In Hospital Management of Acute Alcohol withdrawal Syndrome.

1. Lt Col Ashutosh Ojha
Cl Spl (Med)
151 Base Hospital

2. My Patient
Mr XYZ
Age 39 yrs
NCE ,AF
Att. with small Det for more than 04 month
Resident –Assam ,Distt-Kamrup
Edn-Xth Std
Married
A Chronic Alcohol abuser .

3. Presentation
Noted to have increased tremors, tremulousness and
irritable by colleagues
Blood tinged vomitus while brushing
Also blood ooze from gums
Also had 03 episodes of seizures (not witnessed)
Also had incontinence of urine in lines once
 Yellowness of eyes

4. 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

5. 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

6. Personal History
Alcohol -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 Veg
Non Smoker

7. Personal History…contd
Married
02 children
 staying Single at Guwahati

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

9. Summarily
A case of Alcohol Dependence with relapse and in
Acute withdrawal state with features of Alcoholic liver
disease

10. On Examination
Gloomy look,Confused ,wandering
Pulse-98/min /reg
BP=160/100mmHg
Icteric
Tremors-Digital /Tongue
Resp rate-16/min
Temp-99.8 Deg F (Axillary )

11. Gen Examn…Contd
Parotomegaly
Asterexis –Could not be elicited
Dry blood on lips . fresh blood stains on shirt
Breath –non alcoholic
Testicular sensation intact

12. Systemic examn
Per -Abdomen
Soft ,non distended
Liver-4 cm ,soft ,non-tender, non pulsatile, span
-14cm
Spleen –palapable-3cm,Firm
No ascitis
No Neck Rigidity
Lungs-Clear

13. Mental state Examn
Conscious
Oriented -Time . Person
Memory –Recent and Intermediate compromised
Intelligence- Not tested … Not attentive
Delusion and Visual hallucination –Nil
Anxious

14. Working Diagnosis
A case of Alcohol Dependence Syndrome with relapse
and in Acute withdrawal state with Alcoholic Liver
disease

15. Rx
Admitted with guards in Acute Medical ward
Inj Thiamin
Inj Vit K
Inj Ceftazidime
Inj Lorazepam
Inj MVI Infusion
Inj Pantoprazol

16. Next morning
Febrile -102 deg F
Hallucinating – Visual as well auditory
Tremors
Restless
Running around
Perspiring
Pulse-126/min
BP-could not be recorded

17. Diagnosed -Delirium tremens
Restrained nursing
Inj 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

18. DT Rx..
Placed on DIL
Anti Malarial added (Artesunate)
Continued Rx under advice of Sr Adv(Psy) CH(EC)
After enough sedation …. Pt was kept under constant
observation

19. Investigations
Hb-12.5g/dL,TLC-5600/cmm,DLC-P80L16M02E02,Pl-
1.52 lac/cc
S.Bil-2.8mg/dL
SGOT=128,SGPT=116,SGGT=486IU/L,
Uric acid-5.3mg/dL.
MCV-102fL
RFT,Electrolytes –WNL
ECG-Tachycardia

20. Investigations..contd
USG- Normal scan
HBsAg,Anti HCV,HIV-Neg
INR-1.22
MRI-Brain –Normal study

21. 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

22. Course in Hospital
Gradually calmed down
Attentive
Afebrile
All autonomic dysfunction signs settled
Taken off DIL on day 07
Patient in Psy ward

23. Rx contd……..
Psycho-therapy incl group therapy and Psycho-
education is in progress

24. Disposal
Invalidation is planned after due course

25. Discussion

26. Objectives
Describe the different types of alcohol withdrawal
Recognize the symptoms of alcohol withdrawal
delirium
 Review the management of AWD

27. Scope of the problem
8 million people dependent on alcohol is the US
3.5 million dependent on illicit drugs
500,000 episodes/yr of alcohol withdrawal
15% of pts in primary care have either an alcohol-
related health problem or “at-risk” pattern of alcohol
use

28. ALCOHOL : INDIAN SCENARIO
Estimated numbers of alcohol users - 62.5 million
17.4% (10.6 million) dependant users
 20-30%- admissions alcohol related
15% - general population
10% - patients in family practice
30% co morbidity with a psychiatric condition
 More common in younger people with low SES and
educational status

29. 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

30. Patho-physiology
Alcohol 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

31. 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 seizures
Seizures – 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)

32. Withdrawal Differential Diagnosis
Sepsis/Malaria
Thyrotoxicosis
Heat stroke
Hypoglycemia
Intracranial pathology: trauma/CVA
Encephalitis/encephalopathy
Acute cocaine intoxication
Acute amphetamine intoxication
Olmedo et al. Withdrawal Syndromes. Emergency Med Clinics of North America 2000;18(2): 273-287

33. Assessment
Optimal 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 ofStandardized 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

35. Laboratory tests
Parameter 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

36. Mild Alcohol withdrawal
6hrs after stop drinking (may occur w/ significant
blood-alcohol levels)
Resolves in 1-2 days
CNS overactivity
Insomnia, anxiety
Tremulousness
Diaphoresis
GI upset
Headaches

37. Alcohol Hallucinosis
Begins 12-24 hours after cessation
Lasts 1- 3 days
Patient 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

38. 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 generalized
Focal seizure = structural lesion
High risk of progression to Delirium Tremens

39. ALCOHOL WITHDRAWL SEIZURES
D/D
Structural 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

40. ALCOHOL WITHDRAWAL SEIZURES
MANAGEMENT
 Rule out other causes by history/examination/ lab inv
Treat only for withdrawal
Do not start anticonvulsant
Admission to detoxification centre
Indications for CT head:
Focal seizure
Focal neurologic findings
Signs of head trauma
Clinical deterioration

41. 5% of patients who withdraw
Typically begin b/w 48 and 96 hours
Typically last 1-5 days
Early figures of associated mortality were as high as
37%,present mortality rates - 5%.
Delirium Tremens:

42. Delirium Tremens:: Factors
Risk History of sustained drinking
Previous DTs
old age
Greater number of days since last drink
Presence of other illnesses
Mortality risk is greater:
Elderly
 Concomitant lung Disease
Core body temp >104 deg F
 Co-existing liver Disease

43. Delirium Tremens: symptoms and sign
Sensorium Clouding
Hallucinations
Tremors
Disorientation
Tachycardia
Hypertension
Fever
Agitation
Diaphoresis

44. 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:
↑GABAA
R function
↓ Seizures: 90%
↓ Delirium: 70%
McKinley MG, Crit Care Nurse. 2005;25: 40-48

45. Fixed Schedule Therapy
Day 1, one of these 6 h:

Chlorodiazepoxide, 50 – 100 mg
 Diazepam, 10 – 20 mg
 Lorazepam, 2 – 4 mg
 Then↓ dose 20% each day

46. 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

47. 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)

48. Mortality
Mortality is ~5%
Increased by older age, coexisting lung or liver
disease, and temp>104 F
Death due to arrhythmia, complicating illness
(pneumonia), or failure to recognize trigger illness
(CNS infection, pancreatitis)

49. Associated findings in DTs
Dehydration (increased losses)
Hypokalemia (renal and extrarenal losses)
Hypomagnesemia (increases risk for seizures and
arrhythmias)
Hypophosphatemia (increases risk for
rhabdomyolysis and cardiac failure)

50. Supportive Care for DTs
Replace volume deficits - isotonic fluids
Thiamine 100mg IV and glucose
MVI w/ folate
Aggressively correct abnormal K, Mg, Phos, and
glucose

51. Overview of TreatmentBenzodiazepines = Mainstay of Alcohol withdrawal
treatment
6 prospective trials comparing BZD to placebo
Risk reduction of 7.7 in preventing seizures
Risk reduction of 4.9 in preventing delirium
Work by stimulation GABA receptors
Treats agitation and prevents progression
Kosten TR. NEJM 2003; 348: 1786

52. Benzos vs Neuroleptics
Meta-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.

53. The Bottom Line:
2004 Practice Guidelines
Benzos should be primary agent for managing AWD
(gr A)
Reduce mortality, duration of sx and have less
complications than neuroleptics
Initial goal is control of agitation
Rapid, adequate control of agitation reduces adverse
events
Arch Int Med, vol 164, 2004.

54. Benzodiazepines
Long-acting formulations preferred ..Except Hepatic
Dysfunction
Shorter acting (lorazepam) may be preferred in
elderly or liver disease
Continuous infusions of BZDs are not cost-effective.
Onset of action for BZDs: 15sec – 2min
Peak action: 5-15 min

55. Adjunctive meds: Neuroleptics
Inferior to benzodiazepines
Increased risk of side effects, including lower seizure
threshold, prolonged QTc and hypotension
No studies done on “newer” atypicals
Can be used in conjunction w/ benzo in setting of
perceptual disturbances (gr C)

56. Adjunctive meds
Beta-blockers: not well studied
Mild reduction in autonomic manifestations
One controlled study w/ propranolol: increased
incidence of delirium
Can be used if persistent HTN or tachycardia (gr C)
Carbamazepine
Effective for mild-mod symptoms of withdrawal
Limited data on preventing seizures or delirium

57. Adjunctive meds
Clonidine
Effective for mild-mod symptoms of withdrawal
No studies that show decrease rate of delirium or
seizures
Ethyl Alcohol – not recommended
No controlled trials, potential GI/neuro effects
Difficult to titrate, not readily available

58. 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

59. Humble Acknowledgement
Sr Adv(Psy) and Our Spl Psy Maj Surendra Sharma
Team 151 Base
Hospital

60. References and Reading
Ferguson 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.