MANAGING AT RISK
BEHAVIORS AFTER BRAIN
INJURY
Darryl L Kaelin MD
Medical Director
Frazier Rehab Institute
BEHAVIORAL CHANGES
•
•
•
•
Arousal / Attention
Affect / Depression
Psychosis
Delirium / Agitation
AGITATION
• A heightened state of (cortical)
activity marked by a complex of
deficits in…
• Cognition (Attn., Memory)
• Behavior (Aggressive, Impulsive,
Restless)
• Affect (Emotionally Labile)
DELIRIUM AFTER ABI
• Difficulty in focusing, shifting,
and sustaining attention
• Agitation
• Disturbed Sleep – Wake Cycle
• Memory Impairment – Always
happens during period of PostTraumatic Amnesia
Agitation after TBI:
Impact
•Adults 3x more likely in first 6 months
after head injury to show aggression than
those with multiple traumatic injuries
without head injury
• •25% of adults showed aggressive
behavior 60 months after discharge from
inpatient rehabilitation unit for TBI
• •70% of adults during inpatient TBI
rehabilitation experience agitation
• •Agitation has been shown to negatively
affect rate of recovery in acute inpatient
rehabilitation
INCIDENCE
•
•
•
•
Levin / Grossman (1978) – 30%
Reyes (1981) – 50%
Brooke (1992) – 11-35%
Keyser / Kreutzer – 9%
QUANTIFICATION
•
•
•
•
•
Neurobehavioral Scale
Overt Aggression Scale
Agitation Behavior Scale
Behavior Log
Sleep Charting
AGITATION BEHAVIOR
SCALE
THE CALL
• Johnny is screaming out that he
wants to go home now. He is
very confused and restless. Can
I have some Ativan or Seroquel
to calm him down please.
• How do you respond?
MANAGEMENT
• R/O visual, hearing, and
communication deficits
• R/O medical causes (pain,
metabolic, neurologic)
• R/O pharmacological causes
• R/O environmental causes
CAUSES OF AGITATION
•Identify and address possible cause/contributors
including:
• –Sleep disruption / alteration of sleep wake cycle
• –Sources for discomfort
• •Lines/catheters
• •Unidentified injury (fracture, etc)
• •Inadequate pain control
• •Gastrointestinal distress (reflux, constipation,
ileus)
• Seizures
• •subclinical epilepsy can present as intermittent
aggression
CAUSES OF AGITATION
• – Electrolyte abnormality – Na+,
Glucose, Calcium
• Infection – UTI, Pneumonia, wound
• –Neuroendocrine dysfunction
• –Post-traumatic hydrocephalus
• –Drug withdrawal (pain medications,
other meds from ICU)
• –Polypharmacy
Environmental
Management
ENVIRONMENTAL
MODIFICATION
• Goal: Provide the least
restrictive environment c/w
safety of the patient
• Adequate staff : patient ratio
• Adequate Behavior Modification
Training
• Means of Implementation
• Physical environment needs
PHYSICAL
ENVIRONMENT
•
•
•
•
•
•
•
Locked unit
Alarm system
Enclosure beds
Minimize stimulus
Room / Roommate assignment
Sitter for supervision
Restraints if necessary
RESTRAINTS
• Team determined
• Physician prescribed
• Documentation / Weaning
•
•
•
•
Type
Reason
Goals for use
Reevaluation daily
BEHAVIOR MODIFICATION
PROGRAM
• Interdisciplinary approach
• Documentation
•
•
•
•
Cause of behavior
Purpose of program (Goal)
+ or – Reinforcement
Examples of responses to
appropriate and inappropriate
behavior
NEUROTRANSMITTER
THEORY
•
•
•
•
•
•
Noradrenergic
Serotonergic
Dopaminergic
Cholinergic
Gabaminergic
Peptidinergic
PHARMACOLOGIC
AGENTS
•
•
•
•
•
•
•
Neurostimulants
Anticonvulsants
Anticholinergics
B – lockers (sympatholytic)
SSRI
Atypical Antipsychotics
Lithium
Fugate Et al.
• Study of 129 physicians divided into brain
injury experts or nonexperts surveyed.
• Experts either had published two or
greater articles on pharmacological
interventions for TBI in the last 5 years, or
had > or = 70% of their practice devoted to
treating TBI
• Experts most frequently prescribed
carbamazepine, beta blockers, TCA’s
• Nonexperts chose Haldol four times more
frequently than experts
Pharmacologic Tx
•Cochrane review last updated 2008
• •6 studies met criteria (RCT’s) for metaanalysis
• –Propranolol (2)
• –Pindolol (2)
• –Methylphenidate (1)
• –Amantadine (1)
• •Research supports use of -Blockers
• •Effect seen within 2-6 weeks
• •Response similar in both subacute and
chronic timeframe
HOW DO YOU DECIDE?
• Observation
• Theory
• Trial and error
BENZODIAZIPINES
•Work on GABA molecule to create:
• –Anxiolytic, sedative, antispasticity,
anticonvulsant and AMNESTIC effects
• •Effect duration varies based on
medication
– Short (1-8 hour half life) – e.g. midazolam,
alprazolam
– Intermediate (8-40 hour half life) – e.g.
lorazepam
– Long (>40 hours) – e.g. Diazepam,
clonazepam
BENZO: Side Effects
•Side effects include the following:
– Amnesia/memory loss
– Increased daytime fatigue
– Decreased concentration
– Decreased alertness
• •TBI causes the above effects as well
• •Repeated use of benzodiazepines may
slow/impair neuronal recovery after focal
injury
ANTIPSYCHOTICS
Mechanism of Action
• –Typical antipsychotics block D2-dopamine
receptor
• –Atypical antipsychotics have less D2
receptor activity
• •Atypicals likely act on other
neurotransmitter pathways, including
serotonin, dopamine, 1-adrenergic,
muscarinic, and histamine pathways
Side Effects
•Movement disorders
• –Akathisia – one of more common movement
disorders seen
• a subjective sense of restlessness often
accompanied by involuntary movements of the
limbs or trunk
• • Confusion
• – Extrapyramidal Symptoms
• – Tardive Dyskinesia – choreoathetotic or other
involuntary repetitive movement
• • Weight gain / Metabolic Syndrome
• • Neuroleptic Malignant Syndrome (NMS)
• • Seizures
• • Prolonged QT
COGNITION
Cognitive impact of Antipsychotics
• –Multiple animal studies have
demonstrated either slowed cognitive
improvement or reduced cognitive return
with use of antipsychotic medications
(both typical and atypical)
• –One human study demonstrated negative
cognitive impact with use of
antipsychotics after TBI that improved
with discontinuation of medication
(Stanislav et al, 1997)
TAKE HOME
•Though atypicals may be relatively
safer, likely all antipsychotic
medications have detrimental
effects with long term use (NMS,
Tardive Dyskinesia, etc)
• •May be appropriate to use atypical
antipsychotics for short-term limited
(PRN) use in agitation after TBI
during the acute period when
sedation is not a barrier
Timing of Drug
100%
80%
60%
Series 3
40%
Series 2
Series 1
20%
0%
Category Category Category Category
1
2
3
4
Beta-Blockers
•Proposed mechanism of reducing
hyperadrenergic activity
• •Commonly used for periodic autonomic
instability and dystonia (Storming)
• •In retrospective studies shown to improve
survival when used acutely after ABI
• •Current prospective placebo study looking
at effect of adrenergic blockade acutely
after brain injury on survival and functional
outcomes (clonidine and propranolol)
B-Blockers: Research
– 2 randomized placebocontrolled trials (Brooke 1992,
Greendyke 1986) show benefit
with propranolol for agitation in
the weeks after injury (Brooke)
and for aggressive behavior
months and years after injury
(Greendyke).
ANTICONVULSANTS
Various mechanisms based on medication:
• – Decrease excitatory neurotransmitter
activity
• – Increase inhibitor neurotransmitter
activity
• – Reduce sub-clinical epileptic activity
• •Seizures can be a source for
aggression/confusion/disorientation
• – Provide mood stabilization
ANTICONVULSANTS
Adult Research (all studies without controls)
• –Valproic Acid
• •Retrospective study of 28 patients with
age range 13-89 demonstrated reduction of
agitation symptoms with valproic acid in
26 (90%) patients
• •Authors concluded it may be appropriate
for alert, labile, impulsive, and disinhibited
patients (Chatham Showalter et al, 2000)
ANTICONVULSANTS
–Carbamazepime
• Prospective open trial in 8
patients (400-800 mg daily) had
improved Agitated Behavior
Scale (Azouvi et al, 1999)
• 7 patients showed reduction in
combativeness within 4 days
(Chatham Showalter et al, 1996)
ANTIDEPRESSANTS
Proposed mechanism for
decreasing agitation:
• – Treatment of
depression/anxiety that
contribute to
agitation/irritability
• –Mood stabilization
ANTIDEPRESSANTS
•Very few studies looking at use of
antidepressants with primary outcome of
reduction of agitation
• Multiple studies (including one prospective
RCT) in adults addressing post-TBI
depression noted reduction in symptoms of
depression as well as reduction in
agitation with treatment
• A pilot study demonstrated improved mood,
and improved attention and working
memory with fluoxetine
Kaelin’s Theory of
Agitation
• Two distinct foci of Agitation
• Internal – Restless and more
agitated when left alone and quiet
• External – Aggressive and more
agitated when stimulated or
challenged
Kaelin’s Theory of
Agitation
• Treatments
• Internal cause of Agitation may be
better treated with membrane
stabilizing agents like
anticonvulsants – CBZ, V. Acid
• External causes of Agitation may
be better treated with stimulants
to improve attention and cognitive
processing
• Some may need both
Kaelin’s Theory of
Agitation
• Beta-Blockers may be most
beneficial when there appears
to be sympathetic overdrive
(HR, BP, sweating, outbursts)
• SSRIs may be most beneficial
when there is a clear emotional
component ( depression,
anxiety).
Summary:
Little evidence to guide us so:
• –Identify and treat contributors to agitation
when possible
• –Treatment should include nonpharmacologic environmental and
behavioral management
• –Monitor response to intervention
• •Agitated Behavior Scale (may be most
appropriate for adult patients)
• –Avoid Polypharmacy
• • if something doesn’t work, stop it before
adding more
Questions ?
• Darryl Kaelin, MD
• 502-584-3377
• THANK YOU !!