cardial instability and/or cardiac arrest require active core

rewarming. Available modalities include warmed isotonic

saline (40°C) lavage of the stomach (only if intubated),

HYPOTHERMIA

n�����:�--------:--'��

......._.,.___,f-_.;

f

Figure 61-1. ECG demonstrating Osborn J waves (arrow) in a hypothermic patient.

Shivering

mechanisms intact,

no significant

comorbidities

Impaired

thermogenesis or

significant comorbid

ill ness

rewarming

Admission to

telemetry bed

.6. Figure 61-2. Hypothermia diag nostic algorithm.

CHAPTER 61

bladder, and colon. Peritoneal and pleural irrigation can also

be performed after the insertion of percutaneous catheters.

Emergent thoracotomy with internal cardiac massage and

mediastinal irrigation with warmed saline is a very invasive

technique, but has been used successfully in severely

hypothermic patients with prolonged cardiac arrest. When

available, extracorporeal rewarming with cardiopulmonary

bypass remains the most rapid way (>9°C/hr) to rewarm a

patient with severe symptomatic hypothermia.

Patients with ventricular fibrillation and core temperatures <30°C are often resistant to defibrillation. If the initial

attempt at defibrillation is unsuccessful, begin cardiopulmonary resuscitation and actively rewarm the patient to at least

30°C before reattempting. Standard Advance Cardiac Life

Support medications (eg, atropine, lidocaine, arniodarone)

are typically ineffective for the management of hypothermiainduced dysrhythrnias. Remember that a patient should not

be pronounced dead until first rewarmed to 32°C.

DISPOSITION

� Admission

Most patients with moderate and severe hypothermia

require hospital admission for active rewarming and continued investigation into the etiology of hypothermia if

not clearly environmental. Admit all patients with evidence

of cardiac instability and those undergoing active core

rewarming to an intensive care unit setting.

� Discharge

Patients without serious comorbidities who present with

mild to moderate hypothermia and successfully undergo

passive rewarming can be safely discharged, provided there

is a warm environment for them to go. To prevent recurrent cold exposure, obtain social work consultation to

arrange placement for undomiciled patients and admit to

the hospital if unsuccessful.

SUGGESTED READING

Bessen HA. Hypothermia. In: Tintinalli JE, Stapczynski JS,

Ma OJ, Cline DM, Cydulka RK, Meckler GD. Tintinalli's

Emergency Medicine: A Comprehensive Study Guide. 7th ed.

New York, NY: McGraw-Hill, 201 1, pp. 1231-1234.

Jurkovich GJ. Environment cold-induced injury. Surg Clin North

Am. 2007;87:247-267.

U1rich AS, Rathlev NK. Hypothermia and localized c old injuries.

Emerg Med Clin North Am. 2004;22:28 1-298.

Vanden Hoek TL, Morrison LJ, Shuster M, Donnino M, Sinz E.

Lavonas EJ, Jeejeebhoy FM, Gabrielli. Part 12: Cardiac Arrest in

Special Situations: 20 10 American Heart Association Guidelines

for Cardiopulmonary Resuscitation and Emergency

Cardiovascular Care. Circulation. 2010;122:S829-S861.

Wira CR, Becker JU, Martin G, Donnino MW. Anti-arrhythmic

and vasopressor medications for the treatment of ventricular

fibrillation in severe hypothermia: A systematic review of the

literature. Resuscitation. 2008;78:2 1-29.

Cold-Induced

Tissue Inj u ries

Christine R. Stehman, MD

Key Points

• Address hypothermia, dehydration, and any alternative life threats before focusing on cold-ind uced tissue

injuries.

• When in doubt, treat all cold-induced tissue injuries as

frostbite.

INTRODUCTION

Previously the domain of military physicians, the prevalence

of cold-induced tissue injuries in the civilian population has

increased substantially over the past 20 years as a result of

the growth of homelessness and an expanding interest in

cold weather outdoor activities such as skiing and mountain

climbing. Cold-induced tissue injuries are typically divided

into 2 categories: nonfreezing cold injuries (NFCI) and

frostbite. Examples of NFCis include frostnip, chilblains/

pernio, and immersion/trench foot. Of the 2 types of injury,

frostbite is the more devastating and requires more aggressive treatment. That said, chilblains and immersion foot can

also progress to significant disability and require prompt

recognition and intervention.

Although individuals at the extremes of age are at a

higher risk for cold-induced tissue injuries, frostbite is

fairly uncommon in these cohorts. In fact, adults aged

30-49 are the most likely group to suffer frostbite. The

hands and feet account for more than 90% of all reported

frostbite injuries, whereas almost all NFCis involve the feet.

Other areas of the body at risk for cold-induced tissue

injury include the face (eg, nose, ears), buttocks and

perineum, and penis.

There are 3 major categories of risk factors for coldinduced tissue injury. Behavioral risk factors include

• Rewarm frostbitten extremities rapidly in a warm water

bath (4D-42°C) and nonfreezing injuries slowly in a dry

environment.

• Do not discharge patients with cold-induced tissue injuries

without first ensuring they have a warm, dry place to go.

homelessness, inadequate clothing or shelter, alcohol or

drug use/intoxication, and psychiatric illness. Physiologic

risk factors include comorbid diseases that impair distal

circulation ( eg, diabetes, vasculitis), the use of vasoconstric ­

 

tive medications, and external conditions such as high altitude exposure. Mechanical risk factors compose the final

category and are the most easily correctable. Common

examples include constrictive clothing and jewelry,

prolonged contact with heat conductive materials, and

immobility.

Of the 3 types of NFCI, frostnip is the least severe. It

typically affects the distal extremities after prolonged

exposure to cold but nonfreezing temperatures. Ice crystal

formation and profound vasoconstriction are common in

the superficial tissues, and patients frequently complain of

a dull throbbing pain during rewarming. Essentially a

precursor to frostbite, overt tissue destruction is lacking.

Chilblains (pernio) involve the formation of inflammatory skin lesions after repeated intermittent exposure to a

nonfreezing but cold and wet environment. Although

chilblains can affect any area of the body, the face, dorsal

surfaces of the hands and feet, and pretibial tissues are the

most commonly involved. Permanent tissue damage

secondary to vascular inflammation and tissue bed hypoxia

may develop. Women, children, and patients with

underlying vasculitides are most commonly affected.

263

CHAPTER 62

Immersion foot develops after the prolonged exposure

to persistently wet conditions, both warm and cold,

although the latter typically results in more severe tissue

injury. The long-term exposure to moisture induces tissue

edema and inflammation, whereas the prolonged cold

exposure leads to direct tissue injury. The consequently

encountered vasospasm, intravascular thrombosis, and

neuronal destruction can lead to full-thickness tissue loss.

Immersion foot is most commonly seen in the homeless

population.

Frostbite involves the freezing of tissues and can

result in significant tissue loss and long-term disability.

Ice crystal formation within the extracellular space can

induce intracellular dehydration, enzymatic dysfunc ­

tion, and cellular death. Microvascular occlusion sec ­

ondary to profound vasospasm and intraluminal

thrombosis further the severity of tissue loss. Circulating

tissue inflammatory markers frequently exacerbate the

intensity of tissue injury and complicate the reperfusion

of warmed tissue.

CLINICAL PRESENTATION

� History

Taking an adequate history should never delay the removal

of a patient from a cold environment. Inquire about

previous medical or psychiatric illnesses, drug and alcohol

use, and housing status. Any history of trauma should be

documented. Try to identify the overall duration of cold

exposure and elicit any previous history of frostbite or a

thawing and refreezing pattern of tissue injury. The review

of symptoms should attempt to discover the presence of

altered sensitivity, numbness, or burning pain.

Frostnip generally presents with numbness, pain,

pallor, and paresthesias of the ears, nose, fmgers, and toes.

Patients with chilblains typically present with complaints

of erythema, edema, and an intense pruritus or burning

sensation. Immersion foot is usually associated with

significant pain and swelling and occasionally numbness

and/or the inability to ambulate. Frostbitten patients

generally complain of the inability to feel the affected

areas.

� Physical Examination

Remove all clothing and thoroughly examine the entire

body, focusing primarily on the face, hands, lower legs and

feet, and buttocks and genitalia. Patients with frostnip may

present with paleness of the affected areas, but a normal

exam does not rule out injury. Chilblains frequently present

with erythema and edema and occasionally with vesicles,

bullae, and even ulcerations. The characteristic lesions are

purple or bluish in hue and appear 12-24 hours after exposure. Extremities affected by immersion foot will be swollen

and erythematous. Tissue sloughing is common, and there

may be an associated malodor. Frostbite typically presents

with mottled or violaceous tissue that may have a waxy

Figure 62-1. Deep frostbite of the toes.

.A. Figure 62-2. Superficial frostbite. Note the tissue

edema and clear bl isters.

appearance. Although frostbite can be classified similar to

burns into superficial and deep tissue injuries, this distinction

often cannot be made until the tissue is properly rewarmed.

Secondary blister formation is common, with the early formation of large clear blisters generally imparting a better

prognosis than the delayed development of smaller hemorrhagic bullae (Figures 62-1 and 62-2). Significant tissue

necrosis can complicate cases of deep tissue freezing despite

minimal initial physical exam findings.

DIAGNOSTIC STUDIES

Diagnostic studies of any kind are of limited utility in the

initial evaluation of patients with cold inducted tissue

injuries. That said, pursue radiographic and laboratory

studies as dictated for the evaluation of concurrent medical

COLD-INDUCED TISSUE INJURIES

illness or traumatic injury. Radionuclide bone scanning

and magnetic resonance imaging may a prognostic role in

long-term management.

MEDICAL DECISION MAKING

Include cold-induced tissue injuries in the differential diagnosis of all patients exposed to freezing or near freezing

temperatures, but evaluate and treat for any life-threatening

conditions before dealing with these injuries. Check the c ore

body temperature of all cold exposed patients to rule out

hypothermia. Investigate for and address any concurrent

trauma or dehydration. Attempt to delineate between freezing and nonfreezing injuries, as the treatments will differ. If

unclear between the two, always err on the side of frostbite

and treat accordingly. Consider compartment syndrome in

frostbitten regions if the swelling does not resolve and pulses

do not return after adequate rewarming.

Keep in mind that other injuries or illnesses can both

mimic and contribute to cold-induced tissue injury.

For example, the erythema of rewarmed frostnip and

immersion foot can resemble cellulitis or deeper tissue

infections. Peripheral vascular disease and vasculitides not

only appear similar to both frostbite and chilblains but also

increase their likelihood secondary to impaired microvascular circulation. Finally, the color changes and blisters of

frostbite can be confused with both stasis dermatitis and

autoimmune bullous forming conditions (Figure 62-3 ).

Add ress hypothermia,

dehydration and life

threats

Ambient rewarming

Figure 62-3. Cold-ind uced tissue injuries

diag nostic algorithm.

TREATMENT

All clothing should be removed and replaced with warm

blankets. Wet clothing is especially problematic as it will

continue to cool the patient during treatment. Dehydration

is a common complicating condition and requires

aggressive volume resuscitation with intravenous (IV)

crystalloids to lessen blood hyperviscosity. All body parts

that have suffered cold-induced tissue injury will need

some type of rewarming, with the pattern of injury

sustained determining the appropriate modality.

Frostnip usually resolves spontaneously with dry

rewarming measures at room temperatures and requires

no further intervention. Rewarm chilblains affected skin at

room temperature and then wash, dry, and dress in a soft

sterile bandage. Initiate pain control as needed and elevate

the affected extremity to prevent excessive edema

formation, as this will predispose to subsequent infection.

Patients with recurrent episodes may benefit from

treatment with oral nifedipine (30-60 mg/day), and topical

and systemic corticosteroids have both shown promise in

certain patient cohorts.

Immersion foot requires slightly more detailed care.

Rewarm affected tissues at room temperature and allow

them to air dry. Restrict patients to bed rest and elevate the

affected extremities during the rewarming period. Certain

patients may achieve adequate pain relief with oral

nonsteroidal anti-inflammatory drugs, whereas others may

require parental opioid analgesia. The early use of t ricyclic

antidepressants may help limit the future development of

chronic neuropathic pain. Extreme cases of immersion

foot may be indistinguishable from frostbite and should be

treated as the latter until proven otherwise. Finally, all

patients with NFCI require clear instructions to limit their

potential for recurrent exposure and injury.

Frostbite requires more aggressive treatment to limit

progressive tissue damage. Rewarm all affected areas in a

warm water recirculating bath ( 40-42°C) with a mild antibacterial agent mixed in (eg, povidone-iodine or chlorhexidine).

 

CHAPTER 61

establish the diagnosis. Keep in mind that the majority of

standard ED thermometers will not record temperatures

below 34.4°C (94°F).

Physical exam findings frequently vary based on the

degree of hypothermia. It is imperative to immediately and

completely undress the patient to remove any wet clothing

and identify any signs of coexisting frostbite, trauma, sepsis,

hypothyroidism, adrenal crisis, toxidromes, or cardiac dysfunction. Refrain from any unnecessary movement of the

patient to avoid precipitating life-threatening dysrhythmias, as hypothermic myocardium is exceptionally irritable.

Finally, perform a comprehensive neurologic exam including an evaluation for level of consciousness, pupillary

reactivity, and focal deficits. The following describes findings specific to varying degrees of hypothermia.

Mild Hypothermia

Patients tend to present with shivering, tachycardia, tachypnea, and hyperventilation. As their core temperature

approaches 33°C (9 1.4°F), ataxia and apathy b egin to develop.

Moderate Hypothermia

Patients with moderate hypothermia develop hypoventila ­

tion, hyporeflexia, and an altered sensorium or stupor.

Shivering typically disappears once the core temperature

drops below 32°C (89.6°F), and this should be considered an

ominous finding. As the temperature approaches 30°C

(86°F), the risk for dysrhythrnias increases significantly.

Severe Hypothermia

Patients with severe hypothermia may present with pulmonary edema, areflexia, hypotension, and apnea and are

extremely susceptible to ventricular fibrillation and cardiac

arrest. Nearly all patients with a core body temperature

below 27°C (80.6°F) are comatose.

DIAGNOSTIC STUDIES

� Laboratory

Obtain a STAT bedside glucose level on all hypothermic

patients to rule out concurrent hypoglycemia. Serum

hyperglycemia is actually more common secondary to a

cold-induced inhibition of insulin secretion. Avoid treatment with supplemental insulin in these patients, as this

may precipitate iatrogenic hypoglycemia on rewarming.

Check a metabolic panel to assess electrolyte status and

renal function. Hypothermia can impair the concentrating

ability of the renal tubules, leading to a "cold-diuresis" with

secondary dehydration and hypovolemia.

Hypothermia impairs both platelet aggregation and the

coagulation cascade, and patients may become profoundly

coagulopathic. In spite of this, the laboratory measurement

of the prothrombin time and partial thromboplastin time

will be normal as blood samples are warmed to physiologic

temperatures before running these tests. In addition,

hypothermia classically induces hemoconcentration with

an expected increase of the hematocrit by 2% for every 1 °C

drop in core temperature.

� Electrocardiogram

An electrocardiogram is critical for all moderately to

severely hypothermic patients to assess for potentially lifethreatening cardiac dysrhythmias. Sinus bradycardia and

QT prolongation are the most common early findings.

Although not specific for hypothermia, Osborn J waves,

wide positive deflections at the junction of the QRS complex and ST segment, can be seen once the core temperature drops below 32°C (89.6°F) (Figure 61-1). As the

hypothermia worsens, atrial fibrillation and eventually

ventricular fibrillation often develop.

� Imaging

Imaging studies should be dictated by the clinical

presentation. Obtain a head computed tomography in

patients who exhibit persistent alterations in mental status

despite adequate rewarming and in those with any signs of

cranial trauma.

MEDICAL DECISION MAKING

The history and physical examination, coupled with a

known environmental exposure, are typically adequate to

establish the diagnosis of hypothermia. The absence of a

known environmental exposure or any concern for

secondary hypothermia should prompt an active search for

potential etiologies. That said, treatment should not be

delayed while awaiting the diagnostic work -up (Figure 61-2).

TREATMENT

Passive rewarming is typically adequate for patients with

mild hypothermia (35°-32°C). This technique uses the

body's inherent heat production mechanisms to restore a

normal core temperature. To be successful, the patient

needs an intact shivering response and sufficient energy

stores. Remove any wet clothing and wrap the patient in

warm blankets. Passive rewarming usually raises the core

temperature by < 1 °C per hour.

Most patients with moderate hypothermia (32°-30°C)

require active external rewarming. This includes the infusion of intravenous (N) fluids warmed to 42°C, administering humidified supplemental 0 2 warmed to 46°C, and the

placement of forced-air rewarming blankets (eg, Bair

Hugger). Taken as a whole, these methods can rewarm

patients at a rate of approximately 3.SOC per hour. These

measures are usually adequate for patients with severe hypothermia ( <30°C) as well, provided they exhibit no evidence of

cardiac instability. Those who do demonstrate signs of myo ­

 

Hoffman R, et al. Go!dfronk's Toxicologic Emergencies . 8th ed.

New York: McG raw-Hill, 2006.

cardiotoxicity, coma, and death (Table 60- 1). Antimuscarinic findings are commonly appreciated in poisoned patients, including dry skin and mucous membranes,

diminished or absent bowel sounds, urinary retention, and

sinus tachycardia. Acute cardiovascular toxicity must be

recognized and treated expediently. Sinus tachycardia is a

very common early finding, but typically does not result in

hemodynamic compromise. That said, severe poisonings

frequently progress to induce wide complex tachycardias

and refractory hypotension. CNS toxicity can range from

disorientation and agitation to outright lethargy. Early

subtle alterations in levels of consciousness can quickly

progress to obtundation and coma. Generalized tonicclonic seizures occur in -4o/o of all patients who present

with CA poisoning and in 13o/o of those who subsequently

experience cardiopulmonary arrest.

DIAGNOSTIC STUDIES

� Laboratory

Although quantitative assays for serum CA concentrations

do exist, their limited availability and prolonged turnaround times preclude any clinical utility. Furthermore,

serum levels correlate poorly with clinical significance.

There are no additional laboratory studies useful for the

diagnosis or management of patients with CA poisoning.

� Electrocardiogram

The electrocardiogram (ECG) is the most useful and r eadily available modality for the evaluation of patients with

potential CA poisoning. It not only provides rapid, distinctive, and diagnostic findings suggestive of toxicity, but also

facilitates the provision of targeted therapy. ECG abnor ­

malities develop within the first 6 hours of ingestion and

typically resolve by 36-48 hours.

The classic ECG pattern in moderate to severely poisoned patients is sinus tachycardia with right axis devia ­

tion of the terminal 40 msec of the QRS complex (terminal

R-wave in lead aVR) associated with prolongation of the

PR, QRS, and QT intervals (Figure 60-1). Life-threatening

complications are far more likely when the QRS c omplex is

prolonged beyond 100 msec. Thirty percent of patients will

experience seizures with a QRS > 100 msec, and the risk of

ventricular tachycardia increases drastically when the QRS

complex exceeds 160 msec.

MEDICAL DECISION MAKING

A high index of suspicion combined with a thorough history, physical examination, and ECG analysis is required to

establish the diagnosis of CA toxicity. Keep in mind that

patients with intentional overdoses may neither be reliable

nor forthcoming regarding their ingestions. Every effort

must be made to ascertain the exact time of ingestion,

specific agent and amount consumed, and the presence of

CYCLIC ANTIDEPRESSANTS

Cook County Hospital-ER

Vent. rate

PR interval

QRS duration

QT/QTc

P-R-T axes

1 1 6 BPM

1 58 ms

••• Age and gender specific ECG analysis •••

Sinus tachycardia

1 08 ms Biatrial enlargement

336/467 ms

85 259 71

Right superior axis deviation

No previous ECGs available

..--

rr-

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i I I

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..,. rI ! !

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Figure 60-1 . ECG findings in a patient with chronic pain who mistook his Elavil for Tylenol #3 and ingested

approximately 500 mg. Note sinus tachycardia, the prolonged QRS interva ls, and the terminal R-wave in aVR .

any co-ingestants. Once identified, the treatment for CA

toxicity should be initiated without delay (Figure 60-2).

TREATMENT

All patients require large-bore intravenous (IV) access and

continuous cardiac monitoring. Early intubation is recommended for patients with CNS depression and/or hemodynamic instability, as they have the potential for rapid

deterioration. Furthermore, respiratory acidosis secondary

to ventilatory insufficiency can exacerbate the cardiotoxicity of CA poisoning.

...... Gastrointestinal Decontamination

The induction of emesis with syrup of ipecac is no longer

recommended given the potential for sudden decompensation and secondary aspiration.

 

mia in the standard fashion with sodium bicarbonate,

albuterol nebulizers, glucose with insulin, and sodium

polystyrene sulfonate (Kayexalate), but avoid empiric

treatment with intravenous (IV) calcium due to the

theoretical risk of "stone heart" and fatal dysrhythmias.

That said, N calcium can be given to patients with severe

Check serum

digoxin level and

electrolytes

Consider digibind therapy if:

1) Hyperkalemia

2} Elevated digoxin level

3} Borderline BP or HR

Figure 59-2. Digoxin diag nostic algorithm. BP, blood pressure; ECG,

electroca rd iogram; H R, heart rate.

CHAPTER 59

hyperkalemic cardiotoxicity (sinus arrest, sinusoidal

rhythm) refractive to alternative treatments. In patients

with chronic toxicity, carefully supplement serum hypokalemia and hypomagnesemia to prevent overcorrection.

Treat significant bradycardias and/or AV nodal conduction

disturbances with IV atropine (0.5-2 mg).

Digoxin-specific antibodies (Digibind, Digoxin Fab

fragments) provide an eloquent and effective method for

treating digoxin toxicity. Indications for use include significant dysrhythmias, hypotension, and hyperkalemia secondary to cardiac glycoside ingestion. Although no absolute

contraindications exist, exercise caution in patients with a

known hypersensitivity to ovine (sheep) derived products.

The appropriate dose of Fab fragments can be determined

by 1 of 3 ways and is based on the total body burden of

digoxin. After an acute ingestion, digoxin has a roughly

80% bioavailability and each vial of Fab fragments can bind

0.5 mg of circulating digoxin. Based on this, the proper dose

of Fab fragments can be calculated as follows:

1. Known quantity of ingested digoxin:

Number of Fab vials = [ (Amount of digoxin ingested (mg)

X 0.8)/0.5]

Rounded-up to the nearest whole number

2. Measured serum digoxin concentrations:

Number of Fab vials = [Serum digoxin level (ng!mL)

X patient weight (kg) ] /100

Rounded-up to the nearest whole number

3. Patients demonstrating significant toxicity (lifethreatening dysrhythmias, profound hypotension, and/

or severe hyperkalemia):

Empirically treat acute ingestions with 10-20 vials of

Fab fragments and chronic exposures with 5 vials.

Repeated dosing may be required.

Of note, most lab assays do not distinguish between free

and bound digoxin, and serum levels lose their c linical utility after the administration of Fab fragments. Furthermore,

treatment with Fab fragments may lead to the secondary

decompensation of underlying cardiac conditions such as

CHF or atrial fibrillation, which had been previously controlled with digoxin therapy.

DISPOSITION

� Admission

Admit all patients after a potentially significant ingestion

who either have a history of significant comorbid

conditions or exhibit signs or symptoms of clinical toxicity

including cardiovascular instability, dysrhythmias, GI

distress, and mental status changes. Any patient with

toxicity significant enough to warrant digoxin Fab

fragments requires admission to an intensive care unit

setting. Patients who ingest digoxin as part of a suicide

attempt warrant psychiatric evaluation once they are

medically stabile.

� Discharge

Patients with accidental ingestions and no significant

comorbidities who remain symptom free after an 8- to

12-hour observation period may be safely discharged home.

SUGGESTED READING

Boyle JS, Kirk MA. Digitalis glycosides. In: Tintinalli JE,

Stapczynski JS, Ma OJ, Cline DM, Cydulka RK, Meckler GD.

Tintinalli's Emergency Medicine: A Comprehensive Study Guide.

7th ed. New York, NY: McGraw-Hill, 201 1, pp. 1260-1264.

Hack JB. Cardioactive steroids. In: Nelson LS, Lewin NA,

Howland MA, et al. Go/drank's Toxicologic Emergencies. 9th ed.

New York, NY: McGraw-Hill, 20 1 1, pp. 936-945.

Ma G, Brady WJ, Pollack M, Chan TC. Electrocardiographic

manifestations: digitalis toxicity. ] Emerg Med. 200 1;20: 145-152.

Manini AF, Nelson LS, Hoffman RS. Prognostic utility of serum

potassium in chronic digoxin toxicity. Am J Cardiovasc Drugs.

20 1 1; 1 1:173-178.

Cyclic Antidepressants

Harry C. Karydes, DO

Key Points

• Cyclic antidepressants remain a leading cause of

poisoning-related fatalities among psychoactive

medications.

• Patients will frequently present with minimal signs

and symptoms only to abruptly decompensate from

l ife-threatening card iovascular and central nervous

system toxicity.

INTRODUCTION

Cyclic antidepressants (CA) consist of a group of pharmacologically related medications that were initially developed

in the late 1950s for the treatment of patients with severe

depression. Although used less frequently for this purpose,

their role has expanded to include the management of

various alternative conditions including neuralgic pain,

migraine headaches, enuresis, and attention deficit hyperactivity disorder. Traditional cyclic antidepressants have a

chemical structure built on a 3-ring nucleus and include

such medications such as amitriptyline, nortriptyline, doxepin, imipramine, and clomipramine. Antidepressants have

historically remained a leading cause of pharmacologic

self-poisoning owing to their near ubiquitous availability to

a depressed patient population inherently at risk for selfharming behavior. Although the introduction of selective

serotonin reuptake inhibitors (SSRls) has decreased the

overall incidence of CA poisonings, CA overdoses c ontinue

to account for a greater morbidity and mortality given their

increased potential for significant toxicologic complications, especially in pediatric patients.

Cyclic antidepressants are nonselective agents that

exhibit a wide array of pharmacologic effects with consid ­