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Visine® overdose: Case report of an adult with hemodynamic compromise
The Journal of Emergency Medicine, Vol 13, No 5, pp 649452, 1995 Copyright @ 1995 Elsevier Science Ltd Printed in the USA. All rights reserved 0736~a/579/95 $9.50 f .a0
VlSlNE@ OVERDOSE: CASE REPOWT OF AN ADUtT WITH HEMUDYNAMIG G Roneet Lev,
MD*
and Richard F. Clark, Mot
*Mercy Hospital and Medical Center, San Diego, California tuniversity of California at San Diego Medical Center, San Diego, California Reprint Address: Richard F. Clark, MD, Department of Emergency Medicine, University of California at San Diego MedIcal Center, 200 W. Arbor Drive, San Diego, CA 92103-8676
oxymetazoline (OcuClear@, Afrin@), and xylometazoline (Otrivino) are used as nasal and ocular decongestants and may produce similar clinical effects (3). We present a patient who attempted suicide by ingesting tetrahydrozoline, and discuss the presentation and management of these poisonings.
3 Abstract - Imidazole decongestants are present in a variety of over-the-counter medications, including eye drops and nasal sprays. Tbeir primary mechanism of action is vasoconstriction, aeeomphsbed by direct stimulation of alpha receptors on blood vessels. Accidental and intentional poisonings ittvolvittg these substances are increasing, and can cause mental status and respiratory depression, as well as other effects related to alpha receptor stimulation. We present a caseof tetrabydrozoline ingestion in an adult who preseuted with chest pain, bradycardia, mental status depression, miosis, and otber signs and symptoms of imidazok compound poisoning. It is important for physicians to be famitiar with the adverse effects of these ingestions and to be aware of the potential therapies for management.
CASE PRESENTATION
A 41-year-old male patient presented to the emergency department approximately 2 h after a suicide attempt by ingesting 30 ml of 0.05% tetrahydrozoline (2 bottles of Visine@). Friends told him that Visine@ ingestion was a quick method for suicide and that bartenders frequently use a few drops in a drink to calm down rowdy customers. He also remembered hearing about the use of Visine* by prostitutes as a sedative for their clients. One hour after taking the overdose, the patient developed vague abdominal pain, dry mouth, shortness of breath, dizziness, and pleuritic mid sternal chest tightness. He called a crisis center and an ambulance was sent to his hotel. He was found by paramedics with a sinus bradycardia of 40 beats per minute (bpm) and a systolic blood pressure of 80 mm Hg. Atropine, 0.5 mg, and a 500 ml bolus of normal
n Keywords - Visine@;tetrahydrozoline; overdose
INTRODUCTION
Tetrahydrozoline is an imidazole decongestant that acts as an alpha adrenergic agonist (1,2). It is available as an over-the-counter medication for treatment of eye irritation and nasal congestion. It is found in a concentration of 0.05 to 0.1% in products such as Eye-Zinc@, Murine Plus@, Optigene IIF, Sooth@, Tyzine@,and Visine@( 1). Other imidazole decongestants such as naphazoline (Vasocon@, Naphcon@),
Tozkohtgy is coordinatedby KennethKu&, MD, of Denver, Colorado RECEIVED: 18 July 1994; FINAL SUBMISSION RECEIVED: 28 Novemeber 1994; ACCEPTED: 5 December 1994 649
-
650
saline were administered intravenously with no change in his rhythm or symptoms. An external pacemaker was considered but not applied due to a short transport time to the emergency department. On arrival to the emergency department, he related continued chest tightness, dizziness, and shortness of breath. The past medical history was significant for a previous diagnosis of an “enlarged heart” from an undetermined etiology. There also was a history of depression and one prior suicide attempt. He took no other medications, had no allergies, occasionally tried cocaine, but denied any drug use within the previous 48 h. Physical examination was remarkable for a tympanic temperature of 35OC, pulse of 44 bpm, blood pressure of 135/89 mm Hg, and respiration of 16 breaths per minute. He was lethargic, but arousable. His pupils were miotic at 1 mm, equal and reactive, and his mucous membranes were dry. Lung and cardiovascular examinations were remarkable only for bradycardia. The abdominal examination was significant for diminished bowel sounds, but was otherwise normal. Neurological assessmentof cranial nerves, reflexes, motor, sensory, and cerebellum were normal ; After primary evaluation, the patient was administered atropine, 1 mg intravenously, with a resulting increase in heart rate to 91 bpm and blood pressure to 196/135 mm Hg . The intravenous administration of 2 mg of naloxone did not change the pupil size or degree of lethargy. He was alert enough to drink 50 g of activated charcoal. An electrocardiogram (EKG) in the emergency department revealed a sinus bradycardia, normal intervals, minimal voltage criteria for left ventricular hypertrophy, and 2 mm of ST elevations in leads V 2-6. No previous electrocardiograms were available for comparison. Chest radiograph revealed cardiomegaly. Laboratory tests including complete blood count, electrolytes, blood urea nitrogen, creatinine, and glucose were normal. The creatinine phosphokinase level was 205 IU/liter. A urine toxicology screen was positive for benzoylecgonine (cocaine metabolite), but negative for other drugs of abuse, antidepressants, benzodiazepines, and psychotropic medications. Alcohol, salicylate, and acetaminophen levels were negligible. The blood pressure and pulse remained stable for 2 h in the emergency department, and the patient was admitted to a telemetry floor. Approximately 2 h after admission to the floor, the patient required transfer to the intensive care unit because of hypotension to 86/33 mm Hg and a heart rate of 38 bpm. Administration of 3 mg of atropine
R. Lev and Fi. F. Clark
intravenously and three liters of normal saline raised the pulse to 65 bpm and the blood pressure to 128/ 65 mm Hg. During the episode of hypotension, the patient also experienced midsternal chest pain, but no EKG changes. The ST elevations noted in the previous cardiogram had resolved. He also became increasingly lethargic. In the intensive care unit, he was placed on an isoproterenol drip for recurrent bradycardia, but he developed chest pain after it was begun, and it was discontinued. His blood pressure remained above 100 mm Hg systolic overnight after 2 scopolamine patches were applied. By hospital day 2, the patient was awake and asymptomatic. Acute myocardial infarction was ruled out by serial enzymes and EKGs, and the blood pressure and heart rate remained stable. By hospital day 4, he was discharged to a psychiatric facility, alert, asymptomatic, with normal blood pressure and a heart rate in the 60s. DISCUSSION A case of suicide attempt by tetrahydrozoline ingestion is presented. In this case, tetrahydrozoline overdose was manifested by hypothermia, bradycardia, hypotension, miosis, lethargy, dry mucous membranes, diminished bowel sounds, and atypical chest pain. The American Association of Poison Control Centers recorded 1446 exposures to tetrahydrozoline containing ophthalmic products in 1992 (4). An additional 95 exposures occurred with nasal products containing this substance. The vast majority of these exposures occurred accidentally in children under age 6, and none resulted in fatalities. Most symptoms resolved within 24 h, and few required hospitalization (4). Death has been reported in a single case report of intravenous xylometazoline overdose (5). No fatalities have been reported with oral imidazole toxicity. Tetrahydrozoline may be absorbed systemically after topical administration and has rapid gastrointestinal absorption. Its elimination half life is reported to be from 2 to 4 hours (6,7), and its clinical effects depend on mode of administration. When used topically on the eyes or nasal mucosa, peripheral alpha-l receptor stimulation promotes vasoconstriction. Clinically, this effect will decrease scleral injection and nasal congestion ( 1,2). When taken enterally or parentally, the drug is distributed rapidly into the central nervous system, resulting in stimulation of central alpha-2 adrenoreceptors and imidazole receptors (6,8). The result is
651
VisineQ Overdose
inhibition of sympathetic vasomotor centers and decreasedperipheral vascular tone (9). Clinical manifestations include miosis, dry mouth, central nervous system depression, respiratory depression, hypotension, bradycardia, hypothermia, and hyporeflexia ( 10). Clonidine and imidazoles have similar physiological effects and, in overdose, may exhibit similar clinical manifestations. In clonidine poisoning, both peripheral and central alpha receptors may be stimulated initially, and hypertension may precede hypotension. Although this effect has not been reported with imidazole poisoning, it should be anticipated during the clinical course of managing these individuals. In review of the previously reported casesof tetrahydrozoline overdose, the central bradycardic and hypotensive effects have been predominant (11-15). All reports are of pediatric patients from 6 weeks to 2 years of age. Nasal administration of 0.1% tetrahydrozoline in infants has resulted in immediate drowsiness ( 11). Chronic intranasal dosing of tetrahydrozoline caused coma, cyanosis, bradycardia, hypotension, and respiratory depression in another child (12). Toxicity has also been reported in children after ingestion of tetrahydrozoline. Although symptoms have been reported to be delayed up to 4 h, they usually occur within 2 h and include bradycardia, tachycardia, hypotension, lethargy, respiratory depression, and miosis (13,14). The dosagesingested have ranged up to 15 ml of 0.5% tetrahydrozoline. Most patients remain asymptomatic after ingesting small quantities of these compounds. Maryland Poison Center data from 1979through 1982revealed only two symptomatic patients out of 64 exposures. The two were hospitalized with lethargy, and symptoms resolved within 24 h ( 14). There are no casereports of fatalities with tetrahydrozoline exposure, and all symptoms usually resolve within a day (11-15). Chest pain has not been reported in prior tetrahydrozoline overdoses, although all previous reports involved children (11-15). In this case, the patient presented with atypical midsternal and pleuritic chest tightness. Although there was a history of cardiomegaly and cocaine use, the chest pain resolved upon treatment of his bradycardia. It is unclear if this chest pain was a manifestation of the bradycardia or a direct action of tetrahydrozoline causing coronary artery vasoconstriction and transient ischemia. The physical examination and presenting vital signs did not support recent cocaine use. Acute myocardial infarction was ruled out. Supportive treatment of tetrahydrozoline poisoning has been successful in all reported cases. Gastric
decontamination is probably of little benefit due to the rapid absorption of the solution. Inducing emesis in these individuals is contraindicated, since lethargy may occur rapidly, resulting in airway compromise. The administration of a single oral dose of activated charcoal may be efficacious if given soon after ingestion, and should be considered if a mixed drug overdose is suspected. Tetrahydrozoline-induced cardiotoxicity can result in significant bradycardia that should be treated if the patient is hemodynamically compromised. Atropine may raise the heart rate and perhaps blood pressure in some cases. Increasing the pulse in normotensive or hypertensive individuals could theoretically result in clinically significant hypertension. We have also seen this occur after atropine infusion in normotensive, bradycardic patients with clonidine poisoning. Scopolamine patches were applied to this patient in an attempt to achieve a more sustained atropine-like effect on heart rate. Although this technique has not been described previously, it may be efficacious in producing mild elevations in heart rate for prolonged intervals in some patients. Unfortunately, scopolamine can result in anticholinergic effects that may enhance the dry mouth, mental confusion, and adrenergic findings in patients with imidazole toxicity. The rare hypotensive individual should be treated with intravenous fluids and atropine first. Vasopressors are reserved for refractory cases. Although no data are available using dialysis in the management of these patients, it would likely not be of benefit due to the large volume of distribution of tetrahydrozoline. Plasma imidazole levels are not clinically useful and no specific laboratory work is needed unless otherwise indicated (7,16). There are several case reports of patients with clonidine poisoning becoming more alert with the administration of naloxone (17,18). It is hypothesized that clonidine causesa naloxone reversible inhibition of central sympathetic outflow mediated by the release of an endogenous opioid (19). In addition, this may explain the reported successful management of opiate withdrawal symptoms with clonidine. Although naloxone has never been reported to reverse tetrahydrozoline toxicity, it is certainly indicated as an adjunct to the management of any patient presenting with altered mental status of unknown etiology.
CONCLUSION Tetrahydrozoline is an imidazole alpha adrenergic agonist available over-the-counter for treatment of
652
R. Lev and R. F. Clark
eye irritation and nasal congestion. We present a patient with an intentional ingestion of tetrahydrozoline that produced central nervous system depression, miosis, hypothermia, and other signs of imidazole toxicity. Clinically significant bradycardia and hypotension in this individual required crystalloid fluid boluses and the administration of atropine and scopolamine to maintain perfusion. Hemodynamic com-
promise in these poisonings is uncommon and usually manifests as sinus bradycardia and mild hypotension. Supportive therapy with atropine, vasopressors, and even cardiac pacing may be needed in some severe cases. Symptoms usually resolve within two days. Emergency physicians should consider imidazole compounds in patients with such presentations.
REFERENCES 1. AMA Council on Drugs. AMA drug evaluations annual. Chicago, IL: American Medical Association; 1992:2012. 2. Hoffman BB, Lefkowitz RJ. Catecholamine and sympathomimetic drugs. In Gilman AG, Goodman LS, eds. The pharmacological basis of therapeutics, 7th ed. New York: Macmillan; 1990:214. 3. Ellenhorn MJ, Barceloux DG. Medical toxicology, diagnosis and treatment of human poisoning. New York: Elsevier; 1988: 531. 4. Litovitz TL, Holm KC, Clancy C, Schmitz BF, Clark LR, Odera GM. 1992 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance Systems. Amer J Emerg Med. 1993;11:494-555. 5. Vanezis P, Toseland PA. Xylometazoline poisoning-a report of a case. Med Sci Law. 1980; 20:35-6. 6. Hutcheon PE, P’an SY, Gardocki JF, et al. The sympathomimetic and other pharmacological properties of dl-2-( 1,2,3,4tetrahydro-1-naphthyl)-imidazole (tetrahydrozoline). J Pharmacol Exp Ther. 1955;113:341-52. 7. Poisindex@;Editorial Staff. Denver, Colorado. 1992. 8. Reis DJ, Regunathan S, Meeley MP. Imidazoie receptors and clonidine - displacing substance in relationship to control of blood pressure, neuroprotection, and adrenomedullary secretion. Am J Hypertens. 1992;5:51s-57s. 9. Kobinger W, Walland A. Investigations into the mechanism of the hypotensive effect of 2-(2,6-dichlorophenylamino)-2imidazoline-HCl. Eur J Pharmacol. 1967:2:155-62.
10. Kobinger W, Pichler L. Centrally induced reduction in sympathetic tone-a postsynaptic alpha-adrenoreceptor stimulating action of imidazolines. Eur J Pharmacol. 1976;40:311-20. 11. Brainerd WK, Olmsted RW. Toxicity due to the use of tyzine hydrochloride. J Pediatr. 1956;48:157-64. 12. Wick H. Ueber tyzine-vergiftung. Praxis. 1966;55:791-2. 13. Mindlin RL. Accidental poisoning from tetrahydrozoline eyedrops (letter). N Eng J Med. 1966;275:112. 14. Klein-Schwarz W, Gorman R, Oderda GM, Baig A. Central nervous system depression from ingestion of non prescription eyedrops. Am J Emerg Med. 1984;2(3):217-8. 15. Jensen P, Edgren B, Hall L, Ring JC. Hemodynamic effects following ingestion of an imidazole-containing product. Pediatric Emerg Care. 1989;5(2):110-2. 16. Domino LE, Domino SE, Stockstill MS. Relationship between plasma concentrations of clonidine and mean arterial pressure during an accidental clonidine overdose. Br J Clin Pharmac. 1986;21:71-4. 17. Niemann JT, Getzug T, Murphy W. Reversal of clonidine toxicity by naloxone. Ann Emerg Med. 1986;15:1229-31. 18. North DS, Peterson CD. Efficacy of naloxone in clonidine poisoning. Am J Dis Child. 1983;137:807-8. 19. Farsang C, Kapocsi J, Vajda L, Varga K, et al. Reversal by naloxone of the antihypertensive action of clonidine: involvement of the sympathetic nervous system. Circulation. 1984;69: 461-7.
VlSlNE@ OVERDOSE: CASE REPOWT OF AN ADUtT WITH HEMUDYNAMIG G Roneet Lev,
MD*
and Richard F. Clark, Mot
*Mercy Hospital and Medical Center, San Diego, California tuniversity of California at San Diego Medical Center, San Diego, California Reprint Address: Richard F. Clark, MD, Department of Emergency Medicine, University of California at San Diego MedIcal Center, 200 W. Arbor Drive, San Diego, CA 92103-8676
oxymetazoline (OcuClear@, Afrin@), and xylometazoline (Otrivino) are used as nasal and ocular decongestants and may produce similar clinical effects (3). We present a patient who attempted suicide by ingesting tetrahydrozoline, and discuss the presentation and management of these poisonings.
3 Abstract - Imidazole decongestants are present in a variety of over-the-counter medications, including eye drops and nasal sprays. Tbeir primary mechanism of action is vasoconstriction, aeeomphsbed by direct stimulation of alpha receptors on blood vessels. Accidental and intentional poisonings ittvolvittg these substances are increasing, and can cause mental status and respiratory depression, as well as other effects related to alpha receptor stimulation. We present a caseof tetrabydrozoline ingestion in an adult who preseuted with chest pain, bradycardia, mental status depression, miosis, and otber signs and symptoms of imidazok compound poisoning. It is important for physicians to be famitiar with the adverse effects of these ingestions and to be aware of the potential therapies for management.
CASE PRESENTATION
A 41-year-old male patient presented to the emergency department approximately 2 h after a suicide attempt by ingesting 30 ml of 0.05% tetrahydrozoline (2 bottles of Visine@). Friends told him that Visine@ ingestion was a quick method for suicide and that bartenders frequently use a few drops in a drink to calm down rowdy customers. He also remembered hearing about the use of Visine* by prostitutes as a sedative for their clients. One hour after taking the overdose, the patient developed vague abdominal pain, dry mouth, shortness of breath, dizziness, and pleuritic mid sternal chest tightness. He called a crisis center and an ambulance was sent to his hotel. He was found by paramedics with a sinus bradycardia of 40 beats per minute (bpm) and a systolic blood pressure of 80 mm Hg. Atropine, 0.5 mg, and a 500 ml bolus of normal
n Keywords - Visine@;tetrahydrozoline; overdose
INTRODUCTION
Tetrahydrozoline is an imidazole decongestant that acts as an alpha adrenergic agonist (1,2). It is available as an over-the-counter medication for treatment of eye irritation and nasal congestion. It is found in a concentration of 0.05 to 0.1% in products such as Eye-Zinc@, Murine Plus@, Optigene IIF, Sooth@, Tyzine@,and Visine@( 1). Other imidazole decongestants such as naphazoline (Vasocon@, Naphcon@),
Tozkohtgy is coordinatedby KennethKu&, MD, of Denver, Colorado RECEIVED: 18 July 1994; FINAL SUBMISSION RECEIVED: 28 Novemeber 1994; ACCEPTED: 5 December 1994 649
-
650
saline were administered intravenously with no change in his rhythm or symptoms. An external pacemaker was considered but not applied due to a short transport time to the emergency department. On arrival to the emergency department, he related continued chest tightness, dizziness, and shortness of breath. The past medical history was significant for a previous diagnosis of an “enlarged heart” from an undetermined etiology. There also was a history of depression and one prior suicide attempt. He took no other medications, had no allergies, occasionally tried cocaine, but denied any drug use within the previous 48 h. Physical examination was remarkable for a tympanic temperature of 35OC, pulse of 44 bpm, blood pressure of 135/89 mm Hg, and respiration of 16 breaths per minute. He was lethargic, but arousable. His pupils were miotic at 1 mm, equal and reactive, and his mucous membranes were dry. Lung and cardiovascular examinations were remarkable only for bradycardia. The abdominal examination was significant for diminished bowel sounds, but was otherwise normal. Neurological assessmentof cranial nerves, reflexes, motor, sensory, and cerebellum were normal ; After primary evaluation, the patient was administered atropine, 1 mg intravenously, with a resulting increase in heart rate to 91 bpm and blood pressure to 196/135 mm Hg . The intravenous administration of 2 mg of naloxone did not change the pupil size or degree of lethargy. He was alert enough to drink 50 g of activated charcoal. An electrocardiogram (EKG) in the emergency department revealed a sinus bradycardia, normal intervals, minimal voltage criteria for left ventricular hypertrophy, and 2 mm of ST elevations in leads V 2-6. No previous electrocardiograms were available for comparison. Chest radiograph revealed cardiomegaly. Laboratory tests including complete blood count, electrolytes, blood urea nitrogen, creatinine, and glucose were normal. The creatinine phosphokinase level was 205 IU/liter. A urine toxicology screen was positive for benzoylecgonine (cocaine metabolite), but negative for other drugs of abuse, antidepressants, benzodiazepines, and psychotropic medications. Alcohol, salicylate, and acetaminophen levels were negligible. The blood pressure and pulse remained stable for 2 h in the emergency department, and the patient was admitted to a telemetry floor. Approximately 2 h after admission to the floor, the patient required transfer to the intensive care unit because of hypotension to 86/33 mm Hg and a heart rate of 38 bpm. Administration of 3 mg of atropine
R. Lev and Fi. F. Clark
intravenously and three liters of normal saline raised the pulse to 65 bpm and the blood pressure to 128/ 65 mm Hg. During the episode of hypotension, the patient also experienced midsternal chest pain, but no EKG changes. The ST elevations noted in the previous cardiogram had resolved. He also became increasingly lethargic. In the intensive care unit, he was placed on an isoproterenol drip for recurrent bradycardia, but he developed chest pain after it was begun, and it was discontinued. His blood pressure remained above 100 mm Hg systolic overnight after 2 scopolamine patches were applied. By hospital day 2, the patient was awake and asymptomatic. Acute myocardial infarction was ruled out by serial enzymes and EKGs, and the blood pressure and heart rate remained stable. By hospital day 4, he was discharged to a psychiatric facility, alert, asymptomatic, with normal blood pressure and a heart rate in the 60s. DISCUSSION A case of suicide attempt by tetrahydrozoline ingestion is presented. In this case, tetrahydrozoline overdose was manifested by hypothermia, bradycardia, hypotension, miosis, lethargy, dry mucous membranes, diminished bowel sounds, and atypical chest pain. The American Association of Poison Control Centers recorded 1446 exposures to tetrahydrozoline containing ophthalmic products in 1992 (4). An additional 95 exposures occurred with nasal products containing this substance. The vast majority of these exposures occurred accidentally in children under age 6, and none resulted in fatalities. Most symptoms resolved within 24 h, and few required hospitalization (4). Death has been reported in a single case report of intravenous xylometazoline overdose (5). No fatalities have been reported with oral imidazole toxicity. Tetrahydrozoline may be absorbed systemically after topical administration and has rapid gastrointestinal absorption. Its elimination half life is reported to be from 2 to 4 hours (6,7), and its clinical effects depend on mode of administration. When used topically on the eyes or nasal mucosa, peripheral alpha-l receptor stimulation promotes vasoconstriction. Clinically, this effect will decrease scleral injection and nasal congestion ( 1,2). When taken enterally or parentally, the drug is distributed rapidly into the central nervous system, resulting in stimulation of central alpha-2 adrenoreceptors and imidazole receptors (6,8). The result is
651
VisineQ Overdose
inhibition of sympathetic vasomotor centers and decreasedperipheral vascular tone (9). Clinical manifestations include miosis, dry mouth, central nervous system depression, respiratory depression, hypotension, bradycardia, hypothermia, and hyporeflexia ( 10). Clonidine and imidazoles have similar physiological effects and, in overdose, may exhibit similar clinical manifestations. In clonidine poisoning, both peripheral and central alpha receptors may be stimulated initially, and hypertension may precede hypotension. Although this effect has not been reported with imidazole poisoning, it should be anticipated during the clinical course of managing these individuals. In review of the previously reported casesof tetrahydrozoline overdose, the central bradycardic and hypotensive effects have been predominant (11-15). All reports are of pediatric patients from 6 weeks to 2 years of age. Nasal administration of 0.1% tetrahydrozoline in infants has resulted in immediate drowsiness ( 11). Chronic intranasal dosing of tetrahydrozoline caused coma, cyanosis, bradycardia, hypotension, and respiratory depression in another child (12). Toxicity has also been reported in children after ingestion of tetrahydrozoline. Although symptoms have been reported to be delayed up to 4 h, they usually occur within 2 h and include bradycardia, tachycardia, hypotension, lethargy, respiratory depression, and miosis (13,14). The dosagesingested have ranged up to 15 ml of 0.5% tetrahydrozoline. Most patients remain asymptomatic after ingesting small quantities of these compounds. Maryland Poison Center data from 1979through 1982revealed only two symptomatic patients out of 64 exposures. The two were hospitalized with lethargy, and symptoms resolved within 24 h ( 14). There are no casereports of fatalities with tetrahydrozoline exposure, and all symptoms usually resolve within a day (11-15). Chest pain has not been reported in prior tetrahydrozoline overdoses, although all previous reports involved children (11-15). In this case, the patient presented with atypical midsternal and pleuritic chest tightness. Although there was a history of cardiomegaly and cocaine use, the chest pain resolved upon treatment of his bradycardia. It is unclear if this chest pain was a manifestation of the bradycardia or a direct action of tetrahydrozoline causing coronary artery vasoconstriction and transient ischemia. The physical examination and presenting vital signs did not support recent cocaine use. Acute myocardial infarction was ruled out. Supportive treatment of tetrahydrozoline poisoning has been successful in all reported cases. Gastric
decontamination is probably of little benefit due to the rapid absorption of the solution. Inducing emesis in these individuals is contraindicated, since lethargy may occur rapidly, resulting in airway compromise. The administration of a single oral dose of activated charcoal may be efficacious if given soon after ingestion, and should be considered if a mixed drug overdose is suspected. Tetrahydrozoline-induced cardiotoxicity can result in significant bradycardia that should be treated if the patient is hemodynamically compromised. Atropine may raise the heart rate and perhaps blood pressure in some cases. Increasing the pulse in normotensive or hypertensive individuals could theoretically result in clinically significant hypertension. We have also seen this occur after atropine infusion in normotensive, bradycardic patients with clonidine poisoning. Scopolamine patches were applied to this patient in an attempt to achieve a more sustained atropine-like effect on heart rate. Although this technique has not been described previously, it may be efficacious in producing mild elevations in heart rate for prolonged intervals in some patients. Unfortunately, scopolamine can result in anticholinergic effects that may enhance the dry mouth, mental confusion, and adrenergic findings in patients with imidazole toxicity. The rare hypotensive individual should be treated with intravenous fluids and atropine first. Vasopressors are reserved for refractory cases. Although no data are available using dialysis in the management of these patients, it would likely not be of benefit due to the large volume of distribution of tetrahydrozoline. Plasma imidazole levels are not clinically useful and no specific laboratory work is needed unless otherwise indicated (7,16). There are several case reports of patients with clonidine poisoning becoming more alert with the administration of naloxone (17,18). It is hypothesized that clonidine causesa naloxone reversible inhibition of central sympathetic outflow mediated by the release of an endogenous opioid (19). In addition, this may explain the reported successful management of opiate withdrawal symptoms with clonidine. Although naloxone has never been reported to reverse tetrahydrozoline toxicity, it is certainly indicated as an adjunct to the management of any patient presenting with altered mental status of unknown etiology.
CONCLUSION Tetrahydrozoline is an imidazole alpha adrenergic agonist available over-the-counter for treatment of
652
R. Lev and R. F. Clark
eye irritation and nasal congestion. We present a patient with an intentional ingestion of tetrahydrozoline that produced central nervous system depression, miosis, hypothermia, and other signs of imidazole toxicity. Clinically significant bradycardia and hypotension in this individual required crystalloid fluid boluses and the administration of atropine and scopolamine to maintain perfusion. Hemodynamic com-
promise in these poisonings is uncommon and usually manifests as sinus bradycardia and mild hypotension. Supportive therapy with atropine, vasopressors, and even cardiac pacing may be needed in some severe cases. Symptoms usually resolve within two days. Emergency physicians should consider imidazole compounds in patients with such presentations.
REFERENCES 1. AMA Council on Drugs. AMA drug evaluations annual. Chicago, IL: American Medical Association; 1992:2012. 2. Hoffman BB, Lefkowitz RJ. Catecholamine and sympathomimetic drugs. In Gilman AG, Goodman LS, eds. The pharmacological basis of therapeutics, 7th ed. New York: Macmillan; 1990:214. 3. Ellenhorn MJ, Barceloux DG. Medical toxicology, diagnosis and treatment of human poisoning. New York: Elsevier; 1988: 531. 4. Litovitz TL, Holm KC, Clancy C, Schmitz BF, Clark LR, Odera GM. 1992 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance Systems. Amer J Emerg Med. 1993;11:494-555. 5. Vanezis P, Toseland PA. Xylometazoline poisoning-a report of a case. Med Sci Law. 1980; 20:35-6. 6. Hutcheon PE, P’an SY, Gardocki JF, et al. The sympathomimetic and other pharmacological properties of dl-2-( 1,2,3,4tetrahydro-1-naphthyl)-imidazole (tetrahydrozoline). J Pharmacol Exp Ther. 1955;113:341-52. 7. Poisindex@;Editorial Staff. Denver, Colorado. 1992. 8. Reis DJ, Regunathan S, Meeley MP. Imidazoie receptors and clonidine - displacing substance in relationship to control of blood pressure, neuroprotection, and adrenomedullary secretion. Am J Hypertens. 1992;5:51s-57s. 9. Kobinger W, Walland A. Investigations into the mechanism of the hypotensive effect of 2-(2,6-dichlorophenylamino)-2imidazoline-HCl. Eur J Pharmacol. 1967:2:155-62.
10. Kobinger W, Pichler L. Centrally induced reduction in sympathetic tone-a postsynaptic alpha-adrenoreceptor stimulating action of imidazolines. Eur J Pharmacol. 1976;40:311-20. 11. Brainerd WK, Olmsted RW. Toxicity due to the use of tyzine hydrochloride. J Pediatr. 1956;48:157-64. 12. Wick H. Ueber tyzine-vergiftung. Praxis. 1966;55:791-2. 13. Mindlin RL. Accidental poisoning from tetrahydrozoline eyedrops (letter). N Eng J Med. 1966;275:112. 14. Klein-Schwarz W, Gorman R, Oderda GM, Baig A. Central nervous system depression from ingestion of non prescription eyedrops. Am J Emerg Med. 1984;2(3):217-8. 15. Jensen P, Edgren B, Hall L, Ring JC. Hemodynamic effects following ingestion of an imidazole-containing product. Pediatric Emerg Care. 1989;5(2):110-2. 16. Domino LE, Domino SE, Stockstill MS. Relationship between plasma concentrations of clonidine and mean arterial pressure during an accidental clonidine overdose. Br J Clin Pharmac. 1986;21:71-4. 17. Niemann JT, Getzug T, Murphy W. Reversal of clonidine toxicity by naloxone. Ann Emerg Med. 1986;15:1229-31. 18. North DS, Peterson CD. Efficacy of naloxone in clonidine poisoning. Am J Dis Child. 1983;137:807-8. 19. Farsang C, Kapocsi J, Vajda L, Varga K, et al. Reversal by naloxone of the antihypertensive action of clonidine: involvement of the sympathetic nervous system. Circulation. 1984;69: 461-7.