Toxic ingestion:
Intentional: context of a suicide attempt. Use of illicit substance, prescription drugs, OTC, alcohol.
Accidental: usually involve pediatric patients but may also result from dosing errors. Solvents, pesticides, household cleaning products, cosmetics, or poisonous plants.
History:
Substance ingested, amount ingested, time of ingestion, any subsequent vomiting.
Information from patient, police, EMS run sheet, EMTs, family, etc.
Street names of substance.
OTC, prescription med at home. Look at the bottle. To quantify the ingestion, determine the difference between the expected number or pills based on the date of the medication was filled, the daily amount prescribed, and the number of pills remaining in the bottle at the time to presentation to ED.
Timing of ingestion is critical piece of information, that will guide initial decontamination procedures but also provide a time frame for the determination of specific drug levels, such as acetaminophen level 4 hours after ingestion.
Vomiting eliminates part of the drug ingested from the GI tract.
Visual sx: typical with methanol
Tinnitus: with salicylate intoxication.
Dyspnea secondary to noncardiogenic pulmonary edema due to aspiration pneumonitis.
Sz are almost always generalized with toxic ingestions. Focal sz imply structural lesion secondary to trauma or OD involving theophylline or hypoglycemic agents. Substances that can typically cause sz are anticholinergic agents, TCA, phencyclidine, and sympathomimetics.
Know the number of the regional poison control center. Must be contacted for all cases.
Physical examination:
ABC, ETT if necessary. Take C-spine precautions with possible traumatic injury.
General appearance: diaphoretic skin - cholinergic or sympathomimetic agent, or unusually dry and hot - anticholinergic. Areas of ecchymoses - anticoagulant or trauma. Cyanosis may indicate lack of oxygenation from respiratory depression or, if the cyanosis is unresponsive to the administration of oxygen, methemoglobinemia.
Hyperthermia - anticholinergics, salicylates, and sympathomimetics.
Tachypnea accompanies salicylate intoxication.
Bradycardia - BB, CCB, and opioid OD.
Tachycardia - TCA, sympathomimetics, cocaine, and salicylates.
Hypotension - BB, CCB, opioids.
Hypertension - sympathomimetic intoxication, cocaine.
Miosis: opioid, clonidine OD.
Mydriasis: sympathomimetic, anticholinergics.
Nystagmus: horizontal in ingestion of physiologic depressant. Vertical or rotary nystagmus suggest phencyclidine (PCP) intoxication.
Excessive salivation: cholinergic
Dry mucosa: anticholinergic
Cherry red mucosa: CO poisoning
Crackles on lung auscultation: noncardiogenic pulmonary edema - salicylates, CO, CHF 2° MI induced by cocaine, or myocardial depression from BB, or CCB.
Abdominal distension and abnormal BS: iron OD.
Toxidromes:
Rapid recognition of clusters of signs and symptoms helps identify the causative substances. The patterns of clinical findings resulting from toxic ingestions are called toxidromes.
Anticholinergic: Antihistamines, phenothiazines, cyclobenzaprine, TCA, certain plants and mushrooms. "Blind as a bat, dry as a bone, hot as a hare, and mad as a hatter." Mydriasis, dry skin and mucous membranes, hyperthermia, and altered mental status. Dysrhythmias, seizures, and rhabomyolysis are critical components of this type of ingestion.
Cholinergic: Organophosphate and carbamate insecticides are the classic causes. Excessive salivation, lacrimation, urination, diaphoresis, gastrointestinal distress (diarrhea, cramps, and emesis), muscle fasciculations and weakness. Bradycardia and seizures may also occur.
Opioid: OD of prescription pain medications such as hydrocodone or oxycodone, or street drugs, such as heroin. Respiratory depression, hypotension, and bradycardia. CNS depression, miosis. Similar to that of clonidine poisoning.
Salicylate: ASA overdose initially lead to tachypnea, tachycardia, tinnitus, nausea, and vomiting, and respiratory alkalosis, with altered mental status. Metabolic acidosis occurs later. Methyl salicylate (oil of wintergreen) ingestion is concerning, as small volumes of this substance contains large amounts of salicylates.
Sympathomimetic: Amphetamines, cocaine, and various decongestants most commonly result in sympathomimetic toxidrome. Agitation, HTN, hyperthermia, tachycardia, diaphoresis, and mydriasis are characteristics. Seizures may also occur.
Lab:
UDS, SDS, CBC, CMP, LFTs, UA, ECG, CXR, AXR.
Serum/Urine: salicylates, acetaminophen, lithium, opioids, amphetamines, TCA, benzodiazepines, cannabis, cocaine, alcohol.
AG = Na - (Cl + HCO3) normal 12 (+/-3).
▲ AG in absence of DKA, lactic acidosis, and uremia suggests ingestion of methanol, ethylene glycol, or salicylate.
Estimated serum osmolality = 2(Na) + (glucose/18) + (BUN/2.8)
Osm gap: Sr. Osm - Calc Osm. Normal -10 - 10 (cutoff 14).
▲ Osm gap indicates presence of certain alcohols such as methanol, ethylene glycol, and isopropanol.
Decontamination:
Gastric lavage
May be the decontamination of choice for patients presenting to the ED after a significant ingestion of a toxic substance.
Consider the toxic substance, time from ingestion to ED presentation, and the conditions of the patient.
Non-toxic substance ingestion, insignificant amount of toxic ingestion, vomiting prior to presentation in the ED, or a delay of > 1 hr between time of ingestion and presentation to the ED may not benefit from decontamination with gastric lavage.
Aspiration of stomach contents, oropharyngeal, esophageal, and gastric trauma are risks during gastric lavage. Routine ETT is not needed.
Gastric lavage is usually performed with the patient's head down and in left lateral decubitus position to minimize the risk of aspiration, and to minimize the amount of gastric contents entering the duodenum during lavage.
Length of the tube measured from nose to epigastrium.
36 - 40 F tube for adults and 22 - 28 F for pediatric patients.
Tube is passed orally, carefully. Bite block is place to help prevent injury and to prevent patient from biting on the tube. Coughing and stridor and inability to speak necessitates immediate withdrawal of the tube. Confirm tube position by insuffulation of air and hearing the gastric "gurgle" and by Chest and abdomen X-ray.
Irrigation with room-temperature tap water, 150 - 300 mL of fluid (50 - 100 mL for pediatric) patients, continuing for 1 - 2 L after aspirated fluid clears. Tube is left to administer activated charcoal in a dose of 1 g/kg.
AC is a carbon product that adsorbs a large number of substances. Administered as a slurry and may include a cathartic in the initial dose to decrease GI transit time of the AC-drug complex.
Iron and lithium will not adsorb to AC. Acid and caustic ingestion should not be give AC. It will obscure the endoscopic view.
PEG (polyethyelene glycol) electrolyte ingestion is administered to promote rapid transit time and for whole bowel catharsis. May be used in iron and lithium tablet ingestions. PEG used until fecal effluents are clear.
Disposition:
Assess for potential recurrence
Psychiatric consult, social worker, primary care involvement and poison control center. Inpatient.
Acetaminophen:
Toxicity occurs due to binding of a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), to hepatocytes. Acetaminophen is conjugated into harmless glucuronide and sulfate metabolites when taken in normal doses. If a large dose is taken, however, the metabolic pathway is overwhelmed, and a P450-dependent system converts some of the drug to a reactive intermediate (N-acetyl-p-benzoquinoneimine a.k.a NAPQI). This intermediate is conjugated with glutathione to a third harmless product. However, if glutathione stores are inadequate, the reactive intermediate which is hepatotoxic causes hepatic cell necrosis. Prompt administration of sulfhydryl donors (acetylcysteine) may be life-saving after an overdose. In patients with severe liver disease, stores of glucuronide sulfate, and glutathione may be depleted, making the patient more susceptible to hepatic toxicity with near-normal doses of acetaminophen. Ethanol exhausts glutathione stores, and may increased APAP toxicity. Similarly phenobarbital and phenytoin, may increase APAP toxicity because they increase phase I metabolism more than phase II metabolism, thus resulting in increased production of the reactive metabolite.
Timing of ingestion is critically important to determine potential toxicity, as a 4-h post-ingestion APAP level is required to determine the potential for toxicity, using the Rumack-Matthew nomogram. In general, ingestion of 140 mg/kg is considered toxic. Antidote for APAP is N-acetylcysteine (NAC) in a loading dose of 140 mg/kg by mouth, followed by maintenance doses of 70 mg/kg q4 h for the next 17 doses.
10-15 g can cause fatal hepatic necrosis
Beta blockers:
Beta rcp antagonists.
OD causes profound decrease in heart rate and contractility, hypotension, increased QRS duration, AV conduction delays, and asystole.
Antidote: Glucagon 5 - 10 mg (50 - 150 mcg in pediatrics) diluted to 10 mL saline, IV. Followed by an infusion of 1 - 5 mg/kg/h (10 - 50 mcg/kg/h for pediatrics).
CCB:
Antidote: Calcium chloride 10 - 20 mg/kg IV, with subsequent administration of glucagon if patients do not responding to initial therapy.
CO:
Clinical findings include flu-like symptoms such as headache, nausea, vomiting, and malaise. When a cluster of patients living or working together presents with similar sx, suspicion for CO poisoning is increased. Lab. findings include the findings of metabolic acidosis. Use cooximetry to determine the carboxyhemoglobin level in venous or arterial blood.
Antidote. O2 via NRM or hyperbaric chamber.
Cyanide:
Antidote: Amyl nitrate IH, followed by sodium nitrite 300 mg or 10 mL of a 3% solution IV for adults and 0.33 mL/kg for pediatrics. This is followed by sodium thiosulfate 12.5 mg or 50 mL of a 25% solution for adults, and 1.65 mL/kg for pediatrics.
TCA:
ECG findings include prolonged QRS duration. Seizures, hypotension, respiratory depression - usually occur within 6 h of ingestion and may rise rapidly.
Antidote: sodium bicarbonate for cardiac arrhythmias 1 meq/kg, and benzodiazepines IV for seizures.
Ethylene glycol/methanol:
Ethylene glycol is metabolized into toxic intermediates through a series of steps initiated by alcohol dehydrogenase. The end product is glycolic acid, which is directly nephrotoxic and is also metabolized to oxalate, which precipitates as calcium oxalate in the renal tubules, causing further damage.
Ethylene glycol causes altered mental status, slurred speech, ataxia, and seizures in the first 1 - 12 h after ingestion; subsequently, at 12 - 24 hrs, it leads to HTN, tachycardia, dysrhythmias, and pulmonary edema, and, at 24 - 72 hr, to flank pain, oliguria, and renal failure.
Methanol toxicity also results from the action of alcohol dehydrogenase, leading to the toxic intermediates of formic acid and formaldehyde and causing metabolic acidosis and possible retinal injury.
Antidote: Fomepizole 15 mg/kg over 30 min, followed by 10 mg/kg q12h for four doses.
Ethanol, IV
Organophosphates: commonly used as insecticides. Toxicity results from either ingestion or dermal exposure. It inhibits cholinesterase within the nervous system, resulting in an increase in acetylcholine at the nerve synapses and neuromuscular junctions, producing the cholinergic toxidrome.
Antidote is atropine, a competitive antagonist of acetylcholine, and pralidoxime (2-PAM), which directly restores acetylcholinesterase activity.
Iron: leading cause of accidental ingestion related death in pediatric patients. Direct corrosive effect on GIT, intracellular disruption of mitochondrial oxidative phosphorylation, and oxygen free radical formation. Clinical stages:
Stage 1: Abdominal pain, nausea and vomiting, and diarrhea < 6 h after ingestion, with resolution of symptoms in stage 2.
Stage 3: Shock, metabolic acidosis, renal failure, hepatic dysfunction, and coagulopathy.
Stage 4: Gastric and small bowel outlet obstruction.
Toxic dose of elemental iron ranges from 20 - 60 mg/kg for moderate toxicity, and greater than 60 mg/kg for severe GI toxicity. Mild systemic toxicity is seen when serum iron levels range between 500 - 1000 mcg/dL; and severe toxicity is noted with levels of >1000 mcg/dL.
Antidote: deferoxamine, a chelating agent, administered in a dose of 15 mg/kg/h by IV infusion.
Lithium: Used in bipolar disorders. Mild lithium poisoning results in nausea, vomiting, tremor, altered mental status, rigidity, hypotension, seizures, and cardiovascular collapse. ECG findings include signs of hypokalemia such as U waves, flat or inverted T waves, and ST-segment depression (from intracellular hypokalemia secondary to lithium-induced dysfunction of the sodium-potassium pump), 1st degree AV block, IVCD, and prolonged QT interval. Li does not adsorb on AC. HD is recommended for patients with levels > 3.5 mEq/L, renal failure, or sustained levels after IV hydration.
Opioids: OD result in bradycardia, hypotension, respiratory depression, miosis, altered mental status.
Antidote: Naloxone, 0.1 - 2 mg (0.01 mg/kg for neonates)
Salicylates: ASA OD results in stimulation of chemoreceptors and respiratory center in the medulla, causing nausea, vomiting, and hyperventilation. Intracellular salicylates cause metabolic derangements leading to the production of amino acids, CO2, glucose, ketones, lactate, and pyruvate, producing an AGMA. Ingestion of amounts in excess of 150 mg/kg generally produces mild to moderate toxicity, while doses of 300 mg/kg or more result in more severe presentations. Clinical findings include tachypnea, tinnitus, nausea, vomiting, and respiratory alkalosis early, with altered mental status, seizures, hyperthermia, and metabolic acidosis occurring late. Also look for signs and symptoms of H'ge. Check serum salicylate level.
GI decontamination, alkaline diuresis may enhance elimination. HD is required for patients with severe toxicity.
Max dose 4 g/d
BASICS-DESCRIPTION
Acute toxicity:
Caused by intentional ingestion, malicious poisoning, or medication error
Minimal lethal ingested dose ~2 mg/kg
Chronic toxicity:
Resulting from occupational exposures, water or food contamination, or use of folk remedies containing arsenic
Ingestion is the primary route of exposure
Inhalational toxicity is possible from arsine gas exposure
BASICS-ETIOLOGY
Most cases seen in the ED result from intentional ingestion or malicious poisoning
Sodium arsenate, found in ant killer, is the most common acute exposure in the US
Contaminated food and water supplies are the most common cause worldwide
Inorganic arsenic trioxide has been recently approved as a chemotherapeutic agent for acute myelogenous leukemia (AML)
Melarsoprol, an organic arsenical, has been used to treat trypanosomiasis since 1949
Found in pesticides, certain folk remedies (herbal balls), industrial wood preservatives
May be released as arsine gas from combustion of zinc- and arsenic-containing compounds
Mechanism
Arsenic exists in several forms—gas (arsine, or lewisite), organic, elemental, and inorganic
Inorganic forms (pentavalent and trivalent arsenic) are most frequently involved in toxic exposures:
Pentavalent arsenic uncouples oxidative phosphorylation
Most pentavalent arsenic is converted to the more toxic trivalent arsenic in the body
Trivalent arsenic binds sulfhydryl groups and interferes in hemoglobin production
Some trivalent arsenic may be methylated into species of varying toxicity
The more reactive species are DNA damaging and genotoxic
DIAGNOSIS-SIGNS-SYMPTOMS
CNS:
Altered mental status/encephalopathy
Neurodevelopmental deficits in children
Peripheral neuropathy
Acute: Sensory neuropathy
Subacute: Sensorimotor neuropathy
Peripheral dysesthesias
Headache
Seizures
Cardiovascular:
Prolonged QTc interval
Hypotension (acute) or hypertension (chronic)
Dysrhythmias, primarily ventricular
Nonspecific ST segment changes
Noncardiogenic pulmonary edema
Pulmonary:
Inhalational exposure increases lung cancer risk and respiratory mortality
Large acute ingestion (8 mg/kg) may lead to severe respiratory distress
Pulmonary edema, hemorrhagic bronchitis, and bronchopneumonia
GI:
Nausea, vomiting after ingestion and possibly inhalation
Protracted and may be refractory to antiemetics at usual doses
Can have hemorrhagic gastroenteritis; corrosive to GI tract
Rice water diarrhea
Abdominal pain
Garlic odor to breath, vomit, stools
Causes acute hepatitis; chronically, can cause portal HTN
A possible association with diabetes mellitus in chronic exposure
Miscellaneous (usually associated with chronic exposure)
Acute rhabdomyolysis
Blackfoot disease in Taiwan: Gangrene from loss of circulation to extremities
Dermatitis, such as toxic erythroderma and hyperkeratotic, hyperpigmented lesions
Hemolytic anemia (more pronounced with arsine gas exposure)
Hypothyroidism (antagonizes thyroid hormone)
Increased risk of carcinoma (liver/basal cell/squamous cell of skin/bronchogenic)
Leukopenia (after several days)
Mees lines (white bands across the nails owing to growth arrest caused by arsenic)
Patchy alopecia
Raynaud phenomenon and vasospasticity
DIAGNOSIS-ESSENTIAL-WORKUP
Spot urine arsenic level
CBC
DIAGNOSIS-TESTS
DIAGNOSIS-TESTS-Lab
Spot urine arsenic level >1,000 μg/L may confirm diagnostic suspicion:
Peaks 10–50 hr postingestion
Definitive test is 24 hr urine collection with speciation into organic and inorganic types of arsenic.
Blood levels not routinely helpful owing to short half-life in serum (~2 hr)
CBC to evaluate for anemia, leukopenia, basophilic stippling
Electrolytes, BUN/creatinine, and glucose
Urinalysis to look for evidence of hemolysis/rhabdomyolysis
Liver function tests
Total creatine phosphokinase (CPK) for rhabdomyolysis
Hair and nail arsenic levels:
Do not help in acute setting
May help determine chronicity of exposure in select populations
DIAGNOSIS-TESTS-Imaging
Plain abdominal radiographs to look for radiopaque foreign body
Cranial CT/other studies as indicated by patient’s condition
DIAGNOSIS-DIFF-DIAGNOSIS
Acute toxicity:
Acute appendicitis/colitis/gastroenteritis
Celiac disease
Cholera
Distributive shock
Encephalopathy
Toxic ingestions
Amanita mushroom poisoning
Cyclic antidepressants or other seizure-inducing toxins
Organophosphates
Chronic toxicity:
Addison disease
Guillain–Barré syndrome or other neuropathy
Raynaud phenomenon
Thromboangiitis obliterans, or other vasculitides
Vitamin deficiency (B3, B6, or B12)
Wernicke–Korsakoff syndrome
TREATMENT-PRE-HOSPITAL
If possible to do so safely, bring containers in suspected overdose/poisoning.
Decontaminate skin.
Support airway/breathing/circulation.
Cardiac monitoring
TREATMENT-INITIAL-STABILIZATION
ABCs:
Cardiac monitor
Isotonic crystalloids as needed for hypotension
Naloxone, thiamine, and dextrose (D50W) as indicated for altered mental status
Cardiovascular:
Vasopressors if refractory hypotension is present
Central venous pressure monitoring to prevent pulmonary/cerebral edema
Avoid type IA, IC and III antidysrhythmic agents, which worsen QTc prolongation
Continuous cardiac monitoring for QTc prolongation
Neurologic:
Treat seizures with benzodiazepines
Assist ventilation for respiratory failure from neuromuscular weakness
Renal:
Hemodialysis for renal failure
Alimentary:
Dextrose, enteral or parenteral feeding may be beneficial
TREATMENT-ED-TREATMENT
Decontamination:
Orogastric lavage or aspiration may be helpful within the 1st hr of ingestion
Activated charcoal does not bind arsenic
If opacities are seen on abdominal film, administer whole bowel irrigation (polyethylene glycol) at 1–2 L/hr until repeat radiographs are clear
If dermal exposure, decontaminate skin as 1st step in management
Ensure that no one else is contaminated and environment is evaluated
Ensure that electrolytes such as calcium, magnesium, and potassium are replaced
Evaluate need for chelation therapy, based on levels, acuity of exposure, clinical symptoms:
Consult with medical toxicologist/poison center
Agents
Dimercaprol (British anti-Lewisite)
DMSA (succimer)
Elimination:
Hemodialysis not routinely effective
Consider for patient with renal failure or other hemodialysis indications
Continue chelation throughout hemodialysis sessions
TREATMENT-MEDICATION
Dimercaprol (British anti-Lewisite): 3 mg/kg deep IM q4h for 24 h, then q6h for the next 24 h, then q12h until able to tolerate PO
Caution: Contraindicated in patients with peanut allergies
Dextrose 50%: 25 g (50 mL) (peds: 0.5 g/kg D25W) IV for hypoglycemia
DMSA (succimer): 10 mg/kg PO q8h for 5 d, then q12h for 14 d
Sodium bicarbonate: 1 mEq/kg IV bolus, followed by infusion of 150 mEq in 1 L of D5W at 150 mL/h
Used to treat rhabdomyolysis
Ensure that potassium and other electrolytes are monitored and replaced during infusion
Naloxone: 0.4–2.0 mg (peds: 0.1 mg/kg) IV, may repeat up to 10 mg for suspected opioid intoxication
Thiamine: 100 mg IM or IV (peds: 1 mg/kg)
Vasopressors after sufficient fluids
Dopamine 5 μg/kg/min, increase by 5–10 μg/kg/min (q10–30min) Max.: 20 μg/kg/min
Norepinephrine 0.01–3 μg/kg/min, start at 2 μg/min, titrate to MAP 65–90 mm Hg
Max.: 20 μg/min
FOLLOWUP-DISPOSITION
FOLLOWUP-DISPOSITION-Admission-Criteria
Symptomatic arsenic exposures should be admitted to an intensive care setting.
FOLLOWUP-DISPOSITION-Discharge-Criteria
Asymptomatic patients with a spot urinary arsenic level <50 μg/L may be discharged
Suspected chronic exposures who do not require admission should be referred for outpatient evaluation and 24 hr urine collection
Ensure that home environment is safe for patient prior to discharge
FOLLOWUP-FOLLOWUP-RECOMMENDATIONS
Psychiatric follow-up for intentional overdoses
Primary care follow-up for cancer screening and monitoring
Arsenic poisoning results in a myriad of signs and symptoms
Suspect acute arsenic poisoning when patients present with gastrointestinal distress and neurologic findings.
Suspect chronic arsenic poisoning in patients who present with neurologic deficits, nonspecific wasting, and hyperkeratotic skin lesions.
Consult a medical toxicologist/poison center regarding the need for chelation therapy.
A special thanks goes to Dr. Gerald Maloney Jr, who contributed to the previous edition.
Arsenic Poisoning