Title: Challenges in Managing Alcohol Withdrawal Syndrome in Special Populations:

Focus on the Surgical and Elderly Patients.

Joanna Piechniczek-Buczek, MD

Department of Psychiatry Boston University School of Medicine

Alcohol Medical Scholars Program (Slide1)

I.                    INTRODUCTION (Slide 2)

A.     Alcohol misuse is common in the  general  population

1.      80 % lifetime alcohol use[1]

2.      15 % lifetime alcohol abuse

3.      10 % lifetime  alcohol dependence[2]

B.     Alcohol  Use Disorders (AUD) of abuse or dependence  common among

1.      Medical  inpatients  ~ 20%[3]

2.      Surgical Patients:  ~ 43% otorhinolaryngological patients;  50% gastrointestinal tract cancer patients[4]

3.      Trauma patients ~ 40% -50% intoxicated; 94% of those with intoxication have substance abuse or dependence  [5]

4.      Elderly ~ 17%[6]

C.     Alcohol  abuse, dependence, withdrawal:  DSM IV TR definitions [7] (Slide 3)

1.      Abuse: repeated alcohol–related problems in same 12  months with 1+ :

a.       Inability to fulfill role obligations

b.      Use in physically hazardous situations

c.       Legal problems

d.      Social  or interpersonal difficulties

e.       Never dependent

2.      Dependence: repeated alcohol-related problems over 12 months with 3 +:

a.        Tolerance

b.       Withdrawal

c.       Use heavier or longer than intended

d.       Desire and inability to cut down

e.       Activities aborted

f.        Long time spent in alcohol-related activities

g.       On-going use despite consequences

3.         Alcohol Withdrawal Syndrome (AWS) 2 +: (Slide 4)

a.   Autonomic hyperactivity

b.     Tremor

c.      Insomnia

d.     Nausea or vomiting

e.      Hallucinations or illusions

f.       Agitation

g.      Anxiety

h.      Grand mal seizures

D.     Risk factors for  severe alcohol withdrawal:  (Slide 5)

1.      Quantity and frequency of intake (large amounts over long period of time) [8]

2.      Number and severity of prior episodes

3.      Use of other substances[9]

4.      Medical/surgical co-morbidity[10]

5.      Elevated Blood Alcohol Concentration (BAC)[11]

6.      High severity of withdrawal upon presentation[12]

7.      Advanced age[13]

E.       Development of AWS associated with: (Slide 6)

1.      More complicated hospital stay

2.      Longer stay

3.      ↑ need of intensive care[14]

4.      ↑ mortality

F.      This lecture will cover: (Slide 7)

1.      Neurobiology of Alcohol  Withdrawal Syndrome (AWS)

2.      Signs and symptoms of AWS

3.      Evaluation of  patients

4.      Treatment- general principles

5.    Special  considerations in:

a.       Surgical/ trauma patients

l

b.      Geriatric patients

(Slide 8)

II.     NEUROBIOLOGY OF ALCOHOL

A.   Acute effects of alcohol: (Slide 9)

1.       ­ activity at GABA A receptor [15]

2.        ¯ glutamate transmission  at NMDA receptor

3.       ­dopamine

4.       ­ norepinephrine synthesis and release

5.       ↑ effect of serotonin at 5HT3 receptor

6.       ­ beta endorphins levels / µ binding

B.     Chronic  effects of alcohol:

1.      Down- regulation of GABA receptors [16]

2.      Up-regulation of  NMDA receptors

3.      Down-regulation of dopamine receptors

4.      Serotonin depletion

5.      ¯ postsynaptic  receptor norepinephrine sensitivity

6.      ↓ in β-endorphine levels / binding

C.     Withdrawal   (Slide 10)

1.      ↑excitatory effect by: ↓ GABA, ↑ glutamateà tremor, seizures

2.      ­ norepinephrine sensitivity à  autonomic instability

(Slide 11)

III.       ALCOHOL WITHDRAWAL SYMPTOMS

A.               Phase I[17](Slide 12)

1.     Time abstinent or cut down: 6-24 hrs

2.      Signs and symptoms: 

a.       Tremor:  hands most prominent

b.      ↑ autonomic activity:

                                                                                                               i.     ↑ blood pressure

                                                                                                             ii.      ↑ reflexes

                                                                                                            iii.      Fever

c.       Insomnia

d.      Nausea/vomiting

e.       Sweating

f.        Anxiety

B.            Phase II (Slide 13)

1.      Time abstinent: 7-48 hrs

2.      Signs and symptoms:

a.        Distractibility

b.      Autonomic instability (↑↓heart rate, ↑↓ blood pressure)

c.       Grand mal seizures

3.      5-10% lifetime risk of seizures

C.           Phase III (Slide 14)

1.      Time abstinent: 72-96 hrs

2.      Only in < 5%

3.      Symptoms: (Delirium+ severe autonomic instability + tremor = delirium tremens or DT)

a.          Confusion/disorientation

b.         Severe autonomic instability

c.          Auditory/tactile hallucinations

d.         Agitation

4.      Mortality rate ~ 1 %[18]

(Slide 15)

IV.      ALCOHOL WITHDRAWAL ASSESSMENT

A.       History/Interview: (Slide 16)

1.      Duration of use

Chronic use (weeks, months) à↑ risk of withdrawal

2.      Quantity, frequency and drinking pattern

a.                   > 5-6 drinks/ day

b.                  Daily or almost daily use

c.                   Age of first use, periods of heaviest use,  periods of abstinence

3.      Time since last drink (~6+ hours)

4.      Severity of previous withdrawals (e.g. seizures  or DTs)

5.      Concurrent medical/psychiatric problems

6.      Social /domestic/emotional/occupational problems

B.       History/Screening tools: (Slide 17)

1.      Alcohol Use Disorders Identification Test (AUDIT)

a.   10 items scale

b.     Can be self administered

c.       Assesses: frequency, quantity, lack of control, guilt, blackouts etc.

d.      Sensitivity: 90%;  Specificity: 85% at score of > 8

2.      CAGE  Cut down,  Annoyed,  Guilty, Eye opener

a.          Very brief

b.         2 or > + responsesà high likelihood of alcoholism

c.          Sensitivity 85%; Specificity 90%

d.         Not gender sensitive; does not identify recent or episodic use

3.      Michigan Alcohol Screening Test (MAST)

a.          Structured interview

b.         25 questions

c.           Positive answers to 4 + questions suggest alcohol “problem”

C.       Physical exam: (Slide 18)

1.      Focused on identifying withdrawal symptoms (e.g. sweating, tremors, etc.)

2.      Chronic alcohol exposure stigmata:

a. Spider angiomata-superficial spider-like cluster of capillaries,

b.   Palmar erythema- reddening of the palms

c. . Hepatosplenomegaly-↑ liver and spleen

3.      Assessment of  possible complicating medical conditions:

a.  Cardiac arrhythmias (irregular heart rate)

b. Congestive heart failure (secondary to hypertension or cardiomyopathy)

c.  Gastrointestinal bleeding (blood in vomit or stool),

d.   Cancer (esophagus, stomach, head and neck, lungs)

e.  Liver disease (fatty liver, hepatitis, cirrhosis)

f.   Pancreatitis[19] (abdominal pain, ↑ pancreas enzymes  e.g. amylase)

g.  Nervous system impairment:

                                                                                    i.         Central  (confusion, cerebellar damage)

                                                                                  ii.         Peripheral (neuropathy e.g. “pins+ needles” in hands/feet)

D.               Laboratory investigations:[20] (Slide 19)

1.      Blood count:↑ red blood cells size; mean corpuscular volume (MCV) > 100

2.       Liver functions tests (LFTs)

a.       ↑ Aspartate aminotransferase (AST); > 40 u/l

b.       ↑ Alanine aminotransferase (ALT); > 40 u/l

c.        AST/ALT  ratio > 2 e.g. à suggestive of alcoholic liver disease;

3.      ↑ Carbohydrate deficient transferrin (CDT) : high sensitivity and specificity/ good indicator of early relapse: 20U or 2.6 %

4.       ↑ Gamma-glutamyl transferase (GGT):  levels↑ after 70 drinks/week for several weeks; > 35 u/l

5.      Urine/serum toxicology screen: to exclude other drug use

6.      Electrolytes: ↓ Na, ↓Mg à ↑ risk of seizures

7.      Blood alcohol concentration (BAC):

BAC ~ 150 w/o intoxication or ~ 300 w/o somnolenceà  evidence of tolerance à ↑ risk of withdrawal

(Slide 20)

 V. ALCOHOL WITHDRAWAL TREATMENT[21]

A.     General care: (Slide 21)

1.      Multivitamins (MVI): 1 tablet daily

2.      Thiamine: 100 mg daily

3.      Folic acid: 1 mg daily

4.      Fluid repletion if  dehydration evident

B.     Medication regimen- benzodiazepines (BZDs) [22](Slide 22)

1.      First line treatment

2.      BZD are effective to decrease:

a.       Severity of withdrawal

b.      Incidence of delirium

c.       Incidence of seizures

3.      Are 2 types:

a.       Longer acting ( ½ life  ~ 30 hours)

       E.g. diazepam (Valium)

b.      Shorter acting ( ½ life ~15 hours)

      e.g.  lorazepam (Ativan)

4.      Longer acting better at preventing seizures, but  ­ sedation

5.      Two main strategies:

a.       “ Fixed schedule” (Slide 23)

                                                                                       i.      Description:

ü      Specific doses administered  at specific intervals

ü       Additional doses used as needed  based on the severity of symptoms

                                                                                     ii.      Examples:

ü       Lorazepam 2 mg  every 4 hours; 

ü      Diazepam 10-20 mg every 6 hours;

ü      Chlordiazepoxide (Librium) 25-50 mg  every 6 hours

                                                                                    iii.      Tapered gradually over several days

                                                                                   iv.      Problems: over / under- medication ( too difficult to control symptoms)

b.   “Symptom–triggered” (Slide 24)

                                                                                 i.            Description:

ü    Medication given when CIWA-AR >8

ü      Clinical Institute Withdrawal Assessment, Revised (CIWA- Ar) - severity scale 0-7 on the following items: (Slide 25)

·        Nausea, vomiting

·        Tremor

·        Diaphoresis (sweating)

·        Anxiety

·        Agitation

·        Tactile hallucinations (touch)

·        Auditory hallucinations

·        Visual hallucinations

·        Headache

·        Orientation and clouding of sensorium (confusion)

                                                                                     ii.      Examples:

ü      Lorazepam 2 mg q 1 hour  for  CIWA 8-13

ü      Lorazepam  3 mg q 1 hour for CIWA 14-20

ü      Lorazepam 4 mg q 1 hour for CIWA >20

                  iii.   Problems: ­ cost/ staff time

 

C.     Non-pharmacological treatments: (Slide 26)

1.      Reassurance

2.      Reality-orientation techniques (time, place, situation)

3.      Rest/sleep

4.      Adequate nutrition.

                                                            (Slide 27)

VI. ALCOHOL WITHDRAWAL IN SURGICAL AND TRAUMA PATIENTS

A.      Epidemiology (Slide 28)

1.      50-60% prevalence of alcohol abuse/dependence in trauma patients

2.      16% incident of AWS post-surgery vs. 8% in general population[23]

3.      Pre-operative assessment/prophylaxis prevents post-operative AWS complications in 75% of patients

4.      Highest risk of DTs: in 40+ year olds and  s/p fall or burn

B.     Risks

1.      ­ operative and post operative morbidity and mortality[24]

2.      Postoperative morbidity 2-3 X ↑ if  21+ drinks/week[25]

3.      50%  longer hospital stay

4.      Poorer 3 month outcomes: infections, bleeding, cardiopulmonary

C.     Challenges (Slide 29)

1.      During surgery:

a.       Alcohol can ­or ¯sensitivity to anesthesia[26]

b.      Alcohol ↓ coagulation

c.       ↑ risk of  hypoxia and poor BP control

2.      After surgery:

a.       Alcohol ¯ immune functions; surgery ­ immunosuppressionà ­ risk of inflammation/ infection

b.      Alcohol ↑ metabolic acidosis and ↑ surgery stress response[27]

c.       DTs often  confused with[28]

                                                                                 i.            Sepsis

                                                                               ii.            ↓ Circulation to brain

                                                                              iii.            Worsening of closed head injury

d.      Autonomic instability  ( e.g. ↑ or↓ blood pressure) due to alcohol withdrawal à incorrectly attributed  to traumatic injury

e.       Agitation due to withdrawal

                                                                                 i.  Challenges nursing care

                                                                               ii.  Risks displacement of monitors and dressings

f.        Hallucinations àdifficult to assess in intubated patients

D.      Assessment and treatment

1.      History  (Slide 30)

a.    Scheduled surgeries:[29]

                                                                              i.     Good pre-operative assessment to screen for AUDs

                                                                            ii.     Advise abstinence if not at risk of AWS  

                                                                           iii.     Pre-surgical detoxification should be considered if needed

b.   Trauma and emergency surgeries

                                                                              i.      History taking difficult

                                                                            ii.      Collateral informants (family, friends, witnesses) important

                                                                           iii.      Physical exam/ laboratory findings important

2.      Differential diagnosis/common surgical causes of agitation[30]: (Slide 31)

a.          Bleeding,

b.         Metabolic/electrolyte abnormalities

c.          Infection

d.         Pain

3.      Supportive care (Slide 32)

a.          Pain management

b.         Pulmonary toileting

c.          Eliminate unnecessary catheters

d.         Early mobility

4.      Pharmacological treatment[31]

a.       BZDs

b.      Symptom-triggered approach most effective

c.       Dosages generally larger

 

(Slide 33)

iii.                        A

VII.   ALCOHOL WITHDRAWAL IN THE ELDERLY:

A.     Epidemiology    (Slide 34)

1.      11% of elderly in acute medical settings have alcohol abuse or dependence

2.      20% in psychiatric settings

3.      14%  in emergency departments

B.     Risks[32]

1.      Even moderate drinking in the elderly : ↑ disease burden and ↑ risk of complicated withdrawal

2.      Aging affects alcohol levels:[33]

a.                 ↓ body water à↓ volume of distributionà↑ alcohol concentration

b.               ↓ gastric alcohol dehydrogenase à↑ alcohol concentration

3.      Alcohol ↑ risk of  falls leading to  hip fractures/ subdural  hematomas ( bleed under skull) 

4.      Alcohol interacts with many common medications

 

C.     Challenges (Slide 35)

1.      Age aloneà predictor of ↑ withdrawal severity[34]

2.       Early onset drinkersà long useà ↑ probability of prior withdrawalsà ↑ severity of AWS [35]

3.      Functional reserve and tolerance of physiological stressors ↓ with age[36]

4.      ↑ risk  of adverse effects from use of BZDs [37]

a.       Cognitive impairment[38]

b.      Daytime sedation

c.       Falls

D.      Assessment and treatment (Slide 36)

1.       History:

a.       Difficult because:

                                                                                 i.             Patient  ashamed to admit

                                                                               ii.             Family reluctant to share

                                                                              iii.             Physicians not likely to suspect[39]

b.      Clues that should ↑ suspicion of AUD in the elderly:

                                                                              i.               Frequent falls

                                                                            ii.               Bruises

                                                                           iii.               Many ED visits

                                                                          iv.               ↑ blood pressure

                                                                            v.               Depressed mood and suicidal thoughts

                                                                          vi.               Insomnia

2.  Differential diagnosis[40] (Slide 37)

a.       Withdrawal from other substances (e.g.  BZDs, Barbiturates)

b.      Delirium of other causes ( see DTs differential diagnosis described above)

c.       Psychiatric  conditions (anxiety, dementia, psychosis)

3. Supportive treatment (Slide 38)

a.       Safe/ well lit environment

b.      Gentle/empathic/ non-judgmental approach

c.       Hearing aids/glasses as individually indicated

d.      Extremes of sensory input- to be avoided

e.       Sleep/rest/nutrition

4. Pharmacological interventions (Slide 39)

a.     Shorter acting agents (lorazepam, oxazepam)  preferred because:

a.     No active metabolites

b.     ↓ rate of side effects [41]

b.     Symptom-triggered  approach preferred

c.     For some patients (with history of sz and DTs) àfixed schedule preferred Medication  held for sedation

d.     Medication dosages typically lower.

 

(Slide 40)

 

 

 

 

 

 

 

 

 

 

 

 

 

 


 REFERENCES:

 

 

 

 

 

[1] Foster SE, Vaughan RD, Foster WH, Califano JA, Jr. Alcohol Consumption and expenditures for underage drinking and adult excessive drinking. JAMA 2003;289:989-995

[2] Hasin DS, Stinson FS, Ogburn E, Grant BF. Prevalence, correlates, disability and co morbidity of DSM IV alcohol abuse and dependence in the Unites States: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. Archives of General Psychiatry 2007; 64: 830-842

[3] Mayo-Smith MF, Beecher LH, Fischer TL, Gorelick DA, Guillaume JL. Management of Alcohol Withdrawal Delirium  Archives of Internal Medicine 2004;164:1505-1412

[4] Spies CD, Rommelspacher H Alcohol Withdrawal in surgical patients: prevention and treatment; Anesthesia Analg 1999;88:946-54

[5] Gantillelo L, Donovan D, Dunn C, Rivara F. Alcohol interventions in trauma centers: current practice and future directions. JAMA 1995;274:1043-1047

[6]  Blow F. Substance abuse among older adults. Rockville, MD: Substance Abuse and Mental Health Services Administration, Center for Substance Abuse Treatment. Treatment Improvement protocol #26; 1998

[7] American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 4th edition, text revision. Washington DC: American Psychiatric Press Inc.;2000

[8] Schuckit MA, Tipp JE, Reich T, Hesselbrock VM, Bucholz KK: The histories of withdrawal convulsions and delirium tremens in 1648 alcohol dependent subjects.  Addiction 1995;90:1335-1347

[9]  Schuckit MA, Smith TL, Anthenelli RM, Irwin M: Clinical course of alcoholism in 636 male inpatients. American  Journal of Psychiatry 1993;150:786-792

[10]  Fellin DA, O’Connor PG, Holmboe ES, Horwitz RI: Risk for delirium tremens in patients  with alcohol withdrawal syndrome: Substance Abuse 2002;23:83-94

[11]  Palmisterna T: A model for predicting alcohol withdrawal delirium. Psychiatric Services 2001; 52:820-823

[12] Kreamer KL. Mayo-Smith MF, Calkins DR: Independent clinical correlates of severe alcohol withdrawal. Substance abuse 2003; 23: 197-209

[13] Kraemer Kl, Conigliaro J, Saitz R.  Managing alcohol withdrawal in the elderly. Drugs and Aging 1999, 14:409-425

[14] Baldwin WA, Rosenfeld BA, Breslow MJ: Substance abuse-related admissions to adult intensive care. Chest 1993;103:21-25

[15]  Sanna E, Mastallino MC, Busonero F. Changes in GABA (A) receptor gene expression associated with selective alterations in receptor function and pharmacology after alcohol withdrawal. Journal of Neuroscience 2003;23:11711-24

[16] Krystal JH, Staley J, Mason G, Petrakis IL, Kaufman J, Harris PA, Gelernter J, Lappalainen J. Gama-amnibutyric acid type A receptors and alcoholism: intoxication, dependence, vulnerability, and treatment. Archives of General Psychiatry. 2006;63:957-68

[17] Ciraulo D, Shader R. Clinical manual of chemical dependence. 1991.Chapter 1; 37-38

[18] Schuckit MA, Tipp JE, Reich T, Hesselbrock VM, Bucholz KK. The histories of withdrawal convulsions and delirium tremens in 1648 alcohol dependent subjects. Addiction 1995; 90:1335-1347

[19] Bayard M, McIntyre J, Hill KR, Woodside J.Jr: Alcohol withdrawal syndrome. American Family Physician 2004;69:1443-50

[20] Allen JP, Sillanauke P, Strid N, Litten National Institute of Alcohol Abuse and Alcoholism, National Institute of Health Publications. Biomarkers of heavy drinking.

[21] Mayo-Smith MF. Pharmacological management of alcohol withdrawal. JAMA 1997; 278:144-151

[22] McKeon A, Frye MA, Delanty N. The alcohol withdrawal syndrome. Journal of Neurology, Neurosurgery and Psychiatry. 2008; 79;854-862

[23]  Spies CD, Rommelshacher H. Alcohol withdrawal in the surgical patient: prevention and treatment. Anesthesia Analg. 1999;88;946-54

[24] Chang PH, Steinberg MB. Alcohol withdrawal. Medical Clinics of North America. 2001; 85: 1191-1212

[25] Weinberg JA, Magnotti LJ, Fisher PE, Edwards NM, Schroeppel T, Fabian TC, Croce MA. Comparison of intravenous ethanol versus diazepam for alcohol withdrawal prophylaxis in the trauma ICU; results of randomized trial. Journal of Trauma, Injury, Infection, and Critical Care. 2008;64;99-104

[26] Lieber CS, Medical disorders of alcoholism. New England Journal of medicine. 1995;

333:1058

[27] Neyman KM, Gourin GC, Terris DJ. Alcohol withdrawal prophylaxis in patients undergoing surgical treatment for head and neck squamous cell carcinoma. Laryngoscope 2005;115;786-791

[28] Lukan JK, Reed DN, Looney SW, Spain DA, Blondell RD. Risk factors for delirium tremens in trauma patients. The Journal of Trauma, Injury, Infection and Critical Care. 2002; 53:901-906

[29] Up to date on line. Identification and management of alcohol use disorders in the perioperative period.

[30] Spies C, Rommelspacher H, Schaffartzick W. Chronic alcoholics: high risk patients in intensive care units. In Vincent JL, ed. Yearbook of intensive care medicine. Berlin: Springer. 1995; 777-788

[31]  Spies C, Dubisz N, Funk W. Prophylaxis of alcohol withdrawal syndrome in alcohol dependent patients admitted to the intensive care unit following tumor resection. British Journal of Anesthesiology 1995; 75: 734-739

[32] Council on Scientific Affairs, American Medical Association. JAMA. 1996; 275;797-801

[33] Ozdemir V, Fourie J, Busto U, Naranjo CA. Pharmacokinetic changes in the elderly. Do they contribute to drug abuse and dependence? Clinical Pharmacokinetics. 1996; 31: 372-385

[34] Myrick H, Anton RF. Treatment of alcohol withdrawal. Alcohol Health and Research World 1998; 22:38(6)

[35]  Lechtenberg R, Worner TM. Relative kindling effects of detoxification and nondetoxification admissions in alcoholics. Alcohol. 1991;26:221-225

[36]Lamont CT, Sampson S, Matthias R, Kane R. The outcome of hospitalization for acute illness in the elderly.   Journal of American Geriatrics Society. 1983;31;282-288

[37] Kraemer, KL, Mayo-Smith MF, Calkins R. Impact of age on the severity, course, and complications of alcohol withdrawal. Archives of Internal Medicine. 1997;157:2234-2241

[38] Ozdemir V, Fourie J, Busto U, Naranjo CA. Pharmacokinetic changes in the elderly. Do they contribute to drug abuse and dependence. Clinical Pharmaokinetics.1996. 31;5:372-385

[39] Rehmar MI. Sensitizing practitioners, families and elderly persons. Pride Inst. J. Long-Term Home Health Care. 1988; 7:22-29

[40] Rummans TA, Evans JM, Krahn LE, Fleming KC. Delirium in elderly patients: evaluation and management Mayo Clinic Proceedings. 1995;70:989-998

[41] Kraemer KL, Conigliaro J, Saitz R. Managing alcohol withdrawal in the elderly. Drugs and Aging. 1999;14:409-425