2.5 Management of Minimally Responsive and Hypoarousal State

2.5.1  Cognitive Management of Minimally Responsive and Hypoarousal State

How should this patient be managed from a cognitive standpoint?

  1. Assessment should be conducted by a team with specialized experience to establish     the level of awareness and interaction.
     
  2. Patient will need specialized care wherever available.
     
  3. Graded program to increase tolerance to sitting and standing.

ABIKUS Guidelines 9

Cognitive Management of Minimally Responsive State

  1. “For all patients with a diminished level of consciousness, assessment should be undertaken by a team with specialized experience in profound brain injury to establish the level of awareness and interaction (pg 28).
  2.  Where patients remain in coma or minimally conscious states, management in specializes tertiary centre should be considered if the local services are unable to meet their needs for specialized nursing or rehabilitation (pg 29).
  3.  Every brain-injured patient who remains unconscious or is unable to sit themselves up should have a graded program to increase tolerance to sitting and standing (pg 29).

2.5.2  Pharmacological Management of Minimally Responsive State

Patient is in a prolonged minimally responsive state: How might you try to wake her pharmacologically?

  1. No reliable data to support the use of neurostimulants in the comatose (RLA-I) or vegetative (RLA-II) TBI patient (some evidence for bromocriptine although most clinicians do not find it helpful).
     
  2. Level 2 evidence suggests Amantadine 150 mg BID improves outcomes in patients “emerging” from coma (RLA-III).
     
  3. Neurostimulants such as Methylphenidate have been shown to improve attention (+/- function) in “responsive” patients (RLA IV-VIII) but don’t work so well with RLA-III.

2.5.3   Pharmacological Management of Hypoarousal State

While in rehabilitation, the patient remains at an RLA-III level for several weeks and then is noted to be an RLA-IV whereby she is now responsive but suffers from hypoarousal and is obviously confused and disoriented.

How might you treat her hypoarousal state? 

  1. Neurostimulants such as Methylphenidate or dopaminergic medications have been shown to improve attention (+/- function) in “responsive” patients (RLA IV-VIII).
     
  2. Methylphenidate in an indirect catecholamine agonist with a short half life requiring 2-4 doses per day. There is Level 4 evidence that it enhances recovery and functional status.
     
  3. Amantadineis a dopamineric agent. It assists with recovery of under-responsive patients and distractibility. There is Level 2 evidence it improves consciousness and cognitive functioning in hypoarousal states.
     
  4. Bromocriptineis a dopamine agonist. There is Level 4 evidence it improves recovery of TBI patients in the vegetative state and it is used in hypoarousal states although evidence for its use is lacking in this latter group.
     
  5.  Levodopa-Carbidopaincreases cerebral dopamine. Has been suggested for hypoarousal state but there is very limited evidence of efficacy and side effects include dyskinesias and cognitive changes.
     
  6. Selective serotonin re-uptake inhibitors (SSRIs)(Prozac, Zoloft, Paxil, Celexa) inhibit the reuptake of serotonin. Increase the dosage q 4-6 weeks and if treating depression need to commit to 12 month course (or increased likelihood of recurrence).
     
  7.  Other antidepressantssuch as Effexor and Wellbutrin inhibit serotonin, noradrenaline and dopamine reuptake. No evidence of efficacy.

Describe how these medications work?

Treatment

 

Mechanism of Action

Dosage

Concerns

Methylphenidate

(indirect catecholamine agonist)

 

Neurostimulant

Presynaptic release of dopamine

Inhibition of dopamine uptake

Inhibition of monamine oxidase

Improves learning and memory, attention and distractibility functions in TBI patients (RLA 4-7)

Initiate 5 mg @ 7am and 12 noon, increase by 5-10 mg/day to max 60 mg/day

Half-life = 2-4 hours

If ineffective by 30 mg/day then wean in favour of another agent.

Amantadine

(dopaminergic agent)

Potentiates dopamine (mechanism is unclear)

Level 2 evidence of benefit for RLA-3

100-400 mg/day in BID dosing.

Elevated seizure risk when dose >300 mg/day.  Hallucinations dose-limiting side effect.

Bromocriptine

(dopamine agonist)

Dopamine receptor agonist.  Been suggested for low level patients but of limited proven efficacy

2-15 mg/day in 2 doses.

High incidence of nausea/vomiting and headaches with increasing doses.

 

What evidence is there that these medication are effective?

Treatment

 

Mechanism of Action

Dosage

Concerns

Methylphenidate

(indirect catecholamine agonist)

 

Neurostimulant

Presynaptic release of dopamine

Inhibition of dopamine uptake

Inhibition of monamine oxidase

Improves learning and memory, attention and distractibility functions in TBI patients (RLA 4-7)

Initiate 5 mg @ 7am and 12 noon, increase by 5-10 mg/day to max 60 mg/day

Half-life = 2-4 hours

If ineffective by 30 mg/day then wean in favour of another agent.

Amantadine

(dopaminergic agent)

Potentiates dopamine (mechanism is unclear)

Level 2 evidence of benefit for RLA-3

100-400 mg/day in BID dosing.

Elevated seizure risk when dose >300 mg/day.  Hallucinations dose-limiting side effect.

Bromocriptine

(dopamine agonist)

Dopamine receptor agonist.  Been suggested for low level patients but of limited proven efficacy

2-15 mg/day in 2 doses.

High incidence of nausea/vomiting and headaches with increasing doses.