POISONING OR OVERDOSE
Patients with drug overdoses or poisoning may initially have no symptoms or they may have varying degrees of overt intoxication. The asymptomatic patient may have been exposed to or may have ingested a lethal dose but not yet exhibit any manifestations of toxicity.
It is important to:
- quickly assess the potential danger
- consider gut decontamination to prevent absorption
- treat complications if they occur
- observe the asymptomatic patient for an appropriate interval.
Assess the Danger
If the drug or poison is known, its danger can be assessed by consulting a text or computerized information resource or by calling a regional poison control center. Assessment will usually take into account the dose ingested; the time since inges- tion; the presence of any symptoms or clinical signs; pre-existing cardiac, respiratory, kidney, or liver disease; and occasionally, specific serum drug or toxin levels. Be aware that the history given by the patient or family maybe incomplete or unreliable.
Observation of the Patient
Asymptomatic or mildly symptomatic patients should be observed for at least 4-6 hours. Longer observation is indicated if the ingested substance is a sustained-release preparation or is known to slow gastrointestinal motility (opioids, anticholinergics, salicylate) or may cause delayed onset of symptoms (such as acetaminophen, colchicine, or hepatotoxic mushrooms). After that time, the patient may be discharged if no symptoms have developed. Before discharge, psychiatric evaluation should be performed to assess suicide risk. Intentional ingestions in adolescents should raise the possibility of unwanted pregnancy or sexual abuse.
THE SYMPTOMATIC PATIENT
In symptomatic patients, treatment of life-threatening complications takes precedence over in-depth diagnostic evaluation. Patients with mild symptoms may deteriorate rapidly, which is why all potentially significant exposures should be observed in an acute care facility. The following complications may occur, depending on the type of poisoning.
Assessment & Complications
Coma is commonly associated with ingestion of large doses of antihistamines (eg, diphenhydramine), benzodiazepines and other sedative-hypnotic drugs, ethanol, opioids, anti-psychotic drugs, or antidepressants. The most common cause of death in comatose patients is respiratory failure, which may occur abruptly. Pulmonary aspiration of gastric contents may also occur, especially in victims who are deeply obtunded or convulsing. Hypoxia and hypoventilation may cause or aggravate hypotension, arrhythmias, and seizures. Thus, protection of the airway and assisted ventilation are the most important treatment measures for any poisoned patient.
The initial emergency management of coma can be remembered by the mnemonic ABCD, for Airway, Breathing, Circulation, and Drugs (dextrose, thiamine, and naloxone or flumazenil), respectively.
Establish a patent airway by positioning, suction, or insertion of an artificial nasal or oropharyngeal airway. If the patient is deeply comatose or if airway reflexes are depressed, perform endotracheal intubation. These airway interventions may not be necessary if the patient is intoxicated by an opioid or a benzodiazepine and responds to intravenous naloxone or flumazenil.
Clinically assess the quality and depth of respiration, and provide assistance if necessary with a bag-valve-mask device or mechanical ventilator. Administer supplemental oxygen, if needed. The arterial or venous blood tension is useful in determining the adequacy of ventilation. The arterial blood determination may reveal hypoxemia, which may be caused by respiratory depression, bronchospasm, pulmonary aspiration, or non-cardiogenic pulmonary edema. Pulse oximetry provides an assessment of oxygenation but is not reliable in patients with methemoglobinemia or carbon monoxide poisoning, unless a pulse oximetry device capable of detecting these forms of hemoglobin is used.
Measure the pulse and blood pressure and estimate tissue perfusion (eg, by measurement of urinary output, skin signs, arterial blood pH). Place the patient on continuous ECG monitoring. Insert an intravenous line, and draw blood for glucose, electrolytes, serum creatinine and liver tests, and possible quantitative toxicologic testing.
- DEXROSE AND THIAMINE
Unless promptly treated, severe hypoglycemia can cause irreversible brain damage. Therefore, in all obtunded, comatose or convulsing patients, give 50% dextrose, 50-100 mL by intravenous bolus, unless a rapid bedside blood sugar test rules out hypoglycemia. In alcoholic or very malnourished patients who may have marginal thiamine stores, give thiamine, 100mg intramuscularly or in the intravenous fluids.
- OPIOID ANTAGONISTS
Naloxone, 0.4-2 mg intravenously, may reverse opioid-induced respiratory depression and coma. It is often given empirically to any comatose patient with depressed respirations. If opioid overdose is strongly suspected, give additional doses of naloxone (up to 5-10 mg may be required to reverse the effects of potent opioids). Note: Naloxone has a shorter duration of action (2-3 hours) than most common opioids; repeated doses may be required, and continuous observation for at least 3-4 hours after the last dose is mandatory. Nalmefene, a newer opioid antagonist, has a duration of effect longer than that of naloxone but still shorter than that of the opioid methadone.
Flumazenil, 0.2-0.5 mg intravenously, repeated as needed up to a maximum of 3 mg, may reverse benzodiazepine-induced coma. Caution: Flumazenil should not be given if the patient has coingested a potential convulsant drug, is a user of high-dose benzodiazepines, or has a seizure disorder because its use in these circumstances may precipitate seizures. In most circumstances, use of flumazenil is not advised as the potential risks outweigh its benefits. Note: Flumazenif has a short duration of effect (2-3 hours), and resedation requiring additional doses may occur.
Assessment & Complications
Hypothermia ommonly accompanies coma due to opioids, ethanol, hypoglycemic agents, phenothiazines, barbiturates, benzodiazepines, and other sedative-hypnotics and central nervous system depressants. Hypothermic patients may have a barely perceptible pulse and blood pressure. Hvpothermia may cause or aggravate hypotension, which will not reverse until the temperature is normalized.
Assessment & Complications
Hypotension may be due to poisoning by many different drugs and poisons, including antihypertensive drugs, beta- blockers, calcium channel blockers, disulfiram (ethanol interaction), iron, trazodone, quetiapine, and other anti-psychotic agents and antidepressants. Poisons causing hypotension include cyanide, carbon monoxide, hydrogen sulfide, aluminum or zinc phosphide, arsenic, and certain mushrooms. Hypotension in the poisoned or drug-overdosed patient may be caused by venous or arteriolar vasodilation, hypovolemia, depressed cardiac contractility, or a combination of these effects.
Most hypotensive patients respond to empiric treatment with repeated 200 mL intravenous boluses of 0.9% saline or other isotonic crystalloid up to a total of 1-2 L; much larger amounts may be needed if the victim is profoundly volume depleted (eg, as with Amanita phalloides mushroom poi- soning). Monitoring the central venous pressure (CVP) can help determine whether further fluid herapy is needed. If fluid therapy is not successful, give dopamine or norepinephrine by intravenous infusion, consider bedside cardiac ultrasound or pulmonary artery catheterization (or both) if hypotension persists. Hypotension caused by certain toxins may respond to specific treatment. For hypotension caused by overdoses of tricyclic antidepressants or other sodium channel blockers, administer sodium bicarbonate, 50-100 mEq by intravenous bolus injection. Norepinephrine 4-8 mcg/min intravenous infusion is more effective than dopamine in some patients with overdoses of tricyelic antidepressants or of drugs with predominantly vasodilating effects. For beta-blocker overdose, glucagon (5-10 mg intravenously) may be of value. For calcium channel blocker overdose, administer calcium chloride,1-2 g intravenously (repeated doses may be necessary; doses of 5-10 g and more have been given in some cases). High-dose insulin (0.5-1 units/kg intravenously) euglycemic therapy may also be used (sct the sections on Beta-Adrenergic Blockers and Calcium Channel Blockers, below). Intralipid 20% lipid emulsto has been reported to improve hemodyn amics in human case reports or animal studies of intoxication by high lipid-soluble drugs such as bupivacaine, bupropion, clomipramine, and verapamil.
Engebretsen KM et al.High-dose insulin therapy in beta-blocker and calcium channel －blocker poisoning.Clin Toxicol(Phila). 2011 Apr;49(4):277-83.PMID:215639021 Waring WS.Intravenous lipid administration for drug-induced toxicity:a critical review of the existing data.Expert Rev Clin Pharmacol.2012 Jul;5(4):437-44.[PMID:22943123]
Assessment & Complications
Hypertension may be due to poisoning with amphetamines, anticholinergics, cocaine, performance-enhancing products (containing caffeine, phenylephrine, ephedrine, or yohimbine), monoamine oxidase (MAO) inhibitors, and other drugs. Severe hypertension (eg,diastolic blood pressure ＞105-110 mm Hg in a person who does not have chronic hypertension) can result in acute intracranial hemorrhage, myocardial infarction, or aortic dissection. Treat hypertension if the patient is symptomatic or if the diastolic pressure is>105-110 mm Hg-especially if there is no prior history of hypertension. Hypertensive patients who are agitated or anxious may benefit from a sedative such as lorazepam, 2-3 mg intravenously. For persistent hypertension, administer phentolamine, 2-5 mg intravenously, or nitroprusside sodium, 0.25-8 mcg/kg/min intravenously. If excessive tachycardia Is present, add propranolol, 1-5 mg intravenously, or esmolol, 25-100 mcg/kg/min intravenously, or labetalol 0.2-0.3 mg/kg intravenously. Caution: Do not give beta- blockers alone, since doing so may paradoxically worsen hypertension as a result of unopposed alpha-adrenergic stimulation.
Grossman E et al.Drug-induced hypertension:an unappreciated cause of secondary hypertension.Am J Med.2012 Jan;125(1): 14-22.[PMID:22195528] Perruchoud C et al.Severe hypertension following accidental clonidine overdose during the refilling of an implanted intra- thecal drug delivery system.Neuromodulation.2012 Jan- Feb;15(1):31-4.[PMID:21943355]