Delirium in ICU

Peer reviewed by Maurice Le Guen

OVERVIEW

• Delirium is a disturbance of consciousness with inattention accompanied by a change in cognition or perceptual disturbance that develops over a short period of time and fluctuates over time (DSM4)
• inattention is one of the hallmarks and pivotal features of delirium
• 3 subtypes:
  • hyperactive
  • hypoactive
  • mixed
• prevalence in the critically ill is about 80% (varies in different studies and settings)
• validated instruments such as CAM-ICU are 3 times more sensitive than unstructured clinical assessment at detecting delirium

SIGNIFICANCE

In adult ICU patients:

• increased mortality
  • x 3.2 at 6 months
• prolonged ICU and hospital stay
• increased post-ICU cognitive impairment
  • measurable deficits in ~50% at 12 months
• greater dependency on community services and care on discharge and higher nursing home placement rates

PATHOPHYSIOLOGY

• complex and poorly understood
• altered cerebral blood flow
• numerous biomarkers e.g. s100beta protein, neuron specific enolase, ILs

RISK-FACTORS

Baseline

• age
• preexisting dementia
• history of hypertension
• history of alcoholism
• high severity of illness at admission (APACHEII score)
• Pre-ICU emergency surgery or trauma

In ICU

• Coma
• Sedative use
  • Benzodiapzepine infusions may be a risk factor, and the status of opioids and propofol is uncertain
  • dexmedetomidine is associated with a lower prevalence of delirium
• Mechanical ventilation
• Metabolic acidosis
• Delirium on the prior day

ASSESSMENT

Clinical presentation

• Mixed
  • mixture of hyperactive and hypoactive features
• Hyperactive
  • agitation, hypervigilance, irritability, lack of concentration, and perseveration
• Hypoactive
  • diminished alertness, absence of or slowed speech, hypokinesia, and lethargy

Assessment approach

• focu
• sed history, examination and investigations
• assess for predisposing, precipitating and perpetuating factors (e.g. features of underlying illness)
  • e.g. “pee – poo – pus – pain – poisons”
• use a delirium monitoring tool

Delirium monitoring Tools

• Confusion Assessment Method for the ICU (CAM-ICU) and the Intensive Care Delirium Screening Checklist (ICDSC) are the most valid and reliable delirium monitoring tools in adult ICU patients
• CAM-ICU is a better predictor of outcome compared to ICDSC (Tomasi et al, 2012)
• CAM-ICU summarised:
  1. acute onset/fluctuating course
  2. inattention (squeeze on A in ‘SAVEAHAART’)
  3. altered level of consciousness (RASS not zero)
  4. disorganized thinking (e.g. can a stone float on water)

MANAGEMENT

Early recognition

• routine monitoring with CAM-ICU or ICDSC
• seek and treat cause — especially life-threatening causes (WHIP x 2):
  • Wernicke, Withdrawal
  • Hypertensive encephalopathy, Hypoglycemia and metabolic/endocrine
  • Infection, Intracranial disease
  • Poisons, and Porphyria

Non-pharmacologic treatment

• Recurrent orientation of patients
• Early mobilisation and physiotherapy
• Early removal of catheters
• Day-night routine
• Sleep hygiene
• Involve family
• Noise control at night
• correct vision and hearing impairment

Pharmacologic treatment

• Thiamine
  • if suspect alcohol consumption or poor nutrition
• Atypical antipsychotics
  • evidence suggests may reduce duration of delirium
• Dexmedetomidine
  • less delirium than benzodiazepine infusions, and a recent meta-analysis also suggests less than propofol infusions too
• Decrease analgesics, sedatives and anticholinergic drugs
  • e.g. protcolised sedation or daily interrupted sedation
• Lorazepam/ midazolam and haloperidol/ droperidol may be required for acute chemical restraint
• NOTE there are NO FDA approved drugs for the treatment of delirium
• no strong evidence for a pharmacological delirium protocol or any specific drugs in preventing ICU delirium
• rivastigmine (cholinesterase inhibitor) should not be used
  • increased mortality in one study

EVIDENCE

Treatment

Page VJ, et al.  2013

• DB PC RCT
•  n =141 general critically ill mechanically ventilated patients within 72h of ICU admission, regardless of coma or delirium status
•  haloperidol 2.5 mg IV 8 hourly versus 0.9% saline
• outcomes:
  • no difference in the number of days alive, without delirium, and without coma (median 5 days [IQR 0—10] vs 6 days [0—11] days; p=0·53)
  • more oversedation with haloperidol (11 vs 6 patients)
  • no difference in rates of QTc prolongation ( 7  vs 6 patients)
  • no serious adverse events with haloperidol 

Devlin JW, et al.  2010

• MC DBPC RCT
• 36 adult ICU patients with delirium and tolerating enteral feeds, without complicating neurologic condition
• Quetiapine 50 -200 mg  BD vs placebo
• Outcomes:
  • decreased duration of delirium
  • increased number of patients discharged home or to rehab
  • No change in mortality.
• Commentary:
  • tiny study!

Prevention

Schweickert WD, et al. 2009

• MC PC RCT
• 104 ICU mechanically ventilated ICU patients
• Early mobilization with daily sedation break vs sedation break
• Outcomes:
  • Shorter duration of delirium (median 2 days versus 4 days, p=0.02).
  • More ventilator free days (23.5 vs 21.1 days, p=0.05).
  • Greater return to independent function at discharge (59% vs 35%, OR= 2.7, p=0.02)
• i.e. in a small RCT early mobilization of patients approximately halved delirium rates

Balas MC ,et al.  2014

• Before and after study design in single centre
• n= 296 patients enrolled (146 pre bundle, 150 post)
• Intervention: Awakening and Breathing Coordination, Delirium Monitoring/Management, and Early Exercise/Mobility (ABCDE) Bundle

1. Awakening and Breathing Coordination
   • daily screen for safety of awakening
   • if OK, sedation break and proceed to breathing safety screen and subsequent spontaneous breathing trial aiming for extubation if passed for > 2 hours
2. Delirium Monitoring, and Management
   • 2 hourly RASS, 8 hourly CAM ICU
   • if delirium identified then managed as per medical team
3. Early exercise/Mobilization
   • daily safety screen and mobilization if safe

• Commentary:
  • The ABCDE delirium prevention bundle has yet to be widely recommended and requires further evidence to support its use.
• Outcomes post bundle implementation:
  • 3 more ventilator free days (median  21 versus 24, p= 0.04.)
  • Decreased delirium (91% versus 73 % p=0.02. Adjusted OR= 0.55, p=0.03)
  • Increased early exercise (70% vs 99 % for mobilized at any time out of bed, p=0.002,  adjusted OR = 2.11, p=0.003)
  • No significant difference in self extubation rates
  • No significant difference in adjusted hospital mortality
  • No significant difference in discharge destination

Risk factors and recognition of delirium

Tomasi CD, Grandi C, Salluh J et al. 2012

• CAM-ICU is a better predictor of outcome cf ICDSC
  • Delirium diagnosis using CAM-ICU was predicted more accurately in individuals with higher mortality rates as compared with ICDSC diagnosis
  • Patients with positive ICDSC presenting with a negative CAM-ICU had similar outcomes as compared with those without delirium

Zaal IJ, et al.  2014

• Systematic review of 33 studies (70% of “high quality”) found strong evidence for the following:
• Risk factors for delirium:
  • Age
  • Dementia
  • Hypertension
  • Pre-ICU emergency surgery or trauma
  • APACHEII score
  • Mechanical ventilation
  • Metabolic acidosis
  • Delirium on the prior day
  • Coma
  • [Multiple organ failure: moderate evidence]
• Not associated with delirium:
  • Gender
• Associated with lower prevalence of delirium:
  • Dexmedetomidine

References and Links

FOAM and web resources

• EMCrit – Podcast 115 – A New Paradigm for Post-Intubation Pain, Agitation, and Delirium (2013)
• ICUdelirium.org
• Maryland CCP — Management of Pain, Agitation, & Delirium in the ICU (2013)

Journal articles

• Balas MC, Vasilevskis EE, Olsen KM, Schmid KK, Shostrom V, Cohen MZ, Peitz G, Gannon DE, Sisson J, Sullivan J, Stothert JC, Lazure J, Nuss SL, Jawa RS, Freihaut F, Ely EW, Burke WJ. Effectiveness and safety of the awakening and breathing coordination, delirium monitoring/management, and early exercise/mobility bundle. Crit Care Med. 2014 May;42(5):1024-36.  PMID: 24394627
• Barr J, et al; American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013 Jan;41(1):263-306. PMID: 23269131.
• Cavallazzi R, Saad M, Marik PE. Delirium in the ICU: an overview. Ann Intensive Care. 2012 Dec 27;2(1):49. PMC3539890.
• Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebo-controlled pilot study. Crit Care Med. 2010 Feb;38(2):419-27. PMID: 19915454.
• Girard TD, Pandharipande PP, Ely EW. Delirium in the intensive care unit. Crit Care. 2008;12 Suppl 3:S3. PMC2391269.
• Page VJ, Ely EW, Gates S, et al. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2013 Sep;1(7):515-23. doi: 10.1016/S2213-2600(13)70166-8. Epub 2013 Aug 21. Erratum in: Lancet Respir Med. 2013 Oct;1(8):592. PMID: 24461612. [Free Full Text]
• Schweickert WD, Pohlman MC, Pohlman AS, et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet. 2009 May 30;373(9678):1874-82. PMID: 19446324.
• Tomasi CD, Grandi C, Salluh J et al. Comparison of CAM-ICU and ICDSC for the detection of delirium in critically ill patients focussing on relevant clinical outcomes. J Crit Care 2012 Apr; 27 (2): 212-7 PMID: 21737237 [Free Full Text]