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ALCOHOL WITHDRAWAL SYNDROMESYNDROME
Ravi Dhanisettyy11/30/2007
Veterans Affairs HospitalVeterans Affairs Hospital
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ACGME COREACGME CORE COMPETENCIES
Medical KnowledgePatient CareInterpersonal SkillsPractice Based LearningSystems Based LearningSystems Based LearningProfessionalism
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CASE PRESENTATIONCASE PRESENTATION
xx year old male was admitted for elective i ht h i l tright hemi-colectomy.
Outpatient screening colonoscopy showed a cecal mass - moderately differenciatedadenocarcinoma.ROS: 30 lbs weight loss in 8 weeks.
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CASE PRESENTATIONCASE PRESENTATION
PMHx: Diabetes MellitusCoronary Artery DiseaseChronic 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.
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CASE PRESENTATIONCASE PRESENTATION
PE: 99 138/88 8699 138/88 86 A/Ox3 Neurological: no focal deficitsNeurological: no focal deficits.RRRClear bilaterallyClear bilaterallyAbdomen - soft, no masses, obeseNo edema in extremities.No edema in extremities.
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CASE PRESENTATIONCASE PRESENTATION
Laboratory values:b 4 6 h b 12 6 h 3 l l 208Wbc – 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.
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CASE PRESENTATIONCASE PRESENTATION
OR Details:Episode of hypoxemia after induction ofEpisode of hypoxemia after induction of anesthesia.
Responded to bronchodialators.pPatient underwent exploratory laparotomy, right hemi-colectomy, and 2-layered hand sewn ileo-
l i icolonic anastomosis.Patient remained intubated after the case and transferred to SICUtransferred to SICU.
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CASE PRESENTATIONCASE PRESENTATION
POD #1:i f ll b d iPatient was successfully extubated on morning
rounds.Pl d b li t t t thi i f l tPlaced on nebulizer treatments, thiamine, folate, Ativan for delirium tremens prophylaxis. He remained hemodynamically stable and wasHe remained hemodynamically stable and was out of bed.
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CASE PRESENTATIONCASE PRESENTATION
Overnight (3:00 a.m.), patient became tl d it t drestless 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( )
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CASE PRESENTATIONCASE 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/-155
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CASE PRESENTATIONCASE PRESENTATION
POD #2:Despite discontinuation of all sedation, patient remained p , punarousable. Head CT scan showed changes consistent with diffuse anoxic brain injury. No PE on chest CT No EKG changes or significant troponin elevation.
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CASE PRESENTATIONCASE 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 familywas discussed with the family.POD #7: Patient’s family decided to withdraw supportive care.
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ALCOHOL WITHDRAWALALCOHOL 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 patientspatients, 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.
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A O S O OGPATHOPHYSIOLOGY
Alcohol withdrawal is a neurologic disorder ith ti f i l iwith 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.
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A O S O OGPATHOPHYSIOLOGY
Chronic alcohol consumption has profound effects on central nervous system neurotransmitters. Ch i i i i i C S i llChronic exposure increases overactivity in CNS – especially sympathetic autonomic outflowGABA 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.
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CLINICAL SYNDROMESCLINICAL SYNDROMES
Minor Withdrawal: 6-36 hoursTremulousness, mild anxiety, headache, diaphoresis, anorexia, GI upseth t i d b h t i t h dicharacterized by hypertension, tachycardia
Alcoholic Hallucinosis: 12-48 hoursVisual, auditory, and/or tactile hallucinations
Withd l S i 6 48 hWithdrawal Seizures: 6-48 hoursGeneralized, tonic-clonic seizuresoccur early, usually single with brief post-ictal period
D li i T 48 96 hDelirium Tremens: 48-96 hoursDelirium, tachycardia, hypertension, agitation, fever, diaphoresischaracterized by delirium and autonomic instability
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CLINICAL SYNDROMESCLINICAL SYNDROMES
Alcoholic Hallucinosis25 % of patients.Tactile (formication) and visual hallucinationsNo evidence of autonomic instabilityNot a predictor for subsequent development of DT.p q p
Withdrawal Seizures:In 10% of patients with alcohol withdrawalSelf limited with rapid recoverySelf limited with rapid recoveryStatus epilepticus (rare)
May have underlying seizure disorderSeizure with high alcohol level – poor prognostic indicatorSeizure with high alcohol level poor prognostic indicator.
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CLINICAL SYNDROMESCLINICAL SYNDROMES
DELIRIUM TREMENS: 48-96 hoursSevere autonomic instability along with:Severe autonomic instability along with:
Disturbance of consciousness orChange 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 F104 F.
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RISK FACTORS for DEVELOPMENT OFRISK FACTORS for DEVELOPMENT OF SEVERE ALCOHOL WITHDRAWAL
Strongest predictor: history of prior episodes or family historyor family history.Age >30Hi t f t i d d i kiHistory of sustained drinking.Biochemical markers: homocysteine levels, li f ti t t l h l l lliver function tests, alcohol level
Several studies done with contradictory results and no clear correlationand no clear correlation.
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Cli i l I tit tClinical Institute Withdrawal Assessment Score –bj i iobjective scoring
system to quantify the severity of alcohol
i hd lwithdrawal.
K t T R t l M t f D dKosten, T.R et al. Management of Drug and Alcohol Withdrawal. NEJM 2003: 348:1768-95.
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MANAGEMENTMANAGEMENT
Alcohol withdrawal seizures:S lf li i dSelf limitedBenzodiazepines are the preferred agent and
tprevent recurrence.Dilantin – multiple trials show does not prevent recurrence Most likely secondary to its inabilityrecurrence. Most likely secondary to its inability to regulate GABA or NMDA receptors.
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MANAGEMENT:MANAGEMENT:Severe Alcohol Withdrawal
Autonomic instability could place significant physiological stressphysiological stress. ABCAll patients with chronic alcohol use have vitaminAll patients with chronic alcohol use have vitamin (especially Thiamine) and volume depletion.DVT prophylaxis and aspiration precautionsDVT prophylaxis and aspiration precautions.Correct electrolyte deficiency.
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MANAGEMENTMANAGEMENT Drug of Choice
Landmark study: randomized prospective study.547 patients in acute alcohol withdrawal were randomized to 1 of 4 drugs or placeboof 4 drugs or placebo.
ChlordiazepoxideChlorpromazineHydroxyziney yThiamine
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.
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MANAGEMENTMANAGEMENT Drug of Choice
Diazepam (valium): Prefered agent for moderate to severe AWSPrefered agent for moderate to severe AWSRapid onset of action (avoids oversedation)Long half-life secondary to active metaboliteLong 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
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MANAGEMENTMANAGEMENT Drug of Choice
Phenobarbital and propofol are other options th t b i i dditi tthat can be given in addition to benzodiazepines.Beta- blockers and central acting alpha-agonists (clonidine) as adjuncts.
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MANAGEMENTMANAGEMENT
Severe alcohol withdrawal / delirium tremens.I iti l t tit ti ith i tInitial management: titration with intravenous benzodiazepine to achieve sedation and normal vital signssigns.May need admission to ICU or stepdown unit – for autonomic instability / respiratory depressionautonomic instability / respiratory depressionRepeated reassesment and administration of boluses in a symptom-triggered fashion.y p gg
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SUGGESTED CRITERIA for ICUSUGGESTED CRITERIA for ICU ADMISSION
Age >40Cardiac disease Hemodynamic instabilityM k d id b di bMarked acid-base disturbancesSevere electrolyte defectsRespiratory insufficiencyPotentially 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 requirementsA 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.
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MANAGEMENT:MANAGEMENT:Symptom-triggered
Randomized, double-blinded study:101 ti t d i d t ith fi d ( ith101 patients randomized to either fixed (with boluses as required) or symptom triggered regimentregiment.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 523randomized double-blind controlled trial. JAMA 1994;272:519-523.
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MANAGEMENT:MANAGEMENT:Symptom-triggered
Results: Shorter duration of treatmentShorter duration of treatment.Decreased amount of benzodiazepine used.No significant differences in the severity of withdrawal d iduring 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.
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CONCLUSIONSCONCLUSIONS
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 sedationTreatment includes supportive care and sedation with benzodiazepines in a symptom triggered fashion.
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