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The following general steps represent important components of the initial clinical encounter with a poisoned patient:
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Clinical Stabilization
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The first priority in the treatment of the poisoned patient is stabilization. Assessment of the vital signs and the effectiveness of respiration and circulation are the initial concerns. Some toxins or drugs can cause seizures early in the course of presentation. The steps and clinical procedures incorporated to stabilize a critically ill, poisoned patient are numerous and include, if appropriate, support of ventilation, circulation, and oxygenation. In critically ill patients, sometimes treatment interventions must be initiated before a patient is truly stable.
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Clinical History in the Poisoned Patient
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The primary goal of taking a medical history in poisoned patients is to determine, if possible, the substance ingested or the substance to which the patient has been exposed as well as the extent and time of exposure. In the setting of a suicide attempt, patients may not provide any history or may give incorrect information so as to increase the possibility that they will successfully bring harm to themselves. Information sources commonly employed in this setting include family members, emergency medical technicians who were at the scene, a pharmacist who can sometimes provide a listing of prescriptions recently filled, or an employer who can disclose what chemicals are available in the work environment.
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In estimating the level of exposure to the poison, one generally should maximize the possible dose received. That is, one should assume that the entire prescription bottle contents were ingested, that the entire bottle of liquid was consumed, or that the highest possible concentration of airborne contaminant was present in the case of a patient poisoned by inhalation.
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With an estimate of dose, the toxicologist can refer to various information sources to determine what the range of expected clinical effects might be from the exposure. The estimation of expected toxicity greatly assists with the triage of poisoned patients. Estimating the timing of the exposure to the poison is frequently the most difficult aspect of the clinical history in the setting of treatment of the poisoned patient.
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Taking an accurate history in the poisoned patient can be challenging and in some cases unsuccessful. When the history is unobtainable, the clinical toxicologist is left without a clear picture of the exposure history. In this setting, the treatment proceeds empirically as an “unknown ingestion” poisoning.
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A thorough physical examination is required to assess the patient's condition, categorize the patient's mental status, and, if altered, determine possible additional causes such as trauma or central nervous system infection. Whenever possible, the patient's physical examination parameters are categorized into broad classes referred to as toxic syndromes, constellations of clinical signs that, taken together, are likely associated with exposure from certain classes of toxicologic agents. Categorization of the patient's presentation into toxic syndromes allows for the initiation of rational treatment based on the most likely category of toxin responsible, even if the exact nature of the toxin is unknown. Table 32–1 lists clinical features of the major toxic syndromes. Occasionally a characteristic odor detected on the poisoned patient's breath or clothing may point toward exposure or poisoning by a specific agent (Table 32–2).
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Laboratory Evaluation
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Table 32–3 lists drugs or other chemicals that are typically available for immediate measurement in a hospital facility. As one can see, the number of agents for which detection is possible in the rapid-turnaround clinical setting is extremely limited compared with the number of possible agents that can poison patients. This further emphasizes the importance of recognizing clinical syndromes for poisoning and for the clinical toxicologist to initiate general treatment and supportive care for the patient with poisoning from an unknown substance.
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For the substances that can be measured on a rapid-turnaround basis in an emergency department setting, the quantitative measurement can often provide both prognostic and therapeutic guidance.
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Predictive relationships of drug plasma concentration and clinical outcome and/or suggested concentrations that require therapeutic interventions are available for several agents including salicylates, lithium, digoxin, iron, phenobarbital, and theophylline. Some authors have identified “action levels” or toxic threshold values for the measured plasma concentrations of various drugs or chemicals. Generally, these values represent mean concentrations of the respective substance that have been retrospectively shown to produce a significant harmful effect.
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Because of the limited clinical availability of “diagnostic” laboratory tests for poisons, toxicologists utilize specific, routinely obtained clinical laboratory data—especially the anion gap and the osmol gap—to determine what poisons may have been ingested. An abnormal anion or osmol gap suggests a differential diagnosis for significant exposure. Both calculations are used as diagnostic tools when the clinical history suggests poisoning and the patient's condition is consistent with exposure to agents known to cause elevations of these parameters (i.e., metabolic acidosis, altered mental status, etc.).
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The anion gap is calculated as the difference between the serum Na ion concentration and the sum of the serum Cl and HCO3 ion concentrations. A normal anion gap is <12. When there is laboratory evidence of metabolic acidosis, the finding of an elevated anion gap would suggest systemic toxicity from a relatively limited number of agents (Table 32–4).
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The second calculated parameter from clinical chemistry values is the osmol gap. The osmol gap is calculated as the numerical difference between the measured serum osmolality and the serum osmolarity calculated from the clinical chemistry measurements of the serum sodium ion, glucose, and blood urea nitrogen (BUN) concentrations. The normal osmol gap is <10 mOsm. An elevated osmol gap suggests the presence of an osmotically active substance (methanol, ethanol, ethylene glycol, and isopropanol) in the plasma that is not accounted for by the sodium ion, glucose, or BUN concentrations.
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Radiographic Examination
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The use of clinical radiographs to visualize drug overdose or poison ingestions is relatively limited. Generally, plain radiographs can detect a significant amount of ingested oral medication containing ferrous or potassium salts. In addition, certain formulations that have an enteric coating or certain types of sustained release products are radiopaque as well.
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The most useful radiographs ordered in a case of overdose or poisoning include the chest and abdominal radiographs and the computed tomography (CT) study of the head. The abdominal radiograph has been used to detect recent lead paint ingestion in children, and ingestion of halogenated hydrocarbons, such as carbon tetrachloride or chloroform, that may be visualized as a radiopaque liquid in the gut lumen. Finally, abdominal plain radiographs have been helpful in the setting where foreign bodies are detected in the gastrointestinal tract, such as would be seen in a “body packer,” or one who smuggles illegal substances by swallowing latex or plastic storage vesicles filled with cocaine or some other substance. Occasionally these storage devices rupture and the drug is released into the gastrointestinal tract, with serious and sometimes fatal results.
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Plain radiography and other types of diagnostic imaging in clinical toxicology can also be extremely valuable for the diagnosis of toxin-induced pathology. For example, the detection of drug-induced noncardiac pulmonary edema is associated with serious intoxication with salicylates and opioid agonists. Another example of the use of radiologic imaging in clinical toxicology is with CT of the brain. Significant exposure to carbon monoxide (CO) has been associated with CT lesions of the brain consisting of low-density areas in the cerebral white matter and in the basal ganglia, especially the globus pallidus.
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Prevention of Further Poison Absorption
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During the early phases of poison treatment or intervention for a toxic exposure via the oral, inhalational, or topical route, a significant opportunity exists to prevent further absorption of the poison by minimizing the total amount that reaches the systemic circulation. For toxins presented by the inhalational route, the main intervention used to prevent further absorption involves removing the patient from the environment where the toxin is found and providing adequate ventilation and oxygenation for the patient. For topical exposures, clothing containing the toxin must be removed and the skin washed with water and mild soap.
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The four primary methods to prevent continued absorption of an oral poison are induction of emesis with syrup of ipecac, gastric lavage, oral administration of activated charcoal, and whole bowel irrigation. Although potentially indicated for individuals who are hours away from a medical facility, syrup of ipecac use for induction of emesis in the treatment of a potentially toxic ingestion has declined. Risk of cardio- and neurotoxicity and lower effectiveness at removing the toxicant than desired limit its use. Likewise, gastric lavage, which involves placing an orogastric tube into the stomach and aspirating fluid, and then cyclically instilling fluid and aspirating until the effluent is clear, is limited by the risk of aspiration during the lavage procedure and evidence of limited effectiveness.
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For many years, orally administered activated charcoal has been routinely incorporated into the initial treatment of a patient poisoned by the oral route. The term activated means that the charcoal has been specially processed to be more efficient at adsorbing toxins.
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The usefulness of whole bowel irrigation for a poisoned patient is very limited. Considerable absorption of the toxicant can occur before the procedure “washes” the lumen of the GI tract clear of unabsorbed material.
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Enhancement of Poison Elimination
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There are several methods available to enhance the elimination of specific poisons or drugs once they have been absorbed into the systemic circulation. The primary methods employed for this use today include alkalinization of the urine, hemodialysis, hemoperfusion, hemofiltration, plasma exchange or exchange transfusion, and serial oral activated charcoal.
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The use of urinary alkalinization results in enhancement of the renal clearance of weak acids. The basic principle is to increase the pH of urinary filtrate to a level sufficient to ionize the weak acid and prevent renal tubule reabsorption of the molecule. Although there are potentially similar advantages to be gained from acidification of the urine in order to enhance the clearance of weak bases, this method is not used because acute renal failure and acid–base and electrolyte disturbances are associated with acidification.
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The dialysis technique, either peritoneal dialysis or hemodialysis, relies on passage of the toxic agent through a semipermeable dialysis membrane so that it can subsequently be removed. Hemodialysis incorporates a blood pump to pass blood next to a dialysis membrane, which allows agents permeable to the membrane to pass through and reach equilibrium. Some drugs are bound to plasma proteins and so cannot pass through the dialysis membrane; others are distributed mainly to the tissues and so are not concentrated in the blood, making dialysis impractical. Hemodialysis has been shown to be clinically effective in the treatment of poisoning by the drugs and toxins shown in Table 32–5.
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The technique of hemoperfusion is similar to hemodialysis except there is no dialysis membrane or dialysate involved in the procedure. The patient's blood is pumped through a perfusion cartridge, where it is in direct contact with adsorptive material (usually activated charcoal). Protein binding does not significantly interfere with removal by hemoperfusion.
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The technique of hemofiltration is relatively new in clinical toxicology applications. As in the case of hemodialysis, the patient's blood is delivered through hollow fiber tubes and an ultrafiltrate of plasma is removed by hydrostatic pressure from the blood side of the membrane. The perfusion pressure for the technique is generated either by the patient's blood pressure (for arteriovenous hemofiltration) or by a blood pump (for venovenous hemofiltration). Needed fluid and electrolytes removed in the ultrafiltrate are replaced intravenously with sterile solutions.
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The use of either plasma exchange or exchange transfusions has been relatively limited in the field of clinical toxicology. Although the techniques afford the potential advantage of being able to remove high-molecular-weight and/or plasma protein-bound toxins, their clinical utility in poison treatment has been limited. Plasma exchange, or pheresis, involves removal of plasma and replacement with frozen donor plasma, albumin, or both with intravenous fluid. The risks and complications of this technique include allergic-type reactions, infectious complications, and hypotension. Exchange transfusion involves replacement of a patient's blood volume with donor blood. The use of this technique in poison treatment is uncommon and mostly confined to inadvertent drug overdose in a neonate or premature infant.
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Serial oral administration of activated charcoal, also referred to as Multiple-dose Activated Charcoal (MDAC), has been shown to increase the systemic clearance of various drug substances. The mechanism for the observed augmentation of nonrenal clearance caused by repeated doses of oral charcoal is thought to be transluminal efflux of the drug from the blood to the charcoal passing through the gastrointestinal tract. The activated charcoal in the gut lumen serves as a “sink” for the toxin. A concentration gradient is maintained and the toxin passes continuously into the gut lumen, where it is adsorbed to charcoal. In addition, MDAC is thought to produce its beneficial effect by interrupting the enteroenteric–enterohepatic circulation of drugs. The technique involves continuing oral administration of activated charcoal beyond the initial dosage every 2 to 4 h. An alternative technique is to give a loading dose of activated charcoal via an orogastric tube or nasogastric tube, followed by a continuous infusion intragastrically. A list of agents for which MDAC has been shown to be an effective means of enhanced body clearance is given in Table 32–6.
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Use of Antidotes in Poisoning
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A relatively small number of specific antidotes are available for clinical use in the treatment of poisoning. The U.S. Food and Drug Administration (FDA) has placed incentives for sponsors to develop drugs for rare diseases or conditions through the Orphan Drug Act.
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The mechanism of action of various antidotes is quite different. For example, a chelating agent or Fab fragments specific to digoxin will work by physically binding the toxin, preventing the toxin from exerting a deleterious effect in vivo, and, in some cases, facilitating body clearance of the toxin. Other antidotes pharmacologically antagonize the effects of the toxin. Atropine, an antimuscarinic, anticholinergic agent, is used to pharmacologically antagonize at the receptor level the effects of organophosphate insecticides that produce lethal cholinergic, muscarinic effects. Certain agents exert their antidote effects by chemically reacting with biological systems to increase detoxifying capacity for the toxin. For example, sodium nitrite is given to patients poisoned with cyanide to cause formation of methemoglobin, which serves as an alternative binding site for the cyanide ion, thereby making it less toxic to the body.
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Supportive Care of the Poisoned Patient
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The supportive care phase of poison treatment is very important. Not only are there certain poisonings that have delayed toxicity, but there are also toxins that exhibit multiple phases of toxicity. Close clinical monitoring can detect these later-phase poisoning complications and allow for prompt medical intervention.
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Another important component of the supportive care phase of poison treatment is the psychiatric assessment. For intentional self-poisonings, a formal psychiatric evaluation of the patient should be performed prior to discharge. In many cases, it is not possible to perform a psychiatric interview of the patient during the early phases of treatment and evaluation. Once the patient has been stabilized and is able to communicate, a psychiatric evaluation should be obtained.