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General Management of Poisoned Patients PWM OLLY INDRAJANI 2013 Introduction • 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 - mucous membrane exposure, and - injection. • Historically most poisonings have occurred when substances are tasted or swallowed •Toxins may be airborne in the form of gas or vapors or in a suspension such as dust. • Caustics, vesicants, or irritants may directly affect the skin, or a toxin may pass transdermally and affect internal structures (e.g., methylene chloride, aniline dye). •Parenteral exposure results from IV or SC injection of medications or drugs of abuse Resuscitation The first priority in treating poisoned patients is assessment and stabilization of cardiopulmonary function (e.g., the ABCs, or airway, breathing, and circulation). Once the airway and respiratory status, blood pressure, and pulse are stabilized, abnormalities of core (rectal) temperature, oxygen saturation, and hypoglycemia are addressed Although the proper use of antidotes is essential in the treatment of poisoned patients • Patients may have an altered mental status because of hypoxia, opioid intoxication, hypoglycemia, and Wernicke Encephalopathy, conditions readily treated by specific antidotes. • Empiric administration of antidotes (the "coma cocktail"), including supplemental oxygen, naloxone, glucose, and thiamine, should be considered after the medical history, vital signs, and immediately available laboratory data are taken into account • The dogma that the administration of thiamine should precede the administration of glucose to prevent the precipitation of acute Wernicke encephalopathy is unfounded. • Naloxone is a competitive opioid antagonist without any intrinsic toxicity that can be administered IV or IM and is appropriate to use in a hypoventilating opioid-intoxicated patient who is not intubated. • Naloxone may be given to children as a therapeutic challenge when unintentional or intentional opioid exposure cannot be excluded. • Using miosis as the sole indication for naloxone administration is unreliable, because many other toxins can produce small pupils along with mental status depression, and some opioids classically leave pupil size unaltered (e.g., meperidine, propoxyphene). • Naloxone often completely reverses the effects of the opioid and restores effective ventilations and mental status for 20 to 60 minutes, so patients should be observed for 2 to 3 hours after IV administration • The risks of naloxone treatment are few but include the precipitation of an acute opioid withdrawal syndrome. • Although acute withdrawal is never lifethreatening in adults, vomiting from withdrawal can result in aspiration. • Thus, the reflexive administration of large doses of naloxone should be discouraged ED Diagnosis History It is often difficult to obtain a reliable and accurate history from overdose patients Obtain as much information as possible about the exposure. Ask about the agent or drug, estimated amount or dose, and route of exposure, as well as whether other individuals were exposed. If possible, the patient's intent should be determined Ask about the environment in which the patient was found, the presence of empty pill bottles or containers nearby, any smells or unusual materials in the home, the occupation or hobbies of the patient, and the presence of a suicide note Toxicologic Physical Examination • Undress the patient completely. Check the patient's clothing for objects still retained in the pockets or substances hidden on the patient's body (waistband, groin, or between skinfolds) • Assess the general appearance of the patient and note any agitation, confusion, or obtundation. • Examine the skin for cyanosis or flushing, excessive diaphoresis or dryness, signs of injury or injection, ulcers, or bullae. • Bruising may be a clue to trauma, a prolonged duration of unconsciousness, or coagulopathy. Toxicologic Physical Examination • Examine the eyes for pupil size, reactivity, nystagmus, dysconjugate gaze, or excessive lacrimation. • Examine the oropharynx for hypersalivation or excessive dryness. Auscultate the lung fields to assess for bronchorrhea or wheezing, and the heart for its rhythm, rate, and regularity. • Examine the abdomen, noting the presence of bowel sounds, enlarged bladder, and abdominal tenderness or rigidity. Evaluate the extremities for muscle tone and note any tremor or fasciculation Toxidromes Toxicologic Screen In the emergency setting, toxicologic screening tests of blood and/or urine do not contribute significantly to the evaluation, management, or outcome for most patients. On the other hand, there are toxins for which the serum level does influence emergency treatment and disposition Positive results may occur with many substances because they persist in body fluids for days to weeks, depending on the chronicity of use Interpretation of urine toxicology screening test results requires an understanding of their limitations. positive results may occur from substances that cross-react with the assay (e.g., pseudoephedrine, oxymetazoline, methylphenidate, and selegiline for amphetamines; chlorpromazine, cyclobenzaprine, thioridazine, diphenhydramine, and cyproheptadine for tricyclic antidepressants). Negative results may be due to sampling error (e.g., very dilute urine after hydration) or assay specificity (e.g., opioid screens do not detect methadone and meperidine; amphetamine screens do not detect methylenedioxymethamphetamine; benzodiazepine screens do not detect flunitrazepam General Decontamination • The general approach to most toxic exposures the removal of the patient from the substance and the substance from the patient. • Toxins on the outside of the body washed away. • Toxins within the body, either bound within the gut lumen to make it unavailable for absorption or elimination from the gut, blood, or tissues can be enhanced. Gross Decontamination • Surface decontamination is achieved by completely undressing patients and thoroughly washing them with copious amounts of water. Patients requiring assistance should be attended to by properly gowned staff. • The towels used to dry patients and patients' clothing, shoes, socks, watches, and jewelry should be handled as contaminated material. • If possible, surface decontamination should occur prior to the patient's entry into the ED or other areas in the hospital. • In mass casualty exposures, this typically occurs at a staging area adjacent to the ED Ocular exposures are treated with copious irrigation using isotonic crystalloid, either normal saline or lactated Ringer's solution, typically at 1 to 2 L per eye depending on the agent. Application of an ophthalmic anesthetic, such as 0.5% tetracaine, may be necessary to relieve blepharospasm and facilitate irrigation Eye Decontamination Use of lid retractors may be required for adequate irrigation Lengthy continuous irrigation (possibly 1 or even 2 hours) may be required, until the tears in the conjunctival sac have stabilized to a pH of <8. The pH of normal tears is slightly acidic, whereas the pH of normal saline solution is 5.6. A period of 10 minutes or longer after the cessation of irrigation may be required for accurate pH determination of the tears GI Decontamination • The three general methods of decontamination: 1. Removing the toxin from the stomach via the mouth 2. Binding it inside the gut lumen 3. Enhancing transit through the intestines • GI decontamination should never be initiated as a punitive action. Gastric Emptying Emesis Contraindications to the Ipecac syrup is a plantipecac should be used only administration of ipecac derived compound in rare circumstances, such include ingestions that have composed of two alkaloidal as immediately after the potential to alter mental substances emetine and ingestion of a substance not status, active or prior cephaeline,that work both expected to compromise the vomiting, caustic ingestion, peripherally on the stomach airway or lead to altered exposure to a toxin with and centrally on the mental status, hemodynamic more pulmonary toxicity chemotactic trigger zone to derangement, or seizure, or from inhalation than toxicity induce vomiting. The typical after recent ingestion of a from GI absorption (e.g., dose is 15 mL for children 1 highly toxic pill that is known hydrocarbons), and to 12 years of age and 30 mL not to fit into the holes of ingestions of toxins that for adults, usually followed the appropriately sized have the potential for by sips of water. orogastric tube inducing seizures. Orogastric Lavage The contraindications to lavage include ingestion of pills that are Perform lavage with small amounts of fluid, 200 to 300 mL known not to fit into the holes of the orogastric lavage hose, in adults and 10 mL/kg in children, to avoid stimulating nontoxic ingestions, non–lifethreatening ingestions, caustic the propulsion of gastric ingestions, lack of assurance of contents into the duodenum. Gastric lavage with cool airway integrity, and toxic ingestions that are more solutions can induce hypothermia, so use of bodydamaging to the lungs than the GI tract, such as hydrocarbons temperature or at least roomtemperature solutions is that pose a greater risk from pulmonary aspiration than from recommended. gastrointestinal absorption Although the perceived benefits of orogastric lavage are the immediate return of small pills or pill fragments and a reduction in the amount of substance available for further intoxication, experimental studies typically demonstrate variable drug removal that, at best, is typically about 50% Toxin Adsorption in the Gut Activated Charcoal Activated charcoal works by adsorbing substances in the gut lumen via Van der Waals forces, which makes them less available for absorption into the tissues. Activated charcoal enhances drug and toxin elimination by establishing a concentration gradient favoring movement into the intestinal lumen, entrapping the agent until it can be eliminated out of the body by defecation,can also bind substances excreted in the bile, interrupting enterohepatic circulation. Reviews and recommendations note that clinical benefit is more likely if activated charcoal is administered within 1 hour of toxin ingestion, but that potential benefit of administration after more than 1 hour cannot be excluded. The benefits of this technique include its ability to decontaminate the gut without requiring invasive procedures, the rapidity of its administration, and its overall safety in both adults and children Activated charcoal is typically given in a slurry of water or juice by mouth or through a nasogastric tube. Recommended dosing is a 10:1 ratio of activated charcoal to drug, which is thought to be the smallest dose of activated charcoal that can be given without reducing its efficacy, or 1 gram/kg Clear indications for administration of activated charcoal are recent ingestion of any drug known to adsorb to it or ingestion of an unknown agent by a patient with a protected airway Multidose activated charcoal entails the repeated use of activated charcoal to enhance elimination of ingested toxins Case reports have found that multidose activated charcoal can improve the clearance rates of theophylline, carbamazepine, phenobarbital, quinine, and dapsone in cases of life-threatening ingestion at rates comparable to those of hemodialysis or charcoal hemoperfusion Multidose Activated Charcoal Multidose activated charcoal is usually given with a first dose of 1 gram/kg body weight (50 to 100 grams) followed by subsequent doses of 0.25 to 0.50 gram/kg (12.5 grams) repeated one to three times at intervals ranging from 1 to 4 hours. Intubated patients who have ingested life-threatening toxins often have decreased gut motility and might benefit from multiple doses To prevent excessive fluid loss and electrolyte imbalance, only the first dose of activated charcoal should be given with a cathartic, and only if the toxin itself is not expected to cause diarrhea. Multidose activated charcoal is contraindicated in patients with non–life-threatening ingestions that result in decreased gut motility because of increased risks of aspiration from gastric distention and impaction of charcoal within the gut Enhancement of Bowel Transit Cathartics Activated charcoal is often administered with an osmotic cathartic, such as 70% sorbitol (1 gram/kg) or a 10% solution of magnesium citrate (250 mL for adults and 4 mL/kg for children Indications for the use of cathartics generally mirror those for the administration of activated charcoal. When multidose activated charcoal is used, only the first dose is accompanied by a cathartic to limit complications. Complications of cathartic administration include nausea and abdominal pain, severe volume depletion, electrolyte imbalances and fluid shifts, and hypermagnesemia in patients with renal compromise Cathartics decrease the transit time for the passage of the activated charcoal (and presumably the adsorbed toxin) through the GI tract Contraindications for cathartic use are ingestion of a substance that will result in diarrhea, age of <5 years, renal failure (magnesiumcontaining cathartics are contraindicated), intestinal obstruction, and ingestion of any caustic material Whole-Bowel Irrigation • Whole-bowel irrigation is best accomplished by infusing the polyethylene glycol solution through a nasogastric tube, although in motivated patients, oral ingestion can be used. Typical doses are 1.5 to 2.0 L/h in adults, 1 L/h in children 6 to 12 years of age, and 0.5 L/h in children <6 years of age. • Contraindications include preceding diarrhea, ingestion of substances that are expected to result in significant diarrhea (except for heavy metals, because these substances do not adsorb well to activated charcoal), and bowel obstruction as evidenced by lack of bowel sounds. • Complications include bloating, cramping, and rectal irritation from frequent bowel movements. The first is that only nonionized substances are free to move passively across membranes, whereas ionized particles must remain in the fluid-filled compartments in which they were formed ("ion trap"). The second is that weak acids or bases become more ionized in the opposite environment. After IV administration, bicarbonate becomes concentrated in the urine, which results in significant elevation of urinary pH (provided the patient has a normal serum potassium level) Enhanced Elimination Urinary Alkalinization Urinary alkalinization is typically achieved by the administration of sodium bicarbonate as either a 1 to 2 mEq/kg IV bolus or 3 to 4 mEq/kg IV infusion over 1 hour.15 Urinary pH should be monitored frequently (every 15 to 30 minutes) until the urine pH is 7.5 to 8.5. Urinary alkalinization is sustained by either intermittent bolus or continuous infusion of bicarbonate. Serum pH should not be allowed to rise above 7.5 to 7.55. Pronounced hypokalemia may result from this procedure and should be corrected to maintain treatment benefit Urinary Acidification • Acidification of urine can somewhat enhance elimination of weak bases, such as amphetamines, phencyclidine, and some other drugs. However, the risks, particularly in relation to rhabdomyolysis, far outweigh any benefits • Forced diuresis has never been shown to be effective for ingestion of any toxin, with the possible exception of chlorophenoxy herbicides when diuresis is combined with urinary alkalinization The benefits include the ability to remove toxins that have already been absorbed from the gut lumen, to remove substances that do not adhere to activated charcoal, and to remove both the parent compound and the active toxic metabolites. Hemodialysis is much less effective when the toxin ingested has a large volume of distribution (>1 L/kg), has a large molecular weight (>500 Da), or is highly protein bound relatively contraindicated in patients with hemodynamic instability, very small children, and patients with poor vascular access or profound bleeding diatheses. Risks of hemodialysis are typically minimal in experienced centers, but they include large fluid shifts, electrolyte imbalances, infection and bleeding at the catheter site, and intracranial hemorrhage from the required anticoagulation Hemodialysis/ Hemoperfusion Hemoperfusion, which is also used for decontamination of a patient's systemic circulation, involves placing a filter filled with activated charcoal into the circuit of the hemodialysis device. This filtration alleviates the constraints of protein binding and molecular size, both of which limit the utility of hemodialysis Toxins that can be removed by this method must adsorb well to activated charcoal and have a small volume of distribution. Although potentially useful for toxic ingestions of phenobarbital, phenytoin, and ethchlorvynol, in practice, hemoperfusion is most commonly used for theophylline and carbamazepine overdoses