ABCs, check gag reflex.
For patients with no obvious intoxication: obtain IV access, draw electrolytes, obtain rapid fingerstick glucose, and send urine toxicology screen. Consider ABG (if necessary to look for carbon monoxide, you must order this specifically).
Give isotonic fluid if hypotensive, but with caution (narcotics and naloxone can promote pulmonary edema).
If comatose with pinpoint pupils and decreased respirations, give 1-2 mg naloxone IV.

2. Clinical evaluation:

· History and physical.

· ECG and labs.

3. Elimination of ingested poison from GI tract: may not be useful if more than one hour after ingestion unless drug decreases gastric motility. If timing is in doubt, proceed with gastric emptying (depends on substance—call poison control).

Gastric lavage: for pill fragments, large bore 36 french Ewald tube guarding airway, intubate if obtunded.
Activated charcoal: 50 g in slurry.
Always weigh the risk of aspiration with the benefit of gastric lavage or charcoal.

4. Elimination of absorbed substances:

· Forced diuresis.

· Alkalinization (0.5 to 1 mg/kg/L) for TCA arrhythmias, salicylates, barbiturates, phenylbutazone.

· Hemodialysis for drugs including carbamazepine, digitoxin, ethylene glycol, lithium, methanol, phenobarbitol, salicylate, theophylline, and valproic acid.

ACETAMINOPHEN OVERDOSE

1. Mechanism: acetaminophen is mainly metabolized by glucuronidation and sulfation, with only a small fraction metabolized by the liver p450 oxidase system to a highly toxic reactive intermediate, which is normally detoxified by conjugation with glutathione (GSH) for renal excretion. Excess acetominophen depletes hepatocellular GSH supply, and reactive intermediates damage hepatocytes. Acetylcysteine acts as a GSH substrate.

2. Toxic dose is 140 mg/kg; blood level > 140 mcg/cc after 4 hours is toxic (obtain nomogram or call poison control). Toxicity is worsened by starvation (low GSH) and alcohol (activated p450 creates more toxic metabolites) and may also occur with chronic use—as little as 1 g q4-6 hours for 1-2 days with excess alcohol. Chronic users of anticonvulsants are also at increased risk.

3. Symptoms/signs:

· 2-4 hours: nausea, vomiting, diaphoresis, pallor.

· 24-48 hours: right upper quadrant abdominal pain, jaundice, clotting abnormalities, AST rise followed by ALT rise.

4. Work-up: check acetaminophen levels and check toxicology screen for co–ingestions (salicylate levels must be specifically requested).

5. Treatment:

Insert nasogastric (NG) tube and lavage with two liters normal saline (useful only within first 1-2 hours after ingestion). Gastric lavage is rarely done these days.
Activated charcoal, 1 g/kg PO or via NG tube. Typicall one dose for ingestions within the past 3-4 hours.
Give acetylcysteine if the patient has any chance of having toxic levels of acetaminophen.

- May give simultaneously with charcoal.

- Dose is 140 mg/kg PO, then 70 mg/kg PO q4h thereafter; can also give IV if unable to tolerate oral dose, though not approved in this country (consult poison control for recommended duration and IV use).

- Best if given within 8-10 hours of ingestion, but start treatment for any toxic level. Usual length of therapy is 72 hours (17 doses).

- One observational study suggested that acetaminophen could be stopped at 36 hours in patients with no evidence of hepatotoxicity (AST or ALT < 1000 IU/L) up to that point in time.

Vigorous antiemesis if taking acetylcysteine po (treat patient as if receiving chemotherapy). Re-dose if patient vomits within an hour of dosing.

6. Monitoring: follow acetaminophen levels, liver function tests, and PT/PTT q 12-24 hours for 3-4 days.

7. Evaluate potential need for liver transplant: criteria include pH < 7.3, creatinine > 3.4, INR > 6.5, or rapidly rising AST.

Woo OF, Mueller PD, Olson KR, Anderson IB, Kim SY. Shorter duration of oral N-acetylcysteine therapy for acute acetaminophen overdose. Ann Emerg Med. 2000 Apr;35(4):363-8.

SALICYLATE OVERDOSE

1. Initial management: check salicylate level and check tox screen for co–ingestions. Determine whether salicylate was regular or enteric–coated (affects pharmacokinetics).

· Acute ingestion of < 150 mg/kg = mildly toxic, 150-300 mg/kg = moderate toxicity, > 300 mg/kg = severe toxicity. Blood levels 6 hours after ingestion predict severity of intoxication. Estimate severity of OD by blood levels is invalid in ECASA (enteric coated aspirin) and chronic OD. Plasma half-life 2-3 hours, 20-36 hours following OD.

Chronic ingestion of >100 mg/kg/day over several days is associated with approximately 25% mortality. Use pH and bicarb levels to predict severity of chronic OD.

2. Symptoms/signs: hyperventilation with primary respiratory alkalosis, metabolic acidosis, tinnitus, nausea, vomiting, tachycardia, fever, lethargy, confusion, seizures, cerebral and pulmonary edema (the latter two more common in chronic OD, elderly, smokers)

3. Treatment:

· Call poison control. Check CBC, electrolytes, BUN, creatinine, glucose, PT/PTT, and ABG.

· Insert nasogastric tube, lavage with 2 liters saline.

· Monitor ABGs.

· Intubate for respiratory depression or pulmonary edema if indicated.

· Activated charcoal, 1 g/kg po/per NGT (consult poison control regarding the use of multiple doses of activated charcoal).

· Alkaline urine with IVF: ½ NS & 2 amp NaHCO₃/L at 10–15 cc/kg/hour until urine output good, then D5W + (1–4 amps) NaHCO₃/L & 20–40 mEq KCl/L at 1–3 x maintenance requirement. Check urine pH (goal 7-8) and serum potassium. Be less aggressive with fluids in the elderly (increased risk of pulmonary edema).

· External cooling if febrile (no acetaminophen!).

· Hemodialysis indicated if level >130 mg/dl 6 hours after ingestion, refractory acidosis, persistent CNS symptoms, and renal failure. Useful in chronic intox at levels £ 40 mg/dl.

· Follow salicylate level every 4-8 hours until falling. If not falling, repeat NG lavage and bowel irrigation to rule out concretions or ECASA.

· Correct clotting abnormalities if present with FFP or Vitamin K.

· Plasma half-life 2-3 hours, 20-36 hours following OD.

TRICYCLIC ANTIDEPRESSANT OVERDOSE

1. Symptoms/signs: (may take up to 6 hours) anticholinergic; Hot as a Hare (fever), Dry as a Bone (dry mouth, eyes, urine and stool retention), Mad as a Hatter (agitation, seizures, confusion, stupor, coma) Red as a Beet (flushing and vasodilation), Blind as a Bat (mydriasis).

2. Other signs: cardiac (quinidine-like effects, alpha blocking effects, and anticholinergic): HTN, tachycardia, arrhythmia including SVT, VT, AV block, IVCD, bradycardia with resultant hypotension and pulmonary edema

3. Laboratory: levels are not clinically useful in the overdose and should never be sent.

4. Treatment:

· If AMS: Thiamine, Naloxone, rapid glucose measurement, intubate, monitor.

· NGT, lavage with 2 liters NS. Charcoal 50-75 g x 1. Ipecac contraindicated due to aspiration risk with obtundation.

· Alkalinize blood (pH 7.45-7.55). TCAs bind protein in alkaline pH. Bolus with 1 or more amps of NaHCO₃ IV push for widening QRS or arrhythmias. Hyperventilate if intubated. Follow ABGs and urine pH. Alkalinization does not reverse CNS complications.

· Beware QRS on ECG >0.10 seconds; VT, VF, myocardial depression can ensue.

· Do not use class IAs (quinidine, procainamide) if VT occurs (TCAs are quinidine like). Instead use lidocaine or dilantin to counter ventricular arrhythmias. No Beta blockade for arrhythmias. Pace if Type II second degree or third degree heart block occurs. IV fluids and norepinephrine for hypotension are preferred over dopamine and dobutamine.

· CNS complications: control and prevent seizures (acidosis worsens toxicity). Intubate and monitor if obtunded.

· Half life 25-30 hours, but can be longer in OD. Hemodialysis is not useful in general.

· ICU if altered mental status, respiratory depression, hypotension, arrhythmias, prolonged QT, wide QRS, or seizures. Note: 25% of deaths from TCA overdose occur in patients initially presenting with normal sinus rhythm and clear level of consciousness.

BETA BLOCKER OVERDOSE

1. Symptoms/signs: hypotension, nausea, vomiting, diarrhea, bradycardia, congestive heart failure, CNS depression, seizures, coma (especially with propanolol), bronchospasm, hyperkalemia, hypoglycemia, and metabolic acidosis.

2. Work-up: blood levels often are not helpful. Obtain serum glucose and electrolytes. Obtain ECG: bradycardia, AV block, prolonged QRS, asystole. Sotalol overdose can present with torsades, VF, and/or VT.

3. Treatment:

· Gastric lavage if within 1-2 hours of ingestion (caution: NG tube can increase vagal tone).

· Activated charcoal 50 g via NG tube. Consider multiple doses if ingested beta blocker is a sustained release preparation. Avoid cathartics (sorbitol) after first dose of charcoal (diarrhea = vagal tone).

· Do not induce emesis with risk of seizures.

· Calcium gluconate or carbonate 10% at 0.2 ml/kg over 10 minutes (watch for hypotension).

· Treat bradycardia or heart block with atropine (0.5-2 mg IV), isoproterenol (2-20 ug/min by IV infusion, titrated to HR), or external cardiac pacemaker.

· If above not working, Glucagon 5-10 mg over one minute initial dose, then drip of 1-5 mg/hour in 5% dextrose (glucagon is an inotropic agent that acts at a different receptor); it can cause emesis.

· Use lidocaine, magnesium, and overdrive pacing for sotalol poisoning.

· Beta agonists and theophylline for bronchospasm.

· IV benzodiazapines for seizures.

G-HYDROXYBUTYRATE (GHB) OVERDOSE

1. Initial clues: history of ingestion from friends or witnesses (group parties); check coingestions

2. Symptoms/signs: bradycardia, hypotension, coingestion of ETOH (30%) or other substances (25%), mild hypothermia, respiratory acidosis, unconsciousness (GCS typically below 8), vomiting and myoclonic movements with emergence and recovery. Patients generally continue to breathe despite deep coma.

3. Treatment: Recovery is typically within 2 to 4 hours, occurs spontaneously and correlates with the presenting GCS (lower = longer), usually does not require intubation unless there is a significant co-ingestion or inability to protect the airway.

CARBON MONOXIDE INHALATION

1. Mechanism: carbon monoxide (CO) displaces oxygen from hemoglobin, shifts the oxygen- hemoglobin dissociation curve left, and binds directly to cardiac myocytes thereby depressing pump function.

2. Symptoms and signs generally depend on CO level (i.e. carboxyhemoglobin); all are manifestations of tissue hypoxia.

· 20-40%: dizziness, headache, weakness, poor judgment, decreased visual acuity (flu-like symptoms).

· 40-60%: tachycardia, tachypnea, ataxia, syncope, seizures ± ECG with ST segment changes, AV block, and other arrhythmias.

· 60%: Coma, death.

3. To get CO level, get ABG with carboxyhemoglobin level (this needs to be specifically requested); routine pulse oximetry will be normal. Note: cherry red lips are a late manifestation.

4. Treat with 100% oxygen by tight–fitting mask or endotracheal tube. Hyperbaric treatment is controversial. It is commonly recommended for patients with shock, pulmonary edema, pregnancy, rhabdomyolysis, severe acidosis, coma, seizures, and/or other symptoms not resolving with 100% O₂.

5. Half life 4-6 hours when breathing room air; decreased to 40-80 minutes on 100% O₂.

6. Measure CO level q 2-4 hours until < 10%.

CHEMICAL WARFARE AGENTS

1. Mechanism: nerve agents work by cholinesterase inhibition and are most commonly organo- phosphates. Tobun and Sarin are very potent agents that may be inhaled or absorbed through the skin.

2. Symptoms/signs: miosis, salivation, abdominal cramps, diarrhea, muscle paralysis leading to respiratory arrest, bronchoconstriction, rhinorrhea, and bronchorrhea (with inhalation).

3. Treatment:

· Thorough decontamination of exposed areas with repeated soap and shampoo washings. Health care personnel must wear gloves and protective clothing.

· Atropine 2 mg IV initially, but up to 5 mg IV q 15 minutes may be necessary. Repeat as necessary to reverse symptoms (physiologically blocks acetylcholine).

· Pralidoxime 1-2 g IV initially, followed by 200-500 mg/hour (breaks alkyl-phosphate-cholinesterase bond).

COCAINE OVERDOSE

1. Symptoms/signs:

· Local anesthesia and CNS stimulation via inhibition of catecholamine reuptake, giving generalized sympathetic stimulation.

· Central nervous system: rigidity, agitation, delirium, psychosis, brief seizures, intracranial bleed, mydriasis.

· Cardiac: VT/VF, coronary vasospasm/thrombosis, MI (often without underlying coronary artery disease), hypertension, tachycardia. See also Cardiology: Cocaine chest pain.

· Pulmonary: pneumothorax in ‘crack’ smokers, non-cardiogenic pulmonary edema, pneumomediastinum, tachypnea.

· Gastrointestinal: mesenteric ischemia/infarction.

· Renal: renal failure secondary to renovascular spasm/shock/rhabdomyolysis.

· Systemic: hyperthermia common and can be very impressive.

2. Effects may be exacerbated by co-ingestion of alcohol. Short half life of approximately one hour makes cocaine overdose relatively uncommon.

3. Work-up:

Urine toxicology screen, CBC, electrolytes, glucose, CPK, and urinalysis for myoglobin.

· ECG, CXR, and head CT (if suspected cerebral hemorrhage).

4. Treatment:

· ABCs, vital signs (including rectal temperature) and ECG monitor.

· Tachyarrhythmias: try labetalol (alpha and beta blockade) or calcium channel blocker (especially helpful with coronary vasospasm). The conventional wisdom is that pure beta-blockers in cocaine-induced syndromes can cause unopposed alpha-stimulation, thereby worsening the underlying problem. For VT, use lidocaine.

· Hypertension: give ß–blocker plus phentolamine (to prevent paradoxical HTN via ß₂ blockade) 1-5 mg IV bolus, may repeat in 5-10 min or as drip at 0.1-2 mg/min. Aim for a diastolic BP < 100-110. If uncontrolled, consider nipride infusion in the ICU.

· Agitation and psychosis: droperidol and/or lorazepam PRN.

· Seizures: lorazepam (0.1-0.2 mg/kg IV q10-15 minutes for a total of 30 mg). If status epilepticus, consider other causes such as continued drug absorption from broken bag of cocaine in GI tract (check KUB film). If packing is present, proceed to catharsis with activated charcoal.

· Decontamination via gastric lavage, charcoal and cathartic, or whole bowel irrigation if indicated (consult poison control). Do not induce emesis secondary to risk of seizures.

· For hyperthermia, use cooling blanket and sedation. Rapidly cool for T > 40°C.

ALCOHOL WITHDRAWAL

1. Mechanism: multifactorial; withdrawal symptoms are the opposite of depressant effects of EtOH. (Increased adrenergic, serotonergic, and cholinergic activity).

2. For all alcohol withdrawal hospitalizations, evaluate for co-morbid medical conditions (alcoholic hepatitis, pancreatitis, liver failure, gastrointestinal bleed, infection, trauma, hypoglycemia, co-ingestions, arrhythmias, dilated cardiomyopathy, altered electrolytes). Treat with:

Thiamine, multivitamins, folate while hospitalized. Hydrate and correct electrolytes. Follow blood sugars and always give glucose before giving thiamine.
Restrain for safety PRN.
Seizure precautions if deemed at risk.
Substance abuse counseling services referral (if available).
Charcoal is not helpful with alcohol intoxication.

3. Tremulousness: 6-12 hours after last drink. Occurs in 75-100%.

· Signs/ Symtpoms: Irritable, hypervigilant, diaphoretic, GI upset, tachycardia, HTN, coarse tremor of hands, tongue wag. Resolves in 24-48 h.

· Treatment: Thiamine 100 mg IV x 3 d, MVI, folate. Ativan or Librium per CIWA guidelines. Consider beta blockers for uncontrolled HTN.

4. Seizures: 12-48 hours after last drink; an early phenomenon

· Signs/ Symptoms: Generalized tonic-clonic seizures, post-ictal state. If the patient is febrile, seizure is focal in onset, or if the patient has no history of seizure, evaluate for secondary seizure (LP, CT, electrolytes, tox screen, etc.).

· Treatment: Treat as other seizures with Ativan. No need to load DPH unless patient has focal seizures, brain injury, or is supposed to be on anticonvulsants for other reasons (epilepsy, etc.).

5. Alcoholic hallucinations: 25% of patients within 12-24 hours after the last drink

· Signs/ Symptoms: Unlike DTs, patient’s sensorium is clear except for primarily visual hallucinations.

· Treatment: Follow CIWA protocol, thiamine, MVI, folate. Consider Haldol 1-2 mg q 1 hour prn severe hallucinations.

6. Delerium tremens: 2-7 days after last drink. 4-5% of patients: this is a MEDICAL EMERGENCY-5% mortality (often due to PNA or arrhythmia).

· Signs/ Symptoms: Lasts 2-5 days to weeks. Clouded consciousness, delerium, diaphoresis, agitation, hallucinations (visual> tactile> auditory), hypertension, tachycardia, low grade fever (<38.5).

· Treatment: Thiamine, folate, MVI, replete electrolytes, rule out infection. Admit to telemetry. Benzos per CIWA protocol. Ativan is usually preferred due to IV route. May require gtt. Haldol 1-2 mg q 1 hour prn severe agitation/ hallucination/ delerium.

CLINICAL INSTITUTE WITHDRAWAL ASSESSMENT (CIWA) PROTOCOL

1. Initial considerations: Consider ativan for use in the elderly, those with liver compromise, or NPO. Do not mix benzos. (e.g. if using ativan around the clock, use ativan for breakthrough.) Oral administration of benzodiazepine (BZD) is preferred, if possible.

2. Assess CIWA Score: < 8 = not yet in withdrawal, > 8 = withdrawing, > 25 = needs monitoring.

3. Withdrawal prophylaxis: initial CIWA<8. Assess CIWA and sedation scale q 6 and q 1 hour after admin of BZD. Hold BZD for sedation score > 4, assess vitals and call M.D. Assess risk class based on history, degree of alcohol abuse, etc.

· Mild risk: Librium 25 mg po or Ativan 1 mg po/iv/sl/im q 6 and q 1 prn CIWA>8 (notify M.D.)

· Mod risk: Librium 50mg po or Ativan 2 mg as above.

· Severe risk: Librium 75-100 mg po or Ativan 3-4 mg as above.

4. Initial treatment of acute withdrawal: CIWA 8-25. Goal is to achieve CIWA <8. Assess CIWA and sedation scale q 4 and q 1 hour after admin of BZD. Hold BZD for sedation score >4, assess vitals, and notify M.D.

· Mild (CIWA 8-15): Librium 50 mg po or Ativan 1-2 mg po/sl/iv q 1 hour x 2 and call M.D.

· Moderate (CIWA 16-25): Librium 100 mg po or Ativan 3-4 mg po/sl/iv q 1 hour x 2 and call M.D.

5. Ongoing treatment of acute withdrawal: CIWA < 8 after treatment of acute withdrawal. Goal is to keep CIWA < 8. Assess q 4 hours and q 1 after BZD.

· Librium 50-100 mg po (NTE 600 mg/24 hours) or Ativan 3-4 mg PO/IM/IV/SL q 6 h ATC and Q 1 prn CIWA > 8 (and call M.D.).

· Taper benzodiazepines by 25% per day once stable for 25 hours.

6. Treatment of severe withdrawal: CIWA > 25 or uncontrolled severe symptoms. Transfer/ admit to monitored setting with continuous oxygen and telemetry. CIWA and sedation score q 2 hours and q 15-30 min after IV BZD administration.

· Ativan 2-4 mg IV q 15-30 minutes for six hours. Titrate to CIWA < 8 or sedation scale = 3.

· Assess total six hour use and extrapolate to 24 hour needs. If > 24 mg in 24 hours, start ativan gtt at [total ativan dose over previous 24 hours ¸ 24] mg/hour to address needs.

· Taper by 25% per day once stable CIWA < 8. Allow PRN boluses for breakthrough.

ETHYLENE GLYCOL AND METHANOL

1. Mechanism: Ethylene glycol is found in antifreeze and is metabolized to glycolic acid (may be toxic to renal tubules) and oxalic acid (may precipitate within the tubules). Methanol (wood alcohol) is found in a variety of cleaning products and is a contaminant in bootleg whiskey.

2. Minimal lethal dose for methanol is 50 to 100 mL, though lower quantities can induce permanent blindness. Lethal dose of ethylene glycol is approximately 100 mL. Concurrent ethanol ingestion is protective.

3. Symptoms/signs:

With both substances, serum osmolality is usually elevated, but acidosis is often absent early. After several hours, they are metabolized to toxic organic acids leading to a severe anion gap metabolic acidosis.
Methanol: weakness, nausea, headache, decreased vision which can progress to blindness, coma, and death; retinal sheen on fundoscopic exam due to retinal edema.
Ethylene glycol: Shortly after ingestion, patients appear intoxicated, later developing tachypnea, pulmonary edema, convulsions, coma, flank pain and renal failure which is accompanied by calcium oxalate crystals in urine (needle-shaped monohydrate crystals, which may be misread as hippurate crystals, and envelope-shaped dihydrate crystals; absence of crystalluria does not preclude diagnosis.

4. Treatment:

· If the patient presents within 30-60 minutes, proceed with gastric lavage and give activated charcoal.

· Bicarbonate to correct metabolic acidosis.

· If severe metabolic acidosis, AMS, methanol serum level > 50 mg/dl or ethylene glycol > 20, or visual or mental changes with methanol, proceed to hemodialysis (HD).

· Fomepizole (4-methylpyrazole, Antizol®) rapidly and competitively inhibits alcohol dehydrogenase more potently than ethanol. Should be starte with suspicion of ethylene glycol poisoning or level > 20 mg/dL and used with methanol toxicity as well. Loading dose is 15 mg/kg, followed by 10 mg/hg every 12 hours for 48 hours, then 15 mg/kg every 12 hours until ethylene glycol levels fall below 20 mg/dL. Higher doses are needed after 48 hours (increases its own metabolism) and with HD. Occasionally causes headaches, bradycardia, dizziness, eosinophilia, or mild, transient elevation of liver enzymes.

· If necessary to use ethanol, aim for serum concentrations of 100-200 mg/dl by loading 0.6 g/kg orally or dilute IV solution and maintenance infusion of 66 mg/kg in patients without concurrent ethanol ingestion, 154 mg/kg in drinkers, and 240 mg/kg once HD is started.

· Methanol intoxication: also give folic acid 50 to 70 mg IV q 4 hours for first day.

· Ethylene glycol: initiate forced diuresis with fluids and mannitol (do not give if pulm edema or cont if fails to respond to first dose. Also give pyridoxine 500 mg IM QID and thiamine 100 mg IM QID.

OPIATE OVERDOSE

1. Effects:

· CNS: sedation and respiratory depression, miosis (note: mydriasis may exist if acidotic or after a seizure). Rarely, can have seizures with meperidine, propoxyphene, tramodol, and codeine (especially in renal insufficiency).

· Pulmonary: acute noncardiogenic pulmonary edema (0.5% of all patients who present with a heroin overdose).

· Half life varies: 2-3 hours for morphine, 22 hours for methadone.

· Beware co-contaminants used to cut heroin—caffeine, strychnine, phenacetin, quinine.

2. Diagnosis:

History and physical: pinpoint pupils, hypothermia, CNS and resp depression, possible bradycardia.

· Response to naloxone (be aware of risk for seizure, withdrawal and noncardiogenic pulmonary edema).

· Labs: urine tox screen (certain synthetic opioids such as fentanyl are not detected by routine tox screen), CBC, electrolytes, glucose, ABG, CXR, consider acetaminophen/ASA levels if combination drugs ingested, CK if considering rhabdomyolysis.

3. Treatment:

· ABCs, oxygen.

· Naloxone (to reverse respiratory depression): 0.1–1 mg IV or IM. May repeat dose q2–3 min up to a total of 4 mg. Necessary to monitor at least 2 hours after last naloxone dose (which has half-life of 1 hour vs. most opioids which have longer half life). Recommend 1-2 hour observation after opioid–induced coma and monitor for acute withdrawal syndrome in opiate–dependent patients (yawn, chills, nausea, vomiting, diarrhea, myoclonus). Longer monitoring needed if OD on methadone (24-48 hours). Narcan gtt of 2/3 original effective dose q 1 hour may be necessary to maintain alertness.

· Consider whole bowel irrigation and activated charcoal if drug packets ingested.

OPIATE DEPENDENCE/WITHDRAWAL

1. Background: opiate withdrawal is rarely dangerous but is physically uncomfortable/distressing to the patient. It is best to prevent or quickly deal with withdrawal symptoms in the medically ill patient.

· Heroin withdrawal: begins 12-24 hours after last use, peaks at 2-3 days, lasts 5-7 days.

· Methadone withdrawal: begins 1-3 days after last dose, peaks at 5-7 days, lasts 2-3 weeks.

2. Symptoms/signs:

· Early/mild signs: sweating, yawning, rhinorrhea, dilated pupils, insomnia

· Late/severe signs: piloerection, nausea, vomiting, diarrhea

· Symptoms: body aches/pains, cramps, anxiety, opiate cravings

3. Methadone dosing: because of the variability in content of street heroin, empiric methadone dosing is recommended rather than a conversion based on grams or reported daily use.

· If currently in methadone program (detox or maintenance): verify current dose with case manager. Do NOT give large doses of methadone unless verified first.

· Not in a program (or unable to verify dose) and not yet withdrawing:

- Give 10-20 mg po and provide 10 mg q 4 hours prn x 24 hours. Rarely do patients require > 50 mg/day. On day #2, add total 24 hour dose and provide as the new base daily dose.

- Refer to outpatient methadone detox on discharge. This is an ethical obligation if a patient is given methadone in-house. If long-term hospital stay, initiate detox.

· If not enrolled in a program and withdrawing: Methadone 20-30 mg po once then 10 mg po q 30-60 minutes until withdrawal is suppressed. Afterwards, 10 mg q 4 hours prn for 24 hours. On day #2, add total dose and provide as the new base daily dose. Refer to substance abuse counseling services and outpatient program on discharge.

4. Methadone adjuncts: Hydroxyzine 25 mg po QID prn anxiety/ insomnia, Trazadone 50-100 mg po QHS prn insomnia, Immodium for diarrhea, Clonidine (if BP > 95/60) patch #1-5 (dependent on weight) or 0.1mg-0.2mg q 4 hours prn (NTE 0.8 mg/day), Ibuprofen 400-800 mg po QID prn aches. Do not use methadone for pain; use another analgesic, and obtain pain consult if needed.

PAIN MANAGEMENT

1. Selection of analgesic:

· Pain scale 1-4 (mild): Step I Analgesics: ASA, Tylenol, (NTE 4g/d or 2g/d in liver disease), NSAIDS. Watch GI side effects.

· Pain scale 5-6 (moderate): Combination analgesics: Vicodin, Percacet, Tylenol #3, #4, Tylox (Tylenol component NTE 4g/d or 2g/d in liver dz). Note: Ultram 50 mg = 60 mg codeine-useful in patients who cannot use NSAIDS or Tylenol.

· Pain scale 7-10 (severe): Opiate analgesics.

- Morphine, Roxanol, MS Contin (IV MSO4 = 3x as potent as PO in chronic opiate users, 6x as potent in opiate naïve users)

- Oxycodone, oxycontin

- Hydrocodone

- Hydromorphone (IV Dilaudid is 4x more potent mg for mg than IV morphine; PO Dilaudid is 1/5 as potent as IV Dilaudid)

- Meperidine (Demerol); toxic metabolite, esp. in renal insufficiency

- Darvon

- Fentanyl IV or patch (2:1 conversion with morphine; e.g. 25 mcg Fent=50 mg morphine)

- Codeine (unpredictable liver metabolism to morphine)

2. Dosing: Start with 0.05 mg/kg q 4-6 h of morphine equivalent in acute pain, or base dose on prior history of use/ needs. Alternatively, use PCA for 12-24 hours to determine needs, then convert to PO equivalent. Always provide breakthrough doses equal to 24 hour baseline dose divided q4. Examples:

· PCA: PCA at 5 mg/hour (baseline and boluses added) = 120 mg/24 hours. Multiply by 3 (IV to PO conversion) = 360 mg/day of po morphine equivalents. Therefore, start at 180 mg MS Contin BID and 60 mg PO q 4 hours of Roxanol prn breakthrough.

· MS Contin: 15 mg po BID = 30 mg/d. Breakthrough is 5 mg q 4 h Roxanol (1-2 mg IV).

· Fentanyl patch: 50 mcg = 100 mg po morphine, so breakthrough=15 mg Roxanol q 4 h prn.

3. Side effects: Ask about side effects and warn patients of expected side effects. Chronic opiate users will become tolerant of all side effects except constipation. Toxicity is rare.

· Constipation: all narcotic users should have Colace, Senna, ± Sorbitol provided

· Nausea/vomiting: Treat with compazine or droperidol. Will decrease in 24-48 hours.

· Itching: Treat with Benadryl. Will decrease in 48-72 hours. (Hives are rare and=>allergy)

· Sedation: Will decrease in 48 hours. May be treatable with stimulants.

· Hypoventilation: rare and occurs long after sedation. Reverse with Narcan.

· Myoclonus/ Hallucination: s/s of opiate toxicity.

4. Neuropathic pain: burning, radiating, electrical, pins and needles, numbness (s/p DM, nerve injury or compression, amputation, alcoholism, post-herpetic, etc.)

· TCAs: Desipramine, Amitriptylene, Nortryptyline – 25 mg QD; titrate q 3 days to effect (usually 50-200 mg qd)

· Gabapentin: 100 mg po TID; titrate q 3 days to effect. No max dose. Watch for neurotoxicity (tremor, confusion) especially in renal insufficiency.

· Tegretol: (cleared by liver): 200 mg po BID. Watch CBC and LFTs

· Baclofen: 5-30 mg po BID-TID

· Mexilitene: 150-300 mg po TID (antiarrhythmic with side effects)

· Nerve block (consult anaesthesia).

Opioid Analgesic Dose Conversion Table:

Opioid Analgesic	Equianalgesic Dose (mg)
Opioid Analgesic	Oral	Parenteral
Morphine (Roxanol®, MSContin®)	30	10
Hydromorphone (Dilaudid®)	7.5	1.5
Oxycodone (Percocet®, OxyContin®)	20	—
Methadone (titrate slowly because of long half-life)	20 (acute) 2-4 (chronic)	10 (acute) 2-4 (chronic)
Hydrocodone (Vicodin®, Lortab®, Norco®)	30	—
Codeine (tyco #2 = 15 mg, #3 = 30 mg, #4 = 60 mg)	180-200	130
Fentanyl	—	0.1 (100 mcg)
Fentanyl transdermal patch* (Duragesic®)	2:1 rule**	—

* The onset of analgesia is delayed 8-12 hours so continue to treat pain for the first 12 hours with another medication; there is a residual effect after the patch is removed; do not use in opioid naïve patients. Use only in chornic stable pain.

** If the total 24 hour dose of oral morphine is 100 mg, the approximate equianalgesic dose of transdermal fentaly patch is 50 mcg/hr (the 2:1 rule).

Based on the UCSF Adult Pain Management Guide, 2001.