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Chapter 73 COMMON DRUGS OF ABUSE518

37. What is the appropriate way to decontaminate the gastrointestinal tract?

Administer 1 g/kg of activated charcoal to all patients with signiﬁcant ingestions who arrive

within approximately 1 hour of ingestion. Pulmonary aspiration of activated charcoal causes a

signiﬁcant pneumonitis and occasionally permanent sequelae. Intubate patients with

decreased mental status and airway reﬂexes prior to administering activated charcoal. Do not

perform orogastric lavage for sedative-hypnotic intoxication.

38. Are there speciﬁc antidotes for sedative hypnotic intoxication?

Flumazenil can be used for overdose of benzodiazepine and related medications such as

zolpidem.

39. How does ﬂumazenil work?

Benzodiazepines and zolpidem act as GABA-A receptor agonists. Flumazenil antagonizes the

effects of these drugs by competitively inhibiting the GABA receptor. Administer 0.2 to 0.5 mg

of ﬂumazenil intravenously in increasing doses to a generally accepted maximum dose of

5 mg. If there is no response with 5 mg, consider another intoxication, coingestant, or

etiology for the patient’s responsiveness.

40. Should ﬂumazenil be given empirically to all patients with depressed mental

status?

No. Flumazenil may be used for a patient with iatrogenic toxicity during procedural sedation or

in an unintentional ingestion by a benzodiazepine-naïve child or adult. Consider it with a sole

benzodiazepine overdose causing signiﬁcant CNS depression. It has no role in undifferentiated

or mixed overdose because it can induce seizures, unmask the effects of a coingestant, and

rarely cause life-threatening dysrhythmias. Flumazenil may also induce seizures and withdrawal

symptoms in chronic benzodiazepine users. The onset of ﬂumazenil is 1 to 5 minutes and

duration of effect is 1 to 4 hours. Sedation will resume after its effects have worn off. Most

patients with a benzodiazepine overdose will do well with only supportive care and do not

require ﬂumazenil.

The ideal patient for ﬂumazenil use would be iatrogenic oversedation with none of the

following contraindications:

Prior seizure history

Electrocardiogram (ECG) evidence of cyclic antidepressants

Chronic benzodiazepine use

Abnormal vital signs, including hypoxia

Coingestants that provoke seizures or dysrhythmias

41. What is GHB?

It is an abbreviation for gamma-hydroxybutyrate, which is a naturally occurring human

neurotransmitter similar in structure to GABA. GHB has been used as a sleep aid, anesthetic, and

muscle builder. It is sold on the Internet and abused for its mild sedating and euphoric effects.

Although restricted by the Food and Drug Administration in the 1990s, GHB is available again

(trade name Xyrem) as a tightly controlled treatment for narcolepsy. However, it is easily

synthesized; recipes and materials are widely available. Congeners, including gamma-butyrlactone

and 1,4-butanediol, are metabolized to GHB and have the same effects and are common.

42. How does a GHB overdose present?

Most ingestions of GHB are mild and produce minimal sedation and euphoria. Rarely, patients

overdose on GHB and present to the ED with a decreased level of consciousness. In contrast

to other sedative hypnotic intoxications, the level of consciousness tends to ﬂuctuate between

mild agitation and severe CNS depression. Airway reﬂexes are usually intact and often

hypersensitive. An attempt at direct laryngoscopy may cause the patient to quickly sit up and

be agitated for several minutes. Because the clinical effects of GHB usually last less than

6 hours, decisions about airway management should be based on the patient’s respiratory

status and the ability to monitor oxygenation closely in the ED. Although naloxone, ﬂumazenil,

Chapter 73 COMMON DRUGS OF ABUSE 519

and physostigmine have been described as reversal agents in GHB intoxication, no antidote

has consistently been shown to be effective. Death from GHB intoxication is generally from

respiratory failure.

43. What are the effects of GHB withdrawal?

Recreational users of GHB manifest withdrawal symptoms of anxiety, insomnia, disorientation,

tachycardia, hypertension, and visual and auditory hallucinations. GHB withdrawal is similar in

presentation to benzodiazepine withdrawal, but with greater intensity.

44. How do zolpidem and benzodiazepine overdose differ?

Zolpidem (Ambien) acts similarly to benzodiazepines by binding at the alpha-1 subunit of the

GABA-A receptor, and is useful as a sleep aid. Due to its speciﬁc afﬁnity for the alpha-1 subunit,

zolpidem has minimal muscle relaxant, anxiolytic, and anticonvulsant properties. Therefore,

zolpidem intoxication presents with CNS depression; respiratory depression is uncommon.

45. What is a Mickey Finn?

A Mickey Finn is a drug-laced drink named for a maﬁa-associated bartender from Chicago in

the 1920s. Speciﬁcally it refers to a mixture of chloral hydrate and alcohol. Alcohol and chloral

hydrate act to potentiate each other’s effects, and prolong their duration of effect as they are

metabolized via the same pathway. Mr. Finn would use the drink to induce his victims into

unconsciousness, and then relieve them of all their valuables.

MUSHROOMS

46. What are the symptoms and signs of mushroom poisoning?

Many mushrooms contain toxins that cause gastrointestinal manifestations including nausea,

vomiting, and diarrhea. Certain species have toxins that are associated with more severe

gastrointestinal manifestations or other characteristic symptoms and signs (Table 73-4).

47. Which mushroom’s toxins cause the most concern?

Amatoxins, which are cyclopeptides found in Amanita and some Galerina species. The classic

presentation of amatoxin poisoning includes an initial asymptomatic 6- to 12-hour period

followed by gastrointestinal symptoms. Severe hepatotoxicity becomes evident 24 hours to

several days after the initial ingestion.

Mushroom Species Toxin Symptoms and Signs

Amanita phalloides,

Galerina

Amatoxins Delayed-onset GI manifestations,

hepatic failure

Gyromitra Monomethylhydrazine Delayed-onset GI manifestations, CNS

manifestations, hemolysis

Psilocybe Muscimol, psilocybin Anticholinergic (including hallucinations

and seizures)

Clitocybe Muscarine-containing Cholinergic

Coprinus Coprine Disulﬁram-like reaction with ethanol

TABLE 73-4. MANIFESTATIONS OF MUSHROOM POISONING

CNS, central nervous system; GI, gastrointestinal.

Chapter 73 COMMON DRUGS OF ABUSE520

48. Do symptoms within 6 hours absolutely exclude amatoxin ingestion?

No. Not all patients exhibit the classic presentation. In addition, mushroom ingestion often

involves more than one species. Consider the possibility of amatoxin ingestion in all cases.

49. How do I treat someone who has ingested mushrooms?

Therapy is primarily supportive including volume resuscitation, seizure control, and treatment

of agitation. Identify the mushroom species ingested, if possible, and monitor for delayed

onset of symptoms when orellanine, amatoxin, or monomethylhydrazine are ingested. Speciﬁc

antidote therapy is available for some mushroom toxins.

HALLUCINOGENS

50. What are hallucinogens?

Typically, the term hallucinogen refers to agents that are used recreationally for their mind-

altering effects. Many substances (including mushrooms and stimulants) can cause

hallucinations, perceptions without any basis in reality, or alterations in the perception of reality.

51. List some examples of hallucinogens.

N, N-Diisopropyl-5-methoxytryptamine (Foxy-Methoxy)

Lysergic acid diethylamide (LSD)

Marijuana

Mescaline

3,4-Methylenedioxymethamphetamine (MDMA, Ecstasy)

1-(1-Phenylcyclohexyl) piperidine (PCP)

52. List the life-threatening effects of hallucinogens.

Common effects are seizures, hyperthermia, metabolic acidosis, hypertension, and

dysrhythmias. Rhabdomyolysis can develop subsequently. The effects of hallucinogens are

unpredictable and different with each use. Trauma frequently occurs as a result of the

disinhibition and aggressiveness caused by hallucinogen abuse.

53. Why would you “lick a toad”?

Hallucinations are produced by bufotenine, the substance in the skin secretions of Bufo

(Bufo vulgaris, Bufo marinus) toads. Bufotenine and many other natural toxins have been

used for years for hallucinogenic effects. Mescaline is the toxin in peyote, a cactus found in the

southwestern United States and Mexico. Psilocybin (4-phosphoryloxy-N, N-dimethyltryptamine)

is found in some species of mushrooms; N, N-dimethyltryptamine (DMT) is in many plants and

seeds. Natural agents (such as these) and their synthetic derivatives are used for hallucinogenic

purposes.

54. What is the treatment for hallucinogen toxicity?

Reassurance, a calm environment, avoidance of further trauma, and good supportive care are

important. Administer a benzodiazepine to calm agitated patients or to treat seizures. Consider

an antipsychotic for patients experiencing hallucinations and psychosis. Occasionally, physical

restraint may also be necessary to protect the patient or staff from harm.

STIMULANTS

55. What are examples of stimulants?

Cocaine, crack cocaine, amphetamine, methamphetamines, ecstasy (MDMA), and caffeine

56. What is the difference between cocaine and amphetamines?

Both drugs are stimulants and both work by increasing release of norepinephrine,

epinephrine, dopamine, and serotonin. Cocaine has direct vasoconstrictive effects,

Chapter 73 COMMON DRUGS OF ABUSE 521

blocks nervous system and cardiac sodium channels, and has a shorter duration of

action than amphetamines.

57. How should I screen for cocaine use?

The best way to screen for recent cocaine use is with a urine drug screen. Cocaine is

metabolized rapidly, and detection of the parent compound in blood indicates recent use.

However, blood tests for cocaine are rarely used. Cocaine undergoes nonenzymatic

degradation to benzoylecgonine and ecgonine methyl ester. These metabolites are excreted

renally and may be detected in the urine for several days after the initial exposure. Common

urine drug screens are positive for degradation products of cocaine.

58. What are free-base and crack cocaine?

Cocaine usually arrives in the United States as a white powder, cocaine hydrochloride (CHCl).

This powder is highly water-soluble and therefore crosses mucous membranes and intestinal

mucosa very quickly. Vaporization requires very high temperatures, so the powder is not

suitable for smoking. The powder can be dissolved with sodium bicarbonate (baking soda) or

ammonia and water. This solution may subsequently be treated with diethyl ether, decanted,

and dried to form freebase; or it can be boiled, ice added to reduce the temperature, and dried

to form crack (so called due to the popping sound that occurs during heating). Freebase and

crack are resistant to pyrolysis and can be smoked.

59. What is the signiﬁcance of chest pain after using cocaine?

Pneumothorax or pneumomediastinum may occur after a Valsalva maneuver when cocaine

has been smoked. Aortic dissection is rare. Myocardial infarction and acute coronary

syndrome have followed intranasal, intravenous, and smoked cocaine, even in young

patients with normal coronary arteries. Benzodiazepine is the initial treatment of choice

for cocaine-induced chest pain of cardiac etiology.

60. Does concomitant ingestion of ethanol change the effects of cocaine?

Yes. In the presence of ethanol, cocaine is metabolized to cocaethylene, a metabolite that retains

the cocaine’s vasoconstrictive properties. Cocaine and ethanol cause synergistic depression of

ventricular contraction and relaxation. Simultaneous ethanol ingestion and intranasal cocaine

increase peak plasma concentration of cocaine by 20%, compared with intranasal cocaine alone.

The increased cocaine concentration increases euphoria, and thus concomitant abuse.

61. What is ice?

Ice is the smokable form of methamphetamine, named for its appearance of transparent

crystals. In contrast to cocaine HCl, this pure base form of methamphetamine HCl evaporates

easily at room temperature and is absorbed rapidly from the lungs. Similar to intravenous

methamphetamine, it causes an immediate euphoric effect but without the risks of intravenous

drug administration. The clinical manifestations of methamphetamine are secondary to

heightened catecholamine activity and are the same, regardless of the route of administration.

Potential adverse effects include hypertension, dysrhythmias, intracranial hemorrhage,

seizures, and hyperthermia.

62. What is ecstasy and what is Eve?

Adam, ecstasy, E, and XTC are street names for 3,4-methylenedioxymethamphetamine

(MDMA). Eve is a street name for MDEA (3,4-methylenedioxyethylamphetamine) and is less

commonly used. These are designer drug analogs of amphetamines and are illegal. These

drugs increase serotonin release and reduce degradation more potently than other

amphetamines. Their unique chemical structure results in greater euphoria and less

sympathomimetic toxicity. MDMA causes long-term neurotoxic damage in brains of

experimental animals. Large overdoses of MDMA or MDEA, both phenylethylamines, can

resemble amphetamine toxicity. Hyperthermia (caused by the drug, and hot, crowded

conditions at the raves [dances]) and seizures are associated with death. In addition, ecstasy

Chapter 73 COMMON DRUGS OF ABUSE522

use has been associated with severe hyponatremia related to increased water intake during

raves and drug-induced increased secretion of antidiuretic hormone. Ecstasy and other

designer drugs are not detected on routine urine drug screens for amphetamines.

63. How should I treat someone with toxicity from stimulants?

The triple C method:

Calm them

Cool them

Uncover Complications

Treat agitation and seizures with a benzodiazepine. Large and repeated doses may be required.

Treat hyperthermia aggressively by reducing psychomotor agitation with sedation and by

adding cooling measures (i.e., evaporation, cooling blanket, and cool intravenous ﬂuids).

Stimulant complications include rhabdomyolysis, pyrexia, acidosis, intracranial hemorrhage,

pneumomediastinum, abdominal ischemia, and injection-related complications (i.e., abscess,

endocarditis, and cellulitis). Evaluate patients for these complications through history,

examination, and testing as needed. Cocaine is more likely to cause complications because it

directly causes vasoconstriction, in addition to the secondary effects of increased release and

decreased uptake of norepinephrine, epinephrine, serotonin, and dopamine.

64. How do I treat stimulant-induced high blood pressure?

High blood pressure from stimulant toxicity is usually short-lived. Most cases can be treated

with benzodiazepines. A true hypertensive emergency, although rare, can be treated with

benzodiazepines and nitroglycerin. Phentolamine, nitroprusside, and calcium channel blockers

are rarely needed and supportive data is limited. Nitroglycerin and other cardiac interventions

may be used in patients with ischemic chest pain from vasoconstriction or myocardial

infarction. b-blockers, such as propranolol, should be avoided in the cocaine-toxic patient

because they allow unbridled alpha agonism, which can result in elevated blood pressure and

coronary artery vasoconstriction.

KEY POINTS: COMMON DRUGS OF ABUSE

1. The classic triad of opioid poisoning is CNS depression, respiratory depression, and miosis.

2. In patients with respiratory compromise secondary to opioid intoxication, patient resuscitation

takes precedence over administration of opioid antagonists, such as naloxone.

3. Flumazenil is an antidote to benzodiazepine intoxication, and it is a speciﬁc antagonist to the

GABA A receptor. It has no role in the undifferentiated or mixed overdose.

4. The use of routine toxicologic screens in undifferentiated overdose is generally not helpful

due to the false-positive results, limited number of drugs screened, lack of correlation to

clinical presentation, and prolonged length of time to obtain the results.

5. Mushrooms of the Amanita species are associated with delayed-onset fulminant hepatic failure

produced by amatoxin.

6. Simultaneous cocaine and ethanol use depresses myocardial contractility.

7. Ecstasy (MDMA) can cause hyponatremia and pyrexia.

8. Evaluate patients with stimulant-induced agitation for the OTD: pyrexia, acidosis, and

rhabdomyolysis.

Chapter 73 COMMON DRUGS OF ABUSE 523

65. What is the stimulant-induced OTD?

OTD is the occult triad of death: acidemia, rhabdomyolysis, and pyrexia. These three occult

effects occur often, can be easily missed in the agitated patient, and, if not detected early, can

lead to death. With the moderately or severely agitated patient, obtain an arterial or venous

blood ph. Also, obtain a creatine kinase and repeat it if the patient continues to be physically

agitated. Finally, check the patient’s core temperature early and again before disposition.

WEBSITES

http://dawninfo.samhsa.gov

www.aapcc.org

BIBLIOGRAPHY

1. Babu K, Boyer EW, Hernon C, et al: Emerging drugs of abuse. Clin Pediatr Emerg Med 6:81–84, 2005.

2. Dawson AH: Naloxone, Naltrexone, and Nalmefene. In Dart RC, editor: Medical toxicology, ed 3, Philadelphia,

2004, Lippincott Williams & Wilkins, pp 228–230.

3. Diaz J: Evolving global epidemiology, syndromic classiﬁcation, general management, and prevention of

unknown mushroom poisonings. Crit Care Med 33:419–426, 2005.

4. Diaz J: Syndromic diagnosis and management of conﬁrmed mushroom poisonings. Crit Care Med 33:

427–436, 2005.

5. Ernst T, Chang L, Leonido-Yee M, et al: Evidence for long-term neurotoxicity associated with methamphetamine

abuse. Am Acad Neurol 54:1344–1349, 2000.

6. Farre M, de la Torre R, Gonzalez ML, et al: Cocaine and alcohol interactions in humans, neuroendocrine

effects and cocaethylene metabolism. J Pharmacol Exp Ther 283:164–167, 1997.

7. Henning RJ, Wilson LD, Glauser JM: Cocaine plus ethanol is more cardiotoxic than cocaine or ethanol alone.

Crit Care Med 22:1896–1906, 1994.

8. Keyes DC: Body packers and stuffers. In Dart RC, editor: Medical toxicology, ed 3, Philadelphia, 2004,

Lippincott Williams & Wilkins, pp 59–62.

9. Kirages T, Sule Harsh, Mycyk M: Severe manifestations of Coricidin intoxication. Am J Emerg Med 21:

473–475, 2003.

10. Lange RA, Hillis LD: Cardiovascular complications of cocaine use. N Engl J Med 345:351–358, 2001.

11. Lee DC: Sedative-hypnotic agents. In Goldfrank LR, Flomenbaum NE, Lewin NA, et al editors): Goldfrank’s

toxicologic emergencies, ed 7, New York, 2002, McGraw-Hill, pp 929–945.

12. Milroy CM: Ten years of ecstasy, J R Soc Med 92:68–72, 1999.

13. Nelson LS: Opioids. In Goldfrank LR, Flomenbaum NE, Lewin NA. et al, editors: Goldfrank’s toxicologic

emergencies, ed 7, New York, 2002, McGraw-Hill, pp 901–923.

14. Snead OC, Gibson KM: Gamma hydroxybutyric acid. N Engl J Med 352:2721–2736, 2005.

15. Sporer KA, Firestone J, Isaacs SM. Out-of-Hospital treatment of opioid overdoses in an urban setting.

Acad Emerg Med 3(7):660–667, 1996.

16. Wolfe T, Barton E: Nasal drug delivery in EMS: reducing needlestick risk. JEMS 28(12):52–63, 2003.

524

CARDIOVASCULAR TOXICOLOGY

CHAPTER 74

Jennie A. Buchanan, MD

1. How do different poisons affect heart rate, blood pressure, and QRS duration?

See Table 74-1.

2. What drugs cause cardiovascular toxicity by blocking cardiac sodium

channels?

The major clinical manifestations of sodium channel blockade are QRS prolongation and

ventricular dysrhythmias.

Drugs with primary toxic effects on sodium channel include quinidine, ﬂecainide,

mexiletine, disopyramide, and procainamide.

Drugs with sodium channel effects and other serious effects include tricyclic

antidepressants, propranolol, cocaine, diphenhydramine, carbamazepine, lidocaine

chloroquine, cyclobenzaprine, and norpropoxyphene (a metabolite of propoxyphene).

Patients poisoned with these agents present with other symptoms but should be observed

and treated if prolonged QRS duration or arrhythmias develop.

3. What is the antidote for drugs that cause sodium channel blockade?

Sodium bicarbonate 1 to 2 mEq/kg as a bolus is used for the treatment of dysrhythmias or

prolongation of the QRS duration, which occurs after the ingestion of any of these agents. If

the QRS duration does not narrow after administration of sodium bicarbonate, a second bolus

should be given. Hyperventilation should be initiated to induce a serum pH of 7.5 to 7.55.

Hypertonic saline can also be administered in a dose of 200 mL of 7.5% solution or 400 mL

of a 3% solution. In addition to bicarbonate, patients with cardiovascular toxicity also often

require ﬂuids and vasopressors for hypotension, benzodiazepines for seizures, and

endotracheal intubation for altered mental status.

4. How do patients with a calcium channel blocker (CCB) overdose present?

CCBs decrease calcium inﬂux into cardiac tissue and vascular smooth muscle. The heart

depends on calcium for automaticity, conduction through the atrioventricular node, and

contractility. Vascular smooth muscle requires calcium to maintain tone. Patients with CCB

overdose present with hypotension (secondary to decreased contractility and decreased

vascular tone), bradycardia, and atrioventricular blocks. If hypotension is signiﬁcant, patients

may have altered mental status, organ ischemia, and acidosis. These patients may also be

hyperglycemic.

5. What is the treatment for CCB overdose?

Begin treatment by addressing airway, breathing, and circulation (ABCs). Gastric

decontamination may proceed after the airway is adequately protected. Hypotension is treated

initially with ﬂuid boluses (i.e., 2 L normal saline), and symptomatic bradycardia is treated

with atropine or pacing. Inotropic agents, such as dopamine, norepinephrine, or epinephrine

sometimes at high doses, are used next. Calcium is usually the next step in treatment for

toxicity. The dose is 1 to 2 g of calcium chloride or calcium gluconate intravenously (calcium

chloride requires a central line or large intravenous (IV) line because of risk for vein necrosis)

and may be repeated every 10 minutes three to four times. Occasionally, an infusion of

calcium may be needed. Glucagon (5–10 mg IV push) may be given and if improvement is

Chapter 74 CARDIOVASCULAR TOXICOLOGY 525

Bradycardia with hypertension

Centrally acting presynaptic a

agonists (clonidine, oxymetazoline, and tetrahydrozoline):

Patients progress to bradycardia and hypotension by the time they reach the hospital;

the initial hypertension and bradycardia is transient.

Bradycardia with hypotension and narrow-complex QRS

Centrally acting presynaptic a

agonists (clonidine, oxymetazoline, and tetrahydrozoline):

Inhibit sympathetic outﬂow in the central nervous system, resulting in hypotension,

bradycardia, pinpoint pupils, and somnolence

b-blockers (BBs) without sodium channel effects

Calcium channel blockers (CCBs)

Cardiac glycosides

Sedative-hypnotics, opioids, benzodiazepines and barbiturates decrease CNS

sympathetic outﬂow. Hypotension and bradycardia are usually minimal.

Organophosphates and carbamates by increasing vagal tone

Bradycardia with hypotension and wide-complex QRS

Lidocaine, tocainide (class 1b antiarrhythmics): Bradycardia with hypotension and

wide-complex QRS

BBs with sodium channel effects (i.e., propranolol, acebutolol, or metoprolol)

CCBs (severe toxicity causes ventricular escape rhythms)

Cardiac glycosides (severe toxicity causes ventricular escape rhythms)

Propafenone and ﬂecainide (class 1c antiarrhythmics that cause sodium channel

blockade): Initially, patients bradycardic with wide QRS, due to decreased cardiac

conduction, that may degenerate into ventricular tachycardia

Quinidine, procainamide, and disopyramide (class 1a antiarrhythmics that cause

sodium channel blockade, prolonged QRS and QT intervals): Patients may present with

bradycardia, due to decreased cardiac conduction that may degenerate into ventricular

tachycardia.

Hyperkalemia from cardiac glycosides, BBs, and potassium-sparing diuretics

Tachycardia with hypertension

Sympathomimetics (amphetamines, cocaine, ephedrine, pseudoephedrine) by stimulating

the sympathetic nervous system

Anticholinergics (diphenhydramine and atropine): Due to decrease in vagal tone and

agitation from delirium

TABLE 74-1. CARDIOVASCULAR EFFECTS OF DIFFERENT POISONS

Continued

Chapter 74 CARDIOVASCULAR TOXICOLOGY526

CNS, central nervous system.

Tachycardia with hypotension

Monoamine oxidase inhibitors: Inhibit the breakdown of catecholamines in central

nervous system synapses, tachycardia with hypotension and narrow-complex QRS.

In overdose, hypertension can also be profound.

antagonists (i.e., prazosin, terazosin, doxazosin): Cause vasodilation and reﬂex

tachycardia

Phenothiazines: Due to a

-antagonism causing vasodilation and reﬂex tachycardia

Diuretics: Tachycardia and hypotension usually mild secondary to dehydration

Nitrates: Cause vasodilation and reﬂex tachycardia

Theophylline and caffeine: Inhibition of adenosine receptors, b-adrenergic stimulation

from catecholamine release resulting in tachycardia and hypotension

Tachycardia with hypotension and wide-complex QRS

Tricyclic antidepressants (amitriptyline, and imipramine), cyclobenzaprine and diphen-

hydramine: Sodium channel blockade causing widening of the QRS complex. (In severe

toxicity, this can lead to hypotension despite tachycardia from anticholinergic effects.)

Cocaine: Sodium channel effects that, late in the course, override the ability to maintain

blood pressure from tachycardia and vasoconstriction

TABLE 74-1. CARDIOVASCULAR EFFECTS OF DIFFERENT POISONS—cont’d

noted, a drip at 5 to 10 mg/hr is initiated. Hyperinsulinemia euglycemia (HIE) therapy or high-

dose insulin (1 unit/kg bolus, 25 gm dextrose bolus, then 0.5 units/kg/hr with supplemental

dextrose 0.5 gm/kg/hr and potassium) is the next line of therapy. Heroic measures, such as

Intralipid (1–2 mL/kg of a 20% lipid emulsion followed by an infusion of 0.25 mL/kg/min for

30–60 minutes), extracorporeal membrane oxygenation, intraaortic balloon pump, and

cardiopulmonary bypass, may be used in severe refractory cases.

6. How do patients with b-blocker (BB) overdose present?

BBs compete with endogenous catecholamines for receptor sites; this blunts the normal

adrenergic response, leading to bradycardia, atrioventricular blocks, and hypotension from

decreased contractility. Patients suffering from BB toxicity present similarly to patients with

CCB overdose. There can be a few differences, however, depending on which BB is involved.

Some BBs, such as propranolol, are lipid soluble. This allows entry into the central nervous

system, leading to seizures and altered mental status unrelated to blood pressure. Some BBs

(i.e., propranolol, acebutolol, alprenolol, and oxprenolol) antagonize sodium channels, leading

to a widened QRS. Sotalol also blocks potassium channels, causing a prolonged QT interval

and torsades de pointes. Hypoglycemia may also be evident.

7. Describe the treatment for BB toxicity.

Treatment is similar to that for CCB overdose. Glucagon is utilized for treatment after ﬂuids,

vasopressors, and atropine. The dose of glucagon is the same as for CCB overdose.

High-dose insulin therapy may be beneﬁcial as well. Calcium has not been well studied

for treatment of BB overdose. Seizures unrelated to hypotension should be treated with

benzodiazepines; sodium bicarbonate is used for QRS widening. Refractory sympathetic

bradycardia should be treated with external cardiac pacing.

Chapter 74 CARDIOVASCULAR TOXICOLOGY 527

8. Describe the manifestations of acute and chronic digoxin poisoning.

Acute digoxin toxicity occurs after accidental or intentional ingestion of a supratherapeutic

amount of digoxin-containing products. A dose of more than 1 mg in a child and more than

3 mg in an adult is potentially toxic. Patients with acute digoxin toxicity often develop

gastrointestinal symptoms, such as nausea or vomiting. The most common cardiac effects

are bradycardia and heart block. After acute digoxin ingestion, blockade of the cellular

sodium/potassium exchange pump leads to systemic hyperkalemia. Severe hyperkalemia

(serum level .5.5 mEq/L) is associated with a mortality of greater than 90% if untreated.

Chronic digoxin toxicity occurs when there is a change in the dose or clearance of digoxin

in a patient who is receiving digoxin therapy. Initiation of treatment with quinidine,

amiodarone, spironolactone, or verapamil may change the steady-state clearance of digoxin

and result in toxicity. Decreased clearance of digoxin may occur when patients develop

renal insufﬁciency. Symptoms of chronic digoxin toxicity are often subtle and nonspeciﬁc,

including confusion, anorexia, vomiting, visual changes, and abdominal pain. The patient is

often bradycardic with varying degrees of heart block. Patients may develop premature

atrial and ventricular contractions, supraventricular tachycardia, ventricular tachycardia, or

ventricular ﬁbrillation. In contrast to acute digoxin toxicity, serum potassium is often

normal or depressed, unless the patient has hyperkalemia from renal insufﬁciency.

9. What are the indications for digoxin immune antibody fragments (Fab)?

The most common indications are symptomatic bradycardia, complete heart block, ventricular

tachycardia, or ventricular ﬁbrillation. Often, digoxin immune Fab must be administered to

critically ill patients without laboratory conﬁrmation of elevated digoxin levels. Fab should be

administered to patients who present after an acute ingestion with hyperkalemia or

hemodynamically signiﬁcant dysrhythmias. The indications for Fab therapy in patients with

chronic digoxin toxicity are not well deﬁned. Therapy should be considered for patients with

hemodynamically signiﬁcant bradycardia, multifocal ventricular ectopy, and ventricular

dysrhythmias. Because serum digoxin levels correlate poorly with symptoms, there is no

speciﬁc serum digoxin level that is considered an absolute indication for digoxin Fab.

10. How is digoxin Fab dosed?

Digoxin Fab may be dosed in one of several ways, depending on the information available to

the clinician:

If the patient is critically ill, 10 to 20 vials should be given empirically.

If the amount of digoxin ingested is known, the following formula should be used: Dose

ingested (mg) 3 0.48 5 number of vials.

If the steady-state serum level is known, the following formula should be used: Serum

digoxin level (ng/mL) 3 patient wt (kg)/100 = number of vials. (This normally results in a

patient with chronic toxicity receiving one to three vials.)

KEY POINTS: CARDIOVASCULAR TOXICOLOGY

1. For sodium channel blocking agents, use sodium bicarbonate if there is QRS widening

and clinical signs of toxicity.

2. There is no single proven successful treatment for CCB and BB overdose. Severe ingestions

often require multiple interventions. Start with symptomatic and supportive care ﬁrst (ABCs),

IV ﬂuids, and pressors. Remember atropine, glucagon, calcium, and high-dose insulin.

3. There is no serum digoxin level that is considered an absolute indication for digoxin

immune Fab.