Resuscitation is the first priority in any poisoned patient. After resuscitation, a structured risk assessment is used to identify patients who may benefit from an antidote, decontamination, or enhanced elimination techniques. Most patients only require provision of good supportive care during a period of observation in an appropriate environment.
Treatment of cardiac arrest in poisoned patients follows Advanced Cardiac Life Support guidelines with the addition of interventions potentially beneficial in toxin-induced cardiac arrest (Table 176-1).14 Prolonged resuscitation is generally indicated, as patients are often young with minimal preexisting organ dysfunction. Utilization of extracorporeal cardiac and respiratory assist devices until organ toxicity resolves may be life-saving.
TABLE 176-1Potential Interventions in Toxin-Induced Cardiac Arrest15 ||Download (.pdf) TABLE 176-1 Potential Interventions in Toxin-Induced Cardiac Arrest15
|Toxin or Toxin/Drug Class ||Intervention |
Toxins with a specific antidote (examples)
|Sodium channel blocker or wide-complex tachycardia ||Sodium bicarbonate |
|Calcium channel blocker or β-blocker ||High-dose insulin |
Local anesthetic agents
|IV lipid emulsion |
|Other Therapies to Consider |
Intra-aortic balloon pump
Extracorporeal membrane oxygenation
Stabilization of airway, breathing, and circulation represents initial priorities. Compromised airway patency or reduced respiratory drive may lead to inadequate ventilation; provision of a mechanical airway and assisted ventilation is vital in these circumstances. IV crystalloid bolus (10 to 20 mL/kg) is first-line treatment of hypotension. Since most patients without toxin-induced fluid loss are generally not fluid depleted, avoid administration of excess fluid. Persisting hypotension despite an adequate volume infusion may respond to a specific antidote. Otherwise, cautious administration of an inotropic agent is indicated. Inotrope choice is guided by knowledge of the toxin's toxicodynamic properties and assessment of circulatory status (e.g., cardiac pump failure versus vasodilatory shock).
Stabilization of airway, breathing, and circulation allows further assessment of blood glucose concentration, temperature, and conscious state. Although the proper use of antidotes (Table 176-2) is important, only a few are indicated before cardiopulmonary stabilization (e.g., naloxone for opiate toxicity, cyanide antidotes for cyanide toxicity, and atropine for organophosphate poisoning).
TABLE 176-2Common Antidotes Used in Resuscitation of the Acutely Poisoned Patient ||Download (.pdf) TABLE 176-2 Common Antidotes Used in Resuscitation of the Acutely Poisoned Patient
|Antidote ||Pediatric Dose ||Adult Dose ||Indication |
Calcium chloride 10%
27.2 milligrams/mL elemental Ca
|0.2–0.25 mL/kg IV ||10 mL IV ||Calcium channel antagonists |
Calcium gluconate 10%
9 milligrams/mL elemental Ca
|0.6–0.8 mL/kg IV ||10–30 mL IV || |
Cyanide antidote kit
|Not typically used ||1 ampule O2 chamber of ventilation bag 30 s on/30 s off || |
Hydrogen sulfide (use only sodium nitrite)
| Sodium nitrite (3% solution) ||0.33 mL/kg IV ||10 mL IV ||Cyanide |
| Sodium thiosulfate (25% solution) ||1.65 mL/kg IV ||50 mL IV ||Cyanide |
|Dextrose (glucose) ||0.5 gram/kg IV ||1 gram/kg IV || |
|1–2 vials IV ||5–10 vials ||Digoxin and other cardioactive steroids |
|Flumazenil ||0.01 milligram/kg IV ||0.2 milligram IV ||Benzodiazepines |
|Glucagon ||50–150 micrograms/kg IV ||3–10 milligrams IV || |
Calcium channel blockers
|Hydroxocobalamin ||70 milligrams/kg IV (maximum 5 grams). Can be repeated up to 3 times. Administer with sodium thiosulfate. || |
|IV lipid emulsion 20% ||1.5 mL/kg IV bolus over 1 min (may be repeated two times at 5-min intervals), followed by 0.25 mL/kg per minute ||100-mL IV bolus over 1 min, followed by 400 mL IV over 20 min || |
Local anesthetic toxicity
Rescue therapy for lipophilic cardiotoxins
|Methylene blue || |
1–2 milligrams/kg IV
Neonates: 0.3–1.0 milligram/kg IV
|1–2 milligrams/kg IV ||Oxidizing toxins (e.g., nitrites, benzocaine, sulfonamides) |
|Naloxone || |
As much as required
Start: 0.01 milligram IV
As much as required
Start: 0.1–0.4 milligram IV
|Pyridoxine ||Gram for gram if amount isoniazid ingested is known || |
|70 milligrams/kg IV (maximum 5 grams) ||5 grams IV |
|Sodium bicarbonate ||1–2 mEq/kg IV bolus followed by 2 mEq/kg per h IV infusion || |
Sodium channel blockers
|Thiamine ||5–10 milligrams IV ||100 milligrams IV || |
Treat hypoglycemia with IV dextrose (glucose). Patients at risk of Wernicke's encephalopathy also require thiamine, but do not require that it be administered before the dextrose.15 Altered mental status when hypoglycemia cannot be excluded is an indication for IV dextrose. Supplemental oxygen, thiamine, glucose, and naloxone are often administered empirically as a cocktail in cases of altered mental status. Although relatively safe and affordable in the developed world, this approach may not be cost-effective in developing countries. The decision to administer an antidote should be made after a rapid collateral history is obtained and targeted examination completed. Altered mental status not responding to an antidote or not consistent with exposure history requires further investigation. Metabolic, infective, and surgical (e.g., intracranial injury) causes of altered mental status should be considered.
In general, antiarrhythmic drugs are not first-line treatment for toxin-induced arrhythmias, as most antiarrhythmic drugs have proarrhythmic and negative inotropic properties. Most toxin-induced arrhythmias respond to correction of hypoxia, metabolic/acid–base abnormalities, and administration of an antidote (e.g., digoxin Fab). Sodium bicarbonate is administered for sodium-channel blocker toxicity with cardiovascular complications, such as wide QRS complex tachyarrhythmias. Ventricular tachyarrhythmias may respond to overdrive pacing.
Drug-induced seizures are treated with titrated doses of IV benzodiazepines, with the exception that isoniazid-induced seizures require pyridoxine. Metabolic disorders, such as hypoglycemia and hyponatremia, can also produce seizures and should be rapidly excluded. Barbiturates are second-line agents for benzodiazepine-resistant seizures (once isoniazid-induced seizures are excluded). There is no role for phenytoin in the treatment of toxin-induced seizures; it has neither theoretical nor proven efficacy, and may worsen toxicity.16
Agitation is treated with titrated doses of benzodiazepines. Large doses may be required and are appropriate in monitored settings where advanced airway interventions are available if required. Although antipsychotic agents are often used as second-line agents for toxin-induced agitation, they have theoretical disadvantages, including anticholinergic and extrapyramidal effects.17 Droperidol has been associated (rarely) with QT interval prolongation and cardiac arrhythmias.
HYPERTHERMIA AND HYPOTHERMIA
Patients with core temperatures of >39°C (>102.2°F) require aggressive active cooling measures to prevent complications such as rhabdomyolysis, organ failure, and disseminated intravascular coagulation. Sedation, neuromuscular paralysis, and intubation are required if active measures are ineffective. Several toxidromes associated with hyperthermia are treated with specific pharmaceutical agents: sympathomimetic (benzodiazepines), serotonin (cyproheptadine18), and neuromuscular malignant syndrome (bromocriptine19).
Drug-induced coma with subsequent immobility and environmental exposure or inherent drug toxicity (opioids, phenothiazines, ethanol) may produce hypothermia. A core temperature <32°C (<90°F) is an indication for active rewarming.
Naloxone is a nontoxic, diagnostic, and therapeutic antidote. It is a competitive opioid antagonist administered IV, IM, or intranasally20 to reverse opioid-induced deleterious hypoventilation. Naloxone can be used as a diagnostic agent when history and/or examination findings (respiratory rate of <12 breaths/min is a predictor of response to naloxone) suggest possible opioid exposure. Naloxone is titrated to clinical effect using bolus doses, typically 0.1 to 0.4 milligrams. Large initial bolus doses may precipitate vomiting and aspiration, acute opioid withdrawal, or an uncooperative, agitated patient. Miosis is an unreliable indicator of naloxone's adequate clinical effect, as some opioids do not affect pupil size. Doses are titrated to achieve desirable ventilation and conscious state (adequate respiratory rate, normal arterial oxygen saturations on room air, and verbal or motor response to voice). Although naloxone may reverse the effects of opioids for 20 to 60 minutes, the effect of many opioids will outlast this time frame with possible return of respiratory depression. Patients should be observed for 2 to 3 hours after administration of IV naloxone.
INTRAVENOUS LIPID EMULSION
Animal studies demonstrate the potential for IV lipid emulsion to act as an antidote for lipophilic toxins. Provision of an intravascular "lipid sink" is postulated as the predominant mechanism, as sequestration of lipophilic toxins prevents target receptor interaction. Human case reports indicate that IV lipid emulsion may provide benefit in cases of potentially life-threatening toxicity from a local anesthetic agent, haloperidol, tricyclic antidepressant, lipophilic β-blocker, or calcium channel blocker.21 Currently, IV lipid emulsion can be considered in life-threatening cardiotoxicity caused by lipophilic cardiotoxins that is resistant to conventional therapies.