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Treatment of cardiovascular collapse from caffeine overdose with lidocaine, phenylephrine, and hemodialysis
American Journal of Emergency Medicine (2009) 27, 253.e3–253.e6
www.elsevier.com/locate/ajem
Case Report Treatment of cardiovascular collapse from caffeine overdose with lidocaine, phenylephrine, and hemodialysis
Abstract Caffeine overdoses produce multiple symptoms, most of which are commonly associated with a marked increase in adrenergic tone. These can include hypertension, tachycardia, dysrhythmias, and central nervous and skeletal muscle stimulation. This case illustrates a massive caffeine ingestion with resultant cardiovascular collapse. The patient was stabilized with a combination of lidocaine and phenylephrine in the emergency department and underwent hemodialysis in the intensive care unit, with rapid extubation and return to baseline functioning. To our knowledge, this combination has not been previously used to treat massive caffeine ingestions. An 18-year-old man presented to the emergency department via emergency medical services for altered mental status and vomiting after a suicide attempt. The initial history was limited by the patient's acute medical condition, but he was able to admit to ingesting approximately 10 g of caffeine 1 hour before arrival. He denied any other co-ingestions. The EMS providers also gave the additional history that the patient appeared very anxious and diaphoretic upon their arrival and had since vomited multiple times during transport. The only other information able to be obtained was the empty bottle of trademarked caffeine pills, and an ingestion of its entire contents would have been equivalent to 20 g of caffeine. Verbal report from the prehospital providers yielded a heart rate of 80 beats/min and a blood pressure (BP) of 110/ 60 mm Hg. Initial vitals in the emergency department were BP of 58/43 mm/Hg, heart rate between 70 and 80 beats/min, respiratory rate of 24 breaths/min, and oxygen saturation of 98% to 99% on room air, and the patient was afebrile. He did have altered mental status and was arousable to loud voice or sternal rub only, and when aroused, he acted inappropriately. His pupils were midrange and reactive bilaterally, mucous membranes were dry, and he did not have any nuchal rigidity. His cardiovascular and pulmonary examinations were unremarkable, and his abdomen was nontender. The patient 0735-6757/$ – see front matter © 2009 Elsevier Inc. All rights reserved.
was also significantly diaphoretic and did not appear to have any lateralizing neurologic deficits, but he was uncooperative with that examination. Initial dextrose stick was 206 mg/dL, and the initial electrocardiogram (EKG) was remarkable for a prolonged QTc interval, greater than 600 milliseconds, and diffuse inferolateral ST segment abnormalities (Fig. 1). Resuscitation was initiated with normal saline through 2 large-bore peripheral IVs, and multiple laboratory studies were sent. However, the patient became profoundly bradycardic to heart rates of 30 to 40 beats/min, and his mental status deteriorated significantly to minimal responsiveness. His heart rate did rebound before atropine could be given, but he remained obtunded. Atropine was then held as a premedication for intubation owing to the patient's pronounced tachycardia after that episode. He was intubated at that point using etomidate and succinylcholine, and during and shortly after this procedure, he developed marked cardiac instability. The patient developed an irregular narrow complex tachycardia, which returned to sinus bradycardia fairly rapidly. Subsequently, he developed a pulseless, wide complex rhythm, but autoconverted before defibrillation was attempted. Laboratory results available at that time revealed a mild leukocytosis of 17.22 K/μL, a metabolic panel with mild hypokalemia (2.8 mmol/L), no significant acidosis (HCO3, 23 mmol/L), essentially unremarkable liver function tests, and pH 7.312 on the initial arterial blood gas. The urinalysis revealed only glucosuria and trace ketones, and the urine toxicology screen was positive only for benzodiazepines. Drug substance level testing remained pending. Given his hemodynamic and cardiac instability, a central line was placed for resuscitative purposes, to facilitate vasoactive medication administration, and for dialysis access. An arterial line, orogastric tube, and Foley catheter were also inserted. Continuous infusions of both phenylephrine and lidocaine were administered after loading boluses of each medication, and the patient's hemodynamic status stabilized very rapidly. A second EKG revealed significant improvement in the corrected QT interval and some resolution of the ST-segment changes that were previously evident (Fig. 2). The patient was admitted to the medical intensive care unit (MICU). Further laboratory values from the emergency department and the initial MICU acceptance included nondetectable
253.e4
Fig. 1
Case Report
Initial electrocardiogram demonstrating diffuse inferolateral ST-segment changes with a markedly prolonged QTc interval.
levels of ethanol, salicylates, acetaminophen, and lithium. A detectable but low level of theophylline (2.8 μg/mL; reference range, 10-20 μg/mL) was present, and a caffeine level added on to the initial blood work returned markedly increased at 72.5 μg/dL (reference range, 6.0-20.0 μg/dL). In the MICU, the patient was seen by nephrology and dialyzed, was able to be weaned off of vasopressors quickly, and was extubated approximately 1 day after admission. He was transferred to a medical floor and seen by psychiatry. Unfortunately, he absconded from the floor and has not followed up since. Caffeine, or 1,3,7-trimethylxanthine, is a very commonly ingested substance and has a wider therapeutic range than does its metabolite, theophylline. It is present in many substances, but its specific over-the-counter usage in stimulant products has been limited to 200 mg per dose since 1988 [1]. In overdose, the toxicologic effects of caffeine are related to its antagonism of adenosine receptors, inhibition of phosphodiesterase, and increase in intracellular calcium levels [2,3]. The oral route is the most common means of exposure, and caffeine is 100% bioavailable, with peak levels occurring between 30 to 60 minutes and 3 hours [4]. Caffeine toxicity generally affects the cardiovascular, gastrointestinal, neurologic, and musculoskeletal systems. Although sinus tachycardia is the most common rhythm disturbance, multiple arrhythmias have been reported, including bigeminy, supraventricular tachycardia, premature ventricular contractions, ventricular tachycardia, and ventricular fibrillation [5-9]. Cardiovascular collapse has also been noted in previous case reports [8,10]. Nausea and vomiting are common with caffeine overdoses as well and
may somewhat limit the potential toxicity via elimination of the parent compound [6,11]. Neurologic effects are common even with therapeutic levels of caffeine, but seizures can occur with poisonings [10,12]. Rhabdomyolysis, sometimes severe enough to cause acute renal failure, has also been reported in multiple cases [13,14]. The patient in this particular case did have significant nausea and vomiting along with altered mental status, but his marked cardiovascular instability was predominant in his clinical presentation. Multiple agents have been used to treat both the hemodynamic instability involved in massive caffeine ingestions and the proarrhythmic effects of the poisoning. Hypotension in caffeine overdose has been theorized to be multifactorial in etiology, with β2-receptor agonism causing peripheral vasodilatation and β1-receptor stimulation leading to profound tachycardia with incomplete diastolic filling time. It stands to reason that, although initially counterintuitive, β-blockers may directly act against these mechanisms and restore cardiovascular stability, and this has been borne out in cases of both caffeine and theophylline toxicity [6,15]. However, there is also a theoretical concern that unopposed alpha stimulation could lead to rampant hypertension and the sequelae thereof. Therefore, in this case, phenylephrine, a powerful α-receptor agonist, was chosen to increase peripheral vascular resistance and cause reflex bradycardia, both of which were beneficial effects in this patient. The patient experienced dramatic BP stabilization evident even with the loading bolus of phenylephrine. This therapy has been recommended for hemodynamic instability in caffeine poisoning in multiple sources, but to our knowledge, this
Case Report
253.e5
Fig. 2 Second EKG performed approximately 90 minutes after patient arrival and multiple rounds of treatment, revealing normalization of previous inferolateral ST changes and significant narrowing of the QTc interval.
is the first documented use, and this patient had overwhelmingly positive results [2,16]. With regard to this patient's myriad of cardiac rhythms, multiple efforts were made to remedy this instability. While atropine was to be attempted for his symptomatic bradycardia, and cardioversion for the episode of pulseless ventricular tachycardia, he spontaneously changed rhythms too quickly to allow either therapy to take place. As his BP stabilized with phenylephrine, both Advanced Cardiac Life Support and Pediatric Advanced Life Support would recommend amiodarone, procainamide, or lidocaine for his rhythm disturbances [17,18]. Given his baseline EKG findings (Fig. 1), specifically the significant QTc prolongation, use of amiodarone would be strongly cautioned against [19]. Procainamide, although its predominant electrocardiographic effect is related to QRS prolongation, also prolongs the QT interval, although it has been used successfully in caffeine ingestions previously [9,20]. Lidocaine was chosen in this case given the patient's significant QTc prolongation and electrophysiologic instability, and the patient had significant improvement in his hemodynamic profile with no further dysrhythmias after the bolus and infusion were given (Fig. 2). Dialysis was also required and was performed in our case in the MICU, and its benefits have been discussed in multiple previous case reports. Although the incidence of theophylline exposures has declined over the 1990s owing to fewer continuing prescriptions for the medication, the rate of caffeine exposures has remained fairly constant [2]. And although death from caffeine ingestion is rare, this case illustrates
the potential severity of massive caffeine ingestion, even in a young, previously healthy patient. To the best of our knowledge, this case represents the first documented use of phenylephrine as a treatment for hemodynamic instability and hypotension after massive caffeine overdose. Although lidocaine has been successfully used in mixed overdoses containing caffeine and has not been shown to be effective in a single murine study, this case illustrates significant cardiovascular improvement with its use in a pure caffeine overdose [21,22]. Both of these medications should be considered in the treatment of cardiovascular collapse secondary to methylxanthine poisoning. Rahi Kapur MD Department of Emergency Medicine MetroHealth Medical Center Cleveland, OH 44109, USA Case Western Reserve University Cleveland, OH 44109, USA E-mail address: [email protected] Michael D. Smith MD Department of Emergency Medicine MetroHealth Medical Center Cleveland, OH 44109, USA Case Western Reserve University Cleveland, OH 44109, USA E-mail address: [email protected] doi:10.1016/j.ajem.2008.06.028
253.e6
References [1] FDA. Stimulant drug products for over-the-counter human use; final monograph. FDA: Fed register 1988;53:6100. [2] Goldfrank LR, editor. Goldfrank's toxicologic emergencies. Chapter 39: methylxanthines. 7th ed. New York: McGraw-Hill; 2002. [3] Ford MD, Delaney KA, Ling LJ, Erickson T, editors. Clinical toxicology. Chapter 36: caffeine and other related nonprescription sympathomimetics. 1st ed. WB Saunders: Philadelphia; 2001. [4] Micromedex Healthcare series: Poisondex managements: caffeine. Thompson Healthcare. Accessed through MetroHealth Medical Center, 5/1/2008. [5] Nagesh RV, Murphy KA. Caffeine poisoning treated by hemoperfusion. Am J Kidney Dis 1988;12:316-8. [6] Price KR, Fligner DJ. Treatment of caffeine toxicity with esmolol. Ann Emerg Med 1990;19:44-6. [7] Forman J, Aizer A, Young CR. Myocardial infarction resulting from caffeine overdose in an anorectic woman. Ann Emerg Med 1997;29: 178-80. [8] Holstege CP, Hunter Y, Baer AB, Savory J, Bruns DE, Boyd JC. Massive caffeine overdose requiring vasopressin infusion and hemodialysis. J Toxicol Clin Toxicol 2003;41:1003-7. [9] Chopra A, Morrison L. Resolution of caffeine-induced complex dysrhythmia with procainamide therapy. J Emerg Med 1995;13:113-7. [10] Rouse A, Ford M, Kerns W. Rapid cardiac arrest following massive caffeine ingestion. J Toxicol Clin Toxicol 1999;37:629-30. [11] Dietrich AM, Mortensen ME. Presentation and management of an acute caffeine overdose. Pediatr Emerg Care 1990;6:296-8.
Case Report [12] Shum S, Seale C, Hathaway D, Chucovich V, Beard D. Acute caffeine ingestion fatalities: management issues. Vet Hum Toxicol 1997;39: 228-30. [13] Wrenn KD, Oschner I. Rhabdomyolysis induced by caffeine overdose. Ann Emerg Med 1989;18:94-7. [14] Kamijo Y, Soma K, Asari Y, Ohwada T. Severe rhabdomyolysis following massive ingestion of oolong tea: caffeine intoxication with coexisting hyponatremia. Vet Hum Toxicol 1999;41:381-3. [15] Seneff M, Scoot J, Freidman B, Smith M. Acute theophylline toxicity and the use of esmolol to reverse cardiovascular instability. Ann Emerg Med 1990;19:671-3. [16] Holstege CP, Dobmeier S. Cardiovascular challenges in toxicology. Emerg Med Clin North Am 2005;23:1195-217. [17] American Heart Association. ACLS provider manual. Dallas: AHA; 2002. [18] American Heart Association. PALS provider manual. Dallas: AHA; 2002. [19] Micromedex Healthcare series: Drugdex evaluations: amiodarone. Thompson Healthcare. Accessed through MetroHealth Medical Center, 5/13/2008. [20] Micromedex Healthcare series: Drugdex evaluations: procainamide. Thompson Healthcare. Accessed through MetroHealth Medical Center, 5/13/2008. [21] Zahn KA, Li RL, Purssell RA. Cardiovascular toxicity after ingestion of “herbal ecstasy”. J Emerg Med 1999;17:289-91. [22] Strubelt O, Diederich KW. Experimental treatment of the acute cardiovascular toxicity of caffeine. J Toxicol Clin Toxicol 1999;37: 29-33.
www.elsevier.com/locate/ajem
Case Report Treatment of cardiovascular collapse from caffeine overdose with lidocaine, phenylephrine, and hemodialysis
Abstract Caffeine overdoses produce multiple symptoms, most of which are commonly associated with a marked increase in adrenergic tone. These can include hypertension, tachycardia, dysrhythmias, and central nervous and skeletal muscle stimulation. This case illustrates a massive caffeine ingestion with resultant cardiovascular collapse. The patient was stabilized with a combination of lidocaine and phenylephrine in the emergency department and underwent hemodialysis in the intensive care unit, with rapid extubation and return to baseline functioning. To our knowledge, this combination has not been previously used to treat massive caffeine ingestions. An 18-year-old man presented to the emergency department via emergency medical services for altered mental status and vomiting after a suicide attempt. The initial history was limited by the patient's acute medical condition, but he was able to admit to ingesting approximately 10 g of caffeine 1 hour before arrival. He denied any other co-ingestions. The EMS providers also gave the additional history that the patient appeared very anxious and diaphoretic upon their arrival and had since vomited multiple times during transport. The only other information able to be obtained was the empty bottle of trademarked caffeine pills, and an ingestion of its entire contents would have been equivalent to 20 g of caffeine. Verbal report from the prehospital providers yielded a heart rate of 80 beats/min and a blood pressure (BP) of 110/ 60 mm Hg. Initial vitals in the emergency department were BP of 58/43 mm/Hg, heart rate between 70 and 80 beats/min, respiratory rate of 24 breaths/min, and oxygen saturation of 98% to 99% on room air, and the patient was afebrile. He did have altered mental status and was arousable to loud voice or sternal rub only, and when aroused, he acted inappropriately. His pupils were midrange and reactive bilaterally, mucous membranes were dry, and he did not have any nuchal rigidity. His cardiovascular and pulmonary examinations were unremarkable, and his abdomen was nontender. The patient 0735-6757/$ – see front matter © 2009 Elsevier Inc. All rights reserved.
was also significantly diaphoretic and did not appear to have any lateralizing neurologic deficits, but he was uncooperative with that examination. Initial dextrose stick was 206 mg/dL, and the initial electrocardiogram (EKG) was remarkable for a prolonged QTc interval, greater than 600 milliseconds, and diffuse inferolateral ST segment abnormalities (Fig. 1). Resuscitation was initiated with normal saline through 2 large-bore peripheral IVs, and multiple laboratory studies were sent. However, the patient became profoundly bradycardic to heart rates of 30 to 40 beats/min, and his mental status deteriorated significantly to minimal responsiveness. His heart rate did rebound before atropine could be given, but he remained obtunded. Atropine was then held as a premedication for intubation owing to the patient's pronounced tachycardia after that episode. He was intubated at that point using etomidate and succinylcholine, and during and shortly after this procedure, he developed marked cardiac instability. The patient developed an irregular narrow complex tachycardia, which returned to sinus bradycardia fairly rapidly. Subsequently, he developed a pulseless, wide complex rhythm, but autoconverted before defibrillation was attempted. Laboratory results available at that time revealed a mild leukocytosis of 17.22 K/μL, a metabolic panel with mild hypokalemia (2.8 mmol/L), no significant acidosis (HCO3, 23 mmol/L), essentially unremarkable liver function tests, and pH 7.312 on the initial arterial blood gas. The urinalysis revealed only glucosuria and trace ketones, and the urine toxicology screen was positive only for benzodiazepines. Drug substance level testing remained pending. Given his hemodynamic and cardiac instability, a central line was placed for resuscitative purposes, to facilitate vasoactive medication administration, and for dialysis access. An arterial line, orogastric tube, and Foley catheter were also inserted. Continuous infusions of both phenylephrine and lidocaine were administered after loading boluses of each medication, and the patient's hemodynamic status stabilized very rapidly. A second EKG revealed significant improvement in the corrected QT interval and some resolution of the ST-segment changes that were previously evident (Fig. 2). The patient was admitted to the medical intensive care unit (MICU). Further laboratory values from the emergency department and the initial MICU acceptance included nondetectable
253.e4
Fig. 1
Case Report
Initial electrocardiogram demonstrating diffuse inferolateral ST-segment changes with a markedly prolonged QTc interval.
levels of ethanol, salicylates, acetaminophen, and lithium. A detectable but low level of theophylline (2.8 μg/mL; reference range, 10-20 μg/mL) was present, and a caffeine level added on to the initial blood work returned markedly increased at 72.5 μg/dL (reference range, 6.0-20.0 μg/dL). In the MICU, the patient was seen by nephrology and dialyzed, was able to be weaned off of vasopressors quickly, and was extubated approximately 1 day after admission. He was transferred to a medical floor and seen by psychiatry. Unfortunately, he absconded from the floor and has not followed up since. Caffeine, or 1,3,7-trimethylxanthine, is a very commonly ingested substance and has a wider therapeutic range than does its metabolite, theophylline. It is present in many substances, but its specific over-the-counter usage in stimulant products has been limited to 200 mg per dose since 1988 [1]. In overdose, the toxicologic effects of caffeine are related to its antagonism of adenosine receptors, inhibition of phosphodiesterase, and increase in intracellular calcium levels [2,3]. The oral route is the most common means of exposure, and caffeine is 100% bioavailable, with peak levels occurring between 30 to 60 minutes and 3 hours [4]. Caffeine toxicity generally affects the cardiovascular, gastrointestinal, neurologic, and musculoskeletal systems. Although sinus tachycardia is the most common rhythm disturbance, multiple arrhythmias have been reported, including bigeminy, supraventricular tachycardia, premature ventricular contractions, ventricular tachycardia, and ventricular fibrillation [5-9]. Cardiovascular collapse has also been noted in previous case reports [8,10]. Nausea and vomiting are common with caffeine overdoses as well and
may somewhat limit the potential toxicity via elimination of the parent compound [6,11]. Neurologic effects are common even with therapeutic levels of caffeine, but seizures can occur with poisonings [10,12]. Rhabdomyolysis, sometimes severe enough to cause acute renal failure, has also been reported in multiple cases [13,14]. The patient in this particular case did have significant nausea and vomiting along with altered mental status, but his marked cardiovascular instability was predominant in his clinical presentation. Multiple agents have been used to treat both the hemodynamic instability involved in massive caffeine ingestions and the proarrhythmic effects of the poisoning. Hypotension in caffeine overdose has been theorized to be multifactorial in etiology, with β2-receptor agonism causing peripheral vasodilatation and β1-receptor stimulation leading to profound tachycardia with incomplete diastolic filling time. It stands to reason that, although initially counterintuitive, β-blockers may directly act against these mechanisms and restore cardiovascular stability, and this has been borne out in cases of both caffeine and theophylline toxicity [6,15]. However, there is also a theoretical concern that unopposed alpha stimulation could lead to rampant hypertension and the sequelae thereof. Therefore, in this case, phenylephrine, a powerful α-receptor agonist, was chosen to increase peripheral vascular resistance and cause reflex bradycardia, both of which were beneficial effects in this patient. The patient experienced dramatic BP stabilization evident even with the loading bolus of phenylephrine. This therapy has been recommended for hemodynamic instability in caffeine poisoning in multiple sources, but to our knowledge, this
Case Report
253.e5
Fig. 2 Second EKG performed approximately 90 minutes after patient arrival and multiple rounds of treatment, revealing normalization of previous inferolateral ST changes and significant narrowing of the QTc interval.
is the first documented use, and this patient had overwhelmingly positive results [2,16]. With regard to this patient's myriad of cardiac rhythms, multiple efforts were made to remedy this instability. While atropine was to be attempted for his symptomatic bradycardia, and cardioversion for the episode of pulseless ventricular tachycardia, he spontaneously changed rhythms too quickly to allow either therapy to take place. As his BP stabilized with phenylephrine, both Advanced Cardiac Life Support and Pediatric Advanced Life Support would recommend amiodarone, procainamide, or lidocaine for his rhythm disturbances [17,18]. Given his baseline EKG findings (Fig. 1), specifically the significant QTc prolongation, use of amiodarone would be strongly cautioned against [19]. Procainamide, although its predominant electrocardiographic effect is related to QRS prolongation, also prolongs the QT interval, although it has been used successfully in caffeine ingestions previously [9,20]. Lidocaine was chosen in this case given the patient's significant QTc prolongation and electrophysiologic instability, and the patient had significant improvement in his hemodynamic profile with no further dysrhythmias after the bolus and infusion were given (Fig. 2). Dialysis was also required and was performed in our case in the MICU, and its benefits have been discussed in multiple previous case reports. Although the incidence of theophylline exposures has declined over the 1990s owing to fewer continuing prescriptions for the medication, the rate of caffeine exposures has remained fairly constant [2]. And although death from caffeine ingestion is rare, this case illustrates
the potential severity of massive caffeine ingestion, even in a young, previously healthy patient. To the best of our knowledge, this case represents the first documented use of phenylephrine as a treatment for hemodynamic instability and hypotension after massive caffeine overdose. Although lidocaine has been successfully used in mixed overdoses containing caffeine and has not been shown to be effective in a single murine study, this case illustrates significant cardiovascular improvement with its use in a pure caffeine overdose [21,22]. Both of these medications should be considered in the treatment of cardiovascular collapse secondary to methylxanthine poisoning. Rahi Kapur MD Department of Emergency Medicine MetroHealth Medical Center Cleveland, OH 44109, USA Case Western Reserve University Cleveland, OH 44109, USA E-mail address: [email protected] Michael D. Smith MD Department of Emergency Medicine MetroHealth Medical Center Cleveland, OH 44109, USA Case Western Reserve University Cleveland, OH 44109, USA E-mail address: [email protected] doi:10.1016/j.ajem.2008.06.028
253.e6
References [1] FDA. Stimulant drug products for over-the-counter human use; final monograph. FDA: Fed register 1988;53:6100. [2] Goldfrank LR, editor. Goldfrank's toxicologic emergencies. Chapter 39: methylxanthines. 7th ed. New York: McGraw-Hill; 2002. [3] Ford MD, Delaney KA, Ling LJ, Erickson T, editors. Clinical toxicology. Chapter 36: caffeine and other related nonprescription sympathomimetics. 1st ed. WB Saunders: Philadelphia; 2001. [4] Micromedex Healthcare series: Poisondex managements: caffeine. Thompson Healthcare. Accessed through MetroHealth Medical Center, 5/1/2008. [5] Nagesh RV, Murphy KA. Caffeine poisoning treated by hemoperfusion. Am J Kidney Dis 1988;12:316-8. [6] Price KR, Fligner DJ. Treatment of caffeine toxicity with esmolol. Ann Emerg Med 1990;19:44-6. [7] Forman J, Aizer A, Young CR. Myocardial infarction resulting from caffeine overdose in an anorectic woman. Ann Emerg Med 1997;29: 178-80. [8] Holstege CP, Hunter Y, Baer AB, Savory J, Bruns DE, Boyd JC. Massive caffeine overdose requiring vasopressin infusion and hemodialysis. J Toxicol Clin Toxicol 2003;41:1003-7. [9] Chopra A, Morrison L. Resolution of caffeine-induced complex dysrhythmia with procainamide therapy. J Emerg Med 1995;13:113-7. [10] Rouse A, Ford M, Kerns W. Rapid cardiac arrest following massive caffeine ingestion. J Toxicol Clin Toxicol 1999;37:629-30. [11] Dietrich AM, Mortensen ME. Presentation and management of an acute caffeine overdose. Pediatr Emerg Care 1990;6:296-8.
Case Report [12] Shum S, Seale C, Hathaway D, Chucovich V, Beard D. Acute caffeine ingestion fatalities: management issues. Vet Hum Toxicol 1997;39: 228-30. [13] Wrenn KD, Oschner I. Rhabdomyolysis induced by caffeine overdose. Ann Emerg Med 1989;18:94-7. [14] Kamijo Y, Soma K, Asari Y, Ohwada T. Severe rhabdomyolysis following massive ingestion of oolong tea: caffeine intoxication with coexisting hyponatremia. Vet Hum Toxicol 1999;41:381-3. [15] Seneff M, Scoot J, Freidman B, Smith M. Acute theophylline toxicity and the use of esmolol to reverse cardiovascular instability. Ann Emerg Med 1990;19:671-3. [16] Holstege CP, Dobmeier S. Cardiovascular challenges in toxicology. Emerg Med Clin North Am 2005;23:1195-217. [17] American Heart Association. ACLS provider manual. Dallas: AHA; 2002. [18] American Heart Association. PALS provider manual. Dallas: AHA; 2002. [19] Micromedex Healthcare series: Drugdex evaluations: amiodarone. Thompson Healthcare. Accessed through MetroHealth Medical Center, 5/13/2008. [20] Micromedex Healthcare series: Drugdex evaluations: procainamide. Thompson Healthcare. Accessed through MetroHealth Medical Center, 5/13/2008. [21] Zahn KA, Li RL, Purssell RA. Cardiovascular toxicity after ingestion of “herbal ecstasy”. J Emerg Med 1999;17:289-91. [22] Strubelt O, Diederich KW. Experimental treatment of the acute cardiovascular toxicity of caffeine. J Toxicol Clin Toxicol 1999;37: 29-33.