International Journal of Cardiology 181 (2015) 133–134
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Treatment of Kounis syndrome Volkan Doğan a, Gurbet Özge Mert a, Funda Sungur Biteker b, Kadir Uğur Mert a,⁎, Murat Biteker a a b
Muğla Sıtkı Koçman University, Faculty of Medicine, Department of Cardiology, Turkey Muğla Sıtkı Koçman University, Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Turkey
a r t i c l e
i n f o
Article history: Received 13 November 2014 Accepted 23 November 2014 Available online 25 November 2014
We read with interest the articles recently published by Terlemez, Günaydın and colleagues [1,2]. The authors described two different patients suffering from allergic myocardial infarction from two distinct provinces of Turkey. Both studies underlined the lack of consensus among physicians about treatment of Kounis syndrome. No consensus exists regarding appropriate therapy for Kounis syndrome because the number of reported cases is low and the disorder is possibly under diagnosed. Most data regarding treatment have been derived by case reports. In this letter, we want to discuss therapeutic management of this important syndrome. Kounis syndrome has two aspects which need to be treated: Acute coronary syndrome and allergic reaction (Fig. 1). Treatment of allergic reaction can abolish type I variant alone but concomitant treatment of acute coronary syndrome is mandatory in type II and type III variants of Kounis syndrome [3]. a) Treatment of acute coronary event Supportive measures are the mainstay of management during the acute phase. Supplemental oxygen should be administered to all patients. Since vasospasm is the primary mechanism of acute coronary syndrome in Kounis syndrome, treatment protocols should include vasospasmolytic agents such as nitrates and calcium channel blockers. Current guidelines on acute coronary syndromes should be followed up for the treatment of acute coronary syndrome [4]. As the utility of common medications used in acute coronary syndromes such as aspirin, angiotensin-converting enzyme inhibitors, clopidogrel, heparin, nitroglycerin, and beta-blockers in patients with Kounis syndrome is unknown given the potential risk of aggravating an ongoing anaphylactic reactions all patients should be evaluated individually. It is reasonable to give these drugs in an intensive care unit setting, and monitorize the patients more closely for at least 24 h for the
⁎ Corresponding author at: Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Orhaniye Mah. Haluk Özsoy Cad., 48000 Muğla, Turkey. E-mail address: [email protected] (K.U. Mert).
http://dx.doi.org/10.1016/j.ijcard.2014.11.171 0167-5273/© 2014 Published by Elsevier Ireland Ltd.
development of increased symptoms [4]. Severe left ventricular dysfunction may warrant diuretics, inotropic agents, and/or hemodynamic support with intraaortic balloon-pump counterpulsation. b) Treatment of anaphylaxis Current guidelines for the management of anaphylaxis should be followed up for the treatment of allergic reactions [5]. Airway, breathing, circulation, and level of consciousness should be immediately assessed. Oxygen should be administered to all patients with anaphylaxis and pre-existing hypoxemia or myocardial dysfunction. Increased vascular permeability in anaphylaxis might permit transfer of nearly half of the intravascular fluid into the extravascular space. One to 2 L of normal saline should be administered to adults at a rate of 5 to 10 mL/kg in the first 5 min but patients with congestive heart failure or chronic renal disease should be observed cautiously to prevent volume overload. Antihistamines (H1 and H2 receptor blockers) provide symptomatic control of itching, hives, and angioedema. However, they are considered second-line treatment after administration of epinephrine and should never be administered alone in the treatment of anaphylaxis. Diphenhydramine, 1 to 2 mg/kg or 25 to 50 mg per dose may be given parenterally. Ranitidine, 50 mg in adults and 12.5 to 50 mg (1 mg/kg) in children, might be diluted in 5% dextrose to a total volume of 20 mL and injected intravenously over 5 min. Combination of an H2 antagonist with an H1 antagonist has better results than H1 treatment alone in acute allergic syndromes [5]. Glucocorticosteroids usually are not helpful acutely but potentially might prevent recurrent or protracted anaphylaxis. If given, intravenous glucocorticosteroids should be administered every 6 h at a dosage equivalent to 1.0 to 2.0 mg/kg/d. Oral administration of glucocorticosteroids (eg, prednisone, 0.5 mg/kg) might be sufficient for less critical anaphylactic episodes. The role of corticosteroids in the treatment of Kounis syndrome needs more investigation but is probably safe and appropriate. Anaphylaxis may be triggered by nonimmunologic mechanisms and mast cells may be activated directly by constituents of insect venoms, or by radiocontrast media, opiates, or nonsteroidal antiinflammatory drugs [5]. Opioids such as morphine, codeine, and meperidine, should be used cautiously in this group of patients because they can induce mast cell degranulation and aggravate the allergic reaction. Fentanyl shows only a slight activation of mast cells and may be preferred when narcotic analgesia is necessary. Although their efficacy and potency are questionable, mast cell membrane stabilizers (e.g. sodium cromoglycate, ketotifen) may be considered in
134
V. Doğan et al. / International Journal of Cardiology 181 (2015) 133–134
Treatment of Kounis Syndrome
Treatment of allergic event
Oxygen Fluid resuscitation Antihistamines Steroids Epinephrine Mast cell membrane stabilizers
Treatment of acute coronary event
Antiaggregants Anticoagulants RAS blockers Beta blockers Inotropic agents Mechanical ventricular support Statins Revascularization
Fig. 1. Treatment of Kounis Syndrome.
patients who develop acute coronary syndromes after drug reaction. Epinephrine use is recommended during anaphylaxis as soon as anaphylactic symptoms occur [5]. Aqueous epinephrine in 1:1000 dilution (1 mg/mL), 0.2 to 0.5 mL (0.01 mg/kg in children, maximum 0.3-mg dosage) should be administered intramuscularly or subcutaneously every 5 min, as necessary, and should be used to control symptoms and increase blood pressure. In patients with cardiac arrest intravenous epinephrine (1:10,000 to 1:100,000) can be considered. Although epinephrine is a life-saving medication in anaphylaxis it has a narrow therapeutic window and in cases of allergic reaction and acute coronary syndrome, its risks may outweigh the benefits. Due to the fact that most of the information about Kounis syndrome comes from case reports or small case series and lack of controlled trials, more case studies are needed to establish the appropriate use of epinephrine in patients with Kounis syndrome. We have reported 6 Turkish patients with Kounis syndrome who were treated with oral antihistamines and prednisolone [6]. Although the number of cases is too limited to reach definitive conclusions about the treatment of Kounis syndrome, most clinicians appear to avoid the use of both aspirin and epinephrine. Further studies are needed to determine the most appropriate treatment modalities in Kounis syndrome.
Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] S. Terlemez, U. Eryılmaz, Y. Tokgoz, P. Uysal, A. Coşan, Y. Bulut, Kounis syndrome caused by metranidazole—a case of 14 year-old boy, Int. J. Cardiol. (2014), http:// dx.doi.org/10.1016/j.ijcard.2014.11.049. [2] Zeki Yüksel Günaydın, Osman Bektaş, Recep Akgedik, A. Kaya, T. Acar, Recurrent Kounis syndrome. How should be the long term treatment of Kounis syndrome? Int. J. Cardiol. (2014), http://dx.doi.org/10.1016/j.ijcard.2014.11.048. [3] M. Biteker, N.E. Duran, F.S. Biteker, S. Gündüz, T. Gökdeniz, H. Kaya, M.A. Astarcioğlu, M. Ozkan, Kounis syndrome secondary to cefuroxime—axetil use in an octogenarian, J. Am. Geriatr. Soc. 56 (9) (2008) 1757–1758. [4] P.G. Steg, S.K. James, D. Atar, L.P. Badano, C. Blömstrom-Lundqvist, M.A. Borger, C. Di Mario, et al., ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation, Eur. Heart J. 33 (20) (Oct 2012) 2569–2619. [5] P. Lieberman, R.A. Nicklas, J. Oppenheimer, S.F. Kemp, D.M. Lang, D.I. Bernstein, J.A. Bernstein, A.W. Burks, et al., The diagnosis and management of anaphylaxis practice parameter: 2010 update, J. Allergy Clin. Immunol. 126 (3) (2010) (477–80.e1–42). [6] M. Biteker, N.E. Duran, F. Biteker, H.A. Civan, S. Gündüz, T. Gökdeniz, H. Kaya, M. Ozkan, Kounis syndrome: first series in Turkish patients, Anadolu Kardiyol. Derg. 9 (1) (2009) 59–60.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Treatment of Kounis syndrome Volkan Doğan a, Gurbet Özge Mert a, Funda Sungur Biteker b, Kadir Uğur Mert a,⁎, Murat Biteker a a b
Muğla Sıtkı Koçman University, Faculty of Medicine, Department of Cardiology, Turkey Muğla Sıtkı Koçman University, Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Turkey
a r t i c l e
i n f o
Article history: Received 13 November 2014 Accepted 23 November 2014 Available online 25 November 2014
We read with interest the articles recently published by Terlemez, Günaydın and colleagues [1,2]. The authors described two different patients suffering from allergic myocardial infarction from two distinct provinces of Turkey. Both studies underlined the lack of consensus among physicians about treatment of Kounis syndrome. No consensus exists regarding appropriate therapy for Kounis syndrome because the number of reported cases is low and the disorder is possibly under diagnosed. Most data regarding treatment have been derived by case reports. In this letter, we want to discuss therapeutic management of this important syndrome. Kounis syndrome has two aspects which need to be treated: Acute coronary syndrome and allergic reaction (Fig. 1). Treatment of allergic reaction can abolish type I variant alone but concomitant treatment of acute coronary syndrome is mandatory in type II and type III variants of Kounis syndrome [3]. a) Treatment of acute coronary event Supportive measures are the mainstay of management during the acute phase. Supplemental oxygen should be administered to all patients. Since vasospasm is the primary mechanism of acute coronary syndrome in Kounis syndrome, treatment protocols should include vasospasmolytic agents such as nitrates and calcium channel blockers. Current guidelines on acute coronary syndromes should be followed up for the treatment of acute coronary syndrome [4]. As the utility of common medications used in acute coronary syndromes such as aspirin, angiotensin-converting enzyme inhibitors, clopidogrel, heparin, nitroglycerin, and beta-blockers in patients with Kounis syndrome is unknown given the potential risk of aggravating an ongoing anaphylactic reactions all patients should be evaluated individually. It is reasonable to give these drugs in an intensive care unit setting, and monitorize the patients more closely for at least 24 h for the
⁎ Corresponding author at: Muğla Sıtkı Koçman Üniversitesi Tıp Fakültesi, Orhaniye Mah. Haluk Özsoy Cad., 48000 Muğla, Turkey. E-mail address: [email protected] (K.U. Mert).
http://dx.doi.org/10.1016/j.ijcard.2014.11.171 0167-5273/© 2014 Published by Elsevier Ireland Ltd.
development of increased symptoms [4]. Severe left ventricular dysfunction may warrant diuretics, inotropic agents, and/or hemodynamic support with intraaortic balloon-pump counterpulsation. b) Treatment of anaphylaxis Current guidelines for the management of anaphylaxis should be followed up for the treatment of allergic reactions [5]. Airway, breathing, circulation, and level of consciousness should be immediately assessed. Oxygen should be administered to all patients with anaphylaxis and pre-existing hypoxemia or myocardial dysfunction. Increased vascular permeability in anaphylaxis might permit transfer of nearly half of the intravascular fluid into the extravascular space. One to 2 L of normal saline should be administered to adults at a rate of 5 to 10 mL/kg in the first 5 min but patients with congestive heart failure or chronic renal disease should be observed cautiously to prevent volume overload. Antihistamines (H1 and H2 receptor blockers) provide symptomatic control of itching, hives, and angioedema. However, they are considered second-line treatment after administration of epinephrine and should never be administered alone in the treatment of anaphylaxis. Diphenhydramine, 1 to 2 mg/kg or 25 to 50 mg per dose may be given parenterally. Ranitidine, 50 mg in adults and 12.5 to 50 mg (1 mg/kg) in children, might be diluted in 5% dextrose to a total volume of 20 mL and injected intravenously over 5 min. Combination of an H2 antagonist with an H1 antagonist has better results than H1 treatment alone in acute allergic syndromes [5]. Glucocorticosteroids usually are not helpful acutely but potentially might prevent recurrent or protracted anaphylaxis. If given, intravenous glucocorticosteroids should be administered every 6 h at a dosage equivalent to 1.0 to 2.0 mg/kg/d. Oral administration of glucocorticosteroids (eg, prednisone, 0.5 mg/kg) might be sufficient for less critical anaphylactic episodes. The role of corticosteroids in the treatment of Kounis syndrome needs more investigation but is probably safe and appropriate. Anaphylaxis may be triggered by nonimmunologic mechanisms and mast cells may be activated directly by constituents of insect venoms, or by radiocontrast media, opiates, or nonsteroidal antiinflammatory drugs [5]. Opioids such as morphine, codeine, and meperidine, should be used cautiously in this group of patients because they can induce mast cell degranulation and aggravate the allergic reaction. Fentanyl shows only a slight activation of mast cells and may be preferred when narcotic analgesia is necessary. Although their efficacy and potency are questionable, mast cell membrane stabilizers (e.g. sodium cromoglycate, ketotifen) may be considered in
134
V. Doğan et al. / International Journal of Cardiology 181 (2015) 133–134
Treatment of Kounis Syndrome
Treatment of allergic event
Oxygen Fluid resuscitation Antihistamines Steroids Epinephrine Mast cell membrane stabilizers
Treatment of acute coronary event
Antiaggregants Anticoagulants RAS blockers Beta blockers Inotropic agents Mechanical ventricular support Statins Revascularization
Fig. 1. Treatment of Kounis Syndrome.
patients who develop acute coronary syndromes after drug reaction. Epinephrine use is recommended during anaphylaxis as soon as anaphylactic symptoms occur [5]. Aqueous epinephrine in 1:1000 dilution (1 mg/mL), 0.2 to 0.5 mL (0.01 mg/kg in children, maximum 0.3-mg dosage) should be administered intramuscularly or subcutaneously every 5 min, as necessary, and should be used to control symptoms and increase blood pressure. In patients with cardiac arrest intravenous epinephrine (1:10,000 to 1:100,000) can be considered. Although epinephrine is a life-saving medication in anaphylaxis it has a narrow therapeutic window and in cases of allergic reaction and acute coronary syndrome, its risks may outweigh the benefits. Due to the fact that most of the information about Kounis syndrome comes from case reports or small case series and lack of controlled trials, more case studies are needed to establish the appropriate use of epinephrine in patients with Kounis syndrome. We have reported 6 Turkish patients with Kounis syndrome who were treated with oral antihistamines and prednisolone [6]. Although the number of cases is too limited to reach definitive conclusions about the treatment of Kounis syndrome, most clinicians appear to avoid the use of both aspirin and epinephrine. Further studies are needed to determine the most appropriate treatment modalities in Kounis syndrome.
Conflict of interest The authors report no relationships that could be construed as a conflict of interest. References [1] S. Terlemez, U. Eryılmaz, Y. Tokgoz, P. Uysal, A. Coşan, Y. Bulut, Kounis syndrome caused by metranidazole—a case of 14 year-old boy, Int. J. Cardiol. (2014), http:// dx.doi.org/10.1016/j.ijcard.2014.11.049. [2] Zeki Yüksel Günaydın, Osman Bektaş, Recep Akgedik, A. Kaya, T. Acar, Recurrent Kounis syndrome. How should be the long term treatment of Kounis syndrome? Int. J. Cardiol. (2014), http://dx.doi.org/10.1016/j.ijcard.2014.11.048. [3] M. Biteker, N.E. Duran, F.S. Biteker, S. Gündüz, T. Gökdeniz, H. Kaya, M.A. Astarcioğlu, M. Ozkan, Kounis syndrome secondary to cefuroxime—axetil use in an octogenarian, J. Am. Geriatr. Soc. 56 (9) (2008) 1757–1758. [4] P.G. Steg, S.K. James, D. Atar, L.P. Badano, C. Blömstrom-Lundqvist, M.A. Borger, C. Di Mario, et al., ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation, Eur. Heart J. 33 (20) (Oct 2012) 2569–2619. [5] P. Lieberman, R.A. Nicklas, J. Oppenheimer, S.F. Kemp, D.M. Lang, D.I. Bernstein, J.A. Bernstein, A.W. Burks, et al., The diagnosis and management of anaphylaxis practice parameter: 2010 update, J. Allergy Clin. Immunol. 126 (3) (2010) (477–80.e1–42). [6] M. Biteker, N.E. Duran, F. Biteker, H.A. Civan, S. Gündüz, T. Gökdeniz, H. Kaya, M. Ozkan, Kounis syndrome: first series in Turkish patients, Anadolu Kardiyol. Derg. 9 (1) (2009) 59–60.
