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Acute low back pain during intravenous administration of amiodarone: a report of two cases
International Journal of Cardiology 98 (2005) 355 – 357 www.elsevier.com/locate/ijcard
Letter to the Editor
Acute low back pain during intravenous administration of amiodarone: a report of two cases Panagiotis Korantzopoulos *, Eugenia Pappa, Pavlos Karanikis, Evaggelos Kountouris, Vasiliki Dimitroula, Konstantinos Siogas Department of Cardiology, ‘‘G.Hatzikosta’’ General Hospital of Ioannina, 45001 Ioannina, Greece Received 8 July 2003; received in revised form 26 October 2003 Available online 23 April 2004
Abstract Amiodarone represents an effective antiarrhythmic drug for cardioversion of recent-onset atrial fibrillation (AF) and maintenance of sinus rhythm. We briefly describe two patients suffering from recent-onset atrial fibrillation, who experienced an acute devastating low back pain a few minutes after initiation of intravenous amiodarone loading. Notably, this side effect has not been ever reported in the medical literature. Clinicians should be aware of this reaction since prompt termination of parenteral administration leads to complete resolution. D 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Amiodarone; Low back pain; Side effects; Atrial fibrillation; Lumbar pain
1. Introduction Amiodarone is an antiarrhythmic drug, available for oral and parenteral administration, that exerts class III activity and to a lesser degree class I, II, and IV activities [1,2]. Accumulating evidence suggests that amiodarone represents an effective agent for pharmacological cardioversion of recentonset atrial fibrillation (AF) [3– 5]. We report on two AF patients who experienced an acute devastating low back pain during intravenous loading of amiodarone. The symptom was completely resolved after termination of infusion.
2. Case reports 2.1. Case 1 A 73-year-old woman was admitted to our department because of recurrent episodes of palpitations (associated with dizziness) of 6 months duration. An ambulatory electrocardiographic study (Holter monitoring) 2 months ago had revealed multiple short episodes of paroxysmal * Corresponding author. Tel.: +30-26510-80350; fax: +30-2651080353. E-mail addresses: [email protected], [email protected] (P. Korantzopoulos). 0167-5273/$ - see front matter D 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2004.01.001
AF. The patient refused any further evaluation and was then followed by her family physician. She was placed on diltiazem (200 mg/day) and aspirin (325 mg/day). Subsequently, her symptoms worsened and presented back to our institution for further evaluation and management. Her past medical history was unremarkable. On admission her blood pressure was 140/90 mm Hg with a regular heart rate of 80/ min. Cardiac auscultation revealed a 2/6 holosystolic murmur audible over the mitral area. The rest of the physical examination was normal. Complete blood count and blood chemistries were all within normal limits. An electrocardiogram (ECG) showed sinus rhythm with no abnormality. Six hours after admission, the patient’s symptoms recurred and a second ECG disclosed atrial fibrillation with a mean rate of 120/min. An attempt of pharmacological cardioversion with amiodarone was decided, considering that the patient’s left ventricular contractility had not been assessed. We also considered that the patient would benefit from amiodarone continuation after sinus rhythm restoration since she had suffered recurrent episodes. An intravenous amiodarone loading was commenced (infusion rate 5 mg/min). Interestingly, 5 min after initiation the patient started to scream complaining of an acute devastating low back pain. This reaction was initially perceived as hysterical. The infusion was stopped and the patient returned to previous clinical condition 3 min later while being hemodynamically stable. Subsequently, the infusion was re-initiated but the patient
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P. Korantzopoulos et al. / International Journal of Cardiology 98 (2005) 355–357
was unaware of this process. The symptoms relapsed along with an urticarial rash over the face and the anterior chest. A bolus of hydrocortisone (250 mg) was immediately given and the infusion was stopped again with complete resolution after 4 min. A few hours later, the patient was placed on propafenone and warfarin. The day after the patient was doing well and sinus rhythm had been restored. She strongly denied any previous history of low back pain. An echocardiographic examination revealed a mild mitral regurgitation with an ejection fraction of 0.67 and normal size of all cardiac chambers. Extensive investigations (including CT scanning) for an abdominal or lumbar pathology were negative. The patient was discharged on sinus rhythm receiving propafenone and warfarin. 2.2. Case 2 An 87-year-old man presented to the emergency department complaining of mild dyspnea and palpitations during exertion of 1 month duration. His past medical history was significant for hypertension, mild osteoarthritis of both knees, and smoking. His medications included quinapril (10 mg/day), and aspirin (100 mg/day). Vital signs were as follows: blood pressure 135/85 mm Hg, heart rate 90/min, respiration rate 20 breaths/min, and rectal temperature 36.5 jC. Lung auscultation revealed expiratory ronchi with prolonged expiration, and cardiac auscultation an additional (S4) heart sound. The rest of the physical examination was normal. An ECG showed sinus tachycardia with a first-degree atrioventricular (AV) block and frequent atrial premature beats. A chest X-ray showed hypertranslucent lung fields, and prominent pulmonary artery shadows at both hila. Routine hematological and biochemical studies were all within normal limits. Arterial blood gas analysis (while the patient breathing room air) showed pH 7.38, PaO2 64 mm Hg, PaCO2 58 mm Hg, and HCO3 28 mmol/ l. The patient was hospitalised and his cardiac rhythm and vital signs were closely monitored. Twelve hours after admission the patient’s symptoms relapsed. An ECG showed atrial fibrillation with a mean rate of 110/min and blood pressure was 120/80 mm Hg. Subsequently, intravenous amiodarone loading (infusion rate 5 mg/min) was commenced in order to facilitate restoration of sinus rhythm. Eight minutes later the patient felt presyncopal symptoms (dizziness, numbness throughout his body) and after 1 min he complained of an acute devastating low back pain. Having the experience of the aforementioned case, we promptly stopped the infusion and the patient’s symptoms completely resolved within 4 min. He denied any previous history of lumbar pain or sciatica. Subsequently, he was placed on propafenone and warfarin, and 5 h later sinus rhythm was restored. An echocardiographic study at the bedside was normal (ejection fraction of 0.54, and normal size of all cardiac chambers). A detailed investigation (including CT scanning) for an abdominal or lumbar pathology revealed only some osteophytes in
lumbar spine. Moreover, he was subjected to pulmonary function tests and a diagnosis of chronic obstructive pulmonary disease (COPD) was established. He discharged 3 days later on good clinical condition receiving quinapril, propafenone, warfarin, and inhaled bronchodilators.
3. Discussion High-dose amiodarone is an acceptable choice for pharmacological conversion of recent-onset atrial fibrillation [3 – 5]. Even though spontaneous cardioversion usually occurs in nearly 50% of cases during the first 24 h, an early intervention facilitates sinus rhythm restoration preventing the development of atrial remodeling [4 –6]. Furthermore, it has been clearly demonstrated that amiodarone is the most effective drug in preventing recurrences of AF [4,6]. The drug has variable bioavailability possibly due to its high lipophilicity, large volume of distribution and long half-life [1,2]. It is believed that in-hospital intravenous administration of amiodarone may truncate the loading period and thus this practice has been adopted by many clinicians [7]. However, it is prudent to assume that these recommendations are empiric since they are not based on careful pharmacological trials [7]. Intravenous amiodarone has complex pharmacokinetics and multiple electrophysiologic actions such as slowing of intraventricular and AV node conduction, and prolonging the action potential duration (APD) in all cardiac tissues [2,7]. In fact, most adverse effects of oral amiodarone are attributed to progressive tissue accumulation and usually ensue after long-term administration. These include central nervous system and gastrointestinal disturbances, peripheral neuropathy, dermal photosensitivity and discoloration, thyroid dysfunction, corneal deposits, bradycardia, heart block, pulmonary fibrosis, hepatotoxicity and others. With regard to intravenous amiodarone the principal hemodynamic side effect during the loading phase is hypotension (10 – 30% of patients), most often when infusion rate exceeds 2 mg/min [7]. This effect has been attributed mainly to arterial vasodilation due to its solvent, and to a lesser degree to negative inotropic action of the drug itself [7]. Phlebitis at the site of infusion represents a common problem especially when peripheral venous access is used. Other side effects include severe bradycardia and heart block (<2% of patients). Even though amiodarone prolongs APD and thus QT interval, proarrhythmic action including torsades de pointes is rare [2,7]. To the best of our knowledge, low back pain has not been ever reported as a side effect of amiodarone. Notably, in the first patient a pruritic rash erupted almost simultaneously with lumbar symptoms, whereas in the second, low back pain was accompanied by presyncopal symptoms. We can therefore assume that this rare side effect may represent an allergic or idiosyncratic reaction. Whether amiodarone, solvent, or both trigger this reaction remains unknown. In
P. Korantzopoulos et al. / International Journal of Cardiology 98 (2005) 355–357
addition, it is not known whether, in the same patients, switching to oral administration would provoke similar reactions. Regardless of the underlying mechanism(s) it seems that low back pain as well as the associated symptoms completely resolve after termination of amiodarone infusion. We conclude that clinicians should be aware of this reversible side effect in order to effectively manage such cases.
[3]
[4]
[5]
References [6] [1] Roden DM. Antiarrhythmic drugs. In: Hardman JG, Limbird LE, Goodman Gilman A, editors. Goodman’s and Gilman’s: The Pharmacological Basis of Therapeutics. Tenth edition. Philadelphia: McGrawHill; 2001. p. 933 – 70. [2] Camm AJ, Al-Saady NM, Opie LH. Antiarrhythmic drugs. In: Opie LH,
[7]
357
Gersh BJ, editors. Drugs for the Heart. Fifth edition. New York: WB Saunders; 2001. p. 221 – 72. Jahangir A, Munger TM, Packer DL, Crijns HJGM. Atrial fibrillation. In: Podrid PJ, Kowey PR, editors. Cardiac Arrhythmia: Mechanisms, Diagnosis, and Management. Second edition. Philadelphia: Lippincott Williams and Wilkins; 2001. p. 457 – 99. Naccarelli GV, Wolbrette DL, Khan M, et al. Old and new antiarrhythmic drugs for converting and maintaining sinus rhythm in atrial fibrillation: comparative efficacy and results of trials. Am J Cardiol 2003; 91:15D – 26D. Khan IA, Mehta NJ, Gowda RM. Amiodarone for pharmacological cardioversion of recent-onset atrial fibrillation. Int J Cardiol 2003; 89:239 – 48. Shinagawa K, Shiroshita-Takeshita A, Schram G, Nattel S. Effects of antiarrhythmic drugs on fibrillation in the remodeled atrium: insights into the mechanism of amiodarone’s superior efficacy. Circulation 2003;107:1440 – 6. Kowey PR, Marinchak RA, Rials SJ, Filart RA. Intravenous amiodarone. J Am Coll Cardiol 1997;29:1190 – 8.
Letter to the Editor
Acute low back pain during intravenous administration of amiodarone: a report of two cases Panagiotis Korantzopoulos *, Eugenia Pappa, Pavlos Karanikis, Evaggelos Kountouris, Vasiliki Dimitroula, Konstantinos Siogas Department of Cardiology, ‘‘G.Hatzikosta’’ General Hospital of Ioannina, 45001 Ioannina, Greece Received 8 July 2003; received in revised form 26 October 2003 Available online 23 April 2004
Abstract Amiodarone represents an effective antiarrhythmic drug for cardioversion of recent-onset atrial fibrillation (AF) and maintenance of sinus rhythm. We briefly describe two patients suffering from recent-onset atrial fibrillation, who experienced an acute devastating low back pain a few minutes after initiation of intravenous amiodarone loading. Notably, this side effect has not been ever reported in the medical literature. Clinicians should be aware of this reaction since prompt termination of parenteral administration leads to complete resolution. D 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Amiodarone; Low back pain; Side effects; Atrial fibrillation; Lumbar pain
1. Introduction Amiodarone is an antiarrhythmic drug, available for oral and parenteral administration, that exerts class III activity and to a lesser degree class I, II, and IV activities [1,2]. Accumulating evidence suggests that amiodarone represents an effective agent for pharmacological cardioversion of recentonset atrial fibrillation (AF) [3– 5]. We report on two AF patients who experienced an acute devastating low back pain during intravenous loading of amiodarone. The symptom was completely resolved after termination of infusion.
2. Case reports 2.1. Case 1 A 73-year-old woman was admitted to our department because of recurrent episodes of palpitations (associated with dizziness) of 6 months duration. An ambulatory electrocardiographic study (Holter monitoring) 2 months ago had revealed multiple short episodes of paroxysmal * Corresponding author. Tel.: +30-26510-80350; fax: +30-2651080353. E-mail addresses: [email protected], [email protected] (P. Korantzopoulos). 0167-5273/$ - see front matter D 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2004.01.001
AF. The patient refused any further evaluation and was then followed by her family physician. She was placed on diltiazem (200 mg/day) and aspirin (325 mg/day). Subsequently, her symptoms worsened and presented back to our institution for further evaluation and management. Her past medical history was unremarkable. On admission her blood pressure was 140/90 mm Hg with a regular heart rate of 80/ min. Cardiac auscultation revealed a 2/6 holosystolic murmur audible over the mitral area. The rest of the physical examination was normal. Complete blood count and blood chemistries were all within normal limits. An electrocardiogram (ECG) showed sinus rhythm with no abnormality. Six hours after admission, the patient’s symptoms recurred and a second ECG disclosed atrial fibrillation with a mean rate of 120/min. An attempt of pharmacological cardioversion with amiodarone was decided, considering that the patient’s left ventricular contractility had not been assessed. We also considered that the patient would benefit from amiodarone continuation after sinus rhythm restoration since she had suffered recurrent episodes. An intravenous amiodarone loading was commenced (infusion rate 5 mg/min). Interestingly, 5 min after initiation the patient started to scream complaining of an acute devastating low back pain. This reaction was initially perceived as hysterical. The infusion was stopped and the patient returned to previous clinical condition 3 min later while being hemodynamically stable. Subsequently, the infusion was re-initiated but the patient
356
P. Korantzopoulos et al. / International Journal of Cardiology 98 (2005) 355–357
was unaware of this process. The symptoms relapsed along with an urticarial rash over the face and the anterior chest. A bolus of hydrocortisone (250 mg) was immediately given and the infusion was stopped again with complete resolution after 4 min. A few hours later, the patient was placed on propafenone and warfarin. The day after the patient was doing well and sinus rhythm had been restored. She strongly denied any previous history of low back pain. An echocardiographic examination revealed a mild mitral regurgitation with an ejection fraction of 0.67 and normal size of all cardiac chambers. Extensive investigations (including CT scanning) for an abdominal or lumbar pathology were negative. The patient was discharged on sinus rhythm receiving propafenone and warfarin. 2.2. Case 2 An 87-year-old man presented to the emergency department complaining of mild dyspnea and palpitations during exertion of 1 month duration. His past medical history was significant for hypertension, mild osteoarthritis of both knees, and smoking. His medications included quinapril (10 mg/day), and aspirin (100 mg/day). Vital signs were as follows: blood pressure 135/85 mm Hg, heart rate 90/min, respiration rate 20 breaths/min, and rectal temperature 36.5 jC. Lung auscultation revealed expiratory ronchi with prolonged expiration, and cardiac auscultation an additional (S4) heart sound. The rest of the physical examination was normal. An ECG showed sinus tachycardia with a first-degree atrioventricular (AV) block and frequent atrial premature beats. A chest X-ray showed hypertranslucent lung fields, and prominent pulmonary artery shadows at both hila. Routine hematological and biochemical studies were all within normal limits. Arterial blood gas analysis (while the patient breathing room air) showed pH 7.38, PaO2 64 mm Hg, PaCO2 58 mm Hg, and HCO3 28 mmol/ l. The patient was hospitalised and his cardiac rhythm and vital signs were closely monitored. Twelve hours after admission the patient’s symptoms relapsed. An ECG showed atrial fibrillation with a mean rate of 110/min and blood pressure was 120/80 mm Hg. Subsequently, intravenous amiodarone loading (infusion rate 5 mg/min) was commenced in order to facilitate restoration of sinus rhythm. Eight minutes later the patient felt presyncopal symptoms (dizziness, numbness throughout his body) and after 1 min he complained of an acute devastating low back pain. Having the experience of the aforementioned case, we promptly stopped the infusion and the patient’s symptoms completely resolved within 4 min. He denied any previous history of lumbar pain or sciatica. Subsequently, he was placed on propafenone and warfarin, and 5 h later sinus rhythm was restored. An echocardiographic study at the bedside was normal (ejection fraction of 0.54, and normal size of all cardiac chambers). A detailed investigation (including CT scanning) for an abdominal or lumbar pathology revealed only some osteophytes in
lumbar spine. Moreover, he was subjected to pulmonary function tests and a diagnosis of chronic obstructive pulmonary disease (COPD) was established. He discharged 3 days later on good clinical condition receiving quinapril, propafenone, warfarin, and inhaled bronchodilators.
3. Discussion High-dose amiodarone is an acceptable choice for pharmacological conversion of recent-onset atrial fibrillation [3 – 5]. Even though spontaneous cardioversion usually occurs in nearly 50% of cases during the first 24 h, an early intervention facilitates sinus rhythm restoration preventing the development of atrial remodeling [4 –6]. Furthermore, it has been clearly demonstrated that amiodarone is the most effective drug in preventing recurrences of AF [4,6]. The drug has variable bioavailability possibly due to its high lipophilicity, large volume of distribution and long half-life [1,2]. It is believed that in-hospital intravenous administration of amiodarone may truncate the loading period and thus this practice has been adopted by many clinicians [7]. However, it is prudent to assume that these recommendations are empiric since they are not based on careful pharmacological trials [7]. Intravenous amiodarone has complex pharmacokinetics and multiple electrophysiologic actions such as slowing of intraventricular and AV node conduction, and prolonging the action potential duration (APD) in all cardiac tissues [2,7]. In fact, most adverse effects of oral amiodarone are attributed to progressive tissue accumulation and usually ensue after long-term administration. These include central nervous system and gastrointestinal disturbances, peripheral neuropathy, dermal photosensitivity and discoloration, thyroid dysfunction, corneal deposits, bradycardia, heart block, pulmonary fibrosis, hepatotoxicity and others. With regard to intravenous amiodarone the principal hemodynamic side effect during the loading phase is hypotension (10 – 30% of patients), most often when infusion rate exceeds 2 mg/min [7]. This effect has been attributed mainly to arterial vasodilation due to its solvent, and to a lesser degree to negative inotropic action of the drug itself [7]. Phlebitis at the site of infusion represents a common problem especially when peripheral venous access is used. Other side effects include severe bradycardia and heart block (<2% of patients). Even though amiodarone prolongs APD and thus QT interval, proarrhythmic action including torsades de pointes is rare [2,7]. To the best of our knowledge, low back pain has not been ever reported as a side effect of amiodarone. Notably, in the first patient a pruritic rash erupted almost simultaneously with lumbar symptoms, whereas in the second, low back pain was accompanied by presyncopal symptoms. We can therefore assume that this rare side effect may represent an allergic or idiosyncratic reaction. Whether amiodarone, solvent, or both trigger this reaction remains unknown. In
P. Korantzopoulos et al. / International Journal of Cardiology 98 (2005) 355–357
addition, it is not known whether, in the same patients, switching to oral administration would provoke similar reactions. Regardless of the underlying mechanism(s) it seems that low back pain as well as the associated symptoms completely resolve after termination of amiodarone infusion. We conclude that clinicians should be aware of this reversible side effect in order to effectively manage such cases.
[3]
[4]
[5]
References [6] [1] Roden DM. Antiarrhythmic drugs. In: Hardman JG, Limbird LE, Goodman Gilman A, editors. Goodman’s and Gilman’s: The Pharmacological Basis of Therapeutics. Tenth edition. Philadelphia: McGrawHill; 2001. p. 933 – 70. [2] Camm AJ, Al-Saady NM, Opie LH. Antiarrhythmic drugs. In: Opie LH,
[7]
357
Gersh BJ, editors. Drugs for the Heart. Fifth edition. New York: WB Saunders; 2001. p. 221 – 72. Jahangir A, Munger TM, Packer DL, Crijns HJGM. Atrial fibrillation. In: Podrid PJ, Kowey PR, editors. Cardiac Arrhythmia: Mechanisms, Diagnosis, and Management. Second edition. Philadelphia: Lippincott Williams and Wilkins; 2001. p. 457 – 99. Naccarelli GV, Wolbrette DL, Khan M, et al. Old and new antiarrhythmic drugs for converting and maintaining sinus rhythm in atrial fibrillation: comparative efficacy and results of trials. Am J Cardiol 2003; 91:15D – 26D. Khan IA, Mehta NJ, Gowda RM. Amiodarone for pharmacological cardioversion of recent-onset atrial fibrillation. Int J Cardiol 2003; 89:239 – 48. Shinagawa K, Shiroshita-Takeshita A, Schram G, Nattel S. Effects of antiarrhythmic drugs on fibrillation in the remodeled atrium: insights into the mechanism of amiodarone’s superior efficacy. Circulation 2003;107:1440 – 6. Kowey PR, Marinchak RA, Rials SJ, Filart RA. Intravenous amiodarone. J Am Coll Cardiol 1997;29:1190 – 8.