(Circulation. 2000;102:I-223.)
© 2000 American Heart Association, Inc.
ECC Guidelines |
Part 8: Advanced Challenges in Resuscitation
Section 2: Toxicology in ECC
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General Considerations |
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 Top General Considerations Drug-Induced Emergencies:...SummaryReferences |
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Poisoning is the third leading cause (11%) of injury-related mortality in the United States and is among the top 3 causes in most other countries. In the United States in 1995 there were an estimated 2.4 million exposures to poison and 1 million visits to the Emergency Department (1% of all visits), 215 000 admissions to the hospital, and 18 549 deaths due to poisoning.1 2 3 Although exposure to poison is common, life-threatening or fatal poisoning is not. Poisoning is a relatively infrequent cause of cardiac arrest overall but is a leading cause in victims <40 years old. The long-term survival rate among victims of cardiac arrest due to poisoning is good, averaging 24% in 6 studies.
The relatively small number of life-threatening poisonings and the lack
of a prehospital triage protocol for severe poisonings in the United
States are major obstacles to the performance of high-quality
clinical research. Because the research in this area consists primarily
of small case series (level of evidence [LOE] 5), animal studies (LOE
6), and case reports, the American Heart Association (AHA) class of
recommendation for most recommendations for treating victims of
poisoning is IIb. The following evidence- and consensus-based
guidelines were developed by a toxicology work group of the AHA
Advanced Cardiovascular Life Support (ACLS) Committee
to provide guidance in the management of severe poisoning when standard
ECC guidelines may not be optimal or appropriate. In addition to these
guidelines we recommend consultation with a medical toxicologist or
certified regional poison information center and use of a poison
treatment center for unusual cases of poisoning.4 5 See
Tables 1
and 2.
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Drug-Induced Emergencies: Prearrest |
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TopGeneral ConsiderationsDrug-Induced Emergencies:...SummaryReferences |
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Airway and Respiratory Management
Because poisoned patients can deteriorate rapidly, frequently assess their ability to protect their airway and breathe adequately. International guidelines recommend gastric lavage only for patients who have ingested a potentially lethal amount of drug or toxin and present within 1 hour of ingestion.6 In obtunded or comatose patients, perform rapid-sequence intubation before gastric lavage to prevent aspiration pneumonia. Because reversal of benzodiazepine intoxication with flumazenil is hazardous, we do not recommend routine inclusion of this practice in "coma cocktail" protocols.
Opiate Poisoning
If a patient suspected of overdosing on an opiate has a pulse, try
to reverse respiratory insufficiency with naloxone, an opiate
antagonist, before inserting an endotracheal tube. Do not
withhold naloxone until artificial ventilation is initiated. Heroin is
the opiate taken in most cases of opiate overdose treated in emergency
settings. Severe complications after opiate reversal are uncommon
(<2%). Although the effects of naloxone do not last as long as those
of heroin (45 to 70 minutes compared with 4 to 5 hours), naloxone is
the preferred agent for reversal. Some EMS systems allow selected
patients aroused with naloxone to refuse transport to the hospital
against medical advice. Allowing selected patients to refuse
observation against medical advice rarely leads to serious consequences
such as severe renarcotization or delayed pulmonary
edema.7 8 Naloxone can be administered intramuscularly,
subcutaneously, or intravenously. The IM and SC routes
theoretically provide greater ease of administration, less risk of
needle puncture, and less risk of severe withdrawal in patients
addicted to opiates than the IV route.
The desired end points of opiate reversal are adequate airway reflexes and ventilations, not complete arousal. Acute, abrupt withdrawal from opiates may increase the frequency of severe complications such as pulmonary edema, ventricular arrhythmia, and severe agitation. In 2 studies of opiate reversal with naloxone, only small doses were required for opiate reversal. In emergency settings the recommended initial dose of naloxone is 0.4 to 0.8 mg IV or 0.8 mg IM or SC. In communities in which abuse of naloxone-resistant opiates is prevalent, larger initial doses of naloxone may be needed. When opiate overdose is strongly suspected or in areas where abuse of "China white" is prevalent, titration to a total naloxone dose of 6 to 10 mg is recommended if needed.
Drug-Induced Hemodynamically Significant
Bradycardia
In cases of drug-induced hemodynamically
significant bradycardia (HSB), atropine is seldom helpful but is
acceptable to administer because it is not harmful. The major exception
is acute organophosphate or carbamate poisoning, in which case atropine
may be lifesaving. The recommended starting dose of atropine for adults
with insecticide poisoning is 2 to 4 mg. Avoid use of isoproterenol,
which may induce or aggravate hypotension and ventricular
arrhythmias.
In cases of massive ß-blocker poisoning, however, isoproterenol given in very high doses is reportedly effective. Digoxin-specific Fab antibody fragments are extremely effective therapy for life-threatening ventricular arrhythmias or heart block due to poisoning with digoxin or cardiac glycosides.9 Electrical cardiac pacing is often effective in cases of mild to moderate drug-induced HSB. If external pacing is poorly tolerated or electrical capture is difficult to maintain, use transvenous pacing. When transcutaneous pacing is used, prophylactic transvenous placement of the pacer wire is not recommended because the tip of the catheter may trigger ventricular arrhythmias when the myocardium is irritable. In cases of very severe poisoning, capture may not occur despite proper location of the wire and use of the highest voltage settings. If HSB is resistant to atropine and pacing, use vasopressors with greater ß-agonist activity. Management of more resistant drug-induced HSB is discussed in Drug-Induced Shock.
Drug-Induced Hemodynamically Significant
Tachycardia
Drug-induced hemodynamically significant
tachycardia (HST) may induce myocardial ischemia,
myocardial infarction, or ventricular arrhythmias
and lead to high-output heart failure and shock. Avoid use of routine
measures such as adenosine therapy and synchronized
cardioversion in patients with drug-induced HST because the
tachycardia is likely to recur or to be refractory. In
patients with borderline hypotension, diltiazem and
verapamil are relatively contraindicated because they may
precipitate more severe shock. Pharmacological measures are preferred
when rate control is necessary.
Benzodiazepines such as diazepam or lorazepam are generally safe and effective in patients with drug-induced HST. Avoid using benzodiazepines in amounts that depress the level of consciousness and create the need for respiratory assistance. Physostigmine is a specific antidote that may be preferable for drug-induced HST and central anticholinergic syndrome due to pure anticholinergic poisoning. Very cautious use of a nonselective ß-blocker such as propranolol may be effective in patients with drug-induced HST due to sympathomimetic poisoning.
Drug-Induced Hypertensive Emergencies
A drug-induced hypertensive emergency is often short-lived,
and aggressive therapy is not needed. This is an important caution
because hypotension may occur later in cases of severe stimulant
poisoning. Benzodiazepines are first-line therapy. In patients with a
drug-induced hypertensive emergency refractory to benzodiazepines, use
short-acting antihypertensive agents, such as nitroprusside, as
second-line therapy. Labetalol (a nonselective ß-blocker,
-blocker, and ß2-agonist) in carefully
titrated doses is a third-line agent, effective at times for
drug-induced hypertensive emergencies associated with sympathomimetic
poisoning. Propranolol (a nonselective ß-blocker) is
contraindicated because it may block the ß2-receptors,
leaving -adrenergic stimulation unopposed and worsening
hypertension.10
Drug-Induced Acute Coronary Syndromes
Treatment of drug-induced acute coronary syndromes is
similar to the treatment recommended for drug-induced hypertensive
emergencies. Catheterization studies have shown that
nitroglycerin and phentolamine (an -blocker)
reverse cocaine-induced vasoconstriction, that labetalol has no
significant effect, and that propranolol worsens
it.11 12 13 14 Therefore, benzodiazepines and
nitroglycerin are first-line agents,
phentolamine is a second-line agent, and
propranolol is contraindicated. Although labetalol has been
reported to be effective in isolated cases, use of this agent is
controversial because it is a nonselective
ß-blocker.15 16 Esmolol and metoprolol are selective
ß-blockers (ß1 but not
ß2) that will not aggravate hypertension, but
these agents can induce hypotension.17 Because esmolol has
a very short half-life, the adverse effects of this agent should
disappear a few minutes after the infusion is stopped.
Intracoronary administration of thrombolytics or coronary vasodilators is preferred to blind peripheral administration in cases of a drug-induced acute coronary syndrome resistant to the treatments described here. Thrombolytics are contraindicated if an uncontrolled, severe drug-induced hypertensive emergency is present.
Drug-Induced VT and VF
Drug-induced ventricular tachycardia (VT)
may be difficult to distinguish from drug-induced impaired conduction
(wide complex). When sudden conversion to a wider-complex rhythm occurs
with hypotension, drug-induced VT is likely and cardioversion is
indicated. Use of antiarrhythmics is indicated in cases of
hemodynamically stable drug-induced VT, but there is
scant evidence to guide the choice of agent. Procainamide is
contraindicated in cases of poisoning with tricyclic antidepressants
(TCAs) or poisonings with other drugs that have similar antiarrhythmic
properties. In theory lidocaine should be contraindicated in cases of
cocaine poisoning. The current consensus, however, based on extensive
clinical experience, is that lidocaine is safe and
effective.18
In the past phenytoin was recommended for TCA-induced VT, but more recently the efficacy and safety of this agent have been questioned.19 20 There is no acceptable published data on the use of bretylium tosylate for drug-induced VT or VF. Although magnesium has beneficial effects in certain cases of drug-induced VT, it may also aggravate drug-induced hypotension.21 22 In most cases of drug-induced monomorphic VT or VF, lidocaine is the antiarrhythmic of choice.
Torsades de pointes can occur with exposure to many drugs, either therapeutic or toxic. Correctable factors that increase the risk of torsades de pointes include hypoxemia, hypokalemia, and hypomagnesemia. Treatment of drug-induced torsades de pointes includes correction of risk factors and electrical and pharmacological therapy:
- Magnesium supplementation is recommended for patients with torsades
de pointes even if the serum concentration is normal.
- Lidocaine has produced mixed results in studies of torsades de pointes
and is Class Indeterminate.
- Electrical overdrive pacing at rates of 100 to 120 beats per minute
will usually terminate torsades de pointes.
- Pharmacological overdrive pacing with isoproterenol has also been
recommended.
- Some toxicologists recommend potassium supplementation even if the
serum concentration is normal.
The safety and efficacy of these recommended therapies for drug-induced polymorphic VT has not been established by higher levels of research. From the perspective of evidence-based guidelines, we have only lower-level publications of case reports, case series, and extrapolated data. These recommendations, therefore, are Class Indeterminate. This class neither prohibits nor encourages clinical use. It merely acknowledges that many toxicology approaches are "best guesses."
Drug-Induced Impaired Conduction
Poisoning with membrane-stabilizing agents prolongs
ventricular conduction (increases QRS interval). This
predisposes the heart to monomorphic VT. Hypertonic saline and systemic
alkalinization often reverse the adverse
electrophysiological effects. This prevents
or terminates VT secondary to poisoning from many types of sodium
channel blocking agents.23 Hypertonic sodium bicarbonate
is particularly valuable because it both provides hypertonic saline and
induces systemic alkalinization. This appears to benefit several types
of poisonings caused by sodium channel blockers (eg, TCA). When
hypertonic sodium bicarbonate is used to treat severe poisoning, the
goal is an arterial pH of 7.50 to 7.55. Respiratory
alkalosis can be used as a temporary measure until the appropriate
degree of metabolic alkalosis can be attained with sodium
bicarbonate. Establish systemic alkalinization to the target
arterial pH with repetitive boluses of 1 to 2 mEq/kg sodium
bicarbonate. Maintain the alkalinization via a titrated infusion of an
alkaline solution consisting of 3 ampules of sodium bicarbonate (150
mEq) and KCl (30 mEq) in 850 mL of
D5W.
Drug-Induced Shock
Drug-induced shock usually results when the drug induces decreases
in intravascular volume, falls in systemic vascular resistance (SVR),
diminished myocardial contractility, or a combination
of these factors.
Drug-Induced Hypovolemic Shock
Initial treatment of drug-induced shock usually includes a fluid
challenge to correct hypovolemia and to optimize preload. If the
offending agent is cardiotoxic, it will reduce the patient’s ability
to tolerate a high intravascular volume and may lead to iatrogenic
congestive heart failure. If shock persists after an adequate fluid
challenge, start a vasopressor. Evidence supports dopamine as the most
effective pressor agent in mild to moderate poisoning.24
Most patients with drug-induced shock have decreased
contractility and low SVR. Empirical treatment of
dopamine-resistant shock with more potent vasopressors is based
on the assumption that decreased SVR is present.
When drug-induced shock is unresponsive to volume loading and conventional doses of vasopressors, high-dose vasopressors are indicated. If possible, establish central hemodynamic monitoring using a Swan-Ganz catheter before starting high-dose vasopressors. But do not delay vasopressor therapy to have a central monitoring line in place. Optimize cardiac preload quickly. Then use cardiac output (CO) and SVR to guide vasopressor and inotrope selection.
Drug-Induced Distributive Shock
When CO is normal or high and SVR is low (distributive shock),
more potent vasoconstriction (ie, a greater -adrenergic effect as
produced by norepinephrine or phenyl-ephrine)
is needed. Dobutamine and isoproterenol decrease SVR and
are contraindicated. The dose of an -adrenergic–selective
vasopressor should be increased until the shock is adequately treated
or adverse effects such as ventricular arrhythmias
are observed. Some patients require doses of vasopressors far above the
usual doses. Use of powerful vasoconstrictors such as vasopressin or
endothelin in cases of severe poisoning has not been well studied but
may be considered if ventricular arrhythmia
develops before the shock is adequately treated.
Drug-Induced Cardiogenic Shock
In cases of drug-induced shock characterized by low CO and high
SVR (cardiogenic shock) or low SVR (typical drug-induced shock),
inotropic agents are often required. Agents to choose from include
calcium, amrinone, glucagon, insulin, isoproterenol, and
dobutamine. Sometimes more than one agent is
necessary.25 26 Although these agents may increase
contractility and CO, they may also decrease SVR. A
concomitant vasopressor is often required.27
Drug-Induced Cardiac Arrest
Cardioversion/Defibrillation
Electrical cardioversion or defibrillation is appropriate for
pulseless patients with drug-induced VT or VF. In cases of
sympathomimetic poisoning with refractory VF, the cost-benefit ratio of
epinephrine in management is unknown. If epinephrine is
used in such cases, increase the interval between doses and use only
standard dose amounts (1 mg IV). Avoid high-dose epinephrine.
Furthermore, propranolol is contraindicated in
sympathomimetic poisoning, on the basis of limited human studies in the
cardiac catheterization suite and limited animal
survival studies.
Prolonged CPR and Resuscitation
In ACLS, cardiac resuscitation is usually terminated after 20 to
30 minutes unless there are signs that the central nervous system is
viable. More prolonged CPR and resuscitation are warranted in poisoned
patients. Cerebral blood flow drops dramatically with prolonged CPR in
animal models of cardiac arrest. Nevertheless, in cases of severe
poisoning, recovery with good neurological outcomes has occasionally
been reported in patients who received prolonged CPR, sometimes for up
to 3 to 5 hours.28 29 The marked vasodilatation associated
with many types of severe poisonings may explain these
observations.
Circulatory Assist Devices
Intra-aortic balloon pumps and cardiopulmonary bypass
circuits are circulatory assist devices that have been used
successfully in cases of critical poisoning. Because these techniques
are expensive, personnel intensive, and associated with significant
morbidity, they should be used only in cases refractory to
maximal medical care. A disadvantage of the intra-aortic
balloon pump is the need for an intrinsic cardiac rhythm for
synchronization and diastolic augmentation. Emergency
cardiopulmonary bypass does not require an intrinsic rhythm.
Recent technological advances have made rapid application through
peripheral vessels possible. To be effective, circulatory
assist devices must be used rapidly (ie, before the irreversible
effects of severe shock occur).
Brain Death and Organ Donation Criteria
Electroencephalographic and neurological criteria for brain death
are not valid during acute toxic encephalopathy and can be applied only
when drug concentrations are no longer toxic. In the presence of toxic
drug concentrations the only valid criterion for brain death is the
absence of cerebral blood flow. Successful transplantation of organs
from victims of fatal poisoning with acetaminophen,
cyanide, methanol, and carbon monoxide has been
reported.30 Transplantation of organs from victims
poisoned with agents capable of severe end-organ damage (eg, carbon
monoxide, cocaine, and iron) is controversial but may be appropriate if
the donor is thoroughly evaluated.
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Summary |
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TopGeneral ConsiderationsDrug-Induced Emergencies:...SummaryReferences |
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Use of standard ACLS protocols for all patients who are critically poisoned may not result in an optimal outcome. Care of severely poisoned patients can be enhanced by urgent consultation with a medical toxicologist. Alternative approaches required in severely poisoned patients include
- Higher doses than usual
- Drugs that are rarely used to treat cardiac arrest (amrinone, calcium,
esmolol, glucagon, insulin, labetalol, phenylephrine,
physostigmine, and sodium bicarbonate)
- Heroic measures, such as prolonged CPR and use of circulatory assist
devices
When resuscitation is unsuccessful, organ donation may still be an option.
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Footnotes |
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Circulation. 2000;102(suppl I):I-223–I-228.
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References |
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TopGeneral ConsiderationsDrug-Induced Emergencies:...SummaryReferences |
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