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Acquired Long QT Syndrome and Monomorphic Ventricular Tachycardia After Alternative Treatment With Cesium Chloride for Brain Cancer

      Individuals searching for symptomatic relief or a potential cure are increasingly seeking and using nontraditional therapies for their various diseases. Little is known about the potential adverse effects that patients may encounter while undergoing these alternative treatments. Cesium chloride is an unregulated agent that has been reported to have antineoplastic properties. Cesium chloride is advertised as an alternative agent for many different types of cancers and can be purchased easily on the Internet. Recently, QT prolongation and polymorphic ventricular tachycardia were reported in several patients taking cesium chloride as alternative treatment for cancer. We report acquired QT prolongation and sustained monomorphic ventricular tachycardia in a patient who self-initiated and completed a course of cesium chloride as adjunctive treatment for brain cancer.
      In recent years, patients have been increasingly interested in using complementary and alternative therapies for various medical conditions.
      • Eisenberg DM
      • Davis RB
      • Ettner SL
      • et al.
      Trends in alternative medicine use in the United States, 1990-1997: results of a follow-up national survey.
      • Kessler RC
      • Davis RB
      • Foster DF
      • et al.
      Long-term trends in the use of complementary and alternative medical therapies in the United States.
      • Cirigliano MD
      Overview of herbal medicine. UpToDate. Version 12.1.
      For the most part, federal agencies do not regulate the use of these treatments.
      • Cirigliano MD
      Overview of herbal medicine. UpToDate. Version 12.1.
      • Angell M
      • Kassirer J
      Alternative medicine—the risks of untested and unregulated remedies [editorial].
      • Olshansky B
      • Shivkumar K
      Patient—heal thyself? electrophysiology meets alternative medicine [editorial].
      They are widely advertised, marketed, and easily available to consumers through various means, including the Internet. Traditionally trained allopathic physicians frequently encounter patients who use alternative treatments, often without their knowledge. Acknowledging these treatments, understanding their mechanisms, and recognizing any serious adverse reactions and drug interactions due to unmonitored use are adding to the workload of physicians.
      Cesium chloride is a salt formed by the alkali metal cesium and chloride. Cesium is a group 1a element that has chemical properties similar to potassium, sodium, and lithium. Interest in cesium's antineoplastic properties arose through observations of lower rates of cancer in areas with a high concentration of alkali metals in the soil.
      • Brewer AK
      The high pH therapy for cancer tests on mice and humans.
      • Sartori HE
      Cesium therapy in cancer patients.
      • Sartori HE
      Nutrients and cancer: an introduction to cesium therapy.
      Cesium is thought to cause cancer cell death by increasing the relatively low intracellular pH of neoplastic cells.
      • Brewer AK
      The high pH therapy for cancer tests on mice and humans.
      A small observational study in the 1980s that reported reduction in tumor burden among patients with refractory cancer treated with cesium chloride sparked interest in this substance as alternative/adjunctive treatment for cancer.
      • Sartori HE
      Cesium therapy in cancer patients.
      • Sartori HE
      Nutrients and cancer: an introduction to cesium therapy.
      Adverse effects noted by the authors included nausea, diarrhea, paresthesias, and hypokalemia. Acquired long QT syndrome and ventricular tachyarrhythmias were not reported.
      Although cesium chloride has been used in animal research to induce QT prolongation and ventricular tachyarrhythmias, no reports of such electrocardiographic findings in humans were published until recently. Within the past several years, reports have described patients presenting with sudden syncope, prolonged QT interval, and episodes of polymorphic ventricular tachycardia after taking cesium chloride as alternative/adjunctive treatment for cancer.
      • Saliba W
      • Erdogan O
      • Niebauer M
      Polymorphic ventricular tachycardia in a woman taking cesium chloride.
      • Pinter A
      • Dorian P
      • Newman D
      Cesium-induced torsades de pointes [letter].
      • Lyon AW
      • Mayhew WJ
      Cesium toxicity: a case of self-treatment by alternate therapy gone awry.
      We report a case of cesium toxicity that clearly documents an acquired long QT syndrome and that we hope will expand the list of observed ventricular tachyarrhythmias to include monomorphic ventricular tachycardia. More importantly, we hope this case illustrates the potential serious health hazards for patients who seek unregulated alternatives/adjuncts to conventional medical treatments.

      REPORT OF A CASE

      A 43-year-old woman who recently underwent resection of a brain neoplasm presented to the emergency department after sustaining 2 brief, witnessed seizures, followed by return of consciousness. On arrival, she sustained another brief seizure while undergoing triage. She collapsed subsequently and was unresponsive. She had no pulse; her initial cardiac rhythm was ventricular tachycardia (Figure 1). A 200 J electrical shock was administered, which led to resumption of normal sinus rhythm and circulation. The patient underwent intubation for airway protection. Intravenous lorazepam, mannitol, and dexamethasone were administered for suspected seizure activity and elevated intracranial pressure. Two subsequent episodes of sustained ventricular tachycardia were externally defibrillated at 200 J, and intravenous lidocaine was initiated after the third episode. On admission, an electrocardiogram showed a corrected QT (QTc) of 624 milliseconds (Figure 2). Initial potassium and magnesium levels were 3.1 mEq/L and 1.7 mg/dL, respectively. She was treated with intravenous magnesium and potassium and admitted to the medical intensive care unit for further evaluation and treatment.
      Figure thumbnail gr1
      FIGURE 1Initial electrocardiogram showing monomorphic ventricular tachycardia.
      Figure thumbnail gr2
      FIGURE 2Admission electrocardiogram showing a corrected QT of 624 milliseconds 10 days after treatment with cesium chloride (9 g/d).
      About 3 weeks before the patient presented to our institution, a glioblastoma multiforme was diagnosed, and she underwent resection of her right temporal lobe. The preoperative electrocardiogram showed a QTc of 446 milliseconds (Figure 3). At that time, her potassium and magnesium levels were 4.2 mEq/L and 2.4 mg/dL, respectively.
      Figure thumbnail gr3
      FIGURE 3Preoperative electrocardiogram before treatment with cesium chloride showing a corrected QT of 446 milliseconds.
      The patient's medical history was remarkable for hypertension, gastroesophageal reflux, irritable bowel syndrome, and migraines. She had no history of cardiovascular disease or syncope and no family history of long QT syndrome or sudden death. Her prescription medications at admission included levetiracetam, dexamethasone, metoprolol, hydrochlorothiazide-triamterene, esomeprazole, alprazolam, and prochlorperazine. After surgery, the patient researched alternative/adjunctive treatments for cancer on the Internet and self-initiated a 10-day course of cesium chloride (9 g/d) and supplemental potassium chloride. She completed this regimen 1 day before admission. She noted the development of watery diarrhea, abdominal discomfort, nausea, and vomiting during the course of her treatment. She reported no syncopal events before admission.
      In the medical intensive care unit, the patient received intravenous lidocaine for approximately 18 hours. Her magnesium and potassium levels were repleted intravenously. Valproic acid was administered intravenously for seizure prophylaxis. An echocardiogram revealed normal ventricular function without evidence of structural heart disease. Neurologic evaluation showed no evidence of critically elevated intracranial pressure or recurrent seizure activity. The patient underwent extubation and was transferred to a telemetry unit for further monitoring, electrolyte repletion, and seizure prophylaxis. The QTc remained prolonged during the next several days despite electrolyte repletion and normalization. The serum cesium level was 11,000 µg/dL (reference range, <27 µg/dL, National Medical Laboratories). She had no further episodes of ventricular tachyarrhythmias or ectopy during hospitalization. The diarrhea had diminished substantially before discharge. At discharge, the patient was taking oral medications, including potassium chloride, magnesium oxide, valproic acid, and levetiracetam. Use of cesium chloride was discontinued.
      The patient was reevaluated approximately 2 weeks after discharge. She denied having any additional syncopal events. She continued to take potassium and magnesium supplements as prescribed. The QTc remained prolonged, although it was shorter than on admission. A whole blood cesium level at this time was 16,000 µg/dL (reference range, <27 µg/dL, National Medical Laboratories). At a third follow-up visit approximately 6 weeks after initial presentation, the serum cesium level was 1600 µg/dL, and the whole blood cesium level was 6100 µg/dL. The QTc had shortened to within normal limits. The patient denied taking additional cesium chloride. The time course of serum and whole blood cesium clearance and QTc is shown in Figure 4.

      DISCUSSION

      In this case of acquired long QT syndrome and sustained monomorphic ventricular tachycardia in a patient taking extremely high doses of cesium chloride as adjunctive treatment for brain cancer, we provide direct evidence for a temporal relationship between cesium chloride therapy and abnormal repolarization. Fortuitously, we obtained an electrocardiogram that documented a normal QTc before the patient self-initiated treatment with cesium chloride. Unlike previous reports, we monitored the QTc and the serum and whole blood cesium levels at additional time points until the QTc returned to normal. Our patient had sustained monomorphic ventricular tachycardia that required direct cardioversion, which to our knowledge has not been reported previously. Published reports have shown episodes of self-limited polymorphic ventricular tachycardia and/or torsades de pointes.
      • Saliba W
      • Erdogan O
      • Niebauer M
      Polymorphic ventricular tachycardia in a woman taking cesium chloride.
      • Pinter A
      • Dorian P
      • Newman D
      Cesium-induced torsades de pointes [letter].
      • Lyon AW
      • Mayhew WJ
      Cesium toxicity: a case of self-treatment by alternate therapy gone awry.
      Interestingly, no episodes of polymorphic ventricular tachycardia were noted in the emergency department or during subsequent monitoring of our patient in a telemetry unit.

      Acquired Long QT Syndrome

      Cesium inhibits potassium currents in myocardial cells and has been used in several animal studies to induce QT prolongation to assess for ventricular tachycardia and/or torsades de pointes.
      • Gay LA
      • Stanfield PR
      Cs+ causes a voltage-dependent block of inward K currents in resting skeletal muscle fibres [letter].
      • Levine JH
      • Spear JF
      • Guarnieri T
      • et al.
      Cesium chloride-induced long QT syndrome: demonstration of afterdepolarizations and triggered activity in vivo.
      • Patterson E
      • Szabo B
      • Scherlag BJ
      • Lazzara R
      Early and delayed afterdepolarizations associated with cesium chloride-induced arrhythmias in the dog.
      • Nayebpour M
      • Nattel S
      Pharmacologic response of cesium-induced ventricular tachyarrhythmias in anesthetized dogs.
      In previously reported cases of cesium toxicity in humans, syncope, hypokalemia, prolonged QT interval, and episodes of self-limited polymorphic ventricular tachycardia were documented. In 2 of the 3 case reports, an elevated serum or whole blood level of cesium was documented.
      • Pinter A
      • Dorian P
      • Newman D
      Cesium-induced torsades de pointes [letter].
      • Lyon AW
      • Mayhew WJ
      Cesium toxicity: a case of self-treatment by alternate therapy gone awry.
      One case report showed normalization of the QTc over several weeks after cessation of oral cesium chloride intake; however, clearance of cesium was not documented.
      • Saliba W
      • Erdogan O
      • Niebauer M
      Polymorphic ventricular tachycardia in a woman taking cesium chloride.
      We clearly showed prolongation of the QT interval after initiation of cesium chloride therapy in the absence of other known factors associated with an acquired long QT syndrome. This prolongation corresponds temporally to patient-initiated treatment with cesium chloride. Furthermore, we found a direct correlation between the QTc and serum and whole blood cesium clearance (Figure 4). Hypokalemia and/or hypomagnesemia are unlikely explanations for the prolonged QTc because QT prolongation persisted despite active repletion and normalization of potassium and magnesium.
      Figure thumbnail gr4
      FIGURE 4Time course of serum and whole blood cesium clearance and corrected QT (QTc) after discontinuation of cesium chloride therapy.

      Ventricular Tachyarrhythmias

      We propose that monomorphic ventricular tachycardia may be an additional arrhythmia associated with cesium chloride toxicity in humans. Previous animal studies of ventricular tachyarrhythmias and cesium-induced QT prolongation reported sustained monomorphic ventricular tachycardia.
      • Bailie DS
      • Inoue H
      • Kaseda S
      • Ben-David J
      • Zipes DP
      Magnesium suppression of early afterdepolarizations and ventricular tachyarrhythmias induced by cesium in dogs.
      • Senges JC
      • Sterns LD
      • Freigang KD
      • et al.
      Cesium chloride induced ventricular arrhythmias in dogs: three-dimensional activation patterns and their relation to the cesium dose applied.
      To date, no previous reports have documented this type of ventricular tachyarrhythmia associated with cesium in humans. However, in one previous report, the authors described a prolonged episode of ventricular tachycardia that required direct cardioversion
      • Saliba W
      • Erdogan O
      • Niebauer M
      Polymorphic ventricular tachycardia in a woman taking cesium chloride.
      ; perhaps this case represents a sustained monomorphic ventricular tachycardia associated with cesium toxicity.
      We found a sustained, refractory monomorphic ventricular tachycardia associated with a highly elevated cesium level (Figure 1). Direct cardioversion was used 3 times; ultimately, intravenous lidocaine was necessary to stabilize the patient's arrhythmia. Unfortunately, given the acute and critical nature of this case, we were able to document ventricular tachycardia in only 1 lead; therefore, we cannot absolutely exclude polymorphic ventricular tachycardia as a possibility because it can appear monomorphic in a single lead. Nevertheless, our observations suggest that the type of arrhythmia seen in this patient is most likely a monomorphic ventricular tachycardia developing from an abnormal ventricular focus. We conclude that cesium toxicity could trigger focal ventricular automaticity, resulting in sustained monomorphic ventricular tachycardia.
      Curiously, episodes of self-limited polymorphic ventricular tachycardia were not seen in our patient. In previous cases these arrhythmias were noted in the context of severe hypokalemia (serum potassium level, <3.2 mEq/ L).
      • Saliba W
      • Erdogan O
      • Niebauer M
      Polymorphic ventricular tachycardia in a woman taking cesium chloride.
      • Pinter A
      • Dorian P
      • Newman D
      Cesium-induced torsades de pointes [letter].
      • Lyon AW
      • Mayhew WJ
      Cesium toxicity: a case of self-treatment by alternate therapy gone awry.
      Hypokalemia due to cesium toxicity is thought to develop as a consequence of gastrointestinal losses and cesium-mediated inhibition of renal reabsorption of potassium.
      • Lyon AW
      • Mayhew WJ
      Cesium toxicity: a case of self-treatment by alternate therapy gone awry.
      Self-limited polymorphic ventricular tachycardia (such as torsades de pointes) typically presents as recurrent syncope in the context of a prolonged QT interval and associated electrolyte abnormalities; it tends to be self-limited and usually does not require cardioversion. Early afterdepolarizations, the development of which is potentiated by hypokalemia and hypomagnesemia, are thought to be the initiating mechanism of ventricular ectopy and polymorphic ventricular tachycardia. Our patient reported no episodes of true syncope before presentation to the emergency department. However, we cannot entirely exclude the possibility that the reported seizure activity was secondary to self-limited polymorphic ventricular tachycardia. Nevertheless, no episodes of polymorphic ventricular tachycardia were noted while the patient was being monitored in a telemetry unit during hospitalization. Also, in the weeks after discharge, the patient experienced no additional syncopal events despite persistently elevated serum and whole blood cesium levels and prolongation of the QT interval. Perhaps active electrolyte repletion (our patient had been taking potassium supplements during her 10-day course of cesium chloride and was receiving oral potassium and magnesium supplementation well after discontinuation of cesium chloride therapy) suppressed the development of early afterdepolarizations and hence suppressed the initiation of ventricular ectopy and polymorphic ventricular tachycardia. In fact, electrolyte correction has been shown to suppress early afterdepolarizations and ventricular tachyarrhythmias (ventricular ectopy and polymorphic ventricular tachycardia) induced by cesium chloride in dogs.
      • Bailie DS
      • Inoue H
      • Kaseda S
      • Ben-David J
      • Zipes DP
      Magnesium suppression of early afterdepolarizations and ventricular tachyarrhythmias induced by cesium in dogs.
      Therefore, clinicians should recommend potassium and magnesium repletion as well as frequent electrolyte monitoring in any patient known to be undergoing or to have undergone self-treatment with cesium chloride.

      Cesium Chloride—A Potentially Dangerous Alternative Therapy for Cancer

      Several reports within the past 2 years have clearly documented ventricular tachyarrhythmias associated with cesium chloride in patients seeking alternative/adjunctive treatment for cancer.
      • Saliba W
      • Erdogan O
      • Niebauer M
      Polymorphic ventricular tachycardia in a woman taking cesium chloride.
      • Pinter A
      • Dorian P
      • Newman D
      Cesium-induced torsades de pointes [letter].
      • Lyon AW
      • Mayhew WJ
      Cesium toxicity: a case of self-treatment by alternate therapy gone awry.
      As in previous reports, our patient researched and obtained cesium chloride on the Internet. Using the Google search engine and the key words cesium chloride, we found multiple Web sites (we have referenced only a few) that either provided information on or advertised cesium chloride as alternative/adjunctive treatment for different types of cancer.

      New liquid ionic cesium chloride. Essense-of-life.com Web site Available at: www.essense-of-life.com/info/cesium.htm Accessibility verified June 16, 2004.

      However, we found little or no acknowledgment of ventricular tachyarrhythmias as a potentially serious complication during treatment, probably because it has remained relatively underrecognized and perhaps even unrecognized until recently. Moreover, because this alternative therapy is unregulated and easily purchased, its unrestricted use will likely result in more adverse events, additional morbidity, and perhaps even premature death. We therefore encourage any establishment providing information on cesium chloride for alternative medical purposes to report prolongation of the QT interval and ventricular tachyarrhythmias as possible serious adverse effects. We also recommend that physicians maintain a high degree of suspicion for cesium toxicity in any patient (particularly those with cancer diagnoses) presenting with syncope, unexplained ventricular tachyarrhythmias, and a long QT interval.

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          With the engines of modern industry and the medical community constantly promising or producing one miracle treatment after another, it is ironic that many of the greatest impediments to improved medical care and health, in both industrialized and developing nations, evolve around issues of access, education, distribution, compliance, and cost. At one extreme, those who have absolute financial or access obstruction to health care can expect to reap the downstream consequences of malnutrition, hypertension, diabetes, infections, and other conditions.
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        Mayo Clinic ProceedingsVol. 79Issue 9
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          Incorrect figure placement: In the article by Dalal et al entitled “Acquired Long QT Syndrome and Monomorphic Ventricular Tachycardia After Alternative Treatment With Cesium Chloride for Brain Cancer,” published in the August 2004 issue of the Mayo Clinic Proceedings (Mayo Clin Proc. 2004;79:1065-1069), Figures 2 and 3 were transposed. The illustration above the Figure 2 legend on page 1066 is Figure 3, and the illustration above the Figure 3 legend on page 1067 is Figure 2.
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