Lt Col Ashutosh OjhaCl Spl (Med)

151 Base Hospital

My PatientMr XYZAge 39 yrsNCE ,AF Att. with small Det for more than 04 monthResident –Assam ,Distt-KamrupEdn-Xth Std MarriedA Chronic Alcohol abuser .

PresentationNoted to have increased tremors,

tremulousness and irritable by colleaguesBlood tinged vomitus while brushingAlso blood ooze from gumsAlso had 03 episodes of seizures (not

witnessed)Also had incontinence of urine in lines once Yellowness of eyes

Presentation Contd…..No H/o alcohol consumption X 4 days Taking tablets for Headache Unable to sleep the night before Unable to attend House keeping and

attendant job Noted to be talking to self and unable to pay

attention

Past History Known case of Alcohol Dependence

Syndrome for 3 yrs and was upgraded 1 yr back

Multiple relapses Admitted with DT and seizures

History elicited after recovery of acute stage

Personal HistoryAlcohol -120ml/day since 1993 Been Rxed in different Primary care centres

of services.Come in eval. and observed in Med category

2009-2012 With relapses After up gradation in Dec2012 Indulged in drinking 150 ml to 350ml of

IMFL incl desi off and on Non VegNon Smoker

Personal History…contd Married 02 children staying Single at Guwahati

Family History Alcohol abuse in family –father No h/o psy illness

Summarily A case of Alcohol Dependence with relapse

and in Acute withdrawal state with features of Alcoholic liver disease

On ExaminationGloomy look,Confused ,wandering Pulse-98/min /regBP=160/100mmHg Icteric Tremors-Digital /TongueResp rate-16/minTemp-99.8 Deg F (Axillary )

Gen Examn…ContdParotomegalyAsterexis –Could not be elicited Dry blood on lips . fresh blood stains on shirtBreath –non alcoholicTesticular sensation intact

Systemic examn Per -AbdomenSoft ,non distended Liver-4 cm ,soft ,non-tender, non pulsatile,

span -14cmSpleen –palapable-3cm,Firm No ascitis

No Neck Rigidity Lungs-Clear

Mental state Examn Conscious Oriented -Time . Person Memory –Recent and Intermediate

compromisedIntelligence- Not tested … Not attentive Delusion and Visual hallucination –Nil Anxious

Working Diagnosis A case of Alcohol Dependence Syndrome with

relapse and in Acute withdrawal state with Alcoholic Liver disease

RxAdmitted with guards in Acute Medical wardInj Thiamin Inj Vit KInj Ceftazidime Inj Lorazepam Inj MVI Infusion Inj Pantoprazol

Next morningFebrile -102 deg FHallucinating – Visual as well auditory Tremors RestlessRunning aroundPerspiringPulse-126/min BP-could not be recorded

Diagnosed -Delirium tremens Restrained nursingInj Lorazepam 4mg IV stat and repeated 03

times after every 15 mins Inj Haloperidol 5 mg IV stat given IV fluid-liberally @125-200ml/hr Condom drain placed

DT Rx..Placed on DILAnti Malarial added (Artesunate)Continued Rx under advice of Sr Adv(Psy)

CH(EC)After enough sedation …. Pt was kept under

constant observation

Investigations Hb-12.5g/dL,TLC-5600/cmm,DLC-

P80L16M02E02,Pl-1.52 lac/ccS.Bil-2.8mg/dLSGOT=128,SGPT=116,SGGT=486IU/L,Uric acid-5.3mg/dL.MCV-102fLRFT,Electrolytes –WNLECG-Tachycardia

Investigations..contd USG- Normal scanHBsAg,Anti HCV,HIV-Neg INR-1.22MRI-Brain –Normal study

Course of Rx After adequate sedation gradually the de-

escalation of Benzodiazapines were done Inj Halpopridol stopped Tab Heptral (S Adnosyl amine )400mg BD

added Tab Multi-Vit added after 07 days of IM

Thiamin supplementation

Course in HospitalGradually calmed down Attentive Afebrile All autonomic dysfunction signs settled Taken off DIL on day 07 Patient in Psy ward

Rx contd……..Psycho-therapy incl group therapy and

Psycho-education is in progress

DisposalInvalidation is planned after due course

Discussion

ObjectivesDescribe the different types of alcohol

withdrawalRecognize the symptoms of alcohol

withdrawal delirium Review the management of AWD

Scope of the problem8 million people dependent on alcohol is the

US3.5 million dependent on illicit drugs500,000 episodes/yr of alcohol withdrawal15% of pts in primary care have either an

alcohol-related health problem or “at-risk” pattern of alcohol use

ALCOHOL : INDIAN SCENARIOEstimated numbers of alcohol users - 62.5

million17.4% (10.6 million) dependant users 20-30%- admissions alcohol related 15% - general population10% - patients in family practice30% co morbidity with a psychiatric condition More common in younger people with low SES

and educational status

Alcohol Withdrawal syndrome

A. Cessation of (or reduction in) alcohol use that has been heavy and prolonged.

B. Two (or more) of the following, developing within several hours to a few days after Criterion A. 1. Autonomic hyperactivity (e.g., diaphoresis or HR>100)

2. Increased hand tremor

3. Insomnia

4. Nausea and vomiting

5. Transient visual, tactile, or auditory hallucinations or illusions

6. Psychomotor agitation

7. Anxiety

8. Grand mal seizures

Patho-physiologyAlcohol enhances the effect of GABA on GABA-A neuro-

receptors - decreases overall brain excitability

Chronic exposure to alcohol results in a compensatory

decrease of GABA-A receptor

Alcohol inhibits NMDA receptors

Chronic alcohol exposure results in up-regulation of these receptors

Abrupt cessation of alcohol exposure results in brain hyper excitability

Brain hyper excitability manifests clinically as anxiety, irritability, agitation, and tremors

McKinley MG, Crit Care Nurse. 2005;25: 40-48

STAGES OF WITHDRAWAL TIMING

Tremulousness, mild anxiety, headache, diaphoresis, palpitations, anorexia, GI upset

Mild Withdrawal – resolve 24-48 hr

6 to 36 hours

Visual, auditory, and/or tactile hallucinations

Alcoholic Hallucinosis – resolve 24-48 hr

12 to 24 hours

Generalized, tonic-clonic seizuresSeizures – 3% among chronic alcoholics from which 3% status epilepticus

12 to 48 hours

Delirium, tachycardia, hypertension, agitation, fever, diaphoresis. Delirium Tremens

48 to 96 hours(peaks within 5 days)

Withdrawal Differential Diagnosis

Sepsis/Malaria ThyrotoxicosisHeat strokeHypoglycemiaIntracranial pathology: trauma/CVAEncephalitis/encephalopathy

Acute cocaine intoxicationAcute amphetamine intoxication

Olmedo et al. Withdrawal Syndromes. Emergency Med Clinics of North America 2000;18(2): 273-287

AssessmentOptimal Assessment of AW:Optimal Assessment of AW:

- Complete history- Complete history

- Physical, and mental status exam- Physical, and mental status exam

- Laboratory test- Laboratory test

Standardized assessment of Standardized assessment of AW symptoms - (CIWA-Ar)

- Score 8-10 (mild)

- Score 10-15 (moderate)

- Score > 15 (severe) impending delirium tremens

Every 4-8 hours until score < 8-10 for 24 hours http://www.aafp.org/afp/20040315/1443.html

Laboratory testsParameter Normal value Value in patients with

chronic alcohol use

Mean corpuscular volume (fl )

82-98 Increased

Serum level of γ-glutamyl transferase, U/L

Men 4-25 Women 7-40

Increased

Serum level of uric acid (mg/dL)

4.0-8.5 Increased

Carbohydrate-deficient transferrin, g/L (mg/dL)

2.0-3.8 (200-300) Increased

McKinley MG, Crit Care Nurse. 2005;25: 40-48

Mild Alcohol withdrawal6hrs after stop drinking (may occur w/

significant blood-alcohol levels)Resolves in 1-2 daysCNS overactivity

Insomnia, anxietyTremulousnessDiaphoresisGI upsetHeadaches

Alcohol HallucinosisBegins 12-24 hours after cessation Lasts 1- 3 daysPatient remains oriented Autonomic activation is minimal or absent Varies from tactile, visual, and auditory

hallucinations Visual hallucinations of animals on the walls

common Tactile hallucinations of bugs crawling all over Auditory hallucinations of hearing voices Visual are most common

ALCOHOL WITHDRAWL SEIZURES

40% of seizures are alcohol related seizures Clinical Features Onset usually 6 - 48 hrs (have been

described up to 14 days)Usually generalizedFocal seizure = structural lesion High risk of progression to Delirium Tremens

ALCOHOL WITHDRAWL SEIZURES

D/DStructural lesion

Co ingestant: Stimulants , anticholinergic, phenothiazine

Metabolic cause: Hypoglycemia, Ca, Na, Po4 CNS infections

Non compliance with seizure treatment

Exacerbation of post-traumatic seizure disorder or idiopathic epilepsy

ALCOHOL WITHDRAWAL SEIZURES

MANAGEMENT Rule out other causes by history/examination/ lab

invTreat only for withdrawalDo not start anticonvulsantAdmission to detoxification centre

Indications for CT head: Focal seizure Focal neurologic findings Signs of head trauma Clinical deterioration

5% of patients who withdrawTypically begin b/w 48 and 96 hours Typically last 1-5 daysEarly figures of associated mortality were as

high as 37%,present mortality rates - 5%.

Delirium Tremens:

Delirium Tremens:: FactorsRisk History of sustained drinkingPrevious DTsold ageGreater number of days since last drinkPresence of other illnessesMortality risk is greater:Elderly Concomitant lung DiseaseCore body temp >104 deg F Co-existing liver Disease

Delirium Tremens: symptoms and sign

Sensorium CloudingHallucinationsTremorsDisorientationTachycardiaHypertensionFeverAgitationDiaphoresis

Goals of therapy To provide a safe withdrawal from the drug(s)To prepare the patient for ongoing treatment of

dependence

BZD -First line agent, best efficacy, safety and cost

All are effective:

GABAAR function

Seizures: 90%

Delirium: 70%McKinley MG, Crit Care Nurse. 2005;25: 40-48

Fixed Schedule TherapyDay 1, one of these 6 h:

Chlorodiazepoxide, 50 – 100 mg

Diazepam, 10 – 20 mg

Lorazepam, 2 – 4 mg

Then dose 20% each day

Symptom-triggered Therapy

Treatment triggered by severity threshold

One of these 1 h when CIWA 8: Chlordiazepoxide, 50 - 100 mg Diazepam, 10 - 20 mg Lorazepam, 2 - 4 mg

2 controlled trials vs. fixed schedule: Equal efficacy / safety Dose / side effects / treatment time

Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial

Figure 1 . Kaplan-Meier curves illustrate treatment times for both groups. Treatment time was shorter in the patients receiving symptom-triggered therapy (log rank test P <.001)

MortalityMortality is ~5% Increased by older age, coexisting lung or

liver disease, and temp>104 FDeath due to arrhythmia, complicating illness

(pneumonia), or failure to recognize trigger illness (CNS infection, pancreatitis)

Associated findings in DTsDehydration (increased losses)Hypokalemia (renal and extrarenal losses)Hypomagnesemia (increases risk for seizures

and arrhythmias)Hypophosphatemia (increases risk for

rhabdomyolysis and cardiac failure)

Supportive Care for DTsReplace volume deficits - isotonic fluidsThiamine 100mg IV and glucoseMVI w/ folateAggressively correct abnormal K, Mg, Phos,

and glucose

Overview of TreatmentBenzodiazepines = Mainstay of Alcohol

withdrawal treatment6 prospective trials comparing BZD to placeboRisk reduction of 7.7 in preventing seizures Risk reduction of 4.9 in preventing delirium

Work by stimulation GABA receptorsTreats agitation and prevents progression

Kosten TR. NEJM 2003; 348: 1786

Benzos vs NeurolepticsMeta-analysis based on 5 studies

Benzos more effective in reducing mortality from AWD (RR 6.6 for neuroleptics, CI 1.2-34)

Time to achieve adequate sedation was less w/ BZDs (1.1 vs 3 hr, p=0.02)

Arch Int Med, vol 164, 2004.

The Bottom Line:2004 Practice GuidelinesBenzos should be primary agent for

managing AWD (gr A)Reduce mortality, duration of sx and have less

complications than neurolepticsInitial goal is control of agitation

Rapid, adequate control of agitation reduces adverse events

Arch Int Med, vol 164, 2004.

BenzodiazepinesLong-acting formulations preferred ..Except

Hepatic DysfunctionShorter acting (lorazepam) may be preferred

in elderly or liver diseaseContinuous infusions of BZDs are not cost-

effective.Onset of action for BZDs: 15sec – 2minPeak action: 5-15 min

Adjunctive meds: NeurolepticsInferior to benzodiazepinesIncreased risk of side effects, including lower

seizure threshold, prolonged QTc and hypotension

No studies done on “newer” atypicalsCan be used in conjunction w/ benzo in

setting of perceptual disturbances (gr C)

Adjunctive medsBeta-blockers: not well studied

Mild reduction in autonomic manifestationsOne controlled study w/ propranolol: increased

incidence of deliriumCan be used if persistent HTN or tachycardia

(gr C) CarbamazepineEffective for mild-mod symptoms of withdrawalLimited data on preventing seizures or

delirium

Adjunctive medsClonidine

Effective for mild-mod symptoms of withdrawalNo studies that show decrease rate of delirium

or seizuresEthyl Alcohol – not recommended

No controlled trials, potential GI/neuro effectsDifficult to titrate, not readily available

Take Home Message Alcohol withdrawal includes a number of

clinical syndromes that exists along a time and severity continuum

Benzodiazepines are the mainstay of Treatment Admin should be guided by CIWA scores (>8)

Identification of a trigger for AWD and supportive Rx w/ thiamine, glucose and electrolyte replacement are crucial

Humble AcknowledgementSr Adv(Psy) and Our Spl Psy Maj Surendra

Sharma

Team 151 Base Hospital

References and ReadingFerguson JA, et al. Risk factors for delirium

tremens development. J Gen Intern Med 1996; 11: 410.

Hack JB, et al. Thiamine before glucose to prevent Wernicke Encephalopathy: examining the conventional wisdom. JAMA 1998; 279: 583.

Kosten TR. Management of Drug and Alcohol Witdrawal. NEJM 2003; 348: 1786.

Mayo-Smith MF. Pharmacological management of alcohol withdrawal. JAMA 1997; 278: 144

Mayo-Smith MF, et al. Management of Alcohol Withdrawal Delirium. Arch Intern Med 2004; 164: 1405

Ntais C, et al. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev 2005.

Saitz R, et al. Individualized treatment for alcohol withdrawal. JAMA 1994; 272: 519.