Symptom-Based Diagnosis in Pediatrics (CHOP Morning Report) 1st Ed.

CASE 8-5

Fourteen-Year-Old Girl

NATHAN TIMM

HISTORY OF PRESENT ILLNESS

A previously healthy 14-year-old girl is brought to the emergency department after she was found semiconscious on the floor next to an open bottle. Her mother reports that she had been upset lately because her boyfriend was recently diagnosed with HIV. In the ambulance, she was uncooperative en route and refused vital signs. Although combative upon arrival, within a few minutes she became less and less responsive. Supplemental oxygen was administered. Her initial set of vitals included a heart rate of 100 bpm and a blood pressure of 100/70 mmHg. Her serum glucose was 110 mg/dL. Naloxone and flumazenil were administered without impact on her deteriorating mental status. She was now only responsive to painful stimulation. The patient required endotracheal intubation. Nasogastric lavage did not reveal pill fragments. Activated charcoal was administered via nasogastric tube. While awaiting a head CT, the patient’s heart rate increased to 180 bpm and she became hypotensive. Electrocardiogram revealed supraventricular tachycardia. Her blood pressure improved after cardioversion with adenosine.

MEDICAL HISTORY

The girl’s medical history was unremarkable. She had never attempted suicide. She did not take any prescription medications. Her father had a history of depression.

PHYSICAL EXAMINATION

T 39.0°C; HR 120 bpm; RR 16/min; BP 110/70 mmHg

Physical examination revealed an intubated patient who responded only to painful stimulation. Her head and neck examination revealed no evidence of head injury. There was no hemotympanum. The oropharynx was clear. Pupils were 5 mm and reactive to light. Sharp disc margins were present on fundoscopic examination. She was mildly tachycardiac without murmurs, rubs, or gallops. Lungs were clear bilaterally. Abdomen was soft with absent bowel sounds and no organomegaly. She was incontinent of stool that was hemoccult negative. Her skin examination was significant for linear excoriations on her left wrist. Her neurologic examination was significant for a Glasgow coma scale of 4 with response to deep pain only. A gag reflex was present. Babinski reflexes were downgoing bilaterally.

DIAGNOSTIC STUDIES

Complete blood count revealed a WBC count of 6600/mm3 (54% segmented neutrophils, 35% lymphocytes); hemoglobin, 11.4 g/dL; and 180 000 platelets/mm3. Electrolytes were normal. Calcium, magnesium, and phosphorous were normal. Blood urea nitrogen was 8 mg/dL with a creatinine of 0.6 mg/dL. Prothrombin time, partial thromboplastin time, and liver enzymes were unremarkable. Urinalysis and pregnancy test were both negative. A urine toxicology screen was negative for drugs of abuse including phencyclidine, cocaine, amphetamines, cannabinoid, opiates, and barbiturates. Acetominophen and aspirin levels were undetectable. Head CT was negative. Electrocardiogram revealed a QTC of 0.42 seconds with a QRS duration of 0.110 seconds.

COURSE OF ILLNESS

The patient remained endotracheally intubated and had two additional episodes of supraventricular tachycardia that responded well to adenosine. Her father arrived soon after her last cardioversion and provided the team with the identity of the bottle’s contents.

DISCUSSION CASE 8-5

DIFFERENTIAL DIAGNOSIS

An open bottle next to the young lady is an important clue to the diagnosis; however, additional diagnoses beyond overdose need to be considered. Sepsis, meningitis, or encephalitis should always be considered in someone with fever and rapid mental deterioration. Furthermore, an intracranial bleed either spontaneous or from trauma should be excluded. Nevertheless, the history directs the differential diagnosis toward an ingestion. The presence of an anticholinergic toxidrome (altered mental status, increased temperature, dilated pupils, absent bowel sounds) leads to a number of possible medications: antihistamines, antipsychotics, and muscle relaxants. Ingestion of jimsonweed and certain species of mushrooms produce similar anticholinergic effects. In addition to the specific anticholinergic toxidrome, a prolonged QRS duration was present on the electrocardiogram. Class IA and IC antiarrythmics, cocaine, propranolol, and digoxin can prolong the QRS duration. However, the father’s history of depression provided the final clue to the diagnosis.

DIAGNOSIS

The father reported that his bottle of Doxepin was missing. He was taking the tricyclic antidepressant for his depression. He reported that they were 100 mg tablets and there were approximately 20 pills in the bottle.

INCIDENCE AND EPIDEMIOLOGY

Tricyclic antidepressants (TCAs) are the leading cause of death from a prescription drug overdose in the United States. Despite this propensity for significant mortality following overdose, TCAs continue to be a commonly prescribed medication in the pediatric population for disorders such as enuresis, attention deficit hyperactivity disorder, and depression. Amitriptyline, imipramine, nortriptyline, clomipramine, and doxepin constitute the most commonly prescribed TCAs. Although each is unique in clinical effectiveness, the entire group acts similarly in overdose. Ingestions of 1 g of TCA can result in life-threatening consequences in adults; however, in children only 10-20 mg/kg, or just two 50 mg tablets, can be equally devastating.

CLINICAL PRESENTATION

The clinical picture of TCA toxicity includes the following: hypotension, arrythmias, seizures, altered level of consciousness, and hyperthermia. Alpha-adrenergic blockade results in refractory hypotension—the most common cause of death from TCA overdose. Myocardial depression from sodium channel blockade results in PR, QT, and classically, QRS interval prolongation. Wide-complex tachycardia either supraventricular or ventricular in origin is characteristic of the life-threatening arrhythmia from TCA overdose. However, the most common arrhythmia is sinus tachycardia, a result of the anticholinergic properties of TCAs. Altered levels of consciousness and hyperthermia constitute the other significant components of the anticholinergic effects. Seizures may occur, usually 1-2 hours after ingestion and are usually generalized and brief. Ten to twenty percent of those with seizures will quickly go on to develop cardiovascular deterioration. The clinical picture can change rapidly with TCA overdose requiring prompt diagnosis, therapy, and monitoring.

DIAGNOSTIC APPROACH

Electrocardiogram (ECG). The most helpful diagnostic tool is an electrocardiogram.

Measurement of the QRS interval is a good prognostic aid. QRS intervals greater than 0.1 second reflect significant risk of seizure, while QRS intervals greater than 0.16 second are associated with increased risk of ventricular arrythmias. An additional ECG finding is a large R wave > 3 mm in aVR (Figure 8-6).

Image

FIGURE 8-6. TCA Electrocardiogram. A 12-lead ECG of a patient who ingested a massive quantity of a tricyclic antidepressant, demonstrating QRS widening. (Reproduced, with permission, from Knoop K, Stack L, Storrow A, Thurman RJ, eds. Atlas of Emergency Medicine, NewYork: McGraw-Hill, 2009)(Photo contributors: Thomas Babcock, MD and Clay Smith, MD.)

Other studies. Laboratory testing should be performed including electrolytes, blood urea nitrogen, creatinine, hemoglobin, prothrombin time, and a screen for additional ingested drugs. Serum TCA levels are not helpful in the immediate management of a TCA ingestion. TCAs have a large volume of distribution with tissue concentrations exceeding blood concentrations by 10- to 100-fold; therefore, levels do not correlate well with toxicity.

TREATMENT

Patients with suspected TCA toxicity are at great risk for rapid clinical deterioration; therefore, evaluation and treatment should be started without delay, and frequent reassessment is a necessity. Attention to airway, breathing, and circulation are the critical components of the initial assessment. Mechanical ventilation may be required to secure the airway, and careful attention to perfusion and temperature is crucial. Cardiac monitoring is mandatory, and a 12-lead ECG should be performed immediately to assess for any evidence of cardiac toxicity reflected in a prolonged QRS interval, R wave height is greater than 3 mm in aVR or ventricular arrhythmias.

If cardiac toxicity is evident as conduction delays, hypotension or wide-complex tachycardia, serum alkalinization with hypertonic sodium bicarbonate is the treatment of choice. Empiric treatment should not be initiated in the absence of cardiac toxicity given the potential arrhythmias, hypocalcemia, and seizures from profound alkalemia. Although the exact mechanism of alkalinization’s effectiveness in treating TCA toxicity is unknown, two theories are the correction of acidosis and decreasing the pharmacologically active drug through protein binding. Nevertheless, numerous animal models and anecdotal evidence supports the use of alkalinization in reducing QRS prolongation, increasing blood pressure and reversing ventricular arrhythmias.

The goal for alkalinization is a serum pH of 7.507.55. This can be accomplished using 1-2 mEq/kg boluses of sodium bicarbonate (1 mEq/mL) administered over 1-2 minutes followed by an infusion of sodium bicarbonate (150 mEq of NaHCO3 in 1 L of 5% dextrose in water). If arrhythmias are not responding to alkalinization, hypoxia, acidosis, hyperthermia, and hypotension should be corrected and lidocaine may be used as an antiarrhythmic. Hypotension is the most common cause of death from TCA overdose and should be managed with normal saline boluses (up to 30 cc/kg) and alkalinization. However, if the hypotension is refractory to fluid administration norepinephrine and low-dose dopamine may be effective.

Alkalinization should be continued until mental status is back to baseline, hypotension resolved, and electrocardiogram abnormalities improved. Observation for 24 hours after resolution of toxicity is appropriate. However, patients can be safely discharged to psychiatry services if they have received activated charcoal and show no signs of TCA toxicity after 6 hours of observation.

SUGGESTED READINGS

1. Harrigan RA, Brady WJ. ECG abnormalities in tricyclic antidepressant ingestion. Am J Emer Med. 1999;17: 387-393.

2. Osterhoudt KC, Shannon MD, Henretig FM. Toxicologic emergencies. In: Fleisher GR, Ludwig S, eds. Textbook of Pediatric Emergency Medicine. 4th ed. Philadelphia: Lippincott Williams & Wilkins, 2000:925-927.

3. Pentel PR, Keyler DE, Haddad LM. Tricyclic antidepressants and selective serotonin reuptake inhibitors. In: Haddad LM, Shannon MW, Winchester JF, eds. Clinical Management of Poisoning and Drug Overdoses. 3rd ed. Philadelphia: WB Saunders; 1998:437-451.

4. Shannon M, Liebelt EL. Toxicology reviews: Targeted management strategies for cardiovascular toxicity from tricyclic antidepressant overdose: the pivotal role for alkalinization and sodium loading. Pediatr Emer Care. 1998;14:293-298.