++
The majority of poisoning exposures reported to U.S. poison control centers are judged to be nontoxic or only minimally toxic (Bronstein et al., 2008). When toxicity is expected, or does occur, the priority of poisoning treatment is to support vital functions until the drug or chemical is eliminated from the body. Because of the acute onset of action and finite duration of action of most drugs, the treatment of poisoning must be prompt and goal-directed. The first goal is to maintain vital physiological functions from impairment. The second goal is to keep the concentration of poison in tissues as low as possible by preventing absorption and enhancing elimination. The third goal is to combat the toxicological effects of the poison at the effector sites.
++
Initial Stabilization of the Poisoned Patient. The "ABC" mnemonic of emergency care is popularly taught and applies to the treatment of acute poisoning (Table 4–8). In severe cases, endotracheal intubation, mechanical ventilation, pharmacological blood pressure support, and/or extracorporeal circulatory support may be necessary and appropriate.
++
++
Identification of Clinical Patterns of Toxicity. A carefully obtained medical history may allow for the creation of a list of available medications or chemicals that might be implicated in a poisoning event. Often, an observation of physical symptoms and signs may be the only additional clues to a poisoning diagnosis. Groups of physical signs and symptoms associated with specific poisoning syndromes are known as toxidromes (Erickson, 2007; Osterhoudt, 2004). Table 4–9 describes commonly encountered toxidromes.
++
+
The most typically available urine drug toxicology test is an immunoassay designed to detect common drugs of abuse such as amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, and opiates. Acute poisoning with these substances can usually be determined on clinical grounds, and the results of these assays are infrequently available fast enough to guide stabilization. Additionally, detection of drugs or their metabolites on a urine immunoassay does not mean that the detected drug is responsible for the currently observed poisoning illness. When ingestion of acetaminophen or aspirin cannot clearly be excluded via the exposure history, serum quantification of these drugs is recommended. An electrocardiogram (ECG) may be useful at detecting heart blocks, Na+ channel blockade, or K+ channel blockade associated with specific medication classes (Table 4–10). Further laboratory analysis, such as use of blood gas determinations, serum chemistries, complete blood counts, and other testing, should be tailored to the individual poisoning circumstance.
++
++
Decontamination of the Poisoned Patient. Poisoning exposures may be by inhalation, by dermal or mucosal absorption, by injection, or by ingestion. The first step in preventing absorption of poison is to stop any ongoing exposure. If necessary, eyes and skin should be washed copiously. Gastrointestinal decontamination is the process of preventing or reducing absorption of a substance after it has been ingested. The primary strategies for GI decontamination are gastric emptying, adsorption of poison, and catharsis. Minimal indications for considering GI decontamination include: 1) the poison must be potentially dangerous; 2) the poison must still be unabsorbed in the stomach or intestine, so it must be soon after ingestion; and 3) the procedure must be able to be performed safely and with proper technique. Gastric emptying is rarely recommended anymore, but the administration of activated charcoal and the performance of whole bowel irrigation remain therapeutic options.
+
Gastric emptying may be attempted by induced vomiting or by gastric lavage. Historically, pharmaceutical methods to stimulate vomiting included administration of potentially toxic doses of copper sulfate or apomorphine; more recently, syrup of ipecac took their place as the favored drug to induce emesis. Gastric emptying has been shown in volunteer studies to reduce drug absorption by ~ one-third under optimal conditions (Tenenbein, 1987). A randomized trial of gastric emptying for poisoned patients did not show improvement in clinical outcome (Pond et al., 1995), but the selection of subjects and timing of therapy may have biased the study toward the null hypothesis. Based upon review of existing evidence, the American Academy of Pediatrics no longer recommends syrup of ipecac as part of its childhood injury prevention program (AAP, 2003), and the American Academy of Clinical Toxicology dissuades routine use of gastric emptying in the poisoned patient (AACT, 2004; Manoguerra and Cobaugh, 2005). The declining role of syrup of ipecac in the treatment of poisoning is evident by its use in <0.1% of cases reported to the AAPCC in 2007, compared to ~10% in 1987 (Bronstein et al., 2008).
Syrup of Ipecac. The U.S. FDA approved syrup of ipecac for sale without a prescription in 1965. The alkaloids cephaeline and emetine within syrup of ipecac act as emetics because of both a local irritant effect on the enteric tract and a central effect on the chemoreceptor trigger zone in the area postrema of the medulla. Syrup of ipecac is available in 0.5- and 1-fluid ounce containers. Ipecac is given orally at a dose of 15 mL for children up to 12 years, and 30 mL for older children and adults. Administration of ipecac is typically followed by a drink of water, and reliably produces emesis in 15-30 minutes. Contraindications for syrup of ipecac administration include existing or impending CNS depression, ingestion of a corrosive or hydrocarbon drug (due to the emergence of chemical pneumonia), or presence of a medical condition that might be exacerbated by vomiting. Ipecac has been misused by bulimic patients; in cases of Munchausen syndrome by proxy and with chronic abuse, ipecac may cause serum electrolyte abnormalities, cardiomyopathy, ventricular arrhythmia, and death.
Gastric Lavage. The procedure for gastric lavage involves passing an orogastric tube (24-French for small children, up to 40-French for adults) into the stomach with the patient in the left-lateral decubitus position with head lower than feet. Preferably, the tube will have been designed for lavage purposes, and will have sizable side holes in the tubing. After withdrawing stomach contents, 10 to 15 mL/kg (up to 250 mL) of saline lavage fluid is administered and withdrawn. This process continues until the lavage fluid returns clear. Complications of the procedure include mechanical trauma to the stomach or esophagus, pulmonary aspiration of stomach contents, and vagus nerve stimulation.
++
Adsorption of a poison refers to the binding of a poison to the surface of another substance. An adsorbed poison may be less available for absorption into the body. It is well known that the fullness of the stomach from a meal affects a drug's absorption kinetics. Fuller's earth has been suggested as an adsorbent for paraquat, Prussian blue binds thallium and cesium, and sodium polystyrene can adsorb lithium. The most common adsorbent used in the treatment of acute drug overdose is activated charcoal.
++
Volunteer studies suggest that activated charcoal is more effective at reducing drug absorption than either induced emesis or gastric lavage (Tenebein, 1987). In a position paper of the American Academy of Clinical Toxicology on the use of single-dose activated charcoal, the opinion is given that single-dose charcoal should not be administered routinely in the management of poisoned patients, and that it should only be considered if a patient has ingested a potentially toxic amount of poison up to 1 hour before charcoal administration (AACT, 2005). In 2007, charcoal was used in 4.3% of cases reported to American poison control centers (Bronstein et al., 2008). Clinical evidence of improved patient parameters from treatment with activated charcoal are slowly emerging (Buckley et al., 1999; Isbister et al., 2007; Page et al., 2009), but good outcome data from clinical trials are still lacking.
+
Activated Charcoal. Charcoal is created through controlled pyrolysis of organic matter, and is activated through steam or chemical treatment that increases its internal pore structure and adsorptive surface capacity. The surface of activated charcoal contains carbon moieties, such as carbonyl and hydroxyl groups, that are capable of binding poisons. The recommended dose is typically 0.5-2 g/kg of body weight, up to a maximum tolerated dose of ~75-100 g. As a rough estimate, 10 g of activated charcoal is expected to bind ~1 g of drug. The efficacy of activated charcoal at adsorbing ingested drug diminishes over time. Alcohols, corrosives, hydrocarbons, and metals are not believed to be well adsorbed by charcoal.
Complications of activated charcoal therapy include vomiting, constipation, pulmonary aspiration, and death. Charcoal slurries are black and gritty; in a series of children offered charcoal in a pediatric emergency department, only 44% of the children <6 years accepted the agent orally (Osterhoudt et al., 2004a). Nasogastric administration of charcoal increases the incidence of vomiting (Osterhoudt et al., 2004b), and may increase the risk for pulmonary aspiration. Charcoal should not be given to patients with suspected GI perforation, or to patients who may be candidates for endoscopy.
++
Whole Bowel Irrigation Whole bowel irrigation (WBI) involves the enteral administration of large amounts of a high molecular weight, iso-osmotic polyethylene glycol electrolyte solution with the goal of passing poison by the rectum before it can be absorbed. Potential candidates for WBI include: 1) "body-packers" with intestinal packets of illicit drugs; 2) patients with iron overdose; 3) patients who have ingested patch pharmaceuticals; and 4) patients with overdoses of sustained-release or bezoar-forming drugs.
+
Polyethylene glycol electrolyte solution is typically administered at a rate of 25 to 40 mL/kg/h until the rectal effluent is clear and no more drug is being passed. To achieve these high administration rates a nasogastric tube may be used. Large doses have been administered without adversely affecting serum electrolyte concentrations. WBI is contraindicated in the presence of bowel obstruction or perforation, and may be complicated by abdominal distention or pulmonary aspiration.
Cathartics. The two most common categories of simple cathartics are the magnesium salts, such as magnesium citrate and magnesium sulfate, and the nondigestible carbohydrates, such as sorbitol. The use of simple cathartics has been abandoned as a GI decontamination strategy, although sorbitol is sometimes administered with single-dose activated charcoal in an effort to add sweetness and reduce its predilection toward constipation.
++
Enhancing the Elimination of Poisons. Once absorbed, the deleterious toxicodynamic effects of some drugs may be reduced by methods that hasten their elimination from the body. Urinary excretion of some drugs may be enhanced by the process of ion-trapping in alkaline urine. Gastrointestinal excretion of some drugs may be enhanced through use of multiple doses of activated charcoal. Some drugs may be removed from the body by extracorporeal techniques such as peritoneal dialysis, hemodialysis, or hemoperfusion.
+
Manipulating Urinary pH: Urinary Alkalinization. Drugs subject to renal clearance are excreted into the urine by glomerular filtration and active tubular secretion (Chapter 2); non-ionized compounds may be reabsorbed far more rapidly than ionized polar molecules. Weakly acidic drugs are susceptible to "ion-trapping" in the urine. Aspirin is a weak acid with a pKa = 3.0. As the pH of the urine increases, more salicylate is in its ionized form at equilibrium, and more salicylic acid is diffused into the tubular lumen of the kidney. Urinary alkalinization is also believed to speed clearance of phenobarbital, chlorpropamide, methotrexate, and chlorphenoxy herbicides. The American Academy of Clinical Toxicologists recommends urine alkalinization as first-line treatment only for moderately severe salicylate poisoning that does not meet criteria for hemodialysis (Proudfoot et al., 2004). To achieve alkalinization of the urine, 100-150 mEq of sodium bicarbonate in 1L of D5W is infused intravenously at twice the maintenance fluid requirements and then titrated to effect. Hypokalemia should be treated since it will hamper efforts to alkalinize the urine due to H+-K+ exchange in the kidney. Urine alkalinization is contraindicated in the presence of renal failure, or when the fluid administration may worsen pulmonary edema or congestive heart failure. Acetazolamide is not used to alkalinize urine as it promotes acidemia.
Multiple-Dose Activated Charcoal. Activated charcoal adsorbs drug to its surface and promotes enteral elimination. Multiple doses of activated charcoal can speed elimination of absorbed drug by two mechanisms. Charcoal may interrupt enterohepatic circulation of hepatically metabolized drug excreted in the bile, and charcoal may create a diffusion gradient across the GI mucosa and promote movement of drug from the bloodstream onto the charcoal in the intestinal lumen. Activated charcoal may be administered in multiple doses, 12.5 g/h every 1, 2, or 4 hours (smaller doses may be used for children). Complications of therapy are similar to those listed for single-dose activated charcoal. Charcoal enhances the clearance of many drugs of low molecular weight, small volume of distribution, and long elimination t½. In the absence of good clinical outcomes data, multiple-dose activated charcoal is believed to have the most potential utility in overdoses of carbamazepine, dapsone, phenobarbital, quinine, theophylline, and yellow oleander (AACT, 1999; de Silva et al., 2003).
Extracorporeal Drug Removal. The ideal drug amenable to removal by hemodialysis has a low molecular weight, a low volume of distribution, high solubility in water, and minimal protein binding. Hemoperfusion involves passing blood through a cartridge containing adsorbent particles. The most common poisonings for which hemodialysis is sometimes used include salicylate, methanol, ethylene glycol, lithium, carbamazepine, and valproic acid. For a more exhaustive list of drugs amenable to hemodialyis or hemoperfusion, see Winchester (2002).
++
Antidotal Therapies. Antidotal therapy involves antagonism or chemical inactivation of an absorbed poison. The pharmacodyamics of a poison can be altered by competition at a receptor, as in the antagonism provided by naloxone therapy in the setting of heroin overdose. A physiological antidote may use a different cellular mechanism to overcome the effects of a poison, as in the use of glucagon to stimulate an alternative to the blocked β adrenergic receptor and increase cellular cyclic AMP in the setting of propranolol overdose. Anti-venoms and chelating agents bind and directly inactivate poisons. The biotransformation of a drug can also be altered by an antidote; for instance, fomepizole will inhibit alcohol dehydrogenase and stop the formation of toxic acid metabolites from ethylene glycol and methanol. Many drugs used in the supportive care of a poisoned patient (anticonvulsants, vasoconstricting agents, etc.) may be considered nonspecific functional antidotes.
++
The mainstay of therapy for poisoning is good support of the airway, breathing, circulation, and vital metabolic processes of the poisoned patient until the poison is eliminated from the body; specific antidotes are uncommonly needed. Among the most common specific antidotes used are N-acetyl-L-cysteine for acetaminophen poisoning, opioid antagonists for opioid overdose, and chelating agents for poisoning from certain metal ions. A listing of other commonly used antidotes is presented in Table 4–11.
++