirium Phenotypes

Hypoactive Delirium (~50% to 60% of cases) :

Characterized by psychomotor slowing, apathy, decreased responsiveness, lethargy, and withdrawal.

Most common phenotype in the ICU and carries the poorest long-term prognosis .

Frequently overlooked because patients are quiet, non-combative, and falsely assumed to be "resting peacefully" or "mildly depressed."

Hyperactive Delirium (~5% to 10% of cases) :

Characterized by agitation, restlessness, emotional lability, hallucinations, combativeness, and active attempts to remove endotracheal tubes or central venous catheters.

Readily recognized by clinical staff but represents the minority of ICU presentations.

Mixed Delirium (~30% to 40% of cases) :

Characterized by unpredictable fluctuations between hypoactive and hyperactive states within a 24-hour cycle (e.g., daytime lethargy alternating with nocturnal agitation).

The Confusion Assessment Method for the ICU (CAM-ICU)

The CAM-ICU is the most rigorously validated delirium diagnostic tool for both non-intubated and intubated patients. It employs a structured, two-step hierarchical algorithm: [Step 1: Assess Level of Arousal via RASS]

│

Is RASS -4 (deep) or -5 (unresponsive)?

├── YES ──> PATIENT IS IN COMA. Stop assessment (Delirium cannot be evaluated).

└── NO ──> Proceed to Step 2 (RASS is -3 to +4).

• │
• [Step 2: Delirium Evaluation via 4 Features]
• │
• Feature 1: Acute Change or Fluctuating Course of Mental Status? (MANDATORY)
• └── Must be YES
• │
• Feature 2: Inattention (SAVEAHAART Letter Squeeze)? (MANDATORY)

└── Squeeze on letter 'A' (10 letters total). Errors > 2?

• └── Must be YES
• │

Does the patient meet EITHER Feature 3 OR Feature 4?

├── Feature 3: Altered Level of Consciousness (Current RASS other than 0)?

│ └── If RASS is not 0 (e.g., -3, -2, -1, +1, +2, +3, +4) ──> CAM-ICU POSITIVE!

└── Feature 4: Disorganized Thinking (Only assessed if RASS = 0)

└── 4 logic questions + 2-step command. Errors > 1 ──> CAM-ICU POSITIVE!

CAM-ICU Feature Testing Procedure Diagnostic Threshold

Feature 1: Acute Change or Fluctuating Course Baseline mental status comparison or fluctuating RASS over past 24 hours Present if acute onset or fluctuating over 24h

Feature 2: Inattention Auditory letter test: Recite "S-A-V-E-A-H-A-A-R-T" (10 letters; squeeze on 'A') Errors > 2 > 2 > 2 (squeezing on wrong letter or failing to squeeze on 'A')

Feature 3: Altered Level of Consciousness Current RASS score at time of evaluation Current RASS ≠ 0 \ne 0  = 0 (anything other than alert and calm)

Feature 4: Disorganized Thinking 4 questions (e.g., "Will a stone float on water?", "Are there fish in the sea?") + 2-step command Errors > 1 > 1 > 1 across questions and command

Note

A patient is confirmed CAM-ICU positive if they demonstrate Feature 1 AND Feature 2 , PLUS Feature 3 OR Feature 4 . If the patient is alert and calm (RASS 0), they bypass Feature 3 and must be tested on Feature 4.

PADIS Guidelines, the ABCDEF Bundle, and Delirium Management

The 2018 SCCM PADIS Guidelines (Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption) synthesize evidence-based strategies to optimize ICU recovery.

The ABCDEF Bundle

A (Assess, Prevent, and Manage Pain) : Adopt an "analgesia-first" (analgosedation) paradigm. Untreated pain is a primary driver of agitation and delirium. Assess pain using validated behavioral scales (CPOT, BPS) in non-verbal patients. Utilize multi-modal analgesia (acetaminophen, ketamine infusions, gabapentinoids) to minimize opioid exposure.

B (Both SAT and SBT) : Pair daily Spontaneous Awakening Trials (SAT) —interrupting sedatives—with daily Spontaneous Breathing Trials (SBT) . Paired coordination shortens duration of mechanical ventilation and ICU stay.

C (Choice of Sedation) :

Target light sedation (RASS -1 to 0) over moderate/deep sedation.

Benzodiazepines (midazolam, lorazepam) must be avoided for routine sedation; they act as potent, independent, dose-dependent risk factors for delirium and prolonged hospitalization.

Dexmedetomidine (a selective α 2 \alpha_2 α 2 ​ -adrenergic agonist) or propofol are preferred over benzodiazepines. In mechanically ventilated patients, dexmedetomidine reduces delirium duration, hastens extubation, and decreases ICU length of stay.

D (Delirium: Assess, Prevent, and Manage) : Screen every 8 to 12 hours with CAM-ICU or ICDSC.

E (Early Mobility and Exercise) : Early mobilization within 48 hours of mechanical ventilation significantly reduces delirium duration and improves functional independence at hospital discharge.

F (Family Engagement and Empowerment) : Involve family members in daily reorientation, sensory support, and cognitive stimulation.

Non-Pharmacological Interventions

Non-pharmacological strategies are the best-supported interventions for reducing delirium incidence and duration . Multicomponent bundles include:

Daily circadian rhythm restoration (open blinds during daylight, dim ambient lights from 22:00 to 06:00, consolidate nighttime nursing interventions to allow uninterrupted 4-hour sleep blocks).

Reorientation protocols (clocks, calendars, whiteboards with care team names).

Sensory optimization (early reintroduction of patient's eyeglasses and hearing aids).

Early removal of physical restraints and unnecessary indwelling lines/catheters.

Pharmacological Management and Clinical Pitfalls

Antipsychotic Prophylaxis : The 2018 PADIS guideline suggests against the routine prophylactic administration of haloperidol or atypical antipsychotics (quetiapine, olanzapine, risperidone) to prevent delirium, as large multicenter randomized trials demonstrate no reduction in delirium incidence, duration, or mortality.

Symptomatic Pharmacotherapy : Haloperidol ( 0.5 − 2.5 mg 0.5-2.5\text{ mg} 0.5 − 2.5 mg IV or PO) or atypical antipsychotics (e.g., quetiapine 25 − 50 mg 25-50\text{ mg} 25 − 50 mg PO q12h) should be reserved for short-term control of severe, distressing hyperactive agitation that threatens patient or staff safety (e.g., acute self-extubation or catheter dislodgement) refractory to de-escalation. The 2025 PADIS focused update made no recommendation for or against antipsychotics to treat delirium, because the trial evidence (MIND-USA, AID-ICU) is insufficient.

Cardiotoxicity and QTc Monitoring : Haloperidol and atypical antipsychotics block delayed rectifier potassium channels ( I K r I_{Kr} I Kr ​ ), prolonging ventricular repolarization. Obtain a baseline ECG and monitor the QTc interval daily. Discontinue antipsychotics if the QTc exceeds 500 ms 500\text{ ms} 500 ms or lengthens by > 60 ms >60\text{ ms} > 60 ms from baseline due to the risk of Torsades de Pointes .

Dexmedetomidine in Delirium : In mechanically ventilated patients where delirium is impeding liberation from the ventilator, continuous infusion of dexmedetomidine ( 0.2 − 1.4 μ g/kg/h 0.2-1.4\ \mu\text{g/kg/h} 0.2 − 1.4 μ g/kg/h ) facilitates calm, cooperative sedation without respiratory depression and accelerates successful extubation.