Question 30

List the potential causes of delayed awakening in a patient after a prolonged stay in Intensive Care and outline how you would determine what factors were contributory.

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College Answer

Potential causes include: 
prolonged effects of sedative drugs, metabolic encephalopathy (especially renal or hepatic failure), endocrine problems (especially hypothyroidism), systemic sepsis, and a myriad of specific neurological problems ( eg. status epilepticus, raised intracranial pressure, intracranial haemorrhages, severe Guillain Barre, critical illness polyneuropathy). Residual muscular paralysis must be excluded.

Sedative drugs may have a prolonged effect because of altered kinetics (including context sensitive half-time, or decreased biotransformation or excretion eg. renal or hepatic failure) or altered dynamics (potentiation of effect by other drugs or organ 
failure, sensitivity to effect of usual dosage).

Assessment of contributory factors may be a complex process. Important steps include: 
1) Detailed history of neurological state, drugs administered, previous neurological problems 
2) Careful examination (in particular neurological, but also for signs of other chronic diseases). Detailed neurological exam should include global CNS assessment (including ability to move eyes or poke out tongue if no other apparent motor responses: locked in syndrome, severe myoneuropathy), and search for focal signs (pupils, tone, movement, reflexes). Nerve stimulator should be used to assess residual paralysis. 
3) Biochemical investigations for severity of electrolyte imbalance, creatine kinase, renal and hepatic dysfunction (mcluding ammonia), and to exclude treatable endocrine disorders (including T4/TSH). 
4) Consider use of specific reversal agents (eg. naloxone and flumazenil [may need multiple ampoules]). · 
5) May require other specific investigations (but put into context, and not done as a routine). Such investigations include CT scan of head, MRI, EEG, EMG and lumbar puncture.


This is a question about the approach to the unconscious patient in the ICU, with a view to generate a nice juicy series of differentials. The key feature of the question is that the patient is failing to wake after a prolonged ICU stay.

Let us go though the differentials systematically.

Differential Diagnosis of Unconsciousness

With focal neurological signs

Vascular causes:

  • Stroke
  • Vascular insufficiency of the brain, eg. critical vessel stenosis of some specific vessel
  • Intracranial haemorrhage

Infectious causes:

  • Brain abscess
  • Meningoencephalitis with focal cranial nerve damage

Neoplastic causes

  • Space-occupying tumour

Idiopathic causes

  • Pre-existing focal neurology, superimposed on an acute unconscious state

Autoimmune causes

  • Cerebral vasculitis

Traumatic causes

  • Focal neurological injury due to head trauma
  • Increased intracranial pressure, giving rise to false localising signs

Without focal neurological signs

Vascular causes:

  • brainstem stroke, resulting in damage to the reticular activating system
  • Vascular insufficiency of the brain, eg. diffuse cerebral small vessel disease

Infectious causes:

  • Intracranial infection, eg. meningitis or encephalitis
  • Neurological sequelae of systemic infection, eg. septic encephalopathy

Drug-related causes:

  • Persisting effects of sedatives in context of diminished clearance

Idiopathic causes

  • Delirium of prolonged intensive care stay - a "hypoactive" form thereof
  • Non-convulsive status epilepticus
  • Raised intracranial pressure

Autoimmune causes

  • Cerebral vasculitis

Traumatic causes

  • Sequelae of diffuse brain injury, eg. diffuse axonal injury

Endocrine and metabolic causes:

  • Hypoadrenalism
  • Hypothyroidism
  • Hepatic encephalopathy
  • Uremic encephalopathy
  • Wernicke's encephalopathy

How does one approach such a patient?

  1. A history is mandatory
  2. A physical examination is in order, looking for focal signs and characteristic findings
  3. Some basic bloods, looking for hepatic and renal derangement
  4. One ought to at least think about reversal agents such as naloxone.
  5. A CT brain, to exclude structural cerebral disease
  6. An LP or MRI may be in order depending on the history
  7. An EEG may be the last investigation, to exclude non-convulsive status epilepticus


Oh's Intensive Care manualChapter 49   (pp. 549) Disorders  of  consciousness  by Balasubramanian  Venkatesh