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ToxicologyPWM Olly Indrajani20121IntroductionGiven a large enough exposure, all substances have the potential to be poisons. Poisoning occurs when exposure to a substance adversely affects the function of any system within an organism. The setting of the poison exposure may be occupational, environmental, recreational, or medicinal. Poisoning may result from varied portals of entry, including inhalation, insufflation, ingestion, cutaneous and mucous membrane exposure, and injection. DIFFERENTIAL DIAGNOSIS BY CHIEF COMPLAINTAlthough the poisoned patient may present with varied symptoms and complaints, the chief presenting complaint or symptom may suggest a diagnosisRecognition of grouped symptoms and findings consistent with a toxidrome can guide diagnosis and treatment in the poisoned patient.Primary Considerations for Presenting Chief Complaint in the Poisoned Patient

Toxidromes

Oral ingestion was the commonest route of exposure (Fig 1)Most exposures occurred at the patients own residence, and most patients (75%) were managed on-site with assistance from a poison information center and did not require an emergency department visitOnly 3% of patients required critical care.

Largest number of deaths were: analgesicsAntidepressantssedative/hypnotics/antipsychoticsStimulantsstreet drugscardiovascular drugsalcohols

Of all deaths: 5% increase compared to 199988% occurred in 20- to 99-year old individualThe mortality rate was higher in intentional rather than unintentional exposures (79% vs 10.5%, respectively).

DIAGNOSISHistory and physical examinationVital signsOcular findingsMental status, behaviour and muscle tonePoison control center consultation

Laboratory evaluation:Anion gapOsmolal gapOxygen saturation gapToxicology screening

History and Physical ExaminationAlthough the history is important, it may be unreliable or incompleteConsider that family members, friends, and pharmacists may have additional information

In the absence of a classic presentation or toxidrome, separating patients with suspected poisoning into broad categories based on:vital signsocular findingsmental statusmuscle tone can help determine drug or toxin class

Vital SignsAnticholinergic and sympathomimetic substances increase heart rate, BP, and temperatureIn contrast organophosphates, opiates, barbiturates, -blockers, benzodiazepines, alcohol, and clonidine cause hypothermia, bradycardia, and respiratory depression.

Ocular FindingsAnticholinergics and sympathomimetics cause mydriasisIn contrast to anticholinergics overdose, the pupils remain somewhat light responsive in cocaine intoxicationHorizontal nystagmus is common in alcohol intoxicationOther drugs causing nystagmus are lithium, carbamazepine, solvents, meprobamate, quinine, and primidonePhencyclidine and phenytoin cause horizontal, vertical, and rotary nystagmus

Mental Status, Behavior, and Muscle Tone

Initial Supportive Measures

Airway, Breathing, Circulation

Often required before confirmation of intoxicationWith cervical spine precautions in place (unless trauma has been excluded), airway patency must be ensured in all casesEndotracheal intubation is not always necessary when cough and gag reflexes are present and there is adequate spontaneous ventilation, but when there is concern regarding airway protection and clinical deterioration it is better to secure the airwayIntubation is indicated in acute respiratory failure

Other specific indications include the need for high levels of supplemental oxygen in carbon monoxide poisoning and the need to protect the airway for gastric emptyingEndotracheal intubation decreases (but does not eliminate) the risk of aspiration which is approximately 11% in the comatose patient with drug overdose)

Depending on the intoxication, patients may present with hypotension or hypertension, bradyarrhythmias or tachyarrhythmiasThe pathogenesis of hypotension varies and may include hypovolemia, myocardial depression, cardiac arrhythmias, and systemic vasodilationTreatment should be individualized, but an initial strategy of rapid IV normal saline solution infusion is indicated in most instancesVasopressors may be required for refractory hypotension.

The vasopressor of choice depends on the type of intoxication

Hypertension occurs in the setting of sympathomimetic drugs, anticholinergics, ergot derivatives, phenylpropanolamine overdose, and withdrawal from nicotine, alcohol, and sedatives

Treatment of the hypertension depends on its chronicity and severity and the inciting agent

Hypertension-induced (reflex) bradycardia generally should not be treated.

Coma Cocktail

Thiamine (100 mg by vein) is administered to treat and/or avoid Wernicke-Korsakoff syndrome in comatose patientsComatose patients should receive dextrose, 50 g IVNaloxone rapidly reverses coma, respiratory depression, and hypotension induced by opioids. An initial dose of 0.2 to 0.4 mg is administered IV (or endotracheally).

Prevention of Absorption

Skin decontamination requires removal of the toxin with nonabrasive soap and waterContaminated clothing may serve as a reservoir for continued exposure and must be removed with caution and placed in plastic bags or other containers that are impervious to the toxinOcular decontamination may require prolonged periods of irrigation with normal saline solution

PRINCIPLES OF GASTROINTESTINAL DECONTAMINATIONGastrointestinal (GI) decontamination refers to therapies that may decrease the amount of poison absorbed from the GI tract lumen.

The following methods of GI decontamination are available:

A. Induced emesisB.Gastric emptying or Gastric lavage (GL)C. Activated charcoal combined with a catharticD.Whole-bowel irrigation(WBI)EmesisConsidered only in fully alert patients, and is virtually never indicated after hospital admissionContraindications to its use include poisoning with corrosives, petroleum products, or antiemetics.

A. Induced EmesisInduced emesis utilizes syrup of ipecac to induce vomiting, theoretically emptying the stomach and reducing absorption of an ingested agent. Syrup of ipecac induces vomiting by activation of both local and central emetic sensory receptors.Induced emesis has largely been abandoned in clinical practice. The most recent policy statements released by both the American Academy of Pediatrics(2003) and the American Association of Poison Control Centers (2005) discourage the use of syrup of ipecac in the out-of-hospital setting.Gastric EmptyingGL through a 28F to 40F Ewald tube is similarly aimed at physically removing a toxinPrior to inserting the Ewald tube, the mouth should be inspected for foreign material and equipment should be ready for suctioningLarge gastric tubes (37F to 40F) are less likely to enter the trachea than smaller nasogastric tubes, and are necessary to facilitate removal of gastric debris

Nonintubated patients must be alert (and be expected to remain alert) and have adequate pharyngeal and laryngeal protective reflexesIn semicomatose patients, GL should be performed only after a cuffed endotracheal tube has been inserted.

GL is performed by instilling 200-mL aliquots of warmed tap water until there is clearing of aspirated fluidStomach contents should be retained for analysisTap water may avoid unnecessary salt loading compared to normal saline solutionNeither irrigant has been shown to significantly alter blood cell or electrolyte concentrationsAfter clearing, the Ewald tube may be replaced by a nasogastric tube for subsequent intermittent suctioning and/or administration of activated charcoal.

American Academy of Clinical Toxicologydoes not recommend routine use of GL in the management of poisoning unless a patient has ingested a potentially life-threatening amount of a poison and the procedure can be undertaken within 60 min of ingestion

B. Gastric LavageINDICATIONSIngestion of a substance with high toxic potential and: Within 1 hour of ingestion Ingested substance is not bound by activated charcoal or has no effective antidote. Potential benefits outweigh risks.CONTRAINDICATIONS Substance not meeting above indications Spontaneous emesis Diminished level of consciousness/unprotected airway reflexes (intubate first) Ingestion of hydrocarbons or caustic agents Foreign body ingestion Patient is at high risk for esophageal or gastric injury (GI hemorrhage, recent surgery, etc.).TECHNIQUE Recommended tube size is 3640 French for adults, 2228 French for children. Secure airway via intubation, if necessary. Position patient in left-lateral decubitus position, with head lowered below level of feet. Confirm tube placement following insertion. Aspirate any available stomach contents. Lavage with 250 mL (1015 mL/kg in children) aliquots of warm water or saline. Continue until fluid is clear and a minimum of 2L has been used. Instill activated charcoal through same tube, if indicated.

COMPLICATIONS The primary risks are vomiting, aspiration, and esophageal injury or perforation.C. Activated CharcoalINDICATIONSActivated charcoal (AC) is ingested by the patient in order to adsorb poisons within the GI tract lumen.

Patient presents within 1 to 2 hours after ingestion. Patient has ingested a potentially dangerous amount of a poison adsorbed by charcoalCONTRAINDICATIONS Ingested substance is poorly adsorbed by AC (eg, iron, lithium, heavy metals,toxic alcohols). Diminished level of consciousness/unprotected airway reflexes (AC can be given by naso- or orogastric tube following intubation) Patient presents over 2 hours after ingestion. Ingestion of caustic agents Cases where endoscopy will be requiredDOSE

The recommended dose of AC is a 10:1 ratio relative to the ingested poison(ie, ingestion of 1 g of poison requires 10 g of AC). Hence, the commonED practice of administering 50 to 100 g (1 g/kg) of AC to an overdose patient may be inadequate for larger ingestions.RISKS

The primary risk of single-dose AC is vomiting. Constipation and diarrhea Bowel obstruction does not occur from single-dose AC. Repeated doses of cathartics given with charcoal may cause dehydration or electrolyte abnormalities.INDICATIONSCONTRAINDICATIONS

D. Whole -Bowel Irrigation

Whole-bowel irrigation (WBI) flushes the GI tract to decrease the transit timeof luminal contents, thereby limiting absorption.

INDICATIONS Removal of ingested drug packets (eg, body stuffers) Large ingestion of a sustained-release drug Potentially toxic ingestion that cannot be treated with activated charcoal (eg, lithium, lead, iron)CONTRAINDICATIONS Diminished level of consciousness/unprotected airway reflexes (intubate first) Decreased GI motility or bowel obstruction Significant GI hemorrhage Persistent emesisDOSE

Polyethylene glycol (PEG) solution is administered at a rate of 12 L/hour.This rate of administration usually requires a naso- or orogastric tube. Endpoints for therapy are the appearance of clear rectal effluent or a total irrigation volume of 10 L.COMPLICATIONS

The primary risk associated with WBI is vomiting.Patient discomfort: Bloating, cramping, and flatulenceWBI with balanced PEG solutions does not generally cause electrolyte abnormalities.PRINCIPLES OF ENHANCED ELIMINATIONThe goal of enhanced elimination is to increase the clearance of a poison from the body after it has been systemically absorbed.

The following methods of enhanced elimination are available:A. Multiple-dose activated charcoalB. Urinary alkalinizationC. Hemodialysis Enhanced Elimination: Drug Characteristics and Examples

A. Multiple-Dose Activated CharcoalUses repeated doses of activated charcoal (every 24 hours) to increase poison clearance. MDAC exerts its effects through disruption of enterohepatic circulation or direct adsorption across the GI mucosal surface.

RISKSThe risks associated with MDAC are similar to those with AC; however,there is a greater risk of bowel obstruction with MDAC.INDICATIONSDrugs that have enterohepatic circulation and can possibly be treated with MDAC include:

Phenobarbital Carbamazepine (Tegretol) Theophylline Aspirin DapsoneCONTRAINDICATIONSMDAC is contraindicated in the same settings as AC.B. Urinary AlkalinizationUrinary alkalinization attempts to increase renal elimination of a drug by increasing urine pH.

Urinary acidification to increase the clearance of weak bases is not recommended due to the risk of renal injury.

RISKSCan precipitate hypokalemia and decrease ionized calcium levels INDICATIONS Urinary alkalinization only affects the clearance of drugs that are weak organic acids.

Aspirin (most common use for alkalinization) Phenobarbital Formic acidCONTRAINDICATIONS Poisoning with agents that are not weak organic acids and are not primarily cleared by the kidneys Patients who cannot tolerate excess sodium/water loading (eg, CHF, renal failure)C. HemodialysisHemodialysis (HD) directly removes toxins from a patients plasma, using the same technology applied to renal failure.

RISKS HD requires central venous access, with all the usual accompanying risks (bleeding, pneumothorax, etc.). HD must be used cautiously in patients that are hemodynamically unstable.INDICATIONSFor HD to be useful in a poisoned patient, the ingested poison should have the following characteristics:

Low molecular weight Low plasma protein-binding Small volume of distribution Poor endogenous clearance HD can also treat severe acidosis caused by a toxin, even if the toxin it self is not readily dialyzable.CONTRAINDICATIONS Toxins that do not satisfy the conditions listed above.

Poison Control Center Consultation

Regional poison control center consultation is highly recommended in cases of suspected poisoning and to help guide management in confirmed casesThese centers provide 24-h emergency and up-to date technical information. They are staffed by nurses, pharmacists, pharmacologists, and physicians trained and certified in toxicology

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