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Herbal syncope: ginger-provoked bradycardia
American Journal of Emergency Medicine (2012) 30, 386.e5–386.e7
www.elsevier.com/locate/ajem
Case Report Herbal syncope: ginger-provoked bradycardia Abstract Herbal therapies are widely used in Turkey. Especially, ginger is mostly recommended to patients with symptoms of flu by their relatives. A 59-year-old woman was admitted to the emergency department (ED) because of sudden loss of consciousness. She was recommended ginger for the relief of flu symptoms. As a result of diagnostic and laboratory evaluation, the probable cause of syncope was ginger usage. This case demonstrated that sometimes herbal therapies are harmful and clinicians must be reminded of this effect. Ginger (Zingiber officinale Roscoe, Zingiberaceae) is a world-known spice plant and has been used traditionally in a therapy of variety of diseases. Ginger cultivation began in South Asia and has since spread to East Africa and the Caribbean [1]. It is sometimes called root ginger to distinguish it from other things that share the name ginger. Ginger is reported to have anti-inflammatory, analgesic, antipyretic, antimicrobial, hypoglycemic, antimigraine, antioxidant, hepatoprotective, hypocholesterolemic, and antithrombotic effects [2]. In addition, ginger has hypoglycemic effect [3]. Especially, in Turkey, ginger is widely used to treat flu. In this case, we present a rare and harmful effect of ginger causing symptomatic bradycardia and syncope. A 59-year-old woman was admitted to the emergency department (ED) because of sudden loss of consciousness. She also had an episode of nausea. On admission to the ED, the patient was hypotensive (baseline blood pressure [BP] was 80/50 mm Hg), and resting 12-lead electrocardiogram revealed sinus bradycardia (45 beats/min) and first-degree atrioventricular block (Fig. 1). The patient was on antihypertensive medication (telmisartan plus hydrochlorothiazide of 80/12.5 mg) and had no previous history of coronary artery disease. She had no signs of dehydration (eg, dry mucus membranes and poor capillary refill). Baseline laboratory levels, that is, electrolytes and complete blood cell count, were within normal values. To rule out cardiac ischemic event, cardiac enzymes (creatinine phosphokinase MB fraction and troponin I) were obtained and showed normal limits. The patient used a cup (150 mg) of ginger 0735-6757/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
3 times daily for 5 days because of flu (influenza-like illness). She got the ginger from a local grower. To make sure of the use of ginger, we have accessed to the product she took and identified it as a ginger. Current status of the patient was likely considered to be related to ginger usage. Because of symptomatic bradycardia, she was followed in coronary care unit and hydrated. After hydration therapy, normal sinus rhythm with 75 beats/min was restored and BP normalized. Also, because the patient was hemodynamic, a transient pacemaker implantation was not requested. Bedside echocardiography showed normal ventricular contraction (ejection fraction of 65%) without any valve diseases. To exclude sinus node pathology, 24-hour Holter monitor was recorded and revealed normal sinus rhythm of 107 beats/min without signs of sinus node dysfunction. The patient was discharged 2 days after admission to our clinic. Ginger has been used since the ancient times as a beneficial herbal therapy for gastrointestinal disorders, pulmonary infections, lipid metabolism disturbances, and hypertension [2]. The use of ginger in cardiovascular diseases has long been known. Ginger has a diuretic [3] and BP-lowering effects [4]. Miller and Kazal [5] reported that ginger may lower BP through blockade of voltagedependent calcium channels. Also, Ghayur and Gilani [6] found that ginger can cause a triad such as rapid fall in BP, bradycardia, and apnea in rats. All trials on ginger effect have been investigated in laboratory animals, especially in rats. There are no data indicating the BP- and heart ratelowering effects of ginger in humans. With regard to bradycardia, the possible mechanism was related to a negative inotropic and chronotropic effect and also to a vasodilator effect through specific blockade of the voltagedependent calcium channels [5]. Elkhishin and Awwad [1] showed that ginger in a dose of 500 mg/kg produces both hypotension and bradycardia in rats. These effects of ginger may be partially due to induction of vasodilatation by increasing nitric oxide release or synthesis and partially due to voltage-dependent calciumchannel blocking effect [7]. In the present case, possible cause of bradycardia was related to ginger use. Also, as a consequence of rapid BP lowering (hypotension), the patient may have loss consciousness. Although ginger is a hypotensive and bradycardic in rats at high doses (2500 mg/kg), our patient
386.e6
Case Report
Fig. 1 Twelve-lead electrocardiogram showing a first-degree atrioventricular block and sinus bradycardia (45 beats per minute). Note that PR duration is 280 milliseconds.
have used ginger at 450 mg daily for 5 days. Also, there are no data showing bradycardic and hypotensive effects of ginger in humans. To the best of our knowledge and search of the literature, this is a first case presenting hypotension and symptomatic bradycardia due to ginger therapy. In conclusion, because ginger is hypotensive and bradycardic at high doses, it must be used with caution in normotensive persons. If ginger produce hypotension and bradycardia in high dose, there should be caution on taking ginger as treatment of flu. Further studies on humans need to determine whether ginger can be effective in the treatment of hypertension and tachycardia. Emergency physicians, cardiologists, and internal medicine practitioners should be aware of herbal cardiotoxic effects in cases with unexplained disturbances.
Enes Elvin Gul MD Halil I. Erdogan MD Murat Erer MD Mehmet Kayrak MD Department of Cardiology Meram School of Medicine Selcuk University, Konya, Turkey E-mail address: [email protected] doi:10.1016/j.ajem.2010.12.009
References [1] Elkhishin IA, Awwad IA. A study of the cardiovascular toxic effects of Zingiber officınale (ginger) in adult male albino rats and its possible
Case Report mechanisms of action. Mansoura J Forensic Med Clin Toxicol 2009;2: 109-16 (http://www.mans.edu.eg/FacMed/english/forensic/july2009/ s8.htm). [2] Langner E, Greifenberg S, Gruenwald J. Ginger: history and use. Adv Ther 1998;15:25-44. [3] Sharma M, Shukla S. Hypoglycaemic effect of ginger. J Res Indian Yoga Homoeopath 1977;12:127-30. [4] Gilani AH, Ghayur MN (2005). Ginger: from myths to reality. In: Gottschalk-Batschkus, C.E., Green, J.C. (Eds.), Ethnotherapies in the cycle of life. BOD - Books on Demand / Ethnomed Institut für Ethnomedizin e.V., Munich, pp. 307-15
386.e7 [5] Miller LG, Kazal LA. Herbal medications, nutraceuticals and hypertension. In: Miller LG, Murray WJ, editors. Herbal medicinals—a clinician's guide. New York (NY): Pharmaceutical Products Press; 1998. p. 135-62. [6] Ghayur MN, Gilani AH. Ginger lowers blood pressure through blockade of voltage-dependent calcium channels. J Cardiovasc Pharmacol 2005;45:74-80. [7] Suekawa M, Sone H, Sakakibra I, Ikeya Y, Aburada M, Hosoya E. Pharmacological studies on ginger. V. Pharmacological comparison between (6)-shogalol and capsaicin. Nippon Yakurigaku Zasshi 1986;88:339-47.
www.elsevier.com/locate/ajem
Case Report Herbal syncope: ginger-provoked bradycardia Abstract Herbal therapies are widely used in Turkey. Especially, ginger is mostly recommended to patients with symptoms of flu by their relatives. A 59-year-old woman was admitted to the emergency department (ED) because of sudden loss of consciousness. She was recommended ginger for the relief of flu symptoms. As a result of diagnostic and laboratory evaluation, the probable cause of syncope was ginger usage. This case demonstrated that sometimes herbal therapies are harmful and clinicians must be reminded of this effect. Ginger (Zingiber officinale Roscoe, Zingiberaceae) is a world-known spice plant and has been used traditionally in a therapy of variety of diseases. Ginger cultivation began in South Asia and has since spread to East Africa and the Caribbean [1]. It is sometimes called root ginger to distinguish it from other things that share the name ginger. Ginger is reported to have anti-inflammatory, analgesic, antipyretic, antimicrobial, hypoglycemic, antimigraine, antioxidant, hepatoprotective, hypocholesterolemic, and antithrombotic effects [2]. In addition, ginger has hypoglycemic effect [3]. Especially, in Turkey, ginger is widely used to treat flu. In this case, we present a rare and harmful effect of ginger causing symptomatic bradycardia and syncope. A 59-year-old woman was admitted to the emergency department (ED) because of sudden loss of consciousness. She also had an episode of nausea. On admission to the ED, the patient was hypotensive (baseline blood pressure [BP] was 80/50 mm Hg), and resting 12-lead electrocardiogram revealed sinus bradycardia (45 beats/min) and first-degree atrioventricular block (Fig. 1). The patient was on antihypertensive medication (telmisartan plus hydrochlorothiazide of 80/12.5 mg) and had no previous history of coronary artery disease. She had no signs of dehydration (eg, dry mucus membranes and poor capillary refill). Baseline laboratory levels, that is, electrolytes and complete blood cell count, were within normal values. To rule out cardiac ischemic event, cardiac enzymes (creatinine phosphokinase MB fraction and troponin I) were obtained and showed normal limits. The patient used a cup (150 mg) of ginger 0735-6757/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
3 times daily for 5 days because of flu (influenza-like illness). She got the ginger from a local grower. To make sure of the use of ginger, we have accessed to the product she took and identified it as a ginger. Current status of the patient was likely considered to be related to ginger usage. Because of symptomatic bradycardia, she was followed in coronary care unit and hydrated. After hydration therapy, normal sinus rhythm with 75 beats/min was restored and BP normalized. Also, because the patient was hemodynamic, a transient pacemaker implantation was not requested. Bedside echocardiography showed normal ventricular contraction (ejection fraction of 65%) without any valve diseases. To exclude sinus node pathology, 24-hour Holter monitor was recorded and revealed normal sinus rhythm of 107 beats/min without signs of sinus node dysfunction. The patient was discharged 2 days after admission to our clinic. Ginger has been used since the ancient times as a beneficial herbal therapy for gastrointestinal disorders, pulmonary infections, lipid metabolism disturbances, and hypertension [2]. The use of ginger in cardiovascular diseases has long been known. Ginger has a diuretic [3] and BP-lowering effects [4]. Miller and Kazal [5] reported that ginger may lower BP through blockade of voltagedependent calcium channels. Also, Ghayur and Gilani [6] found that ginger can cause a triad such as rapid fall in BP, bradycardia, and apnea in rats. All trials on ginger effect have been investigated in laboratory animals, especially in rats. There are no data indicating the BP- and heart ratelowering effects of ginger in humans. With regard to bradycardia, the possible mechanism was related to a negative inotropic and chronotropic effect and also to a vasodilator effect through specific blockade of the voltagedependent calcium channels [5]. Elkhishin and Awwad [1] showed that ginger in a dose of 500 mg/kg produces both hypotension and bradycardia in rats. These effects of ginger may be partially due to induction of vasodilatation by increasing nitric oxide release or synthesis and partially due to voltage-dependent calciumchannel blocking effect [7]. In the present case, possible cause of bradycardia was related to ginger use. Also, as a consequence of rapid BP lowering (hypotension), the patient may have loss consciousness. Although ginger is a hypotensive and bradycardic in rats at high doses (2500 mg/kg), our patient
386.e6
Case Report
Fig. 1 Twelve-lead electrocardiogram showing a first-degree atrioventricular block and sinus bradycardia (45 beats per minute). Note that PR duration is 280 milliseconds.
have used ginger at 450 mg daily for 5 days. Also, there are no data showing bradycardic and hypotensive effects of ginger in humans. To the best of our knowledge and search of the literature, this is a first case presenting hypotension and symptomatic bradycardia due to ginger therapy. In conclusion, because ginger is hypotensive and bradycardic at high doses, it must be used with caution in normotensive persons. If ginger produce hypotension and bradycardia in high dose, there should be caution on taking ginger as treatment of flu. Further studies on humans need to determine whether ginger can be effective in the treatment of hypertension and tachycardia. Emergency physicians, cardiologists, and internal medicine practitioners should be aware of herbal cardiotoxic effects in cases with unexplained disturbances.
Enes Elvin Gul MD Halil I. Erdogan MD Murat Erer MD Mehmet Kayrak MD Department of Cardiology Meram School of Medicine Selcuk University, Konya, Turkey E-mail address: [email protected] doi:10.1016/j.ajem.2010.12.009
References [1] Elkhishin IA, Awwad IA. A study of the cardiovascular toxic effects of Zingiber officınale (ginger) in adult male albino rats and its possible
Case Report mechanisms of action. Mansoura J Forensic Med Clin Toxicol 2009;2: 109-16 (http://www.mans.edu.eg/FacMed/english/forensic/july2009/ s8.htm). [2] Langner E, Greifenberg S, Gruenwald J. Ginger: history and use. Adv Ther 1998;15:25-44. [3] Sharma M, Shukla S. Hypoglycaemic effect of ginger. J Res Indian Yoga Homoeopath 1977;12:127-30. [4] Gilani AH, Ghayur MN (2005). Ginger: from myths to reality. In: Gottschalk-Batschkus, C.E., Green, J.C. (Eds.), Ethnotherapies in the cycle of life. BOD - Books on Demand / Ethnomed Institut für Ethnomedizin e.V., Munich, pp. 307-15
386.e7 [5] Miller LG, Kazal LA. Herbal medications, nutraceuticals and hypertension. In: Miller LG, Murray WJ, editors. Herbal medicinals—a clinician's guide. New York (NY): Pharmaceutical Products Press; 1998. p. 135-62. [6] Ghayur MN, Gilani AH. Ginger lowers blood pressure through blockade of voltage-dependent calcium channels. J Cardiovasc Pharmacol 2005;45:74-80. [7] Suekawa M, Sone H, Sakakibra I, Ikeya Y, Aburada M, Hosoya E. Pharmacological studies on ginger. V. Pharmacological comparison between (6)-shogalol and capsaicin. Nippon Yakurigaku Zasshi 1986;88:339-47.