Altered Sensorium in a Non-Neurological Patient: A Systemic Approach

Dr Neeraj Manikath , claude.ai

Abstract

Altered sensorium in critically ill patients presents a complex diagnostic challenge that extends far beyond primary neurological pathology. This comprehensive review examines the multisystem approach to evaluating and managing altered consciousness in non-neurological patients, emphasizing the intricate interplay between metabolic, endocrine, hepatic, renal, and infectious etiologies. Through systematic evaluation of pathophysiological mechanisms, diagnostic strategies, and therapeutic interventions, this article provides critical care physicians with evidence-based approaches to managing these challenging cases. Key focus areas include hepatic encephalopathy, uremic encephalopathy, hypoglycemia, electrolyte disturbances, sepsis-associated encephalopathy, and drug-induced altered mental status.

Keywords: Altered sensorium, delirium, encephalopathy, critical care, metabolic disorders, sepsis

Introduction

Altered sensorium represents one of the most challenging clinical presentations in critical care medicine, occurring in up to 80% of mechanically ventilated patients and carrying significant morbidity and mortality implications. While primary neurological causes such as stroke, traumatic brain injury, or intracranial infections are often immediately considered, the majority of altered mental status cases in critically ill patients stem from systemic, non-neurological etiologies.

The complexity of altered sensorium in non-neurological patients lies in its multifactorial nature, often involving simultaneous dysfunction of multiple organ systems. Understanding the pathophysiological mechanisms underlying these conditions is crucial for developing effective diagnostic and therapeutic strategies. This review provides a systematic approach to evaluating and managing altered sensorium in non-neurological patients, with particular emphasis on metabolic, endocrine, hepatic, renal, and infectious causes.

Pathophysiology of Altered Sensorium

Neurobiological Mechanisms

The pathophysiology of altered sensorium in non-neurological patients involves disruption of normal neurotransmitter balance, cerebral metabolism, and neuroinflammatory processes. The reticular activating system, thalamus, and cerebral cortex form the anatomical substrate for consciousness, and dysfunction at any level can result in altered mental status.

Key mechanisms include:

Neurotransmitter Imbalance: Disruption of dopaminergic, cholinergic, and GABAergic pathways leads to altered arousal and cognition. Excess dopamine contributes to hyperactive delirium, while cholinergic deficiency is associated with hypoactive states.

Cerebral Metabolic Dysfunction: Impaired glucose utilization, oxygen delivery, or substrate availability directly affects neuronal function. The brain's high metabolic demand makes it particularly vulnerable to systemic metabolic derangements.

Neuroinflammation: Systemic inflammation triggers microglial activation and cytokine release, leading to blood-brain barrier disruption and altered neurotransmission. This mechanism is particularly relevant in sepsis-associated encephalopathy.

Osmotic and Electrolyte Disturbances: Rapid changes in serum osmolality or electrolyte concentrations can cause cerebral edema or neuronal dysfunction, manifesting as altered consciousness.

Systematic Approach to Evaluation

Clinical Assessment Framework

The evaluation of altered sensorium requires a systematic approach that simultaneously addresses potential systemic causes while excluding primary neurological pathology. The following framework provides a structured methodology:

Initial Assessment:

Comprehensive history including medication review, substance use, and recent medical interventions
Physical examination focusing on signs of organ dysfunction
Neurological examination to assess level of consciousness, focal deficits, and meningeal signs
Assessment of delirium using validated tools (CAM-ICU, ICDSC)

Diagnostic Workup:

Complete blood count, comprehensive metabolic panel, liver function tests
Arterial blood gas analysis
Thyroid function tests
Inflammatory markers (procalcitonin, C-reactive protein)
Urinalysis and urine toxicology screen
Blood and urine cultures
Neuroimaging when indicated

Pearl: The "DELIRIUM" Mnemonic

A practical approach to remembering systemic causes of altered sensorium:

Drugs and toxins
Electrolyte abnormalities
Liver failure
Infection/sepsis
Renal failure
Ischemia/hypoxia
Uremia
Metabolic disorders (glucose, thyroid, adrenal)

Hepatic Encephalopathy

Pathophysiology

Hepatic encephalopathy (HE) represents a complex neuropsychiatric syndrome resulting from liver dysfunction. The pathophysiology involves multiple mechanisms, with ammonia toxicity being central but not exclusive. Key pathways include:

Ammonia Hypothesis: Impaired hepatic detoxification leads to hyperammonemia, causing astrocyte swelling, altered neurotransmission, and osmotic stress. Ammonia is converted to glutamine in astrocytes, leading to cellular edema and dysfunction.

Inflammation and Cytokines: Systemic inflammation in liver disease triggers neuroinflammation, contributing to cerebral dysfunction through cytokine-mediated pathways.

Manganese Accumulation: Chronic liver disease leads to manganese deposition in the basal ganglia, contributing to extrapyramidal symptoms and altered mental status.

GABA-ergic Dysfunction: Increased GABA-ergic tone, potentially mediated by benzodiazepine-like substances, contributes to sedation and altered consciousness.

Clinical Presentation and Grading

The West Haven Criteria provide standardized grading for hepatic encephalopathy:

Grade 1: Mild confusion, euphoria, anxiety, shortened attention span, impaired computational ability

Grade 2: Lethargy, moderate confusion, slurred speech, inappropriate behavior, asterixis

Grade 3: Stupor, severe confusion, incomprehensible speech, marked asterixis

Grade 4: Coma, absent response to verbal stimuli, decerebrate posturing may be present

Diagnostic Approach

Laboratory Investigations:

Ammonia levels (though correlation with severity is poor)
Liver function tests including albumin, bilirubin, and coagulation studies
Arterial blood gas analysis
Electrolyte panel including phosphate and magnesium

Imaging:

CT or MRI may show cerebral edema in acute cases
MRI may demonstrate T1 hyperintensity in basal ganglia (manganese deposition)

Hack: Arterial vs. Venous Ammonia Arterial ammonia levels are more accurate than venous levels and should be preferred when possible. Venous samples should be processed immediately on ice to prevent falsely elevated results.

Management

Immediate Interventions:

Correction of precipitating factors (GI bleeding, infections, constipation, medications)
Lactulose therapy: 30-45 mL every 2-4 hours, titrated to 2-4 soft bowel movements daily
Rifaximin: 400 mg TID, particularly effective for recurrent episodes

Advanced Therapies:

L-ornithine L-aspartate (LOLA): 20-30 g/day IV, enhances ammonia metabolism
Zinc supplementation: 220 mg BID, corrects deficiency common in liver disease
Branched-chain amino acids: May improve protein synthesis and ammonia clearance

Oyster: Lactulose Titration Over-aggressive lactulose therapy can lead to dehydration, electrolyte imbalances, and paradoxical worsening of encephalopathy. The goal is 2-4 soft bowel movements daily, not continuous diarrhea.

Uremic Encephalopathy

Pathophysiology

Uremic encephalopathy results from the accumulation of uremic toxins in chronic kidney disease or acute kidney injury. The syndrome involves multiple pathophysiological mechanisms:

Uremic Toxin Accumulation: Accumulation of organic compounds such as indoxyl sulfate, p-cresyl sulfate, and guanidino compounds directly affects neuronal function.

Electrolyte Disturbances: Hyperkalemia, acidosis, and altered calcium-phosphate metabolism contribute to neuronal dysfunction.

Inflammation: Chronic kidney disease promotes systemic inflammation, contributing to neuroinflammation and altered mental status.

Osmotic Disturbances: Rapid changes in urea concentration can lead to cerebral edema through osmotic mechanisms.

Clinical Presentation

Uremic encephalopathy typically presents with a fluctuating course, including:

Early signs: Fatigue, decreased concentration, mild confusion
Progressive symptoms: Asterixis, myoclonus, seizures
Advanced stages: Stupor, coma, and focal neurological deficits

Diagnostic Considerations

Laboratory Markers:

Blood urea nitrogen (BUN) typically >100 mg/dL
Creatinine elevation proportional to degree of kidney dysfunction
Electrolyte abnormalities (hyperkalemia, acidosis, hyperphosphatemia)
Uremic toxin levels (when available)

Imaging:

CT may show cerebral edema in severe cases
MRI may demonstrate posterior reversible encephalopathy syndrome (PRES) patterns

Management

Renal Replacement Therapy:

Hemodialysis: Most effective for rapid toxin removal
Continuous renal replacement therapy (CRRT): Preferred in hemodynamically unstable patients
Peritoneal dialysis: Alternative when other modalities unavailable

Supportive Care:

Correction of electrolyte abnormalities
Fluid balance management
Seizure prophylaxis when indicated

Pearl: Dialysis Disequilibrium Syndrome Rapid dialysis in severely uremic patients can cause dialysis disequilibrium syndrome, characterized by cerebral edema due to osmotic shifts. Initial dialysis should be gentle with reduced efficiency to prevent this complication.

Hypoglycemia

Pathophysiology

Hypoglycemia represents a critical metabolic emergency with direct effects on cerebral function. The brain's obligate dependence on glucose makes it particularly vulnerable to hypoglycemic episodes.

Glucose Threshold Effects:

<70 mg/dL: Activation of counterregulatory hormones
<50 mg/dL: Cognitive impairment begins
<30 mg/dL: Severe neuroglycopenia with altered consciousness
<20 mg/dL: Coma and potential irreversible brain damage

Neuronal Energy Failure: Glucose depletion leads to ATP depletion, membrane depolarization, and altered neurotransmission. Prolonged hypoglycemia can cause neuronal death through excitotoxicity.

Clinical Presentation

Adrenergic Symptoms: Tachycardia, diaphoresis, tremor, anxiety (often masked in critically ill patients)

Neuroglycopenic Symptoms: Confusion, altered behavior, focal neurological deficits, seizures, coma

Diagnostic Approach

Whipple's Triad:

Symptoms consistent with hypoglycemia
Documented low glucose level
Resolution of symptoms with glucose administration

Laboratory Workup:

Immediate glucose measurement
Insulin and C-peptide levels
Cortisol and growth hormone levels
Toxicology screen for sulfonylureas

Management

Immediate Treatment:

Conscious patients: 15-20 g oral glucose
Unconscious patients: 50 mL of 50% dextrose IV or 1 mg glucagon IM/SC
Continuous glucose monitoring to prevent rebound hypoglycemia

Severe/Refractory Cases:

Continuous dextrose infusion (D10W or D20W)
Octreotide for sulfonylurea-induced hypoglycemia
Hydrocortisone for adrenal insufficiency

Hack: The "Rule of 15" For conscious patients with hypoglycemia: Give 15 g of glucose, wait 15 minutes, recheck glucose. If still <70 mg/dL, repeat. This prevents overcorrection while ensuring adequate treatment.

Electrolyte Disturbances

Hyponatremia

Hyponatremia is the most common electrolyte disorder in hospitalized patients and a frequent cause of altered mental status.

Pathophysiology:

Osmotic cerebral edema due to water influx into neurons
Severity depends on rate of change and absolute sodium level
Adaptive mechanisms include organic osmolyte efflux from neurons

Clinical Presentation:

Mild (130-135 mEq/L): Often asymptomatic
Moderate (125-130 mEq/L): Nausea, malaise, headache
Severe (<125 mEq/L): Confusion, seizures, coma

Management Approach:

Assess volume status and underlying etiology
Acute symptomatic hyponatremia: 3% saline to increase sodium by 1-2 mEq/L/hour
Chronic hyponatremia: Correction rate <10-12 mEq/L in 24 hours to prevent osmotic demyelination

Pearl: Overcorrection Prevention Use the Adrogué-Madias formula to predict sodium change: Change in serum Na = (Infusate Na - Serum Na) / (Total body water + 1)

Hypernatremia

Pathophysiology:

Cellular dehydration and brain shrinkage
Compensatory mechanisms include idiogenic osmole generation
Rapid correction can cause cerebral edema

Clinical Presentation:

Altered mental status, weakness, seizures
Signs of dehydration and hypervolemia

Management:

Correct underlying cause
Calculate free water deficit: 0.6 × weight × (serum Na/140 - 1)
Correct at rate of 0.5 mEq/L/hour, maximum 10-12 mEq/L in 24 hours

Calcium Disorders

Hypocalcemia:

Tetany, paresthesias, Chvostek's and Trousseau's signs
Altered mental status, seizures, laryngospasm
Treatment: Calcium gluconate 1-2 ampules IV over 10-20 minutes

Hypercalcemia:

"Stones, bones, groans, and psychiatric moans"
Altered mental status, weakness, constipation
Treatment: Aggressive hydration, furosemide, bisphosphonates

Sepsis-Associated Encephalopathy

Pathophysiology

Sepsis-associated encephalopathy (SAE) represents a complex syndrome involving multiple pathophysiological mechanisms:

Neuroinflammation: Systemic inflammation triggers microglial activation, cytokine release, and blood-brain barrier disruption. Pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) directly affect neuronal function.

Cerebrovascular Dysfunction: Endothelial dysfunction, microthrombi, and altered cerebral autoregulation contribute to altered mental status.

Neurotransmitter Disruption: Inflammation affects dopaminergic, cholinergic, and GABAergic pathways, leading to altered consciousness and cognitive dysfunction.

Metabolic Derangements: Hypoglycemia, hypoxia, and altered amino acid metabolism contribute to neuronal dysfunction.

Clinical Presentation

SAE typically presents early in sepsis and may precede other organ dysfunction:

Altered level of consciousness ranging from mild confusion to coma
Disorientation and cognitive impairment
Agitation or lethargy
Focal neurological deficits (less common)

Diagnostic Approach

Clinical Criteria:

Presence of sepsis or septic shock
Altered mental status not explained by other causes
Exclusion of primary neurological pathology

Laboratory Investigations:

Inflammatory markers (procalcitonin, C-reactive protein)
Blood cultures and source identification
Lactate levels
Comprehensive metabolic panel

Imaging:

CT typically normal or shows cerebral edema
MRI may demonstrate microhemorrhages or white matter changes

Management

Sepsis Management:

Early recognition and treatment of sepsis
Appropriate antimicrobial therapy
Source control measures
Hemodynamic support

Supportive Care:

Correction of metabolic abnormalities
Optimization of cerebral perfusion pressure
Sedation minimization strategies

Oyster: Procalcitonin in SAE Elevated procalcitonin levels correlate with SAE severity and may help guide antibiotic therapy duration. However, procalcitonin can remain elevated in non-infectious inflammatory conditions.

Drug-Induced Altered Mental Status

Common Culprits in Critical Care

Sedatives and Analgesics:

Benzodiazepines: Accumulation in renal/hepatic dysfunction
Opioids: Metabolite accumulation (morphine-6-glucuronide)
Propofol: Propofol infusion syndrome with prolonged use

Antimicrobials:

Beta-lactams: Seizures and encephalopathy, especially in renal dysfunction
Fluoroquinolones: CNS toxicity, particularly in elderly patients
Metronidazole: Peripheral neuropathy and encephalopathy

Cardiovascular Medications:

Digoxin: Confusion, visual disturbances, especially in renal dysfunction
Beta-blockers: Particularly lipophilic agents like propranolol
Calcium channel blockers: Altered mental status in overdose

Miscellaneous:

Steroids: Steroid psychosis, particularly with high doses
H2 antagonists: Particularly cimetidine in elderly patients
Anticholinergics: Delirium, especially in combination

Management Approach

Medication Review:

Comprehensive medication reconciliation
Assessment of drug interactions
Dose adjustment for organ dysfunction

Withdrawal Considerations:

Gradual tapering of long-term medications
Alcohol and benzodiazepine withdrawal protocols
Monitoring for withdrawal syndromes

Antidote Therapy:

Naloxone for opioid toxicity
Flumazenil for benzodiazepine toxicity (use with caution)
Specific antidotes for targeted toxins

Hack: The "Med Rec" Priority Always obtain accurate medication history including over-the-counter drugs, supplements, and recreational substances. Family members and pharmacy records are invaluable sources of information.

Endocrine Disorders

Thyroid Dysfunction

Hypothyroidism:

Myxedema coma: Severe hypothyroidism with altered mental status
Hypothermia, hypoventilation, hyponatremia
Treatment: Levothyroxine 200-300 mcg IV, hydrocortisone 100 mg q8h

Hyperthyroidism:

Thyroid storm: Hyperthermia, tachycardia, altered mental status
Delirium, psychosis, seizures
Treatment: Methimazole, propranolol, iodine, steroids

Adrenal Disorders

Adrenal Insufficiency:

Hypotension, hyponatremia, hyperkalemia
Altered mental status, weakness, fatigue
Treatment: Hydrocortisone 100 mg IV q8h, fluid resuscitation

Hyperadrenalism:

Cushing's syndrome: Depression, psychosis, cognitive impairment
Acute adrenal crisis: Severe illness with altered mental status

Diabetic Emergencies

Diabetic Ketoacidosis (DKA):

Hyperglycemia, ketosis, acidosis
Altered mental status correlates with serum osmolality
Treatment: Insulin, fluid resuscitation, electrolyte correction

Hyperosmolar Hyperglycemic State (HHS):

Severe hyperglycemia without ketosis
Profound dehydration and altered mental status
Treatment: Gradual correction with insulin and fluids

Diagnostic Pearls and Clinical Hacks

Rapid Assessment Tools

The "SOILED" Mnemonic for Delirium Risk Factors:

Sepsis
Oxygen (hypoxia)
Immobilization
Low albumin
Electrolyte abnormalities
Drugs

Laboratory Interpretation

Ammonia Level Interpretation:

Normal: <50 μmol/L
Elevated but <100 μmol/L: Consider other causes
100 μmol/L: Likely contributing to altered mental status
200 μmol/L: High risk for cerebral edema

Osmolality Calculations:

Calculated osmolality = 2(Na) + (glucose/18) + (BUN/2.8)
Osmolal gap = measured - calculated osmolality
Gap >10 suggests toxic ingestion

Imaging Considerations

CT vs. MRI Decision Making:

CT: Rapid assessment, structural abnormalities, hemorrhage
MRI: Superior for metabolic encephalopathies, posterior reversible encephalopathy syndrome (PRES)
DWI-MRI: Useful for detecting cytotoxic edema in metabolic disorders

Monitoring Strategies

Continuous EEG Monitoring:

Consider in unexplained altered mental status
May detect non-convulsive seizures
Useful for monitoring treatment response

Intracranial Pressure Monitoring:

Consider in severe hepatic encephalopathy
May guide therapy in acute liver failure
Invasive monitoring requires careful risk-benefit assessment

Therapeutic Interventions and Management Strategies

Non-Pharmacological Approaches

Environmental Modifications:

Consistent nursing staff and room assignments
Adequate lighting with day-night cycles
Noise reduction strategies
Family presence when possible

Mobility and Rehabilitation:

Early mobilization protocols
Physical and occupational therapy
Cognitive stimulation activities

Pharmacological Management

Symptomatic Treatment:

Haloperidol: 0.5-2 mg IV for agitation (monitor QT interval)
Quetiapine: 25-50 mg PO BID for delirium
Dexmedetomidine: Alpha-2 agonist with minimal delirium risk

Avoid:

Benzodiazepines (except for alcohol withdrawal)
Anticholinergic medications
Unnecessary polypharmacy

Specific Interventions by Etiology

Hepatic Encephalopathy:

Lactulose: Primary therapy, titrate to 2-4 bowel movements daily
Rifaximin: 400 mg TID, particularly for recurrent episodes
Zinc supplementation: 220 mg BID

Uremic Encephalopathy:

Dialysis: Hemodialysis preferred for rapid correction
Avoid nephrotoxic medications
Optimize fluid balance

Sepsis-Associated Encephalopathy:

Antimicrobial therapy
Source control
Hemodynamic support
Minimize sedation

Prognosis and Outcomes

Factors Influencing Recovery

Severity and Duration:

Rapid recognition and treatment improve outcomes
Prolonged altered mental status associated with worse prognosis
Severity of underlying illness affects recovery potential

Age and Comorbidities:

Advanced age associated with slower recovery
Multiple comorbidities increase complexity
Baseline cognitive function affects recovery trajectory

Intervention Timing:

Early recognition and treatment crucial
Delayed intervention may lead to irreversible changes
Multidisciplinary approach improves outcomes

Long-term Complications

Cognitive Impairment:

Persistent cognitive deficits in 25-50% of patients
Executive function most commonly affected
May improve over months to years

Functional Decline:

Increased risk of falls and functional dependence
Prolonged hospitalization and institutionalization
Reduced quality of life

Mortality:

Increased short-term and long-term mortality
Independent predictor of adverse outcomes
Varies by underlying etiology

Prevention Strategies

Risk Factor Modification

Medication Management:

Regular medication reconciliation
Dose adjustment for organ dysfunction
Avoidance of high-risk medications

Metabolic Optimization:

Glucose control
Electrolyte balance maintenance
Nutrition support

Infection Prevention:

Standard precautions
Early recognition of sepsis
Appropriate antimicrobial therapy

Systematic Approaches

Delirium Prevention Bundles:

ABCDEF bundle (Assess, Breathe, Coordinate, Delirium, Early mobility, Family)
Multidisciplinary rounds
Standardized protocols

Quality Improvement:

Regular staff education
Monitoring and feedback systems
Continuous improvement processes

Future Directions and Research

Biomarker Development

Neuroinflammatory Markers:

S100B protein
Neuron-specific enolase
Glial fibrillary acidic protein

Metabolic Markers:

Novel uremic toxins
Metabolomic profiles
Inflammatory cytokines

Therapeutic Innovations

Neuroprotective Strategies:

Anti-inflammatory agents
Antioxidants
Neurotransmitter modulators

Monitoring Technologies:

Continuous EEG monitoring
Near-infrared spectroscopy
Advanced imaging techniques

Personalized Medicine

Genetic Factors:

Pharmacogenomics
Susceptibility genes
Personalized treatment approaches

Precision Diagnostics:

Biomarker panels
Machine learning algorithms
Predictive models

Conclusion

Altered sensorium in non-neurological patients represents a complex clinical challenge requiring systematic evaluation and multidisciplinary management. Understanding the pathophysiological mechanisms underlying metabolic, endocrine, hepatic, renal, and infectious causes is essential for effective diagnosis and treatment. Early recognition, prompt intervention, and prevention strategies are crucial for optimizing patient outcomes and reducing long-term complications.

The key to successful management lies in a systematic approach that addresses the underlying pathophysiology while providing appropriate supportive care. As our understanding of these conditions continues to evolve, future research will likely provide new insights into pathogenesis, diagnostic strategies, and therapeutic interventions.

Critical care physicians must remain vigilant for the early signs of altered sensorium and be prepared to implement evidence-based interventions promptly. Through continued education, quality improvement initiatives, and research efforts, we can improve outcomes for patients with these challenging conditions.

References

Slooter AJ, Otte WM, Devlin JW, et al. Updated nomenclature of delirium and acute encephalopathy: statement of ten Societies. Intensive Care Med. 2020;46(5):1020-1022.
Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60(2):715-735.
Seifter JL, Samuels MA. Uremic encephalopathy and other brain disorders associated with renal failure. Semin Neurol. 2011;31(2):139-143.
Cryer PE, Axelrod L, Grossman AB, et al. Evaluation and management of adult hypoglycemic disorders: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2009;94(3):709-728.
Spasovski G, Vanholder R, Allolio B, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant. 2014;29 Suppl 2:i1-i39.
Sonneville R, Verdonk F, Rauturier C, et al. Understanding brain dysfunction in sepsis. Ann Intensive Care. 2013;3(1):15.
Girard TD, Pandharipande PP, Ely EW. Delirium in the intensive care unit. Crit Care. 2008;12 Suppl 3:S3.
Devlin JW, Skrobik Y, Gélinas C, et al. Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Crit Care Med. 2018;46(9):e825-e873.
Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41(1):263-306.
Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-1316.
Brummel NE, Jackson JC, Pandharipande PP, et al. Delirium in the ICU and subsequent long-term disability among survivors of mechanical ventilation. Crit Care Med. 2014;42(2):369-377.
Pun BT, Balas MC, Barnes-Daly MA, et al. Caring for the Critically Ill Patient. The ABCDEF Bundle: Science and Philosophy of How ICU Liberation Serves Patients and Families. Crit Care Med. 2019;47(2):321-330.
Inouye SK, Westendorp RG, Saczynski JS. Delirium in elderly people. Lancet. 2014;383(9920):911-922.
Maldonado JR. Neuropathogenesis of delirium: review of current etiologic theories and common pathways. Am J Geriatr Psychiatry. 2013;21(12):1190-1222.
Ely EW, Inouye SK, Bernard GR, et al. Delirium in mechanically ventilated patients: validity and reliability of the confusion assessment method for the intensive care unit (CAM-ICU). JAMA. 2001;286(21):2703-2710.

Funding: None declared Conflicts of Interest: None declared Ethical Approval: Not applicable for this review article

Saturday, July 12, 2025