Urgent considerations
See Differentials for more details
Given the potential severe consequences of high mortality and morbidity in delirium, it is critically important to consider systemic preventive measures geared towards identifying those at highest risk and avoiding precipitating insults in those patients. This is especially important in certain sub-populations (e.g., patients of advanced age, admissions to the intensive care unit) as there are limited treatment options. Emphasis should be placed on defining and mitigating risk factors (if possible) and precipitating insults.
New-onset neurological illness
New-onset stroke or transient ischaemic attack, subdural haematoma, epilepsy, meningitis, encephalitis, brain abscesses, and neurosyphilis can result in delirium. Neurological evaluation is prudent, with CT and/or MRI imaging.[43]
Myocardial infarction
Delirium is often the only identifiable sign of myocardial infarction in older patients. An ECG should be part of every work-up for delirium.
Severe systemic infection
Delirium is often the only identifiable sign of urinary tract infections and pneumonia in older people. Urinalysis and chest x-ray should be obtained as part of every work-up for delirium. Brain abscesses can also present with delirium, and can be identified by CT or MRI scans of the head.
Sepsis is a spectrum of disease, where there is a systemic and dysregulated host response to an infection.[44] Presentation ranges from subtle, non-specific symptoms (e.g., feeling unwell with a normal temperature) to severe symptoms with evidence of multi-organ dysfunction and septic shock. Patients may have signs of tachycardia, tachypnoea, hypotension, fever or hypothermia, poor capillary refill, mottled or ashen skin, cyanosis, newly altered mental state, or reduced urine output.[45] Sepsis and septic shock are medical emergencies.
Risk factors for sepsis include: age under 1 year, age over 75 years, frailty, impaired immunity (due to illness or drugs), recent surgery or other invasive procedures, any breach of skin integrity (e.g., cuts, burns), intravenous drug misuse, indwelling lines or catheters, and pregnancy or recent pregnancy.[45]
Early recognition and diagnosis is crucial because early treatment is associated with significant short- and long-term benefits in outcome.[45][Evidence C] However, detection can be challenging because the clinical presentation of sepsis can be subtle and non-specific. A low threshold for suspecting sepsis is therefore important. The key to early recognition is the systematic identification of any patient who has signs or symptoms suggestive of infection and is at risk of deterioration due to organ dysfunction.
Screening tools
Several risk stratification approaches have been proposed. All rely on a structured clinical assessment and recording of the patient’s vital signs.[45][46][47][48] It is important to check local guidance for information on which approach your institution recommends. The timeline of ensuing investigations and treatment should be guided by this early assessment.[48]
Sepsis screening tools are designed to promote early identification of sepsis and consist of manual methods or automated use of the electronic health record (EHR). These include the Sequential (or Sepsis-related) Organ Failure Assessment (SOFA) score, the quick SOFA (qSOFA) criteria, National Early Warning Score (NEWS), and Modified Early Warning Score (MEWS). There is a wide variation in diagnostic accuracy of these tools, but they are an important component of identifying sepsis early for timely intervention.[49]
The Third International Consensus Group (Sepsis-3) recommends using the SOFA score (primarily validated in patients in intensive care), with a score ≥2 in a patient with a suspected infection being suggestive of sepsis.[44][Figure caption and citation for the preceding image starts]: Sequential (or Sepsis-related) Organ Failure Assessment (SOFA) criteriaCreated by BMJ, adapted from Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996;22:707-10. [Citation ends].
Although the presence of a positive qSOFA should alert the clinician to the possibility of sepsis in all resource settings, its poor sensitivity has led the Surviving Sepsis Campaign to advise against using the qSOFA compared with National Early Warning Score (NEWS), or Modified Early Warning Score (MEWS) as a single screening tool for sepsis or septic shock.[49]
The National Institute for Health and Care Excellence (NICE) UK guideline on sepsis emphasises the need to 'think sepsis' in any patient presenting with possible infection. It recommends structured observations and stratification of risk of severe illness and death according to patient age and setting.[45]
Management of patients with suspected sepsis
Treatment guidelines have been produced by the Surviving Sepsis Campaign and remain the most widely accepted standards.[49][50]
Recommended treatment of patients with suspected sepsis is:
Measure lactate level, and remeasure lactate if initial lactate is elevated (>2 mmol/L [>18 mg/dL]).
Obtain blood cultures before administering antibiotics.
Administer broad-spectrum antibiotics (with methicillin-resistant Staphylococcus aureus [MRSA] coverage if there is high risk of MRSA) for adults with possible septic shock or a high likelihood for sepsis.
For adults with sepsis or septic shock at high risk of fungal infection, empirical antifungal therapy should be administered.
Begin rapid administration of 30 mL/kg crystalloid for hypotension or lactate level ≥4 mmol/L (≥36 mg/dL).
Administer vasopressors peripherally if hypotensive during or after fluid resuscitation to maintain mean arterial pressure (MAP) ≥65 mmHg, rather than delaying initiation until central venous access is secured. Noradrenaline (norepinephrine) is the vasopressor of choice.
For adults with sepsis-induced hypoxaemic respiratory failure, high-flow nasal oxygen should be given.
Ideally these interventions should all begin in the first hour after sepsis recognition. [50]
For adults with possible sepsis without shock, if concern for infection persists, antibiotics should be given within 3 hours from the time when sepsis was first recognised.[49]
For adults with a low likelihood of infection and without shock, antibiotics can be deferred while continuing to closely monitor the patient.[49]
See Sepsis in adults and Sepsis in children.
Respiratory disorders
Delirium can be commonly associated with hypoxia and pulmonary embolism. These diagnoses need to be considered as part of every delirium work-up.
Alcohol abuse
Delirium can result from alcoholic ketoacidosis (seen after binge drinking and with chronic alcohol abuse) and can occur in Wernicke's encephalopathy and Korsakoff's psychosis, associated with thiamine deficiency. A meta-analysis of risk-prediction models for postoperative delirium found that an increase in preoperative alcohol use was associated with postoperative delirium.[51]
Hip fracture
Delirium is commonly associated with acute pain and this should be a consideration in every patient with delirium, particularly if they are older, frail, and cognitively impaired.[52][53]
Metabolic abnormalities
Patients with life-threatening cases of sodium, potassium, and calcium abnormalities may present with delirium. Metabolic abnormalities may be secondary to renal or liver disease. A metabolic work-up is essential.
Glucose abnormalities
Both hypoglycaemia and hyperglycaemia can present with confusion and reduced consciousness. Plasma glucose levels should be part of the work-up for patients with delirium.
Drug toxicity
Overdoses with anticholinergics, tricyclic antidepressants, stimulants, opiates, corticosteroids, analgesics, cardiac glycosides, and anti-Parkinson's drugs can be associated with delirium. Drug levels should be considered.[54]
Drug withdrawal
Delirium can be associated with drug withdrawal (benzodiazepine, alcohol) and this should be considered in every case.[52]
Acute psychosis
Patients typically show one or more of the following symptoms or signs: delusions, hallucinations, disorganised speech, or grossly disorganised or catatonic behaviour, lasting more than 24 hours but less than 30 days.[13][15]
Malignant disease
Delirium is common in patients with advanced malignant disease, with or without brain tumour or metastasis, because of drug use, especially opioids, metabolic disorders, infection, recent surgery, and brain lesions.[55][56]
Endocrine abnormalities
Myxoedema coma typically occurs in older patients with infections or over-sedation. Adrenal crisis can occur in patients with Addison's disease during stress, trauma, or infection. Thyroid function tests and serum cortisol levels should be considered as part of the work-up for delirium.
Hypoxia
Hypoxia is usually secondary to underlying disease such as systemic infection, pulmonary embolism, severe asthma attack, COPD, cardiac failure or arrhythmia, or carbon monoxide poisoning. Pulse oximetry and arterial blood gases can confirm the presence of hypoxia.
Urinary obstruction
Considered in older patients presenting with delirium. Clinical examination and ultrasound show distended bladder.
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