For more than 5 decades, medical toxicologists and poison information specialists have used a clinical approach to poisoned or overdosed patients that emphasizes treating the patient rather than treating the poison.3 Too often in the past, patients were initially ignored while attention was focused on the ingredients listed on the containers of the product(s) to which they presumably were exposed. Although astute clinicians must always be prepared to administer a specific antidote immediately in instances when nothing else will save a patient, such as with cyanide poisoning,7 all poisoned or overdosed patients benefit from an organized, rapid clinical management plan (Fig. 4–1). However, clinicians should use caution when applying management advice from compendia and other non–toxicologic-specific sources because they may contain serious discrepancies with current standard expert advice.2,10 Consultation with a poison control center or a medical or clinical toxicologist should be obtained if any questions or concerns arise about the management of a potentially poisoned or exposed patient.
This algorithm is a basic guide to the management of poisoned patients. A more detailed description of the steps in management may be found in the accompanying text. This algorithm is only a guide to actual management, which must, of course, consider the patient’s clinical status. ABG = arterial blood gas; AC = activated charcoal; APAP = acetaminophen; β-HCG = β-human chorionic gonadotropin; CBC = complete blood count; CNS = central nervous system; CPK = creatine phosphokinase; CPR = cardiopulmonary resuscitation; Cr, creatinine; ECG = electrocardiograph; ECLS = extracorporeal life support; HD = hemodialysis; HDI = high dose insulin; HP = hemoperfusion; ICU = intensive care unit; MDAC = multiple-dose activated charcoal; Tn = troponin; VBG = venous blood gas; WBI = whole-bowel irrigation.
Over the past 5 decades, some tenets and long-held beliefs regarding the initial therapeutic interventions in toxicologic management have been questioned and subjected to an “evidence-based” analysis. For example, in the mid-1970s, most medical toxicologists began to advocate a standardized approach to a comatose and possibly poisoned adult patient, typically calling for the intravenous (IV) administration of 50 mL of dextrose 50% in water (D50W), 100 mg of thiamine, and 2 mg of naloxone along with 100% oxygen at high flow rates. The rationale for this approach was to compensate for the previously idiosyncratic style of management encountered in different health care settings. It was not unusual then to discover from a laboratory chemistry report more than 1 hour after a supposedly overdosed comatose patient had arrived in the emergency department (ED) that the patient had hypoglycemia—a critical delay in the management of unsuspected and consequently untreated hypoglycemic coma. Today, however, with the widespread availability of accurate rapid bedside testing for capillary blood glucose, pulse oximetry for oxygen saturation, and end-tidal CO2 monitors coupled with a much greater appreciation by all physicians of what needs to be done for each suspected overdose patient, clinicians can safely provide a more rational, individualized approach to determine the need for, and in some instances more precise amounts of, dextrose, thiamine, naloxone, and oxygen.
A second major approach to providing more rational individualized early treatment for patients with toxicologic emergencies involves a closer examination of the actual risks and benefits of various gastrointestinal (GI) decontamination interventions. Appreciation of the potential for significant adverse effects associated with all types of GI decontamination interventions and recognition of the absence of clear evidence-based support of efficacy have led to abandoning of syrup of ipecac-induced emesis, an almost complete elimination of orogastric lavage, and a significant reduction in the routine use of activated charcoal. The value of whole-bowel irrigation (WBI) with polyethylene glycol electrolyte solution (PEG-ELS) appears to be much more specific and limited than originally thought, and some of the limitations and (uncommon) adverse effects of activated charcoal are now more widely recognized (Chap. 5). However, as with many issues in clinical medicine, properly selected procedures performed in properly selected patients can lead to an acceptable risk benefit profile, and blanket elimination of these GI decontamination procedures is not optimal and will lead to suboptimal care.
Similarly, interventions to eliminate absorbed xenobiotics from the body are now much more narrowly defined or, in some cases, have been abandoned. Multiple-dose activated charcoal (MDAC) is useful for select but not all xenobiotics. Ion trapping in the urine is only beneficial, achievable, and relatively safe when the urine can be maximally alkalinized after a significant salicylate or phenobarbital exposure (Antidotes in Depth: A5 and Table A5-1). Finally, the roles of hemodialysis, hemoperfusion, and other extracorporeal techniques are now much more specifically defined.5 With the foregoing in mind, this chapter represents our current efforts to formulate a logical and effective approach to managing a patient with probable or actual toxic exposure.
The management of most patients with toxicologic clinical syndromes cannot be based on specific antidotal therapies but rather relies on the application of directed supportive or pharmacologic care. These forms of care include the extension of therapies from the management of related clinical syndromes caused by other xenobiotics or from other nontoxicologic etiologies. Examples include the use of vasopressors to manage hypotension from dihydropyridine calcium channel blockers and the use of anticonvulsant benzodiazepines to manage bupropion induced seizures. Table 4–1 provides a recommended stock list of antidotes and therapeutics for the treatment of poisoned or overdosed patients (Special Considerations: SC1). Consensus antidote stocking guidelines exist as well.4
|Acetylcysteine (p. 492)||Acetaminophen and other causes of hepatotoxicity|
|Activated charcoal (p. 76)||Adsorbent xenobiotics in the GI tract|
|Antivenom (Centruroides spp) (p. 1563)||Scorpion envenomation|
|Antivenom (Crotalinae) (p. 1627)||Crotaline snake envenomations|
|Antivenom (Micrurus fulvius) (p. 1631)||Coral snake envenomations|
|Antivenom (Latrodectus mactans) (p. 1559)||Black widow spider envenomations|
|Antivenom (Synanceja spp) (p. 1578)||Stonefish envenomation|
|Atropine (p. 1503)||Bradydysrhythmias, cholinesterase inhibitors (organic phosphorus compounds, physostigmine) muscarinic mushrooms (Clitocybe, Inocybe) ingestions|
|Benzodiazepines (p. 1135)||Seizures, agitation, stimulants, ethanol and sedative–hypnotic withdrawal, cocaine, chloroquine, organic phosphorus compounds|
|Botulinum antitoxin (Heptavalent) (p. 586)||Botulism|
|Calcium chloride, calcium gluconate (p. 1403)||Fluoride, hydrofluoric acid, ethylene glycol, CCBs, hypermagnesemia, β-adrenergic antagonists, hyperkalemia|
|L-Carnitine (p. 732)||Valproic acid: hyperammonemia|
|Cyanide kit (nitrites, p. 1698; sodium thiosulfate, p. 1698)||Cyanide|
|Cyproheptadine (p. 1001)||Serotonin toxicity|
|Dantrolene (p. 1029)||Malignant hyperthermia|
|Deferoxamine (p. 676)||Iron, aluminum|
|Dextrose in water (50% adults; 20% pediatrics; 10% neonates) (p. 707)||Hypoglycemia|
|Digoxin-specific antibody fragments (p. 977)||Cardioactive steroids|
|Dimercaprol (British anti-Lewisite [BAL]) (p. 1251)||Arsenic, mercury, gold, lead|
|Diphenhydramine (p. 741)||Dystonic reactions, allergic reactions|
|DTPA (p. 1779) calcium trisodium pentetate||Radioactive isotopes; americium, curium, plutonium|
|Edetate calcium disodium (calcium disodium versenate, CaNa2EDTA) (p. 1315)||Lead, other selected metals|
|Ethanol (p. 1440)||Ethylene glycol, methanol, diethylene glycol|
|Flumazenil (p. 1094)||Benzodiazepines|
|Folinic acid (p. 775)||Methotrexate, methanol|
|Fomepizole (p. 1435)||Ethylene glycol, methanol, diethylene glycol|
|Glucagon (p. 941)||β-Adrenergic antagonists, CCBs|
|Glucarpidase (p. 782)||Methotrexate|
|Hydroxocobalamin (p. 1694)||Cyanide|
|Idarucizumab (p. 911)||Dabigatran|
|Insulin (p. 953)||β-Adrenergic antagonists, CCBs, hyperglycemia|
|Iodide (SSKI) (p. 1775)||Radioactive iodine (I131)|
|Lipid emulsion (p. 1004)||Local anesthetics|
|Magnesium sulfate injection (p. 876)||Cardioactive steroids, hydrofluoric acid, hypomagnesemia, ethanol withdrawal, torsade de pointes|
|Methylene blue (1% solution) (p. 1713)||Methemoglobinemia, ifosfamide, vasoplegic syndrome, shock|
|Naloxone (p. 538)||Opioids, clonidine|
|Norepinephrine (p. 950)||Hypotension|
|Octreotide (p. 713)||Insulin secretagogue induced hypoglycemia|
|Oxygen (Hyperbaric) (p. 1676)||Carbon monoxide, cyanide, hydrogen sulfide|
|D-Penicillamine (p. 1215)||Copper|
|Phenobarbital (p. 1087)||Seizures, agitation, stimulants, ethanol and sedative–hypnotic withdrawal|
|Phentolamine (p. 1129)||Vasoconstriction: cocaine, MAOI interactions, epinephrine, and ergot alkaloids|
|Physostigmine (p. 755)||Anticholinergics|
|Polyethylene glycol electrolyte lavage solution (p. 83)||Decontamination|
|Pralidoxime (p. 1508)||Acetylcholinesterase inhibitors (organic phosphorus compounds and carbamates)|
|Protamine (p. 919)||Heparin anticoagulation|
|Prussian blue (p. 1357)||Thallium, cesium|
|Pyridoxine (vitamin B6) (p. 862)||Isoniazid, ethylene glycol, gyromitrin-containing mushrooms|
|Sodium bicarbonate (p. 567)||Ethylene glycol, methanol, salicylates, cyclic antidepressants, methotrexate, phenobarbital, quinidine, chlorpropamide, class I antidysrhythmics, chlorophenoxy herbicides, sodium channel blockers|
|Starch (p. 1371)||Iodine|
|Succimer (p. 1309)||Lead, mercury, arsenic|
|Thiamine (vitamin B1) (p. 1309)||Thiamine deficiency, ethylene glycol, chronic ethanol consumption (“alcoholism”)|
|Uridine triacetate (p. 789)||Fluorouracil, capecitabine|
|Vitamin K1 (p. 915)||Warfarin or rodenticide anticoagulants|
MANAGING ACUTELY POISONED OR OVERDOSED PATIENTS
Rarely, if ever, are all of the circumstances involving a poisoned patient known. The history may be incomplete, unreliable, or unobtainable; multiple xenobiotics may be involved; and even when a xenobiotic etiology is identified, it may not be easy to determine whether the problem is an overdose, an allergic or idiosyncratic reaction, or a drug–drug interaction. Similarly, it is sometimes difficult or impossible to differentiate between the adverse effects of a correct dose of medication and the consequences of a deliberate or unintentional overdose. The patient’s presenting signs and symptoms may force an intervention at a time when there is almost no information available about the etiology of the patient’s condition (Table 4–2), and as a result, therapeutics must be thoughtfully chosen empirically to treat or diagnose a condition without exacerbating the situation. See Fig. 4-1 for an algorithmic approach to managing poisoned patients.
|Agitation||Anticholinergics,a hypoglycemia, phencyclidine, sympathomimetics,b synthetic cannabinoid receptor agonists, withdrawal from ethanol and sedative–hypnotics|
|Alopecia||Alkylating agents, radiation, selenium, thallium|
|Ataxia||Benzodiazepines, carbamazepine, carbon monoxide, ethanol, hypoglycemia, lithium, mercury, nitrous oxide, phenytoin|
|Blindness or decreased visual acuity||Caustics (direct), cisplatin, cocaine, ethambutol, lead, mercury, methanol, quinine, thallium|
|Blue skin||Amiodarone, FD&C #1 dye, methemoglobinemia, silver|
|Constipation||Anticholinergics,a botulism, lead, opioids, thallium (severe)|
|Deafness, tinnitus||Aminoglycosides, carbon disolfide, cisplatin, loop diuretics, macrolides, metals, quinine, quinolones, salicylates|
|Diaphoresis||Amphetamines, cholinergics,c hypoglycemia, opioid withdrawal, salicylates, serotonin toxicity, sympathomimetics,b withdrawal from ethanol and sedative–hypnotics|
|Diarrhea||Arsenic and other metals, boric acid (blue-green), botanical irritants, cathartics, cholinergics,c colchicine, iron, lithium, opioid withdrawal, radiation|
|Dysesthesias, paresthesias||Acrylamide, arsenic, ciguatera, cocaine, colchicine, thallium|
|Gum discoloration||Arsenic, bismuth, hypervitaminosis A, lead, mercury|
|Hallucinations||Anticholinergics,a dopamine agonists, ergot alkaloids, ethanol, ethanol and sedative–hypnotic withdrawal, LSD, phencyclidine, sympathomimetics,b tryptamines|
|Headache||Carbon monoxide, hypoglycemia, MAOI–food interaction (hypertensive crisis), serotonin toxicity|
|Metabolic acidosis (elevated anion gap)||Methanol, uremia, ketoacidosis (diabetic, starvation, alcoholic), paraldehyde, metformin, iron, isoniazid, lactic acidosis, cyanide, protease inhibitors, ethylene glycol, salicylates, toluene|
|Miosis||Cholinergics,c clonidine, opioids, phencyclidine, phenothiazines|
|Mydriasis||Anticholinergics,a botulism, opioid withdrawal, sympathomimeticsb|
|Nystagmus||Barbiturates, carbamazepine, carbon monoxide, dextromethorphan, ethanol, lithium, MAOIs, phencyclidine, phenytoin, quinine, synthetic cannabinoid receptor agonists|
|Purpura||Anticoagulant rodenticides, corticosteroids, heparin, pit viper venom, quinine, salicylates, anticoagulants, levamisole|
|Radiopaque ingestions||Arsenic, halogenated hydrocarbons, iodinated compounds metals (eg, iron, lead), potassium compounds|
|Red skin||Anticholinergics,a boric acid, disulfiram, hydroxocobalamin, scombroid, vancomycin|
|Rhabdomyolysis||Carbon monoxide, doxylamine, HMG-CoA reductase inhibitors, sympathomimetics,b Tricholoma equestre mushrooms|
|Salivation||Arsenic, caustics, cholinergics,c clozapine, ketamine, mercury, phencyclidine, strychnine|
|Seizures||Bupropion, camphor, carbon monoxide, cyclic antidepressants, Gyromitra mushrooms, hypoglycemia, isoniazid, methylxanthines, ethanol and sedative–hypnotic withdrawal|
|Tremor||Antipsychotics, arsenic, carbon monoxide, cholinergics,c ethanol, lithium, mercury, methyl bromide, sympathomimetics,b thyroid hormones|
|Weakness||Botulism, diuretics, magnesium, paralytic shellfish, steroids, toluene|
|Yellow skin||APAP (late), pyrrolizidine alkaloids, β carotene, amatoxin mushrooms, dinitrophenol|
Similar to the management of any seriously compromised patient, the clinical approach to the patient potentially exposed to a xenobiotic begins with the recognition and treatment of life-threatening conditions, including airway compromise, breathing difficulties, and circulatory problems such as hemodynamic instability and serious dysrhythmias. After the “ABCs” (airway, breathing, and circulation) are addressed, the patient’s level of consciousness should be assessed because it helps determine the techniques to be used for further management of the exposure.
Altered mental status (AMS) is defined as the deviation of a patient’s sensorium from its baseline. Although it is commonly misconstrued as a depression in the patient’s level of consciousness, a patient with agitation, delirium, psychosis, and other deviations from normal is also considered to have an AMS. The spectrum of deviation may range from hyperactive agitated conditions typified by sympathomimetics such as cocaine or amphetamines to depressed levels of consciousness that typify opioid and sedative hypnotic exposures. “Awake” but “altered” conditions also include delirium or psychoses, such as those induced by lithium, salicylate, or antimuscarinic toxicity.
After airway patency is assured, an initial bedside assessment should be made regarding the adequacy of breathing. Although it is often not possible to assess the adequacy of the depth of ventilation, at least the rate and pattern of breathing should be determined. In this setting, any irregular or slow breathing pattern, particularly with an elevated end-tidal CO2 measurement, should be considered a possible sign of the incipient apnea, requiring ventilation using 100% oxygen by bag–valve–mask followed as soon as possible by endotracheal intubation and mechanical ventilation. Endotracheal intubation and mandatory ventilation is often indicated for patients with coma resulting from a toxic exposure to ensure and maintain control of the airway and to enable safe performance of procedures to prevent GI absorption or eliminate previously absorbed xenobiotic.
Although in many instances, the widespread availability of pulse oximetry to determine O2 saturation and end-tidal CO2 monitors have made arterial blood gas (ABG) analysis less of an immediate priority, these technical advances have not entirely eliminated the importance of blood gas analysis. An ABG determination will more accurately define the adequacy not only of oxygenation (PO2, O2 saturation) and ventilation (PCO2) but may also alert the physician to possible toxic-metabolic etiologies of coma characterized by acid–base disturbances (pH, PCO2)11 (Chap. 12). In addition, carboxyhemoglobin determinations are now available by point-of-care testing, and both carboxyhemoglobin and methemoglobin may be determined on either venous or arterial blood specimens (Chaps. 122 and 124). In every patient with an AMS, a bedside rapid glucose concentration should be obtained as soon as possible.
After the patient’s respiratory status is assessed and managed appropriately, the strength, rate, and regularity of the pulse should be evaluated and the blood pressure and rectal temperature determined. Both an initial 12-lead electrocardiogram (ECG) and continuous rhythm monitoring are essential. Monitoring will alert the clinician to dysrhythmias that are related to toxic exposures either directly or indirectly via hypoxemia or electrolyte imbalance. For example, a 12-lead ECG demonstrating QRS widening and a right axis deviation might indicate a life-threatening exposure to a cyclic antidepressant or another xenobiotic with sodium channel–blocking properties. In these cases, the physician can anticipate such serious sequelae as ventricular tachydysrhythmias, seizures, and cardiac arrest and plan for both the early use of specific treatment (antidotes), such as IV sodium bicarbonate, and avoidance of medications, such as procainamide and other class IA and IC antidysrhythmics, that could exacerbate toxicity.
Extremes of core body temperature must be addressed early in the evaluation and treatment of a comatose patient. Life-threatening hyperthermia (temperature >106°F; >41.1°C) is usually appreciated when the patient is touched (although the widespread use of gloves as part of universal precautions has made this less apparent than previously). Individuals with severe hyperthermia, regardless of the etiology, should have their temperatures immediately reduced to about 101.5°F (38.7°C) by sedation if they are agitated or displaying muscle rigidity or by ice water immersion (Chap. 29). Hypothermia is probably easier to overlook than hyperthermia, especially in northern regions during the winter months, when most arriving patients feel cold to the touch. Early recognition of hypothermia, however, helps to avoid administering a variety of medications that are ineffective until the patient warms, at which point iatrogenic toxicity may result because of a sudden response to xenobiotics previously administered.