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.
TABLE 4–2.Clinical and Laboratory Findings in Poisoning and Overdose ||Download (.pdf) TABLE 4–2. Clinical and Laboratory Findings in Poisoning and Overdose
|Agitation ||Anticholinergics,a hypoglycemia, phencyclidine, sympathomimetics,b 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, mercury, methanol, quinine, thallium |
|Blue skin ||Amiodarone, FD&C #1 dye, methemoglobinemia, silver |
|Constipation ||Anticholinergics,a botulism, lead, opioids, thallium (severe) |
|Deafness, tinnitus ||Aminoglycosides, cisplatin, loop diuretics, metals, quinine, salicylates |
|Diaphoresis ||Amphetamines, cholinergics,c hypoglycemia, opioid withdrawal, salicylates, serotonin syndrome, 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, monoamine oxidase inhibitor–food interaction (hypertensive crisis), serotonin toxicity |
|Metabolic acidosis (elevated anion gap) ||Methanol, uremia, ketoacidosis (diabetic, starvation, alcoholic), paraldehyde, phenformin, 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, ethanol, lithium, monoamine oxidase inhibitors, phencyclidine, phenytoin, quinine |
|Purpura ||Anticoagulant rodenticides, clopidogrel, corticosteroids, heparin, pit viper venom, quinine, salicylates, warfarin |
|Radiopaque ingestions ||Arsenic, halogenated hydrocarbons, metals (eg, iron, lead) |
|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 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 replacement |
|Weakness ||Botulism, diuretics, magnesium, paralytic shellfish, steroids, toluene |
|Yellow skin ||APAP (late), pyrrolizidine alkaloids, β carotene, amatoxin mushrooms, dinitrophenol |
Initial Management of Patients with a Suspected Exposure
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) have been addressed, the patient’s level of consciousness should be assessed because this helps determine the techniques to be used for further management of the exposure.
Management of Patients with Altered Mental Status
Altered mental status (AMS) is defined as the deviation of a patient’s sensorium from normal. Although it is commonly construed 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. After airway patency is established or secured, an initial bedside assessment should be made regarding the adequacy of breathing. If it is not possible to assess the depth and rate of ventilation, then at least the presence or absence of regular breathing should be determined. In this setting, any irregular or slow breathing pattern should be considered a possible sign of the incipient apnea, requiring ventilation with 100% oxygen by bag–valve–mask followed as soon as possible by endotracheal intubation and mechanical ventilation. Endotracheal intubation may be indicated for some cases of 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 xenobiotics.
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) (Chap. 19). 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. 125 and 127). In every patient with an AMS, a bedside rapid capillary glucose concentration should be obtained as soon as possible.
After the patient’s respiratory status has been assessed and managed appropriately, the strength, rate, and regularity of the pulse should be evaluated, the blood pressure determined, and a rectal temperature obtained. 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 consider 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, which could exacerbate the situation.
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). Most 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 and by ice water immersion (Chap. 30). Hypothermia is probably easier to miss 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 may be ineffective until the patient becomes relatively euthermic, which may cause iatrogenic toxicity as a result of a sudden response to xenobiotics previously administered.
For a hypotensive patient with clear lungs and an unknown overdose, a fluid challenge with IV 0.9% sodium chloride or lactated Ringer solution may be started. If the patient remains hypotensive or cannot tolerate fluids, an antidote, a vasopressor, or an inotropic agent may be indicated, as may more invasive monitoring.
At the time that the IV catheter is inserted, blood samples for glucose, electrolytes, blood urea nitrogen (BUN), a complete blood count (CBC), and any indicated toxicologic analyses can be obtained. A pregnancy test should be obtained in any woman with childbearing potential. If the patient has an AMS, there may be a temptation to send blood and urine specimens to identify any central nervous system (CNS) depressants or so-called drugs of abuse in addition to other medications. But the indiscriminate ordering of these tests rarely provides clinically useful information. For the potentially suicidal patient, an APAP concentration should be routinely requested along with tests affecting the management of any specific xenobiotic, such as carbon monoxide, lithium, theophylline, iron, salicylates, and digoxin (or other cardioactive steroids), as suggested by the patient’s history, physical examination, or bedside diagnostic tests. In the vast majority of cases, the blood tests that are most useful in diagnosing toxicologic emergencies are not the toxicologic assays but rather the “nontoxicologic” routine metabolic profile tests such as BUN, glucose, electrolytes, and blood gas analysis.
Xenobiotic-related seizures may broadly be divided into three categories: (1) those that respond to standard anticonvulsant treatment (typically using a benzodiazepine); (2) those that either require specific antidotes to control seizure activity or that do not respond consistently to standard anticonvulsant treatment, such as isoniazid-induced seizures requiring pyridoxine administration; and (3) those that may appear to respond to initial treatment with cessation of tonic–clonic activity but that leave the patient exposed to the underlying, unidentified xenobiotic or to continued electrical seizure activity, as is the case with carbon monoxide poisoning and hypoglycemia.
Within the first 5 minutes of managing a patient with an AMS, four therapeutic interventions should be considered, and if indicated, administered:
High-flow oxygen (8–10 L/min) to treat a variety of xenobiotic-induced hypoxic conditions
Hypertonic dextrose: 0.5–1.0 g/kg of D50W for an adult or a more dilute dextrose solution (D10W or D25W) for a child; the dextrose is administered as an IV bolus to diagnose and treat or exclude hypoglycemia
Thiamine (100 mg IV for an adult; usually unnecessary for a child) to prevent or treat Wernicke encephalopathy
Naloxone (0.04 mg IV with upward titration) for an adult or child with opioid-induced respiratory compromise
The clinician must consider that hypoglycemia may be the sole or contributing cause of coma even when the patient manifests focal neurologic findings; therefore, dextrose administration should only be omitted when hypoglycemia can be definitely excluded by accurate rapid bedside testing. Also, while examining a patient for clues to the etiology of a presumably toxic-metabolic form of AMS, it is important to search for any indication that trauma may have caused, contributed to, or resulted from the patient’s condition. Conversely, the possibility of a concomitant drug ingestion or toxic metabolic disorder in a patient with obvious head trauma should also be considered.
The remainder of the physical examination should be performed rapidly but thoroughly. In addition to evaluating the patient’s level of consciousness, the physician should note abnormal posturing (decorticate or decerebrate), abnormal or unilateral withdrawal responses, and pupil size and reactivity. Pinpoint pupils suggest exposure to opioids or organic phosphorus insecticides, and widely dilated pupils suggest anticholinergic or sympathomimetic poisoning. The presence or absence of nystagmus, abnormal reflexes, and any other focal neurologic findings may provide important clues to a structural cause of AMS. For clinicians accustomed to applying the Glasgow Coma Scale (GCS) to all patients with AMS, assigning a score to the overdosed or poisoned patient may provide a useful measure for assessing changes in neurologic status. However, in this situation, the GCS should never be used for prognostic purposes because despite a low GCS score, complete recovery from properly managed toxic-metabolic coma is the rule rather than the exception (Chap. 24).
Characteristic breath or skin odors may identify the etiology of coma. The fruity odor of ketones on the breath suggests diabetic or alcoholic ketoacidosis but also the possible ingestion of acetone or isopropyl alcohol, which is metabolized to acetone. The pungent, minty odor of oil of wintergreen on the breath or skin suggests methyl salicylate poisoning. The odors of other substances such as cyanide (“bitter almonds”), hydrogen sulfide (“rotten eggs”), and organic phosphorus compounds (“garlic”) are described in detail in Chap. 26 and summarized in Table 26–1.
Further Evaluation of All Patients with Suspected Xenobiotic Exposures
Auscultation of breath sounds, particularly after a fluid challenge, helps to diagnose pulmonary edema, acute lung injury, or aspiration pneumonitis when present. Coupled with an abnormal breath odor of hydrocarbons or organic phosphorus compounds, for example, crackles and rhonchi may point to a toxic pulmonary etiology instead of a cardiac etiology; this is important because the administration of certain cardioactive medications may be inappropriate or dangerous in the former circumstances.
Heart murmurs in an injection drug user, especially when accompanied by fever, may indicate bacterial endocarditis. Dysrhythmias may suggest overdoses or inappropriate use of cardioactive xenobiotics, such as digoxin and other cardioactive steroids, β-adrenergic antagonists, calcium channel blockers, and cyclic antidepressants.
The abdominal examination may reveal signs of trauma or alcohol-related hepatic disease. The presence or absence of bowel sounds helps to exclude or to diagnose anticholinergic toxicity and is important in considering whether to manipulate the GI tract in an attempt to remove the toxin. A large palpable bladder may signal urinary retention as a further manifestation of anticholinergic toxicity.
Examination of the extremities might reveal clues to current or former drug use (track marks, skin-popping scars); metal poisoning (Mees lines, arsenical dermatitis); and the presence of cyanosis or edema suggesting preexisting cardiac, pulmonary, or kidney disease (Chap. 29).
Repeated evaluation of the patient suspected of an overdose is essential for identifying new or developing findings or toxic syndromes and for early identification and treatment of a deteriorating condition. Until the patient is completely recovered or considered no longer at risk for the consequences of a xenobiotic exposure, frequent reassessment must be provided even as the procedures described later are carried out. Toxicologic etiologies of abnormal vital signs and physical findings are summarized in Tables 3–1, 3–2,3–3,3–4,3–5, and 3–6. Toxic syndromes, sometimes called “toxidromes,” are summarized in Table 3–1.
Typically in the management of patients with toxicologic emergencies, there is both a necessity and an opportunity to obtain various diagnostic studies and ancillary tests interspersed with stabilizing the patient’s condition, obtaining the history, and performing the physical examination. Chapters 5, 6, and 16 discuss the timing and indications for diagnostic imaging procedures, qualitative and quantitative diagnostic laboratory studies, and the use and interpretation of the ECG in evaluating and managing poisoned or overdosed patients.
The Role of Gastrointestinal Evacuation
A series of highly individualized treatment decisions must now be made. As noted previously and as discussed in detail in Chap. 8, the decision to evacuate the GI tract or administer AC can no longer be considered standard or routine toxicologic care for most patients. Instead, the decision should be based on the type of ingestion, estimated quantity and size of pill or tablet, time since ingestion, concurrent ingestions, ancillary medical conditions, and age and size of the patient. The indications, contraindications, and procedures for performing orogastric lavage and for administering WBI, AC, MDAC, and cathartics are listed in Tables 8–1 through 8–7 and are discussed both in Chap. 8 and in the specific Antidotes in Depth sections immediately following Chap. 8.
Eliminating Absorbed Xenobiotics from the Body
After deciding whether or not an intervention to try to prevent absorption of a xenobiotic is indicated, the clinician must next consider the applicability of techniques available to eliminate xenobiotics already absorbed. Detailed discussions of the indications for and techniques of manipulating urinary pH (ion trapping), diuresis, hemodialysis, hemoperfusion, hemofiltration, and exchange transfusion are found in Chap. 10. Briefly, patients who may benefit from these procedures are those who have systemically absorbed xenobiotics amenable to one of these techniques and whose clinical conditions are both serious (or potentially serious) and unresponsive to supportive care or whose physiologic route of elimination (liver–feces, kidney–urine) is impaired.
Alkalinization of the urinary pH for acidic xenobiotics has only limited applicability. Commonly, sodium bicarbonate can be used to alkalinize the urine (as well as the blood) and enhance salicylate elimination (other xenobiotics are discussed in Chap. 10), and sodium bicarbonate also prevents toxicity from methotrexate (Antidotes in Depth: A5). Acidifying the urine to hasten the elimination of alkaline substances is difficult to accomplish, probably useless, and possibly dangerous and therefore has no role in poison management. Forced diuresis also has no indication and may endanger the patient by causing pulmonary or cerebral edema.
If extracorporeal elimination is contemplated, hemodialysis should be considered for overdoses of salicylates, methanol, ethylene glycol, lithium, valproic acid, and xenobiotics that are both dialyzable and cause fluid and electrolyte problems. If available, hemoperfusion or high-flux hemodialysis should be considered for overdoses of theophylline, phenobarbital, and carbamazepine (although rarely, if ever, for the last two). When hemoperfusion is the method of choice (as for a theophylline overdose) but not available, hemodialysis is a logical, effective alternative and certainly preferable to delaying treatment until hemoperfusion becomes available. Peritoneal dialysis is too ineffective to be of practical utility, and hemodiafiltration is not as efficacious as hemodialysis or hemoperfusion, although it may play a role between multiple runs of dialysis or in hemodynamically compromised patients who cannot tolerate hemodialysis. In theory, both hemodialysis and hemoperfusion in series may be useful for a very few life-threatening overdoses such as thallium or salicylates. Plasmapheresis and exchange transfusion are used to eliminate xenobiotics with large molecular weights that are not dialyzable (Chap. 10).