1. Managing Alcohol and Opioid Withdrawals
Shyam Rao, MD
Chief resident
Adapted From:
Pouneh Nasseri MD

2. Goals of lecture Understand alcohol withdrawal physiology
Recognize alcohol withdrawal and management of withdrawal in patient setting
Management and recognition of inpatient opioid withdrawal
Treatment of cocaine withdrawal

3. Common Presentation
55 year old male presents to the ER with generalized tremors. He is anxious, pacing the hallways and also nauseous. Initial vital signs indicate hypertension and tachycardia. During the interview, he admits to heavy alcohol use and that he is trying to cut down. His last drink was about 6 hours ago.

4. Alcohol use terminology
Standard drink Approximate # of standard drinks in:
Equivalents:

5. Recognizing alcoholism
Terms used: alcohol abuse, alcohol dependence, alcohol use disorder
Typical characteristics
Impaired control over drinking
Preoccupation with alcohol
Use of alcohol despite adverse consequences
Distortions in thinking, most notably denial
Different screening tools:
CAGE
Alcohol use disorder identification Test (AUDIT) or AUDIT-C
AUDIT-10 questions
AUDIT C – 3 questions, designed to be used in a doctor’s office: how many times you have a drink, how many drinks do you have on a typical day, how often do you drink more than 6 drinks
CAGE: eye opener, guilty, need to cut down, annoyed valid screening tool with 75% sensitivity

6. How many drinks are too many?
The National Institute on Alcohol Abuse and Alcoholism (NIAAA) definition:
Men under age 65
More than 14 standard drinks per week on average
More than 4 drinks on any day
Women, adults 65 years and older
More than 7 standard drinks per week on average
More than 3 drinks on any day
amounts of alcohol that increase health risks

7. Alcohol Withdrawal Pathophysiology
ETOH = Depressant
Sudden cessation causes CNS hyperactivity
Enhances inhibitory tone (via modulation of gamma-aminobutyric acid activity)
Inhibits excitatory tone (via modulation of excitatory amino acid activity).
GABA is a inhibitory system in CNS
Chronic ethanol use induces an insensitivity to GABA such that more inhibitor is required to maintain a constant inhibitory tone . As alcohol tolerance develops, the individual retains arousal at concentrations which would normally produce lethargy or even coma.
Ethanol inhibits glutamate binding to the NMDA-receptor which leads to further sedation. When you stop drinking, the excitatory tone increases

8. Alcohol Withdrawal
Gamma aminibutyric acid GABA

9. Alcohol withdrawal symptoms
MINOR WITHDRAWAL SYMPTOMS 
Insomnia
Tremulousness
Mild anxiety
Gastrointestinal upset
Headache
Diaphoresis
Palpitations
Can treat in the outpatient setting
Usually occur 6 hours after the cessation of drinking and should resolve in hours after drinking
A patient will usually experience the same symptoms

10. ETOH Withdrawal and timeline
-seizures (tonic-clonic) occur predominantly in patients with a long history of chronic alcoholism. Usually occur hours after last drink. Can show up from 2 hours and when patient still has ETOH level. Recurrent or prolonged seizures are usually cause for further investigation (think CT scan or LP)
-Alcoholic hallucinosis refers to hallucinations that develop within 12 to 24 hours of abstinence and resolve within 24 to 48 hours .
- Hallucinations are usually visual, although auditory and tactile phenomena may also occur. In contrast to delirium tremens, alcoholic hallucinosis is not associated with global clouding of the sensorium, but with specific hallucinations, and vital signs are usually normal

11. Delirium Tremens
Defined as: Hallucinations, disorientation, altered mental status, tachycardia, hypertension, fever, agitation, and diaphoresis
Can start from hours from last drink
Could last from 1-7 days
Mortality of 5%
-Death usually is due to arrhythmia, complicating illnesses, such as pneumonia, or failure to identify an underlying problem that led to the cessation of alcohol use, such as pancreatitis, hepatitis, or central nervous system injury or infection. Older age, preexisting pulmonary disease, core body temperature greater than 40ºC (104ºF), and coexisting liver disease are associated with a greater risk of mortality

12. Risk factors for Delirium Tremens
History of DT
Age > 30
Longer period of drinking
Multiple medical illness
Significant alcohol withdrawal despite high ETOH level
A longer period since the last drink

13. Management of ETOH Withdrawal
Alleviating symptoms of psychomotor agitation
Volume deficit replacement: Hypovolemic
Correcting metabolic derangements
Electrolyte imbalance : Potassium, Magnesium , Phosphorous
Ketoacidosis
Vitamin deficiencies: Wernicke’s encephalopathy. Give Thiamine with glucose.
Protein calorie malnutrition
Hypovolemic: diaphoresis, hyperthermia, vomiting, and tachypnea
Hypokalemia is common due to renal and extrarenal losses, alterations in aldosterone levels, and changes in potassium distribution across the cell membrane
Hypomagnesemia is common in patients with DT and may predispose to dysrhythmia and seizures
Hypophosphatemia may occur due to malnutrition, may be symptomatic, and if severe, may contribute to cardiac failure and rhabdomyolysis
Wernicke’s encephalopathy: optholmoplegia, ataxia, and confusion, deficiency in thiamine

14. Supportive care
GI absorption can be impaired so using IV in the first 2 days is helpful
Banana bag: D5NS with thiamine, folate, and a multivitamin
If intoxicated and severe withdrawal consider NPO initially to avoid aspiration

15. Treatment of psychomotor agitation CIWA- Ar
Nausea/Vomiting (0-7)
Headache(0-7)
Paroxysmal sweating (0-7)
Anxiety (0-7)
Auditory disturbances (0-7)
Visual disturbances (0-7)
Agitation (0-7)
Tremor (0-7)
Tactile Disturbances (0-7)
Orientation and clouding of sensorium (0-4)
Clinical institute withdrawal assessment for alcohol

16. CIWA-Ar Symptom triggered therapy Start treatment at CIWA score > 8
< 10 : Very Mild withdrawal
10-15: Mild withdrawal
16-20: Modest withdrawal
>20 : severe withdrawal
Start treatment at CIWA score > 8
Clinical Institute Withdrawal Assessment for Alcohol Scale (CIWAS-Ar), a measure of withdrawal severity

17. Benzodiazepines Diazepam (Valium) 5-10 mg IV every 5-10min
Lorazepam (Ativan ) 2-4 mg IV every min
Chlordiazepoxide (Librium) (should be used in PPX)
Should be given IV in modest-severe withdrawal
Dosing: depends on comorbid conditions
Diazepam: longer acting with active matobolites
Lorazepam: shorter acting better with liver disease
Librium should be avoided in all cirrhotic patients
Benzodiazepines act on the GABA receptor which cause sedation
Prefer long acting benzodiazepines preventing the peaks and troughs

18. Prophylaxis Asymptomatic patients who are high risk
Librium taper: 50 to 100 mg POq6hrs for one day and then 25 to 50 mg Q6hrs for 2 days.
Can use Librium for very mild withdrawal in low risk patient mg PO as needed Q1hrs.
Patient’s with a history of seizures or DTs who are admitted to the hospital for other reasons may be give ppx if asymptomatic or mild symptoms

19. Other treatments Ethanol Antipsychotics (such as Haldol)
Anticonvulsants ( such as phenobarbital, Carbamazepine)
Centrally acting alpha-2 (Such as Clonidine)
Beta blockers (Such as Propranolol)
Baclofen
These agents are less well studied than benzodiazepines and may mask the hemodynamic signs of withdrawal, which can precede seizures.
Ethanol: difficult to titrate
Haldol: decreases seizure threshold . Plus prolong QT given all the electrolyte abnormalities
Phenobarb can be used in conjunction with benzos in ICU setting but not alone
Carbamazepine can sometimes be used in mild but not in inpatient settting poor evidence
Clonidine no evidence that helps reduce DT or seizures. Not enough evidence
Beta blocker is the same as alpha. More symptomatic control
Baclofen does bind to GABA but no evidence of controlling severe symptoms

20. ICU Admission Age>40 Cardiac Disease Marked acid-base disturbances
Severe electrolytes abnormalities
Respiratory insufficiency
Signs of gastrointestinal pathology

21. ICU Admission Evidence of rhabdomyolysis and hyperthermia
Prior history of alcohol withdrawal
Evidence of withdrawal with elevated alcohol level
High amounts of sedatives

22. Alcohol Withdrawal
Remains a clinical diagnosis but consider other diagnosis
Spectrum of symptoms with DTs as life threatening
Requires medical treatment and observation
ICU admission may be necessary for some patients
Oral benzodiazepines may be acceptable for asymptomatic or minimally symptomatic

23. Opioid Withdrawal
Signs and symptoms can start within 6-12 hour after short acting opioid and hrs after Methadone
History can help you diagnose.
Severity of symptoms depends on duration, dose of opioid and if there is a iatrogenic withdrawal

24. Opioid withdrawal Natural opioid withdrawal is not life threating
Iatrogenic withdrawal can be dangerous:
reversal agent such as Naloxone or naltrexone can produce sudden surges in catecholamines and hemodynamic instability
Naloxone opoioid anatagonist

25. Opioid withdrawal

27. Opioid withdrawal Opioid agonist therapy: if they missed a dose or two
Methadone:
10 mg IM or Methadone 20 mg PO if they can tolerate PO
Buprenorphine
Methadone: long acting opioid agonist
Buprenorphine: partial agonist (both opioid and antagonist effects)
May produce withdrawal symptoms in patient that is misdiagnosed and also no well-established safe empiric dose, and has a strong affinity to

28. Opioid withdrawal Non-opioid adjunctive medications
Alpha 2 antagonist Clonidine: 0.1 to 0.3 mg every hour as needed
Benzodiazepine: Diazepam mg IV q5-15min PRN
Phenegran: 25 mg IV or PO
Loperamide
Octerotide
-be aware that for iatrogenic opioid withdrawal you must use adjunctive medications
- Binds to a central alpha 2 adrenergic receptor that shares potassium channels with opioids, and blunts symptoms of withdrawal. Look for hypotension
-Benzos: GABAergic drugs reduce catecholamine release during severe withdrawal. helpful in suppressing muscle cramps.
Clonidine for anxiety and restlessness
Octreotide: for stomach cramps and diarrhea -

29. Cocaine Allow the patient to sleep and eat
Bromocriptine and amantadine are theoretically supposed to work
Propanolol: may aggravate coronary vasoconstriction
Lorazepam for supportive care
Bromocriptine and amantadine for dopamine deficiency state of coacaine withdrawal
Propanolol for symptom control but also remember if patient is hypertensive you don’t want to go with beta blocker. Even selective beta 1 antagonists such as esmolol and metoprolol have been associated with paradoxical hypertension.

30. Question
A 39-year-old man is admitted to the hospital for new-onset agitation, fluctuating level of consciousness, and tremors. He is diagnosed with acute alcoholic hepatitis.
On physical examination, temperature is 38.8 °C (101.8 °F), blood pressure is 95/55 mm Hg, pulse rate is 130/min, and respiration rate is 30/min. Jaundice is noted. The abdomen is protuberant with ascites but is soft, with no abdominal rigidity or guarding. There is no blood in the stool. The patient is agitated and disoriented, is unable to maintain attention, and appears to be having visual hallucinations. He believes that the nurse has stolen his wallet (which is in his bedside drawer) in order to obtain his identity. He is diaphoretic and tremulous. Asterixis is absent, and the remainder of the neurologic examination is normal.

31. A) Ceftriaxone
B) CT of head
C)Haldol
D) Lactulose enema
E) Lorazepam

32. 72 yo female with a history pancreatic cancer is admitted for worsening abdominal pain. She is chronic opioids including methadone for pain control. During this admission the patient’s pain regimen was changed and dosage increased. Overnight, the patient became somnolent with respiratory depression and narcan was given. What is the best approach to deal with the patient’s symptoms?

33. Summary
Inpatient alcohol and drug withdrawal should be taken seriously and may be life threatening
Benzodiazepines are commonly used medications for alcohol withdrawal for supportive care
Iatrogenic opioid withdrawal may be life threatening
Opioids and other adjunctive therapy may be used for opioid withdrawal