General Approach to Intoxication/Ingestion Every patient who present with an acute intoxication or poisoning will require rapid diagnosis and treatment, but first must be stabilized and assessed thoroughly. Always have someone contact the poison control center at (800) 222-1222 to help you with your workup and management.
Step 1: ABCs Intubation for respiratory failure and/or airway protection. Place at least 2 large bore (<18 gauge) IVs and/or a central venous catheter. Cardiac monitoring and pulse oximetry. Supplemental oxygenation.
Step 2: Focused History Material (or materials) ingested Time of ingestion Amount ingested (empty pill bottles) Significant past medical history and prescription medications
Step 3: Order appropriate laboratory and radiologic tests EKG, CXR CBC, chemistry panel including Ca, Mg, and Phos, LFTs, ABG, acetaminophen level, salicylates, ethanol level, serum osmoles. Urine toxicologic screen
Step 4: Diagnose and treat based on agent (see below)
Ethanol Intoxication and Withdrawal Ethanol Properties 20% absorbed by the stomach with the rest absorbed in the small intestine >90% eliminated by the liver Clearance rates of ethanol are 20 mg/dL/hr +/- 6 mg/dL/hr, with tolerant drinkers having a higher clearance rate Clinical Signs and Symptoms Based on Blood Alcohol Level Make sure to assess the patient from head-to-toe looking for trauma 1 shot = 1 beer = 1 glass of wine will raise the ethanol blood level of a 70 kg person by 25 mg/dL Note that a blood alcohol concentration (BAC) of 0.08 = 80 mg/dL
Blood Alcohol Concentration and Associated Clinical Signs
BAC (mg/dL)
Drinks (55 kg person)
Clinical Signs
50-100
1-3 drinks
Impaired sensation, incoordination
100-150
3-5 drinks
Behavioral changes, ataxia, cognitive and memory difficulties
Management Think ABCs (airway, breathing, circulation). Obtain baseline labs including a BAC, chemistry panel (including magnesium and phosphorous) to calculate an anion gap, liver function panel, serum ketones, blood glucose (alcohol can induce hypoglycemia) and possibly an illicit drug screen (either serum or urine) if additional drug use suspected. If the patient had a recent binge (usually within 1 hour), activated charcoal and/or gastric lavage can be considered. When a BAC is obtained, determine whether the clinical signs are worse than the measured BAC. If so, look for alternative causes (i.e. trauma, intracranial hemorrhage, infection, severe ketoacidosis). Administer IV fluids (normal saline, as they are usually dehydrated). Usually, add to 1L of IV fluids: IV thiamine 100 mg (poor absorption with concurrent ethanol use), IV folate 1 mg, and an IV multivitamin (this is often referred to as a "Banana Bag" as it is yellow). Traditional teaching is to give thiamine before glucose to prevent precipitating Wernicke's encephalopathy. This is controversial and is only applicable to thiamine deficient individuals (i.e. chronic alcoholics). Measure serum glucose (can use fingerstick): If the patient is hypoglycemic, this is dangerous and should be corrected acutely. Give 5% dextrose in 1L normal saline + thiamine, folate, and a multivitamin (as above). If the patient is not hypoglycemic, give 1L normal saline + thiamine, folate, and a multivitamin (as above), then you can add 5% dextrose to the next liter of fluid (if applicable). Replete magnesium and phosphorus as indicated. Patients may have a large anion gap from alcoholic ketoacidosis. This should correct with administration of IV fluids with dextrose. Serum lactate should be normal (if high, look for reasons to explain this) Usually presents in chronic alcoholics days after a binge (i.e. BAC low or undetectable) Ethanol Withdrawal
Not all patients will have minor withdrawal before the other syndromes occur
Alcoholic hallucinations
10-48 hours
Tactile (formication), visual, or auditory hallucinations with a clear sensorium
25% incidence
Seizures ("Rum Fits")
6-48 hours
Generalized tonic-clonic seizures with a short postictal period with quick recovery of mental status
10% incidence, of those 3% experience status epilepticus
Delirium Tremens
48-96 hours
Hypertension, tachycardia, tremors, diaphoresis, disturbance of consciousness (i.e. delirium) or change in cognition (i.e. memory deficit)
30-40% incidence in those with alcohol withdrawal seizures; Can last up to 2 weeks; 5% mortality
Assessment of alcohol withdrawal Use the Revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale. (Br J Addict 1989;84:1353-1357)*see reference for scale <9 = mild withdrawal 9-15 = moderate withdrawal >15 = severe withdrawal symptoms and an increased risk of delirium tremens and seizures
Treatment Initial treatment (see management of ethanol intoxication)
Minor withdrawal and alcoholic hallucinations Benzodiazepines Diazepam is the first-line drug choice because of its immediate onset and long half-life (20-50 hours) Dose at 10-20 mg IV every hour to achieve sedation but with normal vital signs and spontaneous respirations. Avoid in those with advanced liver disease (inchalf life) Lorazepam can also be used as it has an onset of 5 minutes and a 13 hour half-life. Dose at 0.5-4 mg IV every hour to achieve sedation but with normal vital signs and spontaneous respirations. For patients with minor withdrawal, oral benzodiazepines are acceptable, with chlordiazepoxide being the drug of choice. Dose 50-100 mg every 8 hours as needed (reduce dose in hepatic and renal insufficiency). Can start with 10-20 mg IV or PO diazepam to achieve more rapid sedation. Clonidine can be used to control autonomic hyperactivity (i.e. tachycardia, hypertension) but should never be used as monotherapy, as it can mask the severity of alcohol withdrawal and may lead to underdosing of benzodiazepines. Two RCTs have shown that symptom-triggered dosing of benzodiazepines reduced total benzodiazepine use and duration of treatment without an increase in withdrawal seizures or other adverse events. (Arch Intern Med 2002;162:1117-1121) (JAMA 1994;272:519-523) There are issues, however: All patients were scored with the CIWA-Ar scale. They were assessed and dosed hourly. They were all in minor to moderate withdrawal (mean CIWA-Ar score of 9-11). Therefore, if you plan on using symptom-triggered dosing, you must be able to assess the patient hourly using the validated CIWA-Ar score to determine repeat dosing.
Alcoholic withdrawal seizures Airway protection Fall protection IV lorazepam 2 mg IV every 5 minutes OR IV diazepam 10-20 mg IV every 5 minutes to stop the seizures, then continue either IV or oral lorazepam/diazepam to maintain adequate sedation with normal vital signs and spontaneous breathing. Consider additional causes (i.e. intracranial bleed, meningitis) and workup accordingly.
Delirium tremens Cardiac monitoring Airway protection and fall precautions Judicious use of IV diazepam (or IV lorazepam) to achieve sedation with normal vital signs and spontaneous breathing. For patients who do not respond to benzodiazepines, consider ICU management and phenobarbital or propofol for sedation.
Signs: Respiratory depression, miosis, orthostatic hypotension, bradycardia, flushing, sedation/coma, bronchospasm, non-cardiogenic pulmonary edema Seizures can occur with meperidine and propoxyphene
Symptoms: Pruritus, constipation, euphoria, analgesia Laboratory Testing Opioid metabolites in the urine can be detected for 1-3 days False-positives can be caused by cocaine, rifampin, fluoroquinolones, and poppy seeds Management Gastric lavage and/or activated charcoal for recent oral administration Respiratory support (supplemental oxygen, intubation if needed) Bowel regimen
Naloxone administration Can be given IV (preferred), IM, SQ, and intratracheal Dose at 0.4-2 mg (0.1-0.2 mg in opioid dependent or postoperative patients) and repeat every 2-3 minutes as needed up to 10 mg. Can place on naloxone drip, using 2/3 of the initial dose over an hour as a guide. VERY IMPORTANT: The duration of action of naloxone is 20-60 minutes while all of the opioids (see table above) have much longer durations. Therefore, if you achieve reversal of CNS and respiratory depression initially, monitor the patient closely as you probably will have to redose the naloxone approximately every 45 minutes. Side effects: opioid withdrawal, seizures, myocardial infarction, non-cardiogenic pulmonary edema.
Cocaine Overdose Cocaine Properties Administered IV, IM, inhaled, and snorted Onset of action 6-16 seconds, except when snorted (3-5 min). Half-life 30-90 minutes Works by blocking the reuptake of catecholamines in the brain, impairs nerve conduction by blocking fast sodium channels locally, and decrate and amplitude of the action potential in cardiac myocytes. Clinical Signs and Symptoms
Cardiac: coronary vasospasm and/or myocardial infarction (can occur up to 2 weeks after use), arrhythmias, dilated cardiomyopathy (chronic use)
Abdominal: perforated ulcers, ischemic colitis, bowel obstruction (think body packing)
Musculoskeletal: rhabdomyolysis Laboratory Testing Cocaine metabolites in the urine can be detected for 2-3 days False-positives can be caused by topical anesthetics containing cocaine, amoxicillin, tonic water Consider urine myoglobin, serum creatinine, cardiac enzymes, EKG, CT scans (intracranial hemorrhage, body packing, pulmonary edema/hemorrhage) Management Note that beta-adrenergic antagonists (i.e. beta-blockers) are ABSOLUTELY CONTRAINDICATED as they allow unopposed a-adrenergic activity. Supportive care is the mainstay of therapy unless other signs/symptoms occur:
Chest pain/MI: Give ASA, lots of oxygen, and morphine. Benzodiazepines and nitroglycerin have been shown to be beneficial. Phentolamine can be used for excessive hypertension/tachycardia. Heparins, clopidogrel, glycoprotein IIb/IIIA inhibitors can be considered in those patients with risk factors for coronary artery disease.
Symptoms: Confusion, drowsiness, dysarthria, ataxia, coma Management Supportive care with specific attention to respiratory depression
Flumazenil: Typically NOT indicated in overdose as it can precipitate seizures Its use is contraindicated in patients with seizure disorders and when tricyclic antidepressants may be co-ingested. A good rule of thumb is to consider its use in benzodiazepine-naive patients with severe respiratory depression. Dose at 0.2 mg IV over 15 seconds and can be repeated every minute (maximum dose 1 mg). Like naloxone, its duration of action (~1 hour) is typically less than the benzodiazepines, and patients who respond initially usually need redosing to prevent respiratory depression.
Acetaminophen Overdose Acetaminophen Properties Rapid absorption with a half-life of 2-3 hours (may be prolonged in patients with liver disease) Overdose is typically defined as 7.5 grams ingested within a 4 hour interval. Acetaminophen is metabolized as follows: ~50% by hepatic conjugation to glucuronide. ~35% by hepatic conjugation to sulfate. ~10% by oxidation by CYP2E1 to N-acetyl-p-benzoquinoneimine (NAPQI), which is toxic, but rapidly combines with glutathione creating non-toxic metabolites. <5% remains unchanged and is renally cleared. When the amount of acetaminophen ingested overwhelms the glutathione system, NAPQI builds up resulting in the toxic effects of acetaminophen overdose. Clinical Stages
Stage I (<24 hours): Nonspecific symptoms including diaphoresis, pallor, nausea, and vomiting. Cannot detect hepatotoxicity on labs yet.
Stage II (24-36 hours): Hepatotoxicity (defined as an AST>1000) can be detected at this time.
Stage III (72-96 hours): Fulminant liver failure with abnormalities of liver function (i.e. prolonged PT, elevated bilirubin and lactate) that may result in death from sepsis, ARDS, hemorrhage, or multiorgan system failure.
Stage IV (>5 days): Recovery phase for those who survive stage III, with full return of liver function within days to months. Laboratory Testing Serum acetaminophen levels (µg/mL) should be drawn on presentation. It is important to determine the approximate time of ingestion. If the time of ingestion is <4 hours, a repeat level should be drawn after 4 hours to be able to use the Rumack-Matthew nomogram. If you do not know the time of ingestion, draw levels every 1-2 hours to try and find a peak level. A level of <10 µg/mL within 4 hours of ingestion is not compatible with overdose. Liver function tests and complete chemistry panel
Management If the patient presents within 1-2 hours of ingestion, activated charcoal 1 gm/kg (up to 100 gm) can be administered to prevent further absorption. Separate charcoal and incN-acetylcysteine (NAC) doses by 1-2 hours, and if this is not possible, use IV NAC. Obtain a serum acetaminophen level (see above) and plot on Rumack-Matthew nomogram to determine if treatment with NAC is needed. Treatment is indicated if the acetaminophen level is above the bottom line. If the time of ingestion is unknown, treat any level >150 µg/mL and consider treatment based on history. If toxic dose taken (>=7.5 grams), treat.
When in doubt, always treat!
incN-acetylcysteine (NAC): Oral (Mucomyst) and IV (Acetadote) NAC are equally efficacious, with oral being the therapy of choice. Administer within 8-10 hours of ingestion for best prevention of liver toxicity. Use IV NAC in patients with fulminant liver failure, pregnancy, or recurrent vomiting. Dose the oral form as 140 mg/kg loading dose then 70 mg/kg every four hours for 17 doses total. If vomiting occurs with 1 hour of dose, repeat the dose.
Rumack-Matthew Nomogram Adapted from Ann Emerg Med 1991;20:1058.
Dose the IV form as 150 mg/kg loading dose over 15 minutes followed by 50 mg/kg infused over 4 hours then 100 mg/kg infused over 16 hours. Follow serum levels of liver enzymes and liver function and provide supportive care as needed (i.e. fresh frozen plasma).
Salicylate (Aspirin) Overdose Salicylate Properties Acetylsalicylic acid (aspirin) and methylsalicylic acid (Oil of Wintergreen) are rapidly absorbed in the stomach and hydrolyzed to salicylic acid. The half-life varies on the concentration of salicylate in the body (i.e. at therapeutic concentrations the half-life is 2-4 hours, while at toxic concentrations, the half-life can be as high as 30 hours). Clinical Signs and Symptoms
Signs: Fevers, tachypnea, convulsions, coma
Symptoms: Nausea, vomiting, fatigue, restlessness Laboratory Testing A 6-hour salicylate level best correlates with toxicity, however this will not be accurate with enteric-coated or extended-release formulations. Mild toxicity = 30-60 mg/dL Moderate toxicity = 60-80 mg/dL Severe toxicity = >80 mg/dL The Done nomogram was evaluated in one study and found to have a predictive index of 0.42 (i.e. worse than chance) and therefore should not be used in guiding management. (Ann Emerg Med 1989;1811:1186-1190) Management It is important to first determine, if possible, the time, how much, and what type of aspirin (i.e. enteric-coated) was ingested. Gastric lavage should be considered in patients who have ingested salicylates within one hour of presentation or have ingested enteric-coated or extended-release pills. Activated charcoal 1 gm/kg (up to 100 gm) should be given to all patients. Toxicity may not correlate with amount ingested, especially in chronic users. Obtain basic labs, a serum salicylate level (preferably 6 hours after ingestion), and an ABG to determine pH.
Determine the level of toxicity:
Mild: salicylate level 30-60 mg/dL with nausea, vomiting, tinnitus, and fatigue. Rehydration.
Moderate: salicylate level 60-80 mg/dL with restlessness, tachypnea, diaphoresis, hyperpyrexia, and dehydration. Rehydration + Urinary alkalization (1L D5W + 3 amps HCO3 over 3 hours) Monitor potassium levels closely and consider adding potassium to the maintenance fluids.
Severe: salicylate level >80 mg/dL with coma, acute renal failure, pulmonary edema, convulsions, severe metabolic acidosis, and/or hypotension. Hemodialysis + urinary alkalinization. Continue to check salicylate levels every 2-3 hours or until peak. If the level continues to rise, give additional doses of activated charcoal 1 gm/kg (up to 100 gm). Continue to check urine pH hourly to maintain pH between 7.5-8.5. Adjust bicarbonate drip accordingly. Watch for hypokalemia!
Tricyclic Antidepressants Overdose Tricyclic Antidepressants (TCAs) Properties TCAs exert their effect by blocking the reuptake of serotonin and norepinephrine at the presynaptic membrane.
Properties of Tricyclic Antidepressants
Drug Name
Brand Names
Half-Life
Amitriptyline
Elavil
9-27 hours
Nortriptyline
Aventyl, Pamelor
28-31 hours
Protriptyline
Vivactil
54-92 hours
Imipramine
Tofranil
6-18 hours
Desipramine
Norpramin
7-60 hours
Trimipramine
Surmontil
16-40 hours
Doxepin
Adapin, Sinequan
6-8 hours
Clomipramine
Anafranil
20-30 hours
Clinical Signs and Symptoms Anticholinergic effects: Mydriasis, ileus, urinary retention, hyperthermia Cardiac effects: Hypotension, just about any arrhythmia (including torsades de pointes), AV block CNS effects: Seizures, coma, delirium, myoclonus Laboratory Testing TCA serum levels are not clinically useful (other than confirming that TCAs were ingested). Electrocardiographic findings suggesting severe toxicity: QRS duration > 100 ms aVR R-wave amplitude >= 3 mm Management Acute ingestions may benefit from NG lavage and activated charcoal administration. Inducing emesis may be dangerous as these patients tend to be at high risk for aspiration due to altered mental status and seizures. Obtain baseline labs, EKG, and ABG and place on a cardiac monitor. Consider mechanical ventilation if hypoxic or cannot protect airway. Hypotension: Use sodium bicarbonate 1-2 mEq/kg IV Q3-5 minutes for goal pH 7.45-7.55 first, then use norepinephrine. Arrhythmias: Use sodium bicarbonate first, then use lidocaine and magnesium (avoid class Ia and Ic drugs as they worsen cardiotoxicity, and class III drugs as they prolong the QT interval). Seizures: IV lorazepam 2 mg IV every 5 minutes OR IV diazepam 10-20 mg IV every 5 minutes to stop the seizures, then can place on midazolam or propofol drip if needed.
Carbon Monoxide Intoxication Carbon Monoxide (CO) Properties CO is an odorless, colorless gas that is the leading cause of poison-related deaths in the US. Half-life of 5 hours on room air (dec to 1 hour on 100% FiO2). Binds to hemoglobin with a much higher affinity than oxygen resulting in carboxyhemoglobin reducing the amount of oxygen available to tissues. Decreases oxygen delivery to tissues via a left shift of the oxygen dissociation curve. Causes direct cellular toxicity, interfering with myoglobin, cytochromes, and guanylate cyclase. It also incNO activity resulting in oxidative damage from free radicals. Clinical Signs and Symptoms
Symptoms: Nausea, vomiting, headache, lightheadedness, confusion, weakness, chest pain Delayed effects may result in neurologic deterioration up to 40 days post-intoxication. Laboratory Testing Carboxyhemoglobin Nonsmokers = 1-2% Smokers = 5-10% Mild toxicity = 15-20% Intermediate toxicity = 20-60% (level does not correlate with symptoms or prognosis) Fatal = >60% Management Obtain baseline labs and a carboxyhemoglobin level from either an ABG or VBG. Start high-flow oxygen therapy (nonrebreather face mask with 15 LPM) and consider intubation and mechanical ventilation to provide 100% FiO2. Correct hypoglycemia and hypotension. Consider hyperbaric oxygen administration (usually at 2.5 ATM) in patients who have: Carboxyhemoglobin > 25% CNS manifestations (seizures, coma, altered mental status, abnormal neurologic exam, syncope) Cardiovascular dysfunction Severe metabolic acidosis Pregnancy
Digoxin Toxicity Digoxin Properties Digoxin is used in patients with heart failure to improve contractility via an incintracellular calcium and in patients with SVT via direct suppression of the AV node. Onset of action is 1-2 hours (oral) or 5-30 minutes (IV). Half-life (in adults) is 38-48 hours (prolonged in renal insufficiency). Clinical Signs and Symptoms
Chronic intoxication: GI (nausea, vomiting, abdominal pain, anorexia), CNS (lethargy, hallucinations, delirium), and visual (blurring, photophobia, scotomata) Laboratory Testing
Therapeutic serum concentrations: CHF: 0.5-0.8 ng/mL SVT: 0.8-2 ng/mL Toxic serum concentration is >2.5 ng/mL. Hyperkalemia (with levels higher than 5.5 mEq/L very worrisome for morbidity/mortality). Changes on electrocardiogram may include: Ectopic ventricular rhythm (i.e. PVCs) AV junctional block Enhanced automaticity Prolongation of PR interval AV dissociation Bidirectional ventricular tachycardia (i.e. a wide QRS with an alternating axis) is pathognomonic Management Obtain basic labs including a chemistry panel and digoxin level. Place on a cardiac monitor and obtain an electrocardiogram. Determine if the patient needs "digoxin-immune Fab fragments," and if so, consult your pharmacist to determine dosing. #vials of digibind = [dig level (ng/ml) x weight (kg)]/100 and give over 15-30 min. Reasons to give antidote: Digoxin level >= 15 ng/mL (or >= 10 ng/mL 6-hours post ingestion) Potassium level > 5 mEq/L Severe clinical signs/symptoms Life-threatening arrhythmia Things to look out for: Hypokalemia following administration (make sure potassium is corrected before giving) Return of SVT (i.e. atrial fibrillation with rapid ventricular response) CHF
Other management considerations: Symptomatic bradyarrhythmias: Atropine 0.5 mg IV. Symptomatic tachyarrhythmias: Phenytoin (either as a drip at 50 mg/min or in 100 mg boluses Q5 minutes, maximum dose of 1 gm) or lidocaine (1-1.5 mg/kg IV bolus followed by a drip at 1-4 mg/min). Hyperkalemia: Use insulin + dextrose and bicarbonate. Avoid calcium! GI Absorption: Cholestyramine 4 gm PO Q4 hours and/or activated charcoal 1 gm/kg (up to 100 gm) Q2-4 hours may dechalf-life as digoxin is enterohepatically recirculated.
