According to a Report Issued by the Office of National Drug Control Policy Released In

Attending Version

Drug Addiction, Withdrawal, and Overdoses

Created by Dr. Simson and Dr. Davis

Objectives:

1. Recognize the cost of drug abuse.

2. List two signs and symptoms of opiate and benzodiazepine withdrawal.

3. List four complications of cocaine overdose and their management.

References:

1. Palepu A, Tyndall MW, Leon H, et al.Hospital utilization costs in a cohort of injection drug users. Can Med Assoc J 2001; 165(4):415-20.

2. Adolescent Abuse of Other Drugs Adolescent Medicine Clinics - Volume 17, Issue 2 (June 2006)

Kosten TR, O'Connor PG: Management of drug and alcohol withdrawal. N Engl J Med 2003 May 1; 348(18): 1786-95

Use of this content is subject to the Terms and Conditions

3. Nephrotoxicity of over-the-counter analgesics, natural medicines, and illicit drugs Adolescent Medicine Clinics - Volume 16, Issue 1 (February 2005)
4. HaimD.Y., LippmannM.L.,GoldbergS.K.,et al. The pulmonary complications of crack cocaine: a comprehensive review. Chest (1995) 107 : pp 233-240

5. Robinson M.,Turnipseed S.,Glatter K.:Methamphetamine-associated caridoyopathy: A previously unrecognized cause of heart failure. American Heart Association Annual Scientific Sessions, 2004.

Use of this content is subject to the Terms and Conditions

6. The Association of Methamphetamine Use and Cardiomyopathy in Young Patients
The American Journal of Medicine - Volume 120, Issue 2 (February 2007)
7. Cerebrovascular and Cardiovascular Complications of Alcohol and Sympathomimetic Drug Abuse
8. Medical Clinics of North America - Volume 89, Issue 6 (November 2005).
9. Warren, JD, Blumbergs, PC, Thompson, PD. Rhabdomyolysis: a review. Muscle Nerve 2002; 25:332.

Discussion Outline:

• According to a report issued by the Office of National Drug Control policy released in 2002, the cost of drug abuse (not including alcohol or tobacco) was $180 billion dollars in 2002. Approximately 10% of this was related specifically to direct medical costs. The remainder was societal costs related to loss of productivity (50%) and criminal losses or damage (40%).
• The medical complications of drug abuse are varied and depend in large part on the type of drug and route of administration.

This module will present an overview of the spectrum of complications focusing on non-infectious complications. It is by no means exhaustive.

1.Overview of Addiction and withdrawal

According to DSM-IV addiction is characterized by 3 phases – anticipation, intoxication and withdrawal. This provides a psychological as well as physiologic dependence on the substance. Drugs typically associated with addiction/withdrawal are: benzodiazepines, opiates, stimulants (cocaine, methamphetamines), alcohol, and tobacco. Acute withdrawal syndromes requiring medical intervention are possible with most of these substances, but this module will focus primarily on opiates and benzodiazepines.

A. Opiates

• Dependence usually develops with three weeks of daily usage.
• Highly lipophilic drugs (e.g. heroine) which cross the blood brain barrier the easiest have the highest potential for development of dependence.
• Withdrawal usually begins within 1 half-life of the last dose and is characterized initially by anxiety, restlessness, insomnia, yawning, rhinorrhea, lacrimation, diaphoresis, and stomach cramps. This is followed by muscle spasms, vomiting, diarrhea, hypertension, tachycardia, fever, chills, and piloerection.
• Acute opiate withdrawal is rarely life threatening, but can complicate management of coexisting medical conditions.

Management of opiate withdrawal

1. Methadone: typically not administered in an acute setting, unless the patient is on a maintenance program in which case the patient’s usual dose of methadone can be administered.

2. Buprenorphine: a partial agonist, may be administered in typical starting doses of 4 to 8 mg. This can be administered in an acute setting, even if the patient is not in a treatment program, if the patient’s withdrawal will complicate management of coexisting medical problems during a hospitalization.

3. Clonidine: reduces catecholamine release and may be used to reduce symptoms in patients who take low doses of opiates.

All of these may be supplemented by antiemetics, anxiolytics, or NSAIDS to treat specific withdrawal symptoms.

B. Benzodiazepines

• Withdrawal symptoms are usually evident on discontinuation of medications after 6 weeks of steady usage.
• 27 to 45% of patients who are taken off benzodiazepines develop significant withdrawal symptoms causing them to seek medical attention.
• Withdrawal symptoms range from tremors, anxiety, and panic attacks, to muscle cramps, delusions, hallucinations and seizures. They are similar to symptoms seen with alcohol withdrawal.
• Withdrawal may be precipitated by administration of flumazenil.

Management of Benzodiazepine withdrawal

• Supportive treatment is similar to the treatment for alcohol withdrawal, though the syndrome may last longer and take up to 2 to 3 weeks of tapering benzodiazepine doses to resolve.

2. Overdose

Overdoses are characterized by the expected effects of the drug exaggerated by dose or route of ingestion resulting in potentially deadly consequences. The US Centers for Disease Control reported there were over 19,000 deaths from drug overdoses in 2004. This represents accidental overdoses only, not those ruled to be suicides. Any drug can be taken in excess and result in harm. This module will focus on the most common recreational drug overdoses requiring medical attention:

A. Cocaine

• The classic signs of cocaine overdose are: tachycardia, hypertension, tachypnea, irritability, hyperthermia, agitation, confusion, arrhythmias, and chest discomfort.
• Labs/diagnostic tests: ECG, CPK, Troponin, Chem-10, LFTs, UA, chest x-ray.
• Acutely cocaine overdose can cause MI and cocaine use is associated with development of early coronary artery disease. 25% of nonfatal MIs in patients 18 to 45 are attributable to cocaine.

Treatment

• Generally the treatment of cocaine intoxication is supportive.

1. Sedation:

• Administration of benzodiazepines (diazepam, 10 mg IV q 5 min until the patient is sedated) may help to sedate the patient.

2. Hypertension:

• In patients with hypertension beta-blockers are contraindicated. Labetolol has not been shown to be effective. Again, sedation with benzodiazepines may be helpful.
• Nitroglycerine or nitroprusside may be used. The drug of choice is phentolamine – 1 to 5 mg IV, reassessed every 5 minutes.
• Blood pressure may generally be titrated back into the normal range if the patient does not have a history of HTN.

3. Chest pain:

• For patients with chest pain sedation is indicated.
• Aspirin is useful since cocaine promotes platelet aggregation.
• Nitrates are indicated.
• Phentolamine, 1 mg slow IVP may be given, monitoring the patient’s BP closely. This may be repeated as long as the blood pressure remains stable.

4. Arrhythmias:

• Arrhythmias secondary to cocaine intoxication may be either atrial or ventricular.
• Atrial arrhythmias are treated with sedation and calcium channel blockers can be considered.
• Ventricular arrhythmias are best treated initially with sodium bicarbonate 1 to 2 meq/kG, while closely monitoring the rhythm. If sodium bicarb and sedation do not resolve a wide complex arrhythmia, lidocaine can be considered, though it may lower seizure threshold and should only be given after a patient has received benzodiazepines.

5. Hyperthermia:

• Cocaine induced hyperthermia should be treated with aggressive fluid hydration, sedation, and external cooling.
• If adequate cooling is not possible with these measures, neuromuscular blockade and intubation are indicated.

6. Fluid status:

• Most patients with cocaine intoxication are salt and water depleted so crystalloid infusion is usually indicated.

B. Amphetamines

• The toxic effects of amphetamines are nearly identical to cocaine.

Treatment

• Follows the same guidelines as cocaine, though the duration of toxicity with amphetamines tends to be longer.

C. Opiates

• The predominate cause of morbidity and mortality from opiate intoxication is respiratory compromise – either by direct respiratory compromise or through aspiration secondary to altered mental status.
• The primary role in treating opiate overdose is to protect the airway and maintain ventilation.
• Patients who have recently started or restarted opiates (tolerance is lost after about 1 week of abstinence) are at high risk for intoxication. Also, patients who have a history of “skin popping” who are provided with IV access, such as when hospitalized are at higher risk.
• Labs/Diagnostic tests: Glucose, Chemistry, ABG, CXR, CPK

Treatment

• The primary focus should be on maintaining ventilation.
• Naloxone 0.1 to 0.4 mg can be administered every 1 to 2 minutes. If the patient responds, repeat doses may be required.
• Naloxone has a half life of 20 to 60 minutes. So, intoxication with longer acting opiates may require multiple doses of naloxone, or possibly a naloxone drip.
• Typically a drip can be instituted at 2/3 of the initial effective dose of naloxone given hourly as a continuous infusion.

D. Benzodiazepines

• As with opiates the predominate feature of benzodiazepine intoxication requiring medical intervention is respiratory depression.
• Prolonged intoxication may lead to immobility predisposing the patient to rhabdomyolysis.

Treatment

• Aimed at maintaining the patient’s airway and ventilation.
• Reversal of intoxication with flumazenil is usually not indicated since this may precipitate acute benzodiazepine withdrawal and seizures.

CASE

You are called to see Mr. G., a 47 yo male who is brought to the ED by ambulance. The EMT’s went to his home after his sister called 911. He was found in his bedroom by his sister who asked a friend to take her to his house when he had not answered his phone for about 8 hrs. He was intubated and suctioned in the field and received IV thiamine, glucose, normal saline, narcan and oxygen. The EMT notes say he was unresponsive, cyanotic with shallow, infrequent respirations, barely palpable pulse with bile emesis on his chest. He awoke somewhat after the medications, became combative, and was restrained. No injection paraphernalia was found at the home.

His sister says that he was jailed for 10 days in Santa Fe after being arrested there on a warrant issued for outstanding speeding tickets. They had released him the night before and he had taken a bus home to Belen. He told her he was going to get a friend to take him back to Santa Fe to get his impounded truck so he could return to work and would call her when he got back. She came by when he did not return her calls. When she discovered him in bed she gave him nasal Narcan after calling 911 but was afraid to do rescue breathing.

PHM:

1. IV heroin dependency from age 16 to 32.

2. Methadone maintenance beginning age 32 until present; dose about 130mg/d. None for about 2 weeks.

3. Chronic hepatitis C; genotype 2; treated with 24 weeks of interferon and ribavarin at age 42 with undetectable antigen since then. Annual CEA’s normal.

4. Hepatitis B

MEDS: 13 empty methadone bottles correctly labeled from local methadone clinic in medicine cabinet at 130mg daily dose. Last dated bottle is day after recent arrest. Only other meds were typical OTC’s and no empty Tylenol or ASA bottles.

SH: Divorced. Lives alone and shares custody of 3 kids ages 16,17,19. Technical welder earning $42,000 last year. Hobbies: fishing, stainless steel art fabrication.Smokes ½ ppd x 30 yr. Drank ~6 pack of beer daily from ages 22-36 and then none since

FMH: Brother and 2 cousins died of heroin overdoses. Father with stable CAD and DM.

Mother in remission from breast CA x 8 yrs. Sister’s son with ADHD and her daughter smokes heroin and marijuana.

PE:

BP 138/92 P122 RR 20 T 96.8 rectal O2 100% on rebreather attached to ET tube

IV with D5NS at 125cc/hr running well in rt forearm

General: Muscular male, agitated, in restraints, intubated and breathing well on own. Does respond to commands appropriately.

HEENT: pupils 2mm, EOM’s appear intact without nystagmus, ET tube in mouth well secured. No blood in mouth. TM’s obscured by cerumen. Supple neck, no adenopathy or thyroid felt.

Lung: coarse rhonchi; decreased sounds rt base

Cor: regular tachy no m/r/g. Nl JVP supine. Periph pulses 2+ symmetrical, no edema or cyanosis

Abd: liver felt at rt costal margin; firm but not hard. No bruits or ascites. Lap choly scars.

Genit: nl uncirc male phallus. Nl scrotum. Neg OB on rectal

Ext: extensive tattoos on arms and calves, all old. Antecubital scarring bilat.

Neuro: agitated; follows commands mostly; moves all 4’s with 5/5 strength; DTR’s seem ¾. No clonus. Toes downgoing. Unable to see fundi due to meiosis.

LAB:

WBC 12.8 with nl diff and indices Hgb 14 Hct 42 plts 344K

Na 142 K 5.6 CL 102 CO2 12 BUN 67 CR 6.4 Glu 155 Ca 8.0 PO4 6.6

CK 24,000 97%MM

TP 7.0 alb 3.6 AST 72 ALT 84 LDH 650 GGT 87 AlkP 45

INR 1.1 PTT 28 ammonia 22

UA dark red ; SG 1.030 +ketones, tr blood, +myoglobin ; no WBC, no Bact

Tox screen: pos methadone, opiates; neg cocaine, THC, amphetamines, alcohol, PCP, benzodiazepines, barbiturates, TCA, salicylates, acetaminophen

Portable CXR: atalectasis rt base; Ghon complex lt hilum; nl cardiac shadow; metallic piece in rt neck consistent with needle.

What are the working diagnoses and explanations for the metabolic abnormalities?

mixed opioid overdose, probably heroin+methadone

rhabdomyolysis due to coma and immobility

acute renal failure due to #2 and hypotension from #1.

possible aspiration pneumonia

Inactive pulmonary TB

Hepatitis B by hx

Treated Hepatitis C, in remission by hx

needle “foreign body” from old neck injection, asymptomatic

How would you treat the patient?

Saline/mannitol diuresis following creatinine and other chemistries closely

repeat IV Narcan ; may need several more doses over several hours to completely reverse the effects of the methadone

Follow CXR and exams for possible Dx/Tx of aspiration pneumonia

Hospital course: The patient awakens completely with the 3rd Narcan dose and extubates himself. His creatinine drops quickly to 2.0 over 2 days and his other metabolic abnormalities improve as well. He tells you that when he got home from jail he had only 1 dose of methadone left and took it because he was still “pretty sick” from his acute withdrawal. The “friend” who came over to take him to pick up his truck was a previous injecting partner and gave him some heroin to inject since he seemed so ill. The next thing he remembers were the EMT’s at his house.

What happened?

While in jail the patient lost his opioid tolerance. Even after years of methadone maintenance, methadone tolerance is lost within a week. Consequently, his usual daily dose was toxic especially mixed with a short-acting opioid like heroin. The combination caused acute respiratory depression as well as a prolonged coma-like state leading to rhabdomyolysis. IVDU’s are more likely to die of overdoses when (1) they are naïve and just beginning to use needles and (2) they are chronic users who restart at their previous “dose” after an acute “detox” when hospitalized or jailed. This is the major reason that patients who are on methadone or buprenorphine for chronic opioid replacement therapy should continue their medication throughout the hospitalization or incarceration.

Review Questions:

1. A 48-year-old white man arrives at the emergency department obtunded. He is accompanied by his wife, who states, “He took a lot of pills, trying to hurt himself.” She also reports that he drinks a pint of whiskey every day and more on the weekends and that he has prescription pain pills for chronic back pain. The patient is taken to an examination room; a brief clinical assessment reveals a patent and protected airway. The patient has pinpoint pupils.

Which of the following medications is NOT appropriate for this patient?

A. 25 g of 50% dextrose

B. 100mg of vitamin B1 (thiamine)

C. Nalaxone, 0.2 to 0.4 mg

D. Flumazenil

Answer: D

Poisoning or drug overdose depresses the sensorium; symptoms may range from stupor or obtundation to unresponsive coma. All patients with a depressed sensorium should be evaluated for hypoglycemia because many drugs and poisons can directly reduce or contribute to the reduction of blood glucose levels. A fingerstick blood glucose test and bedside assessment should be performed immediately; if such testing and assessment are impractical, in intravenous bolus of 25 g of 50% dextrose in water should be administered empirically before the laboratory report arrives. For alcoholic or malnourished persons, who may have vitamin deficiencies, 50 to 100 mg of viatmin B1 (thiamine) should be administered I.V. or I.M. to prevent the development of Wernicke syndrome. If signs of recent opioid use (e.g., suspicious-looking pill bottles or I.V. drug paraphernalia) are in evidence or if the patient has clinical manifestations of excessive opioid effect (e.g., miosis or respiratory depression), the administration of naloxone may have both therapeutic and diagnostic value. Flumazenil, a short-acting, specific benzodiazepine antagonist with no intrinsic agonist effects, can rapidly reverse coma caused by diazepam and other benzodiazepines. However, it has not found a place in the routine management of unconscious patients with drug overdose, because it has the potential to cause seizures in patients who are chronically consuming large quantities of benzodiazepines or who have ingested an acute overdose of benzodiazepines and tricyclic antidepressant or other potentially convulsant drug.

2. A 33-year-old man who suffers from depression and chronic pain attempts suicide by overdosing on the collection of pain killers he has accumulated from multiple physicians. He is in the emergency department with stupor, pinpoint pupils, and hypotension.

Which of the following tests should you order for this patient?

A. Electrocardiogram

B.Benzodiazepine level

C.Acetaminophen level

D. Aspirin level

E. Electrocardiogram, acetaminophen level, and aspirin level

Answer: E

Prescription narcotic pain killer are often compounded with either aspirin or acetaminophen. Early recognition and treatment of toxic levels of either of these are critical to preventing subsequent metabolic acidosis (aspirin) or hepatic injury (acetaminophen). This patient, who has had multiple physicians and has been diagnosed with depression, may also have ingested tricyclic antidepressants. Electrocardiographic abnormalities, including widening of the QRS interval, prolongation of the QT interval, and right axis deviation of the terminal 40 msec of the QRS complex, may provide early clues to this potentially lethal ingestion. Although this patient is at risk for having a coexistent benzodiazepine ingestion, management is limited to supportive measures, so there is no clinical utility to checking a serum level. If he has or is suspected of having also ingested tricyclic antidepressants, use of flumazenil is contraindicated because of the risk of seizures.

Post Module Evaluation

Please place completed evaluation in an interdepartmental mail envelope and address to Dr. Wendy Gerstein, Department of Medicine, VAMC (111).

1) Topic of module:______

2) On a scale of 1-5, how effective was this module for learning this topic? ______

(1= not effective at all, 5 = extremely effective)

3) Were there any obvious errors, confusing data, or omissions? Please list/comment below:

______

4) Was the attending involved in the teaching of this module? Yes/no (please circle).

5) Please provide any further comments/feedback about this module, or the inpatient curriculum in general:

6) Please circle one:

Attending Resident (R2/R3)Intern Medical student