INITIAL MANAGEMENT OF THE POISONED PATIENT
The initial management of a patient with coma, seizures, or oth-erwise altered mental status should follow the same approach regardless of the poison involved: supportive measures are the basics (“ABCDs”) of poisoning treatment.
First, the airway should be cleared of vomitus or any other obstruction and an oral airway or endotracheal tube inserted if needed. For many patients, simple positioning in the lateral, left-side-down position is sufficient to move the flaccid tongue out of the airway. Breathing should be assessed by observation and pulse oxi-metry and, if in doubt, by measuring arterial blood gases. Patients with respiratory insufficiency should be intubated and mechanically ventilated. The circulation should be assessed by continuous moni-toring of pulse rate, blood pressure, urinary output, and evaluation of peripheral perfusion. An intravenous line should be placed and blood drawn for serum glucose and other routine determinations.
At this point, every patient with altered mental status should receive a challenge with concentrated dextrose, unless a rapid bedside blood glucose test demonstrates that the patient is not hypoglycemic. Adults are given 25 g (50 mL of 50% dextrose solution) intravenously, children 0.5 g/kg (2 mL/kg of 25% dex-trose). Hypoglycemic patients may appear to be intoxicated, and there is no rapid and reliable way to distinguish them from poi-soned patients. Alcoholic or malnourished patients should also receive 100 mg of thiamine intramuscularly or in the intravenous infusion solution at this time to prevent Wernicke’s syndrome.
The opioid antagonist naloxone may be given in a dose of 0.4–2 mg intravenously. Naloxone reverses respiratory and CNS depression due to all varieties of opioid drugs . It is useful to remember that these drugs cause death primarily by respiratory depression; therefore, if airway and breathing assistance have already been instituted, naloxone may not be necessary. Larger doses of naloxone may be needed for patients with overdose involv-ing propoxyphene, codeine, and some other opioids. The benzodi-azepine antagonist flumazenil may be of value in patients with suspected benzodiazepine overdose, but it should not be used if there is a history of tricyclic antidepressant overdose or a seizure disorder, as it can induce convulsions in such patients.
Once the essential initial ABCD interventions have been instituted, one can begin a more detailed evaluation to make a specific diagno-sis. This includes gathering any available history and performing a toxicologically oriented physical examination. Other causes of coma or seizures such as head trauma, meningitis, or metabolic abnor-malities should be sought and treated. Some common intoxications are described under Common Toxic Syndromes.
Oral statements about the amount and even the type of drug ingested in toxic emergencies may be unreliable. Even so, family members, police, and fire department or paramedical personnel should be asked to describe the environment in which the toxic emergency occurred and should bring to the emergency depart-ment any syringes, empty bottles, household products, or over-the-counter medications in the immediate vicinity of the possibly poisoned patient.
A brief examination should be performed, emphasizing those areas most likely to give clues to the toxicologic diagnosis. These include vital signs, eyes and mouth, skin, abdomen, and nervous system.
· Vital signs—Careful evaluation of vital signs (blood pressure,pulse, respirations, and temperature) is essential in all toxicologic emergencies. Hypertension and tachycardia are typical with amphetamines, cocaine, and antimuscarinic (anticholinergic)
drugs. Hypotension and bradycardia are characteristic features of overdose with calcium channel blockers, β blockers, clonidine, and sedative hypnotics. Hypotension with tachycardia is commonwith tricyclic antidepressants, trazodone, quetiapine, vasodilators, and β agonists. Rapid respirations are typical of salicylates, carbon monoxide, and other toxins that produce metabolic acidosis or cellular asphyxia. Hyperthermia may be associated with sympath-omimetics, anticholinergics, salicylates, and drugs producing sei-zures or muscular rigidity. Hypothermia can be caused by any CNS-depressant drug, especially when accompanied by exposure to a cold environment.
· Eyes—The eyes are a valuable source of toxicologic information.Constriction of the pupils (miosis) is typical of opioids, clonidine, phenothiazines, and cholinesterase inhibitors (eg, organophosphate insecticides), and deep coma due to sedative drugs. Dilation of the pupils (mydriasis) is common with amphetamines, cocaine, LSD, and atropine and other anticholinergic drugs. Horizontal nystagmus is characteristic of intoxication with phenytoin, alcohol, barbiturates, and other sedative drugs. The presence of both vertical and horizon-tal nystagmus is strongly suggestive of phencyclidine poisoning. Ptosis and ophthalmoplegia are characteristic features of botulism.
· Mouth—The mouth may show signs of burns due to corro-sive substances, or soot from smoke inhalation. Typical odors of alcohol, hydrocarbon solvents, or ammonia may be noted. Poisoning due to cyanide can be recognized by some examiners as an odor like bitter almonds.
· Skin—The skin often appears flushed, hot, and dry in poison-ing with atropine and other antimuscarinics. Excessive sweating occurs with organophosphates, nicotine, and sympathomimetic drugs. Cyanosis may be caused by hypoxemia or by methemoglo-binemia. Icterus may suggest hepatic necrosis due to acetamino-phen or Amanita phalloides mushroom poisoning.
· Abdomen— Abdominal examination may reveal ileus, whichis typical of poisoning with antimuscarinic, opioid, and sedative drugs. Hyperactive bowel sounds, abdominal cramping, and diar-rhea are common in poisoning with organophosphates, iron, arsenic, theophylline, A phalloides, and A muscaria.
· Nervous system—A careful neurologic examination is essen-tial. Focal seizures or motor deficits suggest a structural lesion (eg, intracranial hemorrhage due to trauma) rather than toxic or meta-bolic encephalopathy. Nystagmus, dysarthria, and ataxia are typi-cal of phenytoin, carbamazepine, alcohol, and other sedative intoxication. Twitching and muscular hyperactivity are common with atropine and other anticholinergic agents, and cocaine and other sympathomimetic drugs. Muscular rigidity can be caused by haloperidol and other antipsychotic agents, and by strychnine or by tetanus. Generalized hypertonicity of muscles and lower extremity clonus are typical of serotonin syndrome. Seizures areoften caused by overdose with antidepressants (especially tricyclic antidepressants and bupropion [as in the case study]), cocaine, amphetamines, theophylline, isoniazid, and diphenhydramine. Flaccid coma with absent reflexes and even an isoelectric electro-encephalogram may be seen with deep coma due to sedative-hypnotic or other CNS depressant intoxication and may be mistaken for brain death.
Hypoventilation results in an elevated PCO2 (hypercapnia) and a low PO2 (hypoxia). The PO2 may also be low in a patient with aspiration pneumonia or drug-induced pulmonary edema. Poor tissue oxygenation due to hypoxia, hypotension, or cyanide poisoning will result in metabolic acidosis. The PO2 measures only oxygen dissolved in the plasma and not total blood oxygen content or oxyhemoglobin saturation and may appear normal in patients with severe carbon monoxide poisoning. Pulse oxi-metry may also give falsely normal results in carbon monoxide intoxication.
Sodium, potassium, chloride, and bicarbonate should be mea-sured. The anion gap is then calculated by subtracting the mea-sured anions from cations:
Anion gap = (Na+ + K+) – (HCO3– + Cl–)
Normally, the sum of the cations exceeds the sum of the anions by no more than 12–16 mEq/L (or 8–12 mEq/L if the formula used for estimating the anion gap omits the potassium level). A larger-than expected anion gap is caused by the presence of unmeasured anions (lactate, etc) accompanying metabolic acidosis. This may occur with numerous conditions, such as diabetic ketoacidosis, renal failure, or shock-induced lactic acidosis. Drugs that may induce an elevated anion gap metabolic acidosis (Table 58–1) include aspirin, metformin, methanol, ethylene glycol, isoniazid, and iron.
Alterations in the serum potassium level are hazardous because they can result in cardiac arrhythmias. Drugs that may cause hyper-kalemia despite normal renal function include potassium itself, β blockers, digitalis glycosides, potassium-sparing diuretics, and fluo-ride. Drugs associated with hypokalemia include barium, β ago-nists, caffeine, theophylline, and thiazide and loop diuretics.
Some toxins have direct nephrotoxic effects; in other cases, renal failure is due to shock or myoglobinuria. Blood urea nitrogen and creatinine levels should be measured and urinalysis performed. Elevated serum creatine kinase (CK) and myoglobin in the urine suggest muscle necrosis due to seizures or muscular rigidity. Oxalate crystals in large numbers in the urine suggest ethylene glycol poisoning.
The calculated serum osmolality is dependent mainly on the serum sodium and glucose and the blood urea nitrogen and can be estimated from the following formula:
This calculated value is normally 280–290 mOsm/L. Ethanol and other alcohols may contribute significantly to the measured serum osmolality but, since they are not included in the calcula-tion, cause an osmol gap:
Table 58–2 lists the concentration and expected contribution to the serum osmolality in ethanol, methanol, ethylene glycol, and isopropanol poisonings.
Widening of the QRS complex duration (to more than 100 milli-seconds) is typical of tricyclic antidepressant and quinidine over-doses (Figure 58–1). The QTc interval may be prolonged (to more than 440 milliseconds) in many poisonings, including quinidine, antidepressants and antipsychotics, lithium, and arsenic (see also http://www.torsades.org/). Variable atrioventricular (AV) block and a variety of atrial and ventricular arrhythmias are common with poisoning by digoxin and other cardiac glycosides. Hypoxemia due to carbon monoxide poisoning may result in ischemic changes on the electrocardiogram.
A plain film of the abdomen may be useful because some tablets, particularly iron and potassium, may be radiopaque. Chest radio-graphs may reveal aspiration pneumonia, hydrocarbon pneumo-nia, or pulmonary edema. When head trauma is suspected, a computed tomography (CT) scan is recommended.
It is a common misconception that a broad toxicology “screen” is the best way to diagnose and manage an acute poisoning. Unfortunately, comprehensive toxicology screening is time-consuming and expensive and results of tests may not be available for days. Moreover, many highly toxic drugs such as calcium chan-nel blockers, β blockers, and isoniazid are not included in the screening process. The clinical examination of the patient and selected routine laboratory tests are usually sufficient to generate a tentative diagnosis and an appropriate treatment plan. Although screening tests may be helpful in confirming a suspected intoxica-tion or for ruling out intoxication as a cause of apparent brain death, they should not delay needed treatment.
When a specific antidote or other treatment is under consid-eration, quantitative laboratory testing may be indicated. For example, determination of the acetaminophen level is useful in assessing the need for antidotal therapy with acetylcysteine. Serum levels of salicylate (aspirin), ethylene glycol, methanol, theophylline, carbamazepine, lithium, valproic acid, and other drugs and poisons may indicate the need for hemodialysis (Table 58–3).
Decontamination procedures should be undertaken simultane-ously with initial stabilization, diagnostic assessment, and labora-tory evaluation. Decontamination involves removing toxins from the skin or gastrointestinal tract.
Contaminated clothing should be completely removed and double-bagged to prevent illness in health care providers and for possible laboratory analysis. Wash contaminated skin with soap and water.
Controversy remains regarding the efficacy of gut emptying by emesis or gastric lavage, especially when treatment is initiated more than 1 hour after ingestion. For most ingestions, clinical toxicologists recommend simple administration of activated char-coal to bind ingested poisons in the gut before they can be absorbed (as in the case study). In unusual circumstances, induced emesis or gastric lavage may also be used.
· Emesis—Emesis can be induced with ipecacsyrup(neverextract of ipecac), and this method was previously used to treatsome childhood ingestions at home under telephone supervision of a physician or poison control center personnel. However, the risks involved with inappropriate use outweighed the unproven benefits, and this treatment is rarely used in the home or hospital. Ipecac should not be used if the suspected intoxicant is a corrosive agent, a petroleum distillate, or a rapid-acting convulsant. Previously popular methods of inducing emesis such as fingertip stimulation of the pharynx, salt water, and apomorphine are inef-fective or dangerous and should not be used.
· Gastric lavage—If the patient is awake or if the airway isprotected by an endotracheal tube, gastric lavage may be per-formed using an orogastric or nasogastric tube—as large a tube as possible. Lavage solutions (usually 0.9% saline) should be at body temperature to prevent hypothermia.
· Activated charcoal—Owing to its large surface area, acti-vated charcoal can adsorb many drugs and poisons. It is most effective if given in a ratio of at least 10:1 of charcoal to estimated dose of toxin by weight. Charcoal does not bind iron, lithium, or potassium, and it binds alcohols and cyanide only poorly. It does not appear to be useful in poisoning due to corrosive mineral acids and alkali. Studies suggest that oral activated charcoal given alone may be just as effective as gut emptying (eg, ipecac-induced emesis or gastric lavage) followed by charcoal. Repeated doses of oral activated charcoal may enhance systemic elimination of some drugs (including carbamazepine, dapsone, and theophylline) by a mechanism referred to as “gut dialysis,” although the clinical ben-efit is unproved.
· Cathartics— Administration of a cathartic (laxative) agentmay hasten removal of toxins from the gastrointestinal tract and reduce absorption, although no controlled studies have been done. Whole bowel irrigation with a balanced polyethylene glycol-electrolyte solution (GoLYTELY, CoLyte) can enhance gut decon-tamination after ingestion of iron tablets, enteric-coated medicines, illicit drug-filled packets, and foreign bodies. The solution is administered orally at 1–2 L/h (500 mL/h in children) for several hours until the rectal effluent is clear.
There is a popular misconception that there is an antidote for every poison. Actually, selective antidotes are available for only a few classes of toxins. The major antidotes and their characteristics are listed in Table 58–4.
After appropriate diagnostic and decontamination procedures and administration of antidotes, it is important to consider whether measures for enhancing elimination, such as hemodialysis or uri-nary alkalinization, can improve the clinical outcome. Table 58–3 lists intoxications for which dialysis may be beneficial.
· Peritoneal dialysis—Although it is a relatively simple andavailable technique, peritoneal dialysis is inefficient in removing most drugs.
· Hemodialysis—Hemodialysis is more efficient than perito-neal dialysis and has been well studied. It assists in correction of fluid and electrolyte imbalance and may also enhance removal of toxic metabolites (eg, formic acid in methanol poisoning; oxalic and glycolic acids in ethylene glycol poisoning). The efficiency of both peritoneal dialysis and hemodialysis is a function of the molecular weight, water solubility, protein binding, endogenous clearance, and distribution in the body of the specific toxin. Hemodialysis is especially useful in overdose cases in which the precipitating drug can be removed and fluid and electrolyte imbal-ances are present and can be corrected (eg, salicylate intoxication).
Previously popular but of unproved value, forced diuresis may cause volume overload and electrolyte abnormalities and is not recom-mended. Renal elimination of a few toxins can be enhanced by alteration of urinary pH. For example, urinary alkalinization is use-ful in cases of salicylate overdose. Acidification may increase the urine concentration of drugs such as phencyclidine and amphet-amines but is not advised because it may worsen renal complications from rhabdomyolysis, which often accompanies the intoxication.