Cardiovasc Toxicol DOI 10.1007/s12012-015-9310-6
Cardiac Effects of Mad Honey Poisoning and Its Management in Emergency Department: A Review from Turkey Ali Kemal Erenler
Ó Springer Science+Business Media New York 2015
Abstract Mad honey poisoning occurs when honey containing grayanotoxin is digested. The most common clinical signs and symptoms of poisoning involve findings of digestive system irritation, severe bradycardia and hypotension and central nervous system reaction. In this review, we aimed to underline the cardiac effects of mad honey poisoning. We also aimed to raise the awareness of physicians about early diagnosis and treatment of this rare entity. Keywords Mad honey poisoning Cardiac effects Emergency department
Introduction Mad honey is obtained from Rhododendron ponticum and Luteum species of Rhododendron plant family [1]. When honey containing grayanotoxin is ingested, mad honey poisoning develops [2]. Several plants of the Ericaceae (e.g., Rhododendron, Pieris, Agarista and Kalmia) family produce grayanotoxins which can cause poisoning among humans. Grayanotoxins are a family of lipid-soluble toxins of nitrogen-free polyhydroxy cyclic hydrocarbons and are known to occur in honey produced from the nectar of Rhododendrons. As far as is known, there are 18 forms of grayanotoxins. Grayanotoxins such as grayanotoxin I–IV are a unique class of toxic diterpenoids which are polyhydroxylated cyclic hydrocarbons that do not contain
A. K. Erenler (&) Department of Emergency Medicine, Samsun Education and Research Hospital, Barıs¸ Bulvarı Kadıko¨y Mahallesi No: 199, I˙lkadım, 55090 Samsun, Turkey e-mail: [email protected]
nitrogen. The main isomer responsible for toxic effects in Rhododendron is grayanotoxin III [3–8]. Grayanotoxin II is responsible for suppression of the spontaneous beating of the sinoatrial node. The possible mechanism of this effect was attributed to depolarization caused by GTX II, owing to inflow of Na ions, which in turn produces inactivation of the slow inward current and as the slow inward current becomes small, the activation of the outward current may be reduced [9]. In summary, grayanotoxin binds to sodium channels in the cell membrane, which are involved in voltage-dependent activation and inactivation, and it prevents inactivation [10]. Plants containing grayanotoxin grow in the eastern parts of the Black Sea Region of Turkey. There are reports from different parts of the world such as South America, Europe and Japan [11]. There are also reports from Spain, Portugal, Brazil, USA and Nepal in the literature [1]. Historically, it was first identified by Xenophon, a historian and army commander in Athens [12]. The symptoms of poisoning from this substance, also known as mad or bitter honey, are dose dependent and appear after a specific length of time [2]. However, the symptoms of toxicity may occur with the consumption of a small amount of honey [8].The typical clinical manifestations of poisoning involve findings of digestive system irritation, severe bradycardia and hypotension and central nervous system reaction [13]. Clinically, grayanotoxin in low doses causes dizziness, hypotension and bradycardia; high doses cause impaired consciousness, syncope, AV block and asystole due to vagal stimulation [14]. In this review, we aimed to focus on cardiac effects of mad honey poisoning. Cardiac effects may be lethal when untreated. Early detection and treatment in the Emergency department (ED) are essential to reduce morbidity and mortality.
123
Cardiovasc Toxicol
Cardiac Effects of Mad Honey Poisoning
70/40 mmHg. An ECG has revealed atrial fibrillation with slow ventricular response. The patient suffered chest pain, and therefore, a broad cardiac testing was performed. The cardiac enzyme was normal in follow-up, and echocardiographic and angiographic examination was normal. After 48-h hospitalization, the patient was discharged [20]. Bayram et al. [21] also reported a case of a patient developing atrial fibrillation with a slow ventricular response after ingestion of honey containing grayanotoxin.
Bradycardia
Asystole
Typical symptoms of mad honey poisoning are known to be fatigue, nausea, dizziness, bradycardia and hypotension [8]. In a study with 42 patients, Okuyan et al. reported that majority of the patients had sinus bradycardia followed by complete atrioventricular (AV) block and nodal rhythm. All of the patients were treated symptomatically and none of them needed pacing [15]. In another study, with a proportion of 91 %, bradycardia was the most common finding among poisoned patients [16]. In another study with 47 patients presented to three different institutions due to mad honey poisoning, patient rhythms on arrival were determined as sinus bradycardia, nodal rhythm, normal sinus rhythm and complete AV block, respectively, [17]. In a case series, Turedi et al. as well determined that the largest proportion of patients suffered bradycardia [18]. In another study, 30 patients were reported to be admitted to an emergency service due to mad honey poisoning in a 1-year period. The most common symptoms and findings were low blood pressure and bradycardia [19]. In a study by Yaylaci et al., it was reported that in the evaluation of the heart rhythms of the patients of 16 patients on admission to the emergency room, nine patients had sinus bradycardia, three patients had nodal rhythm, two patients had first degree AV block and two patients had atrial fibrillation. Patients were treated with atropin and saline. All of the patients were discharged with total recovery [8].
In a report, Gunduz et al. presented a patient admitted to ED due to dizziness and syncope after honey ingestion. On admission, his blood pressure was 160/60 mm Hg, and pulse rate was 75 beats/min. While ECG was being administered, a sudden bradycardia followed by asystole occured. After atropine administration in the ED, patient was transferred for catheterization, and a pacemaker was applied. After 3 days of follow-up, the pacemaker was removed, and the patient was discharged [12].
Materials and Methods The MEDLINE/PubMed database was searched for publications with the medical subject heading ‘‘mad honey’’ and ‘‘cardiac effects’’. Research articles, case reports, case series and reviews from Turkey were selected and investigated.
Atrial Fibrillation In a case study, a 70-year-old patient presented to ED with weakness, palpitation, nausea and vomiting after eating a small amount of honey. On admission, an ECG was performed and revealed paroxysmal atrial fibrillation and intermittent left bundle branch block. After 6 h of symptomatic treatment, his rhythm returned to a normal sinus rhythm [3]. In another case report, a 54-year-old patient was admitted to ED with complaints of nausea, vomiting, dizziness and chest pain beginning approximately two hours after honey ingestion. On physical examination, it was determined that patient was conscious, cooperative, with a heart rate of 40 beats/min and blood pressure of
123
Atrioventricular Block Two hours after honey consumption, a patient was transferred to a university ED with complaints of lightheadedness, cold sweating, dizziness, nausea, asthenia and discomfort in epigastric region. Vital signs of the patient were as follows: arterial blood pressure: 70/50 mmHg and with a pulse rate: 44 per minute. On the patient’s ECG taken, AV complete block was determined. Patients were treated with atropine and asline infusion in the ED. After admission to Intensive care unit, patient was discharged after 24 h [1]. In another report by Cagli et al., a 48-yearold patient presented to an ED due to syncope. It was reported that atropine was administered by the paramedics and his syncope had resolved before arrival to the hospital. Initial electrocardiography of the patient revealed complete AV block, with a ventricular rate of 31 beats/min. After 2 h, normal sinus rhythm was obtained [10]. Acute Myocardial Infarction Yarlioglues et al. reported that a husband and his wife presented to ED due to confusion and chest pain after eating honey. They were both hypotensive. Their ECGs revealed complete AV block, a ventricular rate of 42 beats/ min, and ST-segment elevation in the inferior leads in the man and AV nodal rhythm, a ventricular rate of 42 beats/ min, and ST-segment elevation in the inferior leads in the woman. After atropin administration, hypotension and STsegment elevation in both patients resolved. Coronary angiography results were normal in both patients [14]. In a
Cardiovasc Toxicol
case by Sumerkan et al., a patient with acute anterior wall myocardial infarction after ingestion of mad honey was presented. Patient was hospitalized, and a stent was implanted to the 99 % stenosis lesion in the mid-portion of left anterior descending coronary artery [22]. QT Interval Prolongation Sayin et al. [23] reported the only case of an extremely long QT interval to be associated with mad honey consumption. Nodal Rhythm Aliyev et al. reported a case of 70-year-old man admitted to ED with complaints of syncope and severe hemodynamic instability following ingestion of one teaspoon of honey. In the ECG, nodal rhythm alternating with sinus bradycardia and intermittent ventricular parasystole was determined [24]. Approach in the ED The toxic effects of mad honey are rarely fatal and generally last for no more than 24 h [10]. The main symptoms are believed to be caused by continued sodium channel activation, cell depolarization followed by stimulation of the vagal nervous system [7]. When the physiological mechanisms of GTX were investigated, it was found that it binds to sodium channels in cell membranes, where it increases sodium channel permeability and inhibits repolarization. This process maintains the cell in a state of depolarization. In particular, the increasing inward current and decreasing outward current of sodium on the cell membrane at the sinoatrial node weaken the action potential. Finally, a decreased action potential brings about sinus node dysfunction [25, 26].
Among symptoms of mad honey poisoning, vertigo, nausea, vomiting, lethargy, hypersalivation, diplopia and paresthesia are seen in mild forms of poisoning, while cardiovascular complications such as complete AV block, sinusal bradycardia and hypotension are seen in severe forms [2]. Hypotension due to mad honey poisoning responds to appropriate fluids, and bradycardia and conduction defects usually respond to atropine treatment [12]. There are also several results from other parts of the World; however, majority of the poisonings have been reported in Turkey. Eller et al. reported a patient presented with somnolence and vomiting to the emergency department after honey consumption. His ECG revealed complete atrioventricular block with idioventricular escape rhythm. Patient was of Turkish descent and treated with atropine [27]. In another study in 2007 in Austria, a Turkish patient was admitted to emergency department due to syncope after homemade honey consumption. The electrocardiogram showed a second degree heart block type Wenckebach with intermittent 2:1 conduction and preterminal negative T waves. The patient has undergone angiogram, and any abnormalities were not determined [28]. For the treatment of symptoms, intravenous atropine (0.5–2 mg) and normal saline infusion (100 ml/h) administration are known to be beneficial [18, 29]. In rare lifethreatening cases, cardiac arrhythmias requiring cardiac pacemaker implementation may occur [12]. In a study from Nepal, 15 patients with mad honey poisoning were investigated. It was reported that, in all patients, initial vital signs showed hypotension and bradycardia. The initial electrocardiogram showed sinus bradycardia in eight patients, junctional bradycardia in four patients, complete atrioventricular block in two patients and atrial fibrillation with slow ventricular response in one patient. All patients were treated with atropine and/or normal saline infusion. In this study, it was also reported that grayanotoxin poisonings caused by the ingestion of
Table 1 Cardiac effects and treatment of mad honey poisoning Effect of poisoning
Signs and symptoms
Approach in the ED
Bradycardia
Fatigue, nausea, dizziness, hypotension
Fluid and atropine administration
Atrial fibrillation
Weakness, nausea, vomiting, dizziness
Symptomatic treatment
Asystole
Pulselessness, hemodynamic instability
Cardiopulmonary resuscitation, pacemaker
Atrioventricular block
Lightheadedness, syncope, cold sweating, dizziness, nausea
Fluid and atropine administration, pacemaker
Acute myocardial infarction
Chest pain
Atropine, stenting
QT interval prolongation
Fatigue, dizziness
Supportive treatment
Nodal rhythm
Syncope, hemodynamic instability
Cardiopulmonary resuscitation, fluid and atropine administration
123
Cardiovasc Toxicol
mad honey from Nepal were similar with those of mad honey from the Black Sea Region of Turkey [30]. Cardiac effects of the poisoning and approach in the ED are summarized in Table 1.
14.
15.
Conclusion 16.
Mad honey consumption causes poisoning which can only be diagnosed when emergency physician suspects. Accurate anamnesis is essential for the diagnosis. In majority of the cases, supportive therapy is sufficient.
17.
18.
References 19. 1. Oguzturk, H., Ciftci, O., Turtay, M. G., & Yumrutepe, S. (2012). Complete atrioventricular block caused by mad honey intoxication. European Review for Medical and Pharmacological Sciences, 16, 1748–1750. 2. Uzun, H., Narci, H., Tayfur, I., Karabulut, K. U., & Karcioglu, O. (2013). Mad honey intoxication: What is wrong with the blood glucose? A study on 46 patients. European Review for Medical and Pharmacological Sciences, 17, 2728–2731. 3. Saritas, A., Kandis, H., Baltaci, D., & Erdem, I. (2011). Paroxysmal atrial fibrillation and intermittent left bundle branch block: An unusual electrocardiographic presentation of mad honey poisoning. Clinics (Sao Paulo), 66, 1651–1653. 4. Koca, I., & Koca, A. F. (2007). Poisoning by mad honey: A brief review. Food and Chemical Toxicology, 45, 1315–1318. 5. Jordan, J. (2006). Research highlights from the literature. Clinical Autonomic Research, 16, 198–201. 6. Kan, T., Hosokawa, S., Nara, S., et al. (1994). Total synthesis of (-)-grayanotoxin III. Journal of Organic Chemistry, 59, 5532–5534. 7. Jansen, S. A., Kleerekooper, I., Hofman, Z. L., Kappen, I. F., Stary-Weinzinger, A., & van der Heyden, M. A. (2012). Grayanotoxin poisoning: ‘Mad honey disease’ and beyond. Cardiovascular Toxicology, 12, 208–215. 8. Yaylaci, S., Kocayigit, I., Aydin, E., Osken, A., Genc, A. B., Cakar, M. A., & Tamer, A. (2014). Clinical and laboratory findings in mad honey poisoning: A single center experience. Nigerian Journal of Clinical Practice, 17, 589–593. 9. Nakao, M., & Seyama, I. (1984). Effect of a dihydrograyanotoxin II on the electrical activity of the rabbit sinoatrial node. Journal of Physiology, 357, 79–91. 10. Cagli, K. E., Tufekcioglu, O., Sen, N., Aras, D., Topaloglu, S., Basar, N., & Pehlivan, S. (2009). Atrioventricular block induced by mad-honey intoxication: Confirmation of diagnosis by pollen analysis. Texas Heart Institute Journal, 36, 342–344. 11. Gunduz, A., Bostan, H., Turedi, S., Nuhog˘lu, I., & Patan, T. (2007). Wild flowers and mad honey. Wilderness and Environmental Medicine, 18, 69–71. 12. Gunduz, A., Durmus, I., Turedi, S., Nuhoglu, I., & Ozturk, S. (2007). Mad honey poisoning-related asystole. Emergency Medicine Journal, 24, 592–593. 13. Oztasan, N., Altinkaynak, K., Akcay, F., Gocer, F., & Dane, S. (2005). Effects of made honey on blood glucose and lipid levels
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in rats with Streptozocin-induced diabetes. Turkish Journal of Veterinary and Animal Sciences, 29, 1093–1096. Yarlioglues, M., Akpek, M., Ardic, I., Elcik, D., Sahin, O., & Kaya, M. G. (2011). Mad-honey sexual activity and acute inferior myocardial infarctions in a married couple. Texas Heart Institute Journal, 38, 577–580. Okuyan, E., Uslu, A., & Ozan Levent, M. (2010). Cardiac effects of ‘‘mad honey’’: A case series. Clinical Toxicology (Philadelphia), 48, 528–532. Bostan, M., Bostan, H., Kaya, A. O., Bilir, O., Satiroglu, O., Kazdal, H., et al. (2010). Clinical events in mad honey poisoning: A single centre experience. Bulletin of Environment Contamination and Toxicology, 84, 19–22. Gunduz, A., Meric¸e´, E. S., Baydin, A., Topbas¸ , M., Uzun, H., Tu¨redi, S., & Kalkan, A. (2009). Does mad honey poisoning require hospital admission? American Journal of Emergency Medicine, 27, 424–427. Gunduz, A., Turedi, S., Uzun, H., & Topbas, M. (2006). Mad honey poisoning. American Journal of Emergency Medicine, 24, 595–598. Gunduz, A., Kalkan, A., Turedi, S., Durmus, I., Turkmen, S., Ayaz, F. A., & Ayar, A. (2012). Pseudocholinesterase levels are not decreased in grayanotoxin (mad honey) poisoning in most patients. Journal of Emergency Medicine, 43, 1008–1013. Osken, A., Yaylacı, S., Aydın, E., Kocayigit, I., Cakar, M. A., Tamer, A., & Gu¨ndu¨z, H. (2012). Slow ventricular response atrial fibrillation related to mad honey poisoning. Journal of Cardiovascular Disease research, 3, 245–247. Bayram, N. A., Keles, T., Durmaz, T., Dogan, S., & Bozkurt, E. (2012). A rare cause of atrial fibrillation: Mad honey intoxication. Journal of Emergency Medicine, 43, 389–391. Sumerkan, M. C., Agirbasli, M., Altundag, E., & Bulur, S. (2011). Mad-honey intoxication confirmed by pollen analysis. Clinical Toxicology (Philadelphia), 49, 872–873. Sayin, M. R., Dogan, S. M., Aydin, M., & Karabag, T. (2011). Extreme QT interval prolongation caused by mad honey consumption. Canadian Journal of Cardiology, 27(870), 17–19. Aliyev, F., Tu¨rkoglu, C., & Celiker, C. (2009). Nodal rhythm and ventricular parasystole: An unusual electrocardiographic presentation of mad honey poisoning. Clinical Cardiology, 32, 52–54. Dubey, L., Maskey, A., & Regmi, S. (2009). Bradycardia and severe hypotension caused by wild honey poisoning. Hellenic Journal of Cardiology, 50, 426–428. Seyama, I., Yamaoka, K., Yakehiro, M., Yoshioka, Y., & Morihara, K. (1985). Is the site of action of grayanotoxin the sodium channel gating of squid axon? Japanese Journal of Physiology, 35, 401–410. Eller, P., Hochegger, K., Tancevski, I., Pechlaner, C., & Patsch, J. R. (2008). Sweet heart block. Circulation, 118, 319. Weiss, T. W., Smetana, P., Nurnberg, M., & Huber, K. (2008). The honey man–second degree heart block after honey intoxication. International Journal of Cardiology, 142, 6–7. Gunduz, A., Tatli, O., & Turedi, S. (2008). Mad honey poisoning from the past to the present. Turkish Journal of Emergency Medicine, 8, 46–49. Sohn, C. H., Seo, D. W., Ryoo, S. M., Lee, J. H., Kim, W. Y., Lim, K. S., & Oh, B. J. (2014). Clinical characteristics and outcomes of patients with grayanotoxin poisoning after the ingestion of mad honey from Nepal. Internal and Emergency Medicine, 9, 207–211.
Cardiac Effects of Mad Honey Poisoning and Its Management in Emergency Department: A Review from Turkey Ali Kemal Erenler
Ó Springer Science+Business Media New York 2015
Abstract Mad honey poisoning occurs when honey containing grayanotoxin is digested. The most common clinical signs and symptoms of poisoning involve findings of digestive system irritation, severe bradycardia and hypotension and central nervous system reaction. In this review, we aimed to underline the cardiac effects of mad honey poisoning. We also aimed to raise the awareness of physicians about early diagnosis and treatment of this rare entity. Keywords Mad honey poisoning Cardiac effects Emergency department
Introduction Mad honey is obtained from Rhododendron ponticum and Luteum species of Rhododendron plant family [1]. When honey containing grayanotoxin is ingested, mad honey poisoning develops [2]. Several plants of the Ericaceae (e.g., Rhododendron, Pieris, Agarista and Kalmia) family produce grayanotoxins which can cause poisoning among humans. Grayanotoxins are a family of lipid-soluble toxins of nitrogen-free polyhydroxy cyclic hydrocarbons and are known to occur in honey produced from the nectar of Rhododendrons. As far as is known, there are 18 forms of grayanotoxins. Grayanotoxins such as grayanotoxin I–IV are a unique class of toxic diterpenoids which are polyhydroxylated cyclic hydrocarbons that do not contain
A. K. Erenler (&) Department of Emergency Medicine, Samsun Education and Research Hospital, Barıs¸ Bulvarı Kadıko¨y Mahallesi No: 199, I˙lkadım, 55090 Samsun, Turkey e-mail: [email protected]
nitrogen. The main isomer responsible for toxic effects in Rhododendron is grayanotoxin III [3–8]. Grayanotoxin II is responsible for suppression of the spontaneous beating of the sinoatrial node. The possible mechanism of this effect was attributed to depolarization caused by GTX II, owing to inflow of Na ions, which in turn produces inactivation of the slow inward current and as the slow inward current becomes small, the activation of the outward current may be reduced [9]. In summary, grayanotoxin binds to sodium channels in the cell membrane, which are involved in voltage-dependent activation and inactivation, and it prevents inactivation [10]. Plants containing grayanotoxin grow in the eastern parts of the Black Sea Region of Turkey. There are reports from different parts of the world such as South America, Europe and Japan [11]. There are also reports from Spain, Portugal, Brazil, USA and Nepal in the literature [1]. Historically, it was first identified by Xenophon, a historian and army commander in Athens [12]. The symptoms of poisoning from this substance, also known as mad or bitter honey, are dose dependent and appear after a specific length of time [2]. However, the symptoms of toxicity may occur with the consumption of a small amount of honey [8].The typical clinical manifestations of poisoning involve findings of digestive system irritation, severe bradycardia and hypotension and central nervous system reaction [13]. Clinically, grayanotoxin in low doses causes dizziness, hypotension and bradycardia; high doses cause impaired consciousness, syncope, AV block and asystole due to vagal stimulation [14]. In this review, we aimed to focus on cardiac effects of mad honey poisoning. Cardiac effects may be lethal when untreated. Early detection and treatment in the Emergency department (ED) are essential to reduce morbidity and mortality.
123
Cardiovasc Toxicol
Cardiac Effects of Mad Honey Poisoning
70/40 mmHg. An ECG has revealed atrial fibrillation with slow ventricular response. The patient suffered chest pain, and therefore, a broad cardiac testing was performed. The cardiac enzyme was normal in follow-up, and echocardiographic and angiographic examination was normal. After 48-h hospitalization, the patient was discharged [20]. Bayram et al. [21] also reported a case of a patient developing atrial fibrillation with a slow ventricular response after ingestion of honey containing grayanotoxin.
Bradycardia
Asystole
Typical symptoms of mad honey poisoning are known to be fatigue, nausea, dizziness, bradycardia and hypotension [8]. In a study with 42 patients, Okuyan et al. reported that majority of the patients had sinus bradycardia followed by complete atrioventricular (AV) block and nodal rhythm. All of the patients were treated symptomatically and none of them needed pacing [15]. In another study, with a proportion of 91 %, bradycardia was the most common finding among poisoned patients [16]. In another study with 47 patients presented to three different institutions due to mad honey poisoning, patient rhythms on arrival were determined as sinus bradycardia, nodal rhythm, normal sinus rhythm and complete AV block, respectively, [17]. In a case series, Turedi et al. as well determined that the largest proportion of patients suffered bradycardia [18]. In another study, 30 patients were reported to be admitted to an emergency service due to mad honey poisoning in a 1-year period. The most common symptoms and findings were low blood pressure and bradycardia [19]. In a study by Yaylaci et al., it was reported that in the evaluation of the heart rhythms of the patients of 16 patients on admission to the emergency room, nine patients had sinus bradycardia, three patients had nodal rhythm, two patients had first degree AV block and two patients had atrial fibrillation. Patients were treated with atropin and saline. All of the patients were discharged with total recovery [8].
In a report, Gunduz et al. presented a patient admitted to ED due to dizziness and syncope after honey ingestion. On admission, his blood pressure was 160/60 mm Hg, and pulse rate was 75 beats/min. While ECG was being administered, a sudden bradycardia followed by asystole occured. After atropine administration in the ED, patient was transferred for catheterization, and a pacemaker was applied. After 3 days of follow-up, the pacemaker was removed, and the patient was discharged [12].
Materials and Methods The MEDLINE/PubMed database was searched for publications with the medical subject heading ‘‘mad honey’’ and ‘‘cardiac effects’’. Research articles, case reports, case series and reviews from Turkey were selected and investigated.
Atrial Fibrillation In a case study, a 70-year-old patient presented to ED with weakness, palpitation, nausea and vomiting after eating a small amount of honey. On admission, an ECG was performed and revealed paroxysmal atrial fibrillation and intermittent left bundle branch block. After 6 h of symptomatic treatment, his rhythm returned to a normal sinus rhythm [3]. In another case report, a 54-year-old patient was admitted to ED with complaints of nausea, vomiting, dizziness and chest pain beginning approximately two hours after honey ingestion. On physical examination, it was determined that patient was conscious, cooperative, with a heart rate of 40 beats/min and blood pressure of
123
Atrioventricular Block Two hours after honey consumption, a patient was transferred to a university ED with complaints of lightheadedness, cold sweating, dizziness, nausea, asthenia and discomfort in epigastric region. Vital signs of the patient were as follows: arterial blood pressure: 70/50 mmHg and with a pulse rate: 44 per minute. On the patient’s ECG taken, AV complete block was determined. Patients were treated with atropine and asline infusion in the ED. After admission to Intensive care unit, patient was discharged after 24 h [1]. In another report by Cagli et al., a 48-yearold patient presented to an ED due to syncope. It was reported that atropine was administered by the paramedics and his syncope had resolved before arrival to the hospital. Initial electrocardiography of the patient revealed complete AV block, with a ventricular rate of 31 beats/min. After 2 h, normal sinus rhythm was obtained [10]. Acute Myocardial Infarction Yarlioglues et al. reported that a husband and his wife presented to ED due to confusion and chest pain after eating honey. They were both hypotensive. Their ECGs revealed complete AV block, a ventricular rate of 42 beats/ min, and ST-segment elevation in the inferior leads in the man and AV nodal rhythm, a ventricular rate of 42 beats/ min, and ST-segment elevation in the inferior leads in the woman. After atropin administration, hypotension and STsegment elevation in both patients resolved. Coronary angiography results were normal in both patients [14]. In a
Cardiovasc Toxicol
case by Sumerkan et al., a patient with acute anterior wall myocardial infarction after ingestion of mad honey was presented. Patient was hospitalized, and a stent was implanted to the 99 % stenosis lesion in the mid-portion of left anterior descending coronary artery [22]. QT Interval Prolongation Sayin et al. [23] reported the only case of an extremely long QT interval to be associated with mad honey consumption. Nodal Rhythm Aliyev et al. reported a case of 70-year-old man admitted to ED with complaints of syncope and severe hemodynamic instability following ingestion of one teaspoon of honey. In the ECG, nodal rhythm alternating with sinus bradycardia and intermittent ventricular parasystole was determined [24]. Approach in the ED The toxic effects of mad honey are rarely fatal and generally last for no more than 24 h [10]. The main symptoms are believed to be caused by continued sodium channel activation, cell depolarization followed by stimulation of the vagal nervous system [7]. When the physiological mechanisms of GTX were investigated, it was found that it binds to sodium channels in cell membranes, where it increases sodium channel permeability and inhibits repolarization. This process maintains the cell in a state of depolarization. In particular, the increasing inward current and decreasing outward current of sodium on the cell membrane at the sinoatrial node weaken the action potential. Finally, a decreased action potential brings about sinus node dysfunction [25, 26].
Among symptoms of mad honey poisoning, vertigo, nausea, vomiting, lethargy, hypersalivation, diplopia and paresthesia are seen in mild forms of poisoning, while cardiovascular complications such as complete AV block, sinusal bradycardia and hypotension are seen in severe forms [2]. Hypotension due to mad honey poisoning responds to appropriate fluids, and bradycardia and conduction defects usually respond to atropine treatment [12]. There are also several results from other parts of the World; however, majority of the poisonings have been reported in Turkey. Eller et al. reported a patient presented with somnolence and vomiting to the emergency department after honey consumption. His ECG revealed complete atrioventricular block with idioventricular escape rhythm. Patient was of Turkish descent and treated with atropine [27]. In another study in 2007 in Austria, a Turkish patient was admitted to emergency department due to syncope after homemade honey consumption. The electrocardiogram showed a second degree heart block type Wenckebach with intermittent 2:1 conduction and preterminal negative T waves. The patient has undergone angiogram, and any abnormalities were not determined [28]. For the treatment of symptoms, intravenous atropine (0.5–2 mg) and normal saline infusion (100 ml/h) administration are known to be beneficial [18, 29]. In rare lifethreatening cases, cardiac arrhythmias requiring cardiac pacemaker implementation may occur [12]. In a study from Nepal, 15 patients with mad honey poisoning were investigated. It was reported that, in all patients, initial vital signs showed hypotension and bradycardia. The initial electrocardiogram showed sinus bradycardia in eight patients, junctional bradycardia in four patients, complete atrioventricular block in two patients and atrial fibrillation with slow ventricular response in one patient. All patients were treated with atropine and/or normal saline infusion. In this study, it was also reported that grayanotoxin poisonings caused by the ingestion of
Table 1 Cardiac effects and treatment of mad honey poisoning Effect of poisoning
Signs and symptoms
Approach in the ED
Bradycardia
Fatigue, nausea, dizziness, hypotension
Fluid and atropine administration
Atrial fibrillation
Weakness, nausea, vomiting, dizziness
Symptomatic treatment
Asystole
Pulselessness, hemodynamic instability
Cardiopulmonary resuscitation, pacemaker
Atrioventricular block
Lightheadedness, syncope, cold sweating, dizziness, nausea
Fluid and atropine administration, pacemaker
Acute myocardial infarction
Chest pain
Atropine, stenting
QT interval prolongation
Fatigue, dizziness
Supportive treatment
Nodal rhythm
Syncope, hemodynamic instability
Cardiopulmonary resuscitation, fluid and atropine administration
123
Cardiovasc Toxicol
mad honey from Nepal were similar with those of mad honey from the Black Sea Region of Turkey [30]. Cardiac effects of the poisoning and approach in the ED are summarized in Table 1.
14.
15.
Conclusion 16.
Mad honey consumption causes poisoning which can only be diagnosed when emergency physician suspects. Accurate anamnesis is essential for the diagnosis. In majority of the cases, supportive therapy is sufficient.
17.
18.
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