Neha N. Goel1, Stephanie Hernandez1, and Lisa Rho2
1 Icahn School of Medicine at Mount Sinai, New York, NY, USA
2 Reid Health, Richmond, IN, USA
Background
Definition of disease
Specific toxic syndromes or toxidromes are a symptom complex of a specific poisoning.
Given the similarities of the pharmacology of many toxins, treatment can be tailored to various toxidromes based on clinical presentation.
Incidence/prevalence
In its 2014 annual report, the American Association of Poison Control Centers compiled data from 56 poison centers in the USA, which reported a total of 2 165 142 human toxin exposure cases, 58% of which were adult exposures.
The five substance classes most frequently involved in all human exposures were analgesics (11.3%), cosmetics/personal care products (7.7%), household cleaning substances (7.7%), sedatives/hypnotics/antipsychotics (5.9%), and antidepressants (4.4%).
Etiology
The etiology of a poisoning is variable and can be from intentional drug overdose, illicit drug abuse, unintentional drug interactions, or environmental or occupational toxin exposures.
Prevention
Primary prevention
Community, family, and school‐based programs implemented in early childhood can help mitigate the risk of drug and alcohol abuse.
Educate patients regarding safe use, storage, side effects, and interactions of all prescription and over‐the‐counter medications.
Secondary prevention
Drug and alcohol rehabilitation as well as psychiatric evaluation should be considered when appropriate.
Diagnosis
Differential diagnosis
It is important to consider alternative or coexisting conditions for altered mental status other than toxin and drug ingestion such as sepsis, stroke, and seizures.
Typical presentation
The typical presentation of an intoxicated patient involves altered mental status as well as alteration of vital signs and physical exam findings specific for each toxidrome. Detailed presentations of the different toxidromes and associated drugs are listed in Table 32.1.
Clinical diagnosis
History
A history from an altered patient is usually unreliable. Efforts should be made to obtain the types and quantities of prescribed, over‐the‐counter, or illicit drugs that the patient may have ingested.
Emergency responders, friends, family members, and outpatient pharmacists can help provide information.
Physical examination:
See Table 32.1 for the typical presentations and different physical exam findings for different toxidromes.
Initial laboratory tests should include a comprehensive metabolic panel, complete blood count, and arterial blood gas. Serum levels of acetaminophen, salicylates, and ethanol should be assessed.
Serum and urine drug assays can help identify exposures to different drugs or their metabolites but cannot confirm that they are the reason for the poisoning. It is important to identify the specific toxin through history, physical exam, and clinical toxidrome and use these assays as validating tests.
The serum anion gap, osmolal gap, and oxygen saturation gap can help narrow down specific toxins:
Serum anion gap = [Na+] – ([Cl–] + [HCO3–]).
An elevated serum anion gap of >12 mEq/L is usually seen with ingestions of salicylates, methanol, ethylene glycol, isoniazid, paraldehyde, formaldehyde, NSAIDs, and metformin.
A low serum anion gap of <7 mEq/L is seen with ingestion of lithium.
An osmolal gap reflects the presence of an osmotically active substance, usually an alcohol, that has been ingested. It is the difference between the measured and the calculated osmolality of a serum.
Osmolal gap (normal <10) = Osmmeasured – Osmcalculated.
Causes of an elevated osmolal gap are acetone, isopropanol, mannitol, methanol, ethylene glycol, formaldehyde, and paraldehyde.
Winter’s formula can be used to calculate the expected PCO2 compensation in a pure metabolic acidosis.
PCO2 = 1.5 × HCO3 + 8 ± 2.
It identifies a mixed acid–base disorder, often a respiratory acidosis, reflecting inadequate respiratory compensation for the metabolic acidosis. This signifies the patient’s need for non‐invasive or invasive positive pressure ventilation.
Salicylate toxicity usually produces a mixed metabolic acidosis and respiratory alkalosis.
The oxygen saturation gap is the difference between the percentage oxygen saturation on an arterial blood gas and the percentage saturation measured by multi‐wavelength co‐oximetry.
The oxygen saturation gap is usually elevated from the presence of carboxyhemoglobin, methemoglobin, or sulfhemoglobin.
Cyanide poisoning does not result in an elevated oxygen saturation gap.
List of imaging techniques
Imaging techniques should be guided by clinical presentation and physical examination; this can include brain imaging for altered mental status and chest imaging for hypoxemia or respiratory insufficiency.
Abdominal X‐rays may help in certain toxicities, such as body packers, ingestion of radio‐opaque iron pills or leaded foreign bodies, and caustic ingestions.
Potential pitfalls/common errors made regarding diagnosis of disease
It is important to consider complications related to toxin ingestion as well as coexisting conditions when treating patients. For example, patients can come in with both an acute MI as well as cocaine intoxication and both should be treated appropriately.
Some drug assays may result in false positive results, false negative results, or reflect the patient’s drug exposure rather than the drug poisoning. History, physical exam, and clinical toxidrome must be used to diagnose and treat the drug poisoning.
All intentional drug overdoses should be screened for an acetaminophen concentration since it is a common ingestion, it may not be disclosed in the history, and there is no clinical toxidrome to identify the acute ingestion.
Be aware that several newer synthetic drugs such as synthetic cannabinoids and bath salts can have a varied presentation depending on their composition.
Treatment
Treatment rationale
Initial treatment of all toxin ingestions should focus on managing airway, breathing, circulation, and neurologic deficits (the ABCDs) of toxicology.
Reverse the toxin if possible with specific antidotes (Table 32.2).
Consider therapies that will reduce absorption (GI decontamination) or enhance elimination (urine alkalization, hemodialysis, intravenous lipid emulsion):
Activated charcoal is most effective within 1–2 hours of ingestion and can help reduce GI absorption by binding the toxin. Activated charcoal is not recommended in heavy metals, caustic agents, hydrocarbon, and toxic alcohol ingestion. Multiple‐dose activated charcoal is most effective for ingestions with theophylline, quinine, carbamazepine, dapsone, and phenobarbital, among others. It is contraindicated in patients at risk for bowel obstruction or perforation, or at risk of aspiration due to vomiting, altered mental status, or an unprotected airway.
Whole bowel irrigation is used for lithium, iron, sustained‐release or enteric‐coated medication overdose, or in cases of body packing. It is contraindicated with bowel obstruction, perforation, ileus, nausea/vomiting, or an unprotected airway.
Routine use of gastric lavage or induced emesis is not recommended.
Once toxin reversal and elimination have been attempted, supportive care should be the basis of treatment.
When to hospitalize
Patient who present with acute intoxication should be hospitalized or placed under observation for monitoring since the severity of ingestion can be unknown at the time of presentation.
Table of treatment
Toxin
Treatment and antidotes
Acetaminophen
N‐acetylcysteine:
PO: 140 mg/kg load then 70 mg/kg every 4 hours × 17 doses
IV: 150 mg/kg over 60 minutes; then 50 mg/kg over 4 hours; then 100 mg/kg over 16 hours
Treatment should not be delayed while waiting for levels if known acetaminophen ingestion Rumack–Matthew nomogram uses time from ingestion and the acetaminophen level to determine if N‐acetylcysteine is necessary Referral to liver transplant center if patient is at risk for developing fulminant hepatic failure Potential list for transplant according to King’s College Criteria:
Arterial pH <7.3 after adequate fluid resuscitation OR
Creatinine >3.4 mg/dL, INR> 6.5, and grade III hepatic encephalopathy or worse within 24 hour period
Anticholinergics
Physostigmine 0.5–2 mg IV over 5 minutes May repeat in 5–10 minutes
Benzodiazepines
Flumazenil 0.2 mg IV over 2 minutes Repeat 0.2 mg dose at 1 minute intervals to desired level of consciousness (max. dose 1 mg) Caution with patient on chronic benzodiazepines as flumazenil can precipitate withdrawal or possible seizures
Beta‐blockers
Glucagon 5–10 mg IV bolus over 1 minute then infusion of 1–10 mg/h titrated to symptom response Consider cardiac pacing Hyperinsulinemia–euglycemia therapy:
Insulin 1 U/kg IV bolus
Then, 0.5–1 U/kg/h IV drip
Monitor glucose every 30 minutes
If BG ≤250, give dextrose 25–50 g IV bolus then 0.5 g/kg/h IV infusion
Monitor potassium for hypokalemia
Botulinum
Botulinum antitoxin 1 vial IV; repeat every 2–4 hours PRN Epinephrine at bedside
Calcium channel blockers
2–3 g calcium gluconate or 1 g calcium chloride every 10 minutes Monitor serum calcium for hypercalcemia Glucagon 5–10 mg IV bolus over 1 minute then infusion of 1–10 mg/h can reduce vasopressor requirements Hyperinsulinemia–euglycemia therapy:
Insulin 1 U/kg IV bolus
Then, 0.5–1 U/kg/h IV drip
Monitor glucose every 30 minutes
If BG ≤250, give dextrose 25–50 g IV bolus then 0.5 g/kg/h IV infusion
Monitor potassium for hypokalemia
Carbon monoxide
100% supplemental O2 with 4.5–4.8% CO2 Hyperbaric O2 therapy for severe symptoms such as COHgb ≥25% (≥15% in pregnancy), coma, syncope, altered mental status, seizure, fetal distress, myocardial ischemia
Cocaine
Supportive therapy:
Benzodiazepines for agitation
Active and passive cooling for hyperthermia
Calcium channel blockers and nitrates for hypertension
Cyanide
100% oxygen Amyl nitrate 1 amp inhalation for 15–30 seconds every 30 seconds Sodium thiosulfate 12.5 g IV over 10–30 minutes; can repeat half dose in 2 hours or if symptoms reappear Hydroxycobalamin 5 g IV over 30 minutes Sodium nitrite 300 mg IV over 3 minutes; can repeat half dose if symptoms reappear
Digoxin
Digibind or digifab Acute ingestion: 10 vials:
No. of vials = [amount ingested (mg)] × 0.8/0.5 mg
Chronic ingestion: 3–6 vials:
No. of vials = [digoxin level (ng/mL)] × [weight (kg)]/100
Ethylene glycol
Goal: treat until levels <20 mg/dL:
Fomepizole 15 mg/kg IV load over 30 minutes, then 10 mg/kg IV every 12 hours × 4 doses
Continue 15 mg/kg IV bolus every 12 hours as needed
Thiamine 50–100 mg daily Pyridoxine 100 mg daily Hemodialysis in severe organ dysfunction Ethanol infusion (less preferred)
Iron
Deferoxamine 5 mg/kg/h IV and titrate to 15 mg/kg/h IV; max. dose 68 g. Limit to 24 hours
Isoniazid
Pyridoxine 1 g IV for every gram of isoniazid For unknown quantities, 5 g IV at 0.5 g/min until seizures stop
Lead
Succimer 10 mg/kg PO every 8 hours × 5 days; then 10 mg/kg PO every 12 hours × 14 days For lead encephalopathy:
Dimercaprol 75 mg/m2 deep IM every 4 hours x 5 days; first dose precedes EDTA by 4 hours
Followed by edetate calcium disodium 1500 mg/m2/day continuous IV or IM divided twice to four times a day
Lithium
Renal replacement therapy for serum lithium levels >3.5 mEq/L in acute ingestion and >2.5 mEq/L in chronic ingestion Monitor for rebound increase in lithium levels when using hemodialysis as it does not affect intracellular lithium
Methanol
Goal: treat until levels <25 mg/dL:
Fomepizole 15 mg/kg IV loading dose over 30 minutes, then 10 mg/kg IV bolus every 12 hours × 48 hours
Followed by 15 mg/kg IV bolus every 12 hours as needed
Folate 1–2 mg/kg (50–75 mg) IV every 4 hours × 24 hours. Extra dose at completion of hemodialysis Hemodialysis in severe organ dysfunction or levels >50 mg/dL Ethanol infusion (less preferred)
Methemoglobinemia
Methylene blue 1–2 mg/kg or 0.1–0.2 mL/kg of 1% solution over 5 minutes
Neuroleptic malignant syndrome
Bromocriptine 2.5–10 mg PO three to four times a day
Opiates
Naloxone 0.04–0.05 mg IV initial dose, can increase to 1–2 mg IV if no response after 2–3 minutes to max. dose of 10 mg If repeated boluses are required, consider naloxone infusion with hourly rate two‐thirds of IV bolus dose given Goal: adequate ventilation or respiratory rate ≥12. Do not titrate to normal level of consciousness Caution in patients with chronic opiate use as high doses of naloxone can induce withdrawal
Organophosphates/cholinergic toxidrome
For respiratory symptoms the goal is atropinization (mydriasis, dry mouth, tachycardia): atropine 1–2 mg IV push initially with subsequent doses doubled every 2–3 minutes until symptoms resolve Glycopyrrolate 1–2 mg IV if atropine dose required is high enough to cause additional CNS toxicity For severe toxicity, muscle fasciculation, and weakness: pralidoxime 1–2 g or 25–50 mg/kg IV over 30 minutes, then 200–500 mg/h or 10–20 mg/kg/h infusion Benzodiazepines such as diazepam 10–20 mg IV can be used for seizures, anxiety, or fasciculation
Salicylates
Multiple dose activated charcoal NaHCO3 150 mEq in 1 L D5W IV infusion: goal is urine pH to 8.1 or plasma pH 7.45–7.50 Hemodialysis:
Chronic ingestion: serum salicylate level >60 mg/dL or for symptomatic patient
Serotonin toxidrome
Cyproheptidine 4–12 mg PO initial dose then 2 mg every 2 hours until clinical response Maintenance dose 4–8 mg every 6 hours (max. 32 mg/day)
Sulfonylureas
25 g of 50% dextrose (D50W) IV Octreotide 50–150 μg IM/SQ every 6 hours
Tricyclic antidepressants
NaHCO3 1–2 mEq/kg IV bolus for QRS widening NaHCO3 150 mEq in 1 L D5W IV at 1–3 mEq/mg/h to target serum pH 7.45–7.50 Lidocaine for ventricular arrhythmias 200 mL of 3% NaCl hypertonic saline for refractory arrhythmias despite pH >7.55
Valproic acid
l‐carnitine:
Symptomatic: 100 mg/kg IV (max. 6 g) load over 30 minutes; then 15 mg/kg IV every 4 hours over 10–30 minutes
Asymptomatic: 100 mg/kg/day (max. 3 g) PO divided over 6 hours
Prevention/management of complications
Some patients presenting with severe intoxications can require prolonged ventilation or ICU support. It is important to ensure that measures be taken to avoid complications related to supportive therapy, such as minimizing sedation, providing daily spontaneous awakening trials, and mobilizing patients.
Once the patient is recovering, psychiatric evaluation is necessary for intentional ingestions, and drug and alcohol rehabilitation should be considered to prevent readmissions and relapse.
