Article, Toxicology

The electrocardiographic toxidrome: the ECG presentation of hydrofluoric acid ingestion

The electrocardiographic toxidrome: the ECG presentation of hydrofluoric acid ingestion

Christopher Holstege MD, Andrew Baer MD, William J. Brady MD*

Department of Emergency Medicine, University of Virginia Medical Center, Box 800699, Charlottesville, VA 22908, USA

Received 23 April 2004; accepted 24 April 2004

Abstract The clinician can approach the poisoned patient using the toxidrome system of toxin identification; this approach makes use of findings noted on the physical examination, highlighting the importance of abnormalities in blood pressure, heart rate, respiratory effort, body temperature, mental status, pupillary size, Skin color, diaphoresis, and gastrointestinal sounds. Such a method provides structure and guidance to the clinical evaluation, providing the clinician with rapid diagnostic information and suggesting urgent Management issues. A case of hydrofluoric acid poisoning is used as an example of this Diagnostic approach. The patient demonstrated systemic toxicity accompanied by oral irritation and electrocardiographic abnormality (QRS complex widening and QT interval prolongation). The constellation of these findings suggested the possibility of a caustic agent (history and examination) with potential effect on potassium and calcium metabolism (electrocardiographic abnormalities). Such a constellation strongly suggested hydrofluoric acid as the culprit toxin.

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Introduction

The clinician can approach the poisoned patient using the toxidrome system of toxin identification. Such a method provides structure and guidance to the clinical evaluation, providing the clinician with rapid diagnostic information and suggesting urgent management issues. The toxidrome method emphasizes the use of the physical examination, highlighting the importance of abnormalities in blood pressure, heart rate, respiratory effort, body temperature, mental status, pupillary size, skin color, sweat presence, and gastrointestinal sounds.

* Corresponding author. Tel.: +1 804 924 8485; fax: +1 804 924 2877.

E-mail address: [email protected] (W.J. Brady).

We present a case of hydrofluoric acid poisoning which initially presented as an unknown ingestion. The patient demonstrated systemic toxicity accompanied by oral irritation and electrocardiographic abnormality (QRS complex widening and QT interval prolongation). The constellation of these findings suggested the possibility of a caustic agent (history and examination) with potential effect on potassium and calcium metabolism (electrocar- diographic abnormalities). Such a constellation strongly suggested hydrofluoric acid as the culprit toxin. Such rapid recognition of these findings enabled the clinician to provide specific life-saving therapy in rapid fashion to the patient. With this case, we review the electrocardio- graphic differential diagnosis of QRS complex widening and QT interval prolongation, suggesting that such findings be incorporated into the clinician’s toxidrome

0735-6757/$ – see front matter D 2005 doi:10.1016/j.ajem.2004.04.032

case presentation“>Fig. 1 ECG #1 on presentation. Sinus tachycardia with prominent T waves in the Right precordial leads.

evaluation strategy in the initial management of the poisoned patient.

Case presentation

A previously healthy 47-year-old man accidentally ingested a blue liquid he thought was a sport drink. He immediately noted throat irritation. Within five minutes of the ingestion, he developed nausea and vomiting. He presented to the emergency department (ED) within 1 hour of the ingestion with a complaint of nausea, weakness, and intense pleuritic chest pain. His initial vital signs revealed the following: temperature 34.58C, pulse 130 beats/min, blood pressure 102/66 mm Hg, and respiratory rate 20 breaths/min. His voice was hoarse and he had difficulty swallowing his secretions. His oropharynx revealed eyrthema without edema

or ulceration. Auscultation of his chest revealed diffuse rhonchi and tachycardia without murmurs, rubs, or gallops. His abdomen was soft with mild tenderness diffusely and audible hyperactive bowel sounds. His skin was warm and diaphoretic. He was alert, orientated, and demonstrated good strength throughout without tremor or clonus.

His initial electrocardiogram (ECG) 1 hour after ingestion revealed a sinus tachycardia with a QRS complex duration of 110 milliseconds and prominent T waves (Fig. 1). His initial arterial blood gas revealed the following: pH 7.28, Pco2 29, Po2 of 209, and HCO3 13. Within one-half hour of his arrival, he became increasingly agitated and his systolic blood pressure dropped to 80. A repeat ECG (Fig. 2) showed an increased widening of the QRS complex to 152 milliseconds, a QTc interval of 742 milliseconds, and further peaking of the T waves. Initial bedside evaluation of the ingested fluid by litmus paper revealed a pH less than 4.0.

Fig. 2 ECG #2 with continued sinus tachycardia, prominent T waves, and QRS complex widening.

Fig. 3 ECG #3 with continued sinus tachycardia and narrowing of the QRS complex.

Based upon the apparent caustic nature of the ingestion with an acidic pH and electrocardiographic abnormalities suggestive of calcium and potassium effect, hydrofluoric acid ingestion was suspected. The patient received intravenously 4 g of Calcium gluconate, 4 g of magnesium sulfate, 2 g of calcium chloride, and 200 mEq of sodium bicarbonate over the ensuing 30 minutes. His blood pressure increased to 158/ 94 with associated QRS complex narrowing to 102 milli- seconds (Fig. 3). Initial laboratory values, drawn upon the patient’s arrival, were remarkable for a white blood cell count of 12.5 x 109/L, hematocrit of 49%, platelet count of 191 x 109/L; sodium was 138 mmol/L, potassium 5.7 mmol/L, chloride 103 mmol/L, bicarbonate 12 mmol/L, urea nitrogen

10 mg/L, creatinine 1.4 mg/L, glucose 193 mg/L, calcium less than 4.0 mmol/L, and magnesium 0.7 mmol/L.

His electrolyte abnormalities and metabolic acidosis resolved within 12 hours of admission after receiving an additional 3 g of calcium chloride, 6 g of magnesium sulfate, 200 mEq of sodium bicarbonate, and 15 mmol of

sodium phosphate. The electrocardiographic abnormalities resolved within 12 hours (Fig. 4). He was intubated within the first 24 hours, however, secondary to progressive respiratory distress and hypoxemia. His chest radiograph revealed acute interstitial changes consistent with Aspiration pneumonia. The patient ultimately was discharged after a 21-day hospitalization complicated by gastrointestinal bleeding, pneumonia, tracheal stenosis requiring placement of a tracheostomy, and pulmonary embolism requiring placement of an inferior vena cava filter.

Further laboratory evaluation of the ingested liquid revealed a pH of 0.8. The fluid was identified as hydro- fluoric acid through flame ionization and atomic absorption.

Discussion

In this case, the patient ingested an unknown liquid substance. His initial symptoms of throat burning, emesis,

Fig. 4 ECG #4 with normalization of abnormalities.

Fig. 5 Action potential with accompanying ECG. Note the effects of Sodium channel blockade with QRS complex widening and potassium efflux blockage with QT interval prolongation.

difficulty with phonation, inability to manage secretions, and chest and abdominal pain were consistent with a caustic ingestion. A rapid bedside litmus paper test revealed that the substance had an acidic pH. An initial arterial blood gas revealed a metabolic acidosis with concomitant respiratory alkalosis. The patient subsequently progressed to hypoten- sion with electrocardiographic changes of both QRS complex widening and QT interval prolongation. For the astute clinician who considers the differential diagnosis for an acidic agent that produces metabolic acidosis, hypoten- sion, and electrocardiographic abnormalities (QRS complex widening and QT interval prolongation), the diagnosis is readily determined to be hydrofluoric acid ingestion.

Hydrofluoric acid is utilized in many industrial settings for the production of integrated circuits, fluorides, plastics, germicides, insecticides, and for the etching and cleaning of silicone, glass, metal, stone, and porcelain. Hydrofluoric acid-containing products are sold as automotive cleaning products in local stores. In 2002, just over 1000 hydro- fluoric acid exposures were reported to US poison centers, with 23 major outcomes and 5 deaths reported [1]. Hydro- fluoric acid rapidly corrodes and penetrates skin and mucous membranes. Ingestion of hydrofluoric acid may result in local mucosal caustic effects, nausea, vomiting, abdominal pain, and hemorrhagic gastritis. Systemic elec- trolyte abnormalities may occur. The absorbed fluoride ions rapidly bind to available calcium and magnesium ions, decreasing the body’s levels of these divalent cations. Hyperkalemia often follows due to an efflux of potassium out of cells into the extracellular space.

There are numerous causes of QRS prolongation. The electrocardiographic differential diagnosis of Wide complex tachycardia classically includes ventricular tachycardia vs Paroxysmal supraventricular tachycardia with aberrant ventricular conduction. Aberrant ventricular conduction may be due to a preexisting bundle branch block (BBB), a functional (rate-related) bundle malfunction resulting in a widened QRS complex when the heart rate exceeds a

characteristic maximum for that patient, or accessory atrioventricular conduction as encountered in preexcitation syndromes, such as that described by Wolff, Parkinson, and White. Other clinical syndromes less frequently encountered in this wide complex tachycardia differential, although very important to the acute care physician, include scenarios related to marked sinus tachycardia with preexisting BBB configuration, recent electrical cardioversion, and ischemic electrocardiographic forms (the giant R wave) misinter- preted as a widened QRS complex with tachycardia.

In a btoxicologicQ setting, QRS complex widening likely results directly from sodium channel blockage or indirectly from toxin-induced hyperkalemia. Direct toxin-induced blockade of cardiac sodium channels will cause QRS complex widening, also known as a membrane stabilizing effect [2,3]. Cardiac voltage-gated sodium channels reside in the cell membrane and open in response to depolarization of the cell. The Sodium channel blockers bind to the transmembrane sodium channels and decrease the number available for subsequent depolarization. This phenomenon creates a delay of sodium entry into the cardiac myocyte during phase 0 of the cardiac depolarization. As a result, the upslope of depolarization is slowed and the QRS complex widens (Fig. 5).

Amantadine Amitriptyline Amoxapine Carbamazepine Chloroquine Cocaine Desipramine Diltiazem Diphenhydramine Disopyramide Doxepin Encainide Flecainide

Hydroxychloroquine Imipramine Loxapine Maprotiline Moricizine Nortriptyline Orphenadrine Phenothiazines Procainamide Propranolol Propafenone Propoxyphene Saxitoxin Tetrodotoxin Thioridazine Quinidine

Quinine Verapamil

Table 1 Cardiac sodium channel blocking agents

Fig. 6 Progression of electrocardiographic abnormalities in this case (lead V3).

Sodium channel blockers not only result in widening of the QRS complex–other abnormal QRS complex config- urations are also possible. In some cases, the QRS complexes may assume the pattern of recognized BBBs. In the most severe cases, the QRS complex widening becomes so profound that the ultimate origin of the rhythm disturbance is impossible; in fact, it is difficult to distinguish between ventricular and supraventricular rhythms in this clinical scenario [4]. Continued widening of the QRS complex may result in a Sine wave pattern and, eventually, asystole. Sodium channel blockers may also induce a monomorphic ventricular tachycardia. It has been theorized that the sodium channel blockers can cause slowed intraventricular conduc- tion, unidirectional block, and the development of a reentrant circuit, ultimately resulting in ventricular tachycardia. This dysrhythmia can then degenerate into ventricular fibrillation. The agents listed in Table 1 are similar in that they may induce myocardial sodium channel blockade.

Myocardial sodium channel blocking drugs comprise a diverse group of pharmaceutical agents. As a result, patients poisoned with these agents will have a variety of clinical presentations. For example, the following agents–triCyclic antidepressants, propoxyphene, and cocaine–are all potent sodium channel blockers; yet these same agents will produce other findings (anticholinergic, opioid, and sympa- thomimetic syndromes, respectively) as well.

The other major mechanism of QRS complex widening in this case is hyperkalemia. The earliest electrocardio- graphic sign of hyperkalemia is the appearance of tall, symmetric T waves (Fig. 6); this T-wave morphology is described as bhyperacuteQ and may be confused with the Hyperacute T wave of early transmural myocardial infarc- tion. As the serum potassium level increases, the T waves tend to become taller, peaked, and narrowed in a symmetric fashion in the anterior distribution. With further increases in the serum concentration, the PR interval is prolonged followed eventually–and most ominously–with QRS complex widening (Fig. 6). Ultimately in hyperkalemia, the QRS complex assumes a sine wave configuration and the rhythm is described as sinoventricular. At any point or time in this pathophysiologic worsening, ventricular fibril- lation may appear.

This patient also manifested progressive QT interval prolongation which may result from either toxin-induced

electrolyte alterations or direct myocardial effects of the poison. Electrolyte abnormalities associated with QT inter- val prolongation include hypokalemia, hypomagnesemia, and hypocalcemia. QT interval prolongation may also be due to toxin-induced blockade of potassium efflux channels during phase 3 of the action potential corresponding with repolarization (Fig. 5). These events may place the patient at risk for Polymorphic ventricular tachycardia or Torsades de pointes [5]. Some medications, such as sotalol, are prescribed specifically for this mechanism [6]. Other medications possess this activity as an unwelcome side effect at Therapeutic doses, such as cisapride and terfenadine, which have been removed from the North American market because of reports of sudden cardiac death [7,8]. Other medications have rarely been reported to cause QT interval prolongation except when taken in massive overdose. A number of chemicals found within the home and workplace are also associated with QT interval prolongation. A complete listing of the reported agents associated with QT interval prolongation is noted in Table 2 [9].

Amiodarone Arsenic Astemizole Chloroquine Cisapride

Cyclic antidepressants Diphenhydramine Disopyramide Droperidol Erythomycin Flecainide Haloperidol Hydroxychloroquine Ketoconazole Organophosphates Pentamidine Phenothiazines Procainamide Quinidine

Quinine Sotalol Terfenadine Venlafaxine

Table 2 Cardiac potassium efflux channel blocking agents

All patients presenting with signs and symptoms consistent with hydrofluoric acid ingestion should be aggressively managed. The patient’s airway should be patent and adequate ventilation assured. If necessary, endotracheal tube intubation should be performed early before edema leads to airway obstruction. The patient should be placed on continuous cardiac monitoring with pulse oximetry and frequent neurological checks should be made. The initial treatment of hypotension consists of intravenous fluids, followed by pressors as needed. The patient’s pulmonary status should be monitored closely for clinical signs consistent with pulmonary aspiration. Acti- vated charcoal, syrup of ipecac, and gastric lavage are absolutely contraindicated in patients who have ingested caustics. Serum electrolytes should be obtained hourly and include serial calcium, magnesium, and Potassium levels. The clinician should obtain serial ECGs looking for signs of hypocalcemia (prolonged QTc interval) and hyperkalemia (peaked T waves). Large amounts of calcium and magne- sium may be needed to normalize serum levels. Fluoride- induced hyperkalemia has been reported to be difficult to reverse. Early aggressive therapy with glucose, insulin, and/ or sodium bicarbonate may be effective. Quinidine has been shown to be effective in preventing the K+ efflux from cells and preventing cardiotoxicity in fluoride-toxic dogs [11].

Conclusion

This patient manifested findings consistent with caustic ingestion and concomitant electrocardiographic findings including sinus tachycardia, QRS complex prolongation, and QT interval prolongation. Only hydrofluoric acid ingestion would account for all the findings noted in this case. Because of its acidic nature, hydrofluoric acid can result in nausea, vomiting, abdominal pain, chest pain, inability to swallow secretions, gastrointestinal bleeding, voice changes, and respiratory distress. Hydrofluoric acid ingestion also could result in electrolyte abnormalities. The fluoride ions chelate serum calcium and magnesium, thereby leading to precipitous drops of both of these electrolytes [10]. The

subsequent hypomagnesemia and hypocalcemia can lead to prolongation of the QT interval. Published reports also have noted the development of hyperkalemia after significant hydrofluoric exposures [11,12] This hydrofluoric acid- induced hyperkalemia can subsequently result in prolonga- tion of the QRS complex. The treatment of the above toxicity consists of supportive care for the caustic effects and correction of electrolyte and fluid abnormalities.

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