ALCOHOL WITHDRAWAL
SYNDROME
SYNDROME
Ravi Dhanisetty
y
11/30/2007
Veterans Affairs Hospital
Veterans Affairs Hospital
ACGME CORE
ACGME CORE
COMPETENCIES
Medical Knowledge
Patient Care
Interpersonal Skills
Practice Based Learning
Systems Based Learning
Systems Based Learning
Professionalism
CASE PRESENTATION
CASE PRESENTATION
xx year old male was admitted for elective
i ht h
i
l t
right hemi-colectomy.
Outpatient screening colonoscopy showed a
cecal mass - moderately differenciated
adenocarcinoma.
ROS: 30 lbs weight loss in 8 weeks.
CASE PRESENTATION
CASE PRESENTATION
PMHx:
Diabetes Mellitus
Coronary Artery Disease
Chronic Obstructive Pulmonary Disease
PSHx: Removal of sharpnel from right shoulder.
Home Medications: Lopressor, albuterol, atrovent
Social History:
Alcohol - 4-6 beers daily and liquor on weekends. Tobacco - 80 pack year history.
CASE PRESENTATION
CASE PRESENTATION
PE:
99 138/88 86 99 138/88 86 A/Ox3 Neurological: no focal deficits Neurological: no focal deficits. RRR
Clear bilaterally Clear bilaterally
Abdomen - soft, no masses, obese No edema in extremities.
No edema in extremities.
CASE PRESENTATION
CASE PRESENTATION
Laboratory values:
b 4 6 h b 12 6 h 3 l l 208 Wbc – 4.6, hgb -12.6, hct – 35, platlets - 208 Electrolytes, LFTs – wnl. PT – 16.6, INR – 1.4, PTT – 34.6
CT of abdomen & pelvis – no evidence of
metastatic disease.
CASE PRESENTATION
CASE PRESENTATION
OR Details:
Episode of hypoxemia after induction of
Episode of hypoxemia after induction of
anesthesia.
z Responded to bronchodialators.p
Patient underwent exploratory laparotomy, right
hemi-colectomy, and 2-layered hand sewn
ileo-l i i
colonic anastomosis.
Patient remained intubated after the case and
transferred to SICU transferred to SICU.
CASE PRESENTATION
CASE PRESENTATION
POD #1:
i f ll b d i
Patient was successfully extubated on morning
rounds.
Pl d b li t t t thi i f l t
Placed on nebulizer treatments, thiamine, folate,
Ativan for delirium tremens prophylaxis.
He remained hemodynamically stable and was
He remained hemodynamically stable and was
out of bed.
CASE PRESENTATION
CASE PRESENTATION
Overnight (3:00 a.m.), patient became
tl
d
it t d
restless and agitated.
115/75 HR: 95 sat – 100%
Given IM ativan (4 mg) and haldol (5 mg),
soft restraints placed.
(3:51 a.m.)
ABG (face mask): 7.41/40.9/63.3/25.5/92.5/0.0( )
CASE PRESENTATION
CASE PRESENTATION
4:30 a.m. Patient became unresponsive and
asystolic.
Code 33: Patient was intubated and
resuscitated as per ACLS.
5:00 a.m (post code). :
7.16/36/119/12.4/99/-15
5
CASE PRESENTATION
CASE PRESENTATION
POD #2:
Despite discontinuation of all sedation, patient remained p , p
unarousable.
Head CT scan showed changes consistent with diffuse
anoxic brain injury.
No PE on chest CT
No EKG changes or significant troponin elevation.
CASE PRESENTATION
CASE PRESENTATION
No change in patients neurological status over next several days.
After consultation with neurology, palliative care, and hospital ethics committee, patient’s condition was discussed with the family
was discussed with the family.
POD #7: Patient’s family decided to withdraw supportive care.
ALCOHOL WITHDRAWAL
ALCOHOL WITHDRAWAL
SYNDROME
Epidemiology:
Common condition in inpatient setting.
Symptoms developed in 8% of all general
hospital admissions, 16% of all postsurgical patients and 31% of all trauma patients
patients, and 31% of all trauma patients.
Development of alcohol withdrawal increased
mortality 3 fold in post surgical patients. mortality 3 fold in post surgical patients.
A
O
S O OG
PATHOPHYSIOLOGY
Alcohol withdrawal is a neurologic disorder
ith
ti
f
i
l
i
with a continuum of progressively worsening
symptoms.
Secondary to effects of chronic alcohol use
on the central nervous system.
Exacerbated by the co-morbid conditions
associated with alcoholism.
A
O
S O OG
PATHOPHYSIOLOGY
Chronic alcohol consumption has profound effects on central nervous system neurotransmitters.
Ch i i i i i C S i ll
Chronic exposure increases overactivity in CNS – especially sympathetic autonomic outflow
GABA receptor: “great inhibitor”
Alcohol downregulates GABA -R leading to loss of inhibition.
NMDA receptor:
Alcohol upregulates NMDA leading to increased excitation.
This combination of increased excitation and loss of
inhibition results in the clinical manifestations of autonomic excitability and psychomotor agitation.
CLINICAL SYNDROMES
CLINICAL SYNDROMES
Minor Withdrawal: 6-36 hours
Tremulousness, mild anxiety, headache, diaphoresis, anorexia, GI upset
h t i d b h t i t h di
characterized by hypertension, tachycardia
Alcoholic Hallucinosis: 12-48 hours
Visual, auditory, and/or tactile hallucinations
Withd l S i 6 48 h
Withdrawal Seizures: 6-48 hours
Generalized, tonic-clonic seizures
occur early, usually single with brief post-ictal period
D li i T 48 96 h
Delirium Tremens: 48-96 hours
Delirium, tachycardia, hypertension, agitation, fever, diaphoresis
characterized by delirium and autonomic instability
www.downstatesurgery.org
CLINICAL SYNDROMES
CLINICAL SYNDROMES
Alcoholic Hallucinosis
25 % of patients.
Tactile (formication) and visual hallucinations
No evidence of autonomic instability
Not a predictor for subsequent development of DT.p q p
Withdrawal Seizures:
In 10% of patients with alcohol withdrawal
Self limited with rapid recovery
Self limited with rapid recovery
Status epilepticus (rare)
z May have underlying seizure disorder
Seizure with high alcohol level – poor prognostic indicator
Seizure with high alcohol level poor prognostic indicator.
CLINICAL SYNDROMES
CLINICAL SYNDROMES
DELIRIUM TREMENS: 48-96 hours
Severe autonomic instability along with:
Severe autonomic instability along with: z Disturbance of consciousness or
z Change in cognition (such as memory deficit, g g ( y ,
disorientation, language disturbance)
5 - 37% mortality.
Increased mortality if other co-morbidities:
pulmonary disease, liver disease, temperature > 104 F
104 F.
RISK FACTORS for DEVELOPMENT OF
RISK FACTORS for DEVELOPMENT OF
SEVERE ALCOHOL WITHDRAWAL
Strongest predictor: history of prior episodes
or family history
or family history.
Age >30
Hi t
f
t i
d d i ki
History of sustained drinking.
Biochemical markers: homocysteine levels,
li
f
ti
t t
l
h l l
l
liver function tests, alcohol level
Several studies done with contradictory results
and no clear correlation and no clear correlation.
Cli i l I tit t Clinical Institute Withdrawal Assessment Score – bj i i objective scoring
system to quantify the severity of alcohol
i hd l
withdrawal.
K t T R t l M t f D d
Kosten, T.R et al. Management of Drug and Alcohol Withdrawal. NEJM 2003: 348:1768-95.
MANAGEMENT
MANAGEMENT
Alcohol withdrawal seizures:
S lf li i d
Self limited
Benzodiazepines are the preferred agent and
t
prevent recurrence.
Dilantin – multiple trials show does not prevent
recurrence Most likely secondary to its inability recurrence. Most likely secondary to its inability to regulate GABA or NMDA receptors.
MANAGEMENT:
MANAGEMENT:
Severe Alcohol Withdrawal
Autonomic instability could place significant physiological stress
physiological stress.
ABC
All patients with chronic alcohol use have vitamin
All patients with chronic alcohol use have vitamin (especially Thiamine) and volume depletion.
DVT prophylaxis and aspiration precautions
DVT prophylaxis and aspiration precautions.
Correct electrolyte deficiency.
MANAGEMENT
MANAGEMENT
Drug of Choice
Landmark study: randomized prospective study.
547 patients in acute alcohol withdrawal were randomized to 1 of 4 drugs or placebo of 4 drugs or placebo. Chlordiazepoxide Chlorpromazine Hydroxyziney y Thiamine
Patients receiving chlordiazepoxide had the lowest incidence of both delirium tremens and alcohol withdrawal seizures.
BENZODIAZEPINES - first-line agent for treatment of Alcohol Withdrawal Syndrome.
Alcohol Withdrawal Syndrome.
Kaim SC, Klett CJ, Rothfeld B: Treatment of the acute alcohol withdrawal state: A comparison of four drugs. Am J Psychiatry 1969;125: 1640-1646.
MANAGEMENT
MANAGEMENT
Drug of Choice
Diazepam (valium):
Prefered agent for moderate to severe AWS
Prefered agent for moderate to severe AWS Rapid onset of action (avoids oversedation) Long half-life secondary to active metabolite Long half life secondary to active metabolite
Chlordiazepoxide (librium): most commonly used
Lorazepam (ativan)Lorazepam (ativan)
No active metabolites, better tolerated in patients with
compromized liver function
MANAGEMENT
MANAGEMENT
Drug of Choice
Phenobarbital and propofol are other options
th t
b
i
i
dditi
t
that can be given in addition to
benzodiazepines.
Beta- blockers and central acting
alpha-agonists (clonidine) as adjuncts.
MANAGEMENT
MANAGEMENT
Severe alcohol withdrawal / delirium tremens.
I iti l t tit ti ith i t
Initial management: titration with intravenous
benzodiazepine to achieve sedation and normal vital signs
signs.
May need admission to ICU or stepdown unit – for autonomic instability / respiratory depression
autonomic instability / respiratory depression
Repeated reassesment and administration of boluses in a symptom-triggered fashion.y p gg
SUGGESTED CRITERIA for ICU
SUGGESTED CRITERIA for ICU
ADMISSION
Age >40
Cardiac disease
Hemodynamic instability M k d id b di b
Marked acid-base disturbances Severe electrolyte defects
Respiratory insufficiency
Potentially serious infections (wounds, pneumonia, trauma, urinary tract infection)y ( p y ) Signs of gastrointestinal pathology (pancreatitis, GI bleeding, hepatic insufficiency,
suspected peritonitis)
Persistent hyperthermia (T >39ºC [103ºF])
Renal insufficiency or increased fluid requirementsRenal insufficiency or increased fluid requirements A history of prior alcohol withdrawal complications
Need for frequent or high doses of sedatives or an intravenous infusion to control symptoms
Carlson, RW, Keske, B, Cortez, D, J Crit Illness 1998; 13:311.
MANAGEMENT:
MANAGEMENT:
Symptom-triggered
Randomized, double-blinded study:
101 ti t d i d t ith fi d ( ith
101 patients randomized to either fixed (with boluses as required) or symptom triggered regiment
regiment.
Severity of symptoms quantified by using Clinical Institute Withdrawal Assessment score.
Institute Withdrawal Assessment score.
Saitz R, Mayo-Smith MF, Roberts MS, et al: Individualized treatment for alcohol withdrawal. A randomized double blind controlled trial JAMA 1994;272:519 523
randomized double-blind controlled trial. JAMA 1994;272:519-523.
MANAGEMENT:
MANAGEMENT:
Symptom-triggered
Results:
Shorter duration of treatment Shorter duration of treatment.
Decreased amount of benzodiazepine used.
No significant differences in the severity of withdrawal
d i
during treatment
No difference in the incidence of seizures or delirium
tremens between two groupsg p
Saitz R, Mayo-Smith MF, Roberts MS, et al: Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial. JAMA 1994;272:519-523.
CONCLUSIONS
CONCLUSIONS
Alcohol withdrawal is a complex neurological disorder.
disorder.
Physiologic process involving both neuronal excitation and reduced inhibition leading to autonomic excitability that can lead to altered mental status and seizures.
Treatment includes supportive care and sedation
Treatment includes supportive care and sedation with benzodiazepines in a symptom triggered fashion.
