e-Herz: Case study Herz 2013 DOI 10.1007/s00059-012-3734-6 Received: 25 October 2012 Revised: 18 November 2012 Accepted: 18 November 2012 © Urban & Vogel 2013
C. Kaplan1 · S.A. Kocaman2, 3 · M.E. Durakoğlugil3 · E. Kaya4 · M.G. Şenol5 1 Department of Neurology, Bursa Military Hospital, Bursa 2 Department of Cardiology, Bursa Military Hospital, Bursa 3 Medical Faculty, Department of Cardiology, Rize University, Rize Education and Research Hospital, Rize 4 Department of Physical Medicine and Rehabilitation, Bursa Military Hospital, Bursa 5 Department of Neurology, GATA Haydarpaşa Education and Research Hospital, Istanbul
Cardiac syncope due to pain Report of a case responsive to duloxetine treatment
Neurocardiogenic syncope comprises situations triggered by neurological reflexes resulting in abnormal responses of the neurocardiovascular system that cause loss of consciousness. A vast number of clinical conditions may cause this disorder including pain, defecation, micturition, swallowing, cough, sudden fear or excitement, exercise, and long-time standing [1]. The pathophysiology of neurally mediated syncope is still not clarified. A series of reflex reactions that paradoxically result in decreased sympathetic activity, bradycardia, and hypotension remains the most accepted mechanism. Nevertheless, how these reflex mechanisms are triggered in certain conditions like pain is still not known [2]. Treatment options for syncope prevention are mostly not satisfactory. Several agents including β-blockers, disopyramide, ephedrine, etilefrine, clonidine, and serotonin re-uptake inhibitors were implicated for pharmacological treatment; however, without success [1]. Selective inhibitors of neuronal norepinephrine transporter (NET) like duloxetine may have a role in neurally mediated syncope by increasing synaptic norepinephrine levels. Therefore, we report the effect of duloxetine in a patient with pain induced syncope resistant to standard regimens.
Case report A 34-year-old female patient was admitted to our cardiology clinic complaining of syncope triggered by trauma-induced pain. A previous diagnosis of cardioinhibitory syncope by tilt-table testing had been made in another facility 2 years previously. The patient had 15 syncope episodes during a 2-year follow-up, initially under β-blocker treatment and then with sertraline therapy. Afterwards, duloxetine 30 mg/day was initiated and was increased to 60 mg/day after 1 month. A pain of 4–5 degrees according to the visual analogue scale (VAS) triggered syncope under treatment with β-blocker or sertraline, whereas a sharp pain with a scale of 9, due to a twisted ankle, during duloxetine treatment did not. The patient remained asymptomatic under duloxetine treatment during a 1-year follow-up period.
Discussion The pathophysiology of neurocardiogenic syncope is still not understood. Nonpharmacological interventions are the frontline of treatment that includes avoiding triggering factors, recognizing prodromal symptoms, and implementing physical counter-pressure maneuvers. Triggering causes should be controlled if possible, for example, curing a cough if it is the ini-
tiator or relieving pain if pain is the trigger, as in our case. Recently, neuronal norepinephrine transporter (NET) function has gained considerable interest. Approximately 80% of released norepinephrine is taken back through NET. Pharmacological studies using NET inhibitors revealed that NET inhibition increases synaptic norepinephrine concentrations opposed to sympatholytic activity in the brain. NET inhibition has been demonstrated to have varying effects in peripheral organs. Importantly, NET inhibition in the heart increases cardiac norepinephrine spillover, which in turn increases cardiac adrenergic activity [3]. NET inhibition increases supine blood pressure and heart rate [4]. Consequently, NET inhibition prevented neurally mediated presyncope during the head-up tilt table test, which is characterized by sympathetic withdrawal [5]. Duloxetine is a selective serotonin and norepinephrine re-uptake inhibitor (SNRI). Being marketed initially as an antidepressant agent, duloxetine proved to be an effective option in the treatment of pain due to diabetic neuropathy [6]. Serotonin and norepinephrine diminish pain perception by hindering pain signals from the periphery to the central nervous system. The beneficial effect of duloxetine, as seen in our patient, may have two mechanisms: Either duloxetine may have preHerz 2013
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Abstract · Zusammenfassung vented syncope by reducing pain severity and perception and/or a rise in blood pressure and heart rate may have increased central perfusion. However, since sertraline, a selective serotonin reuptake inhibitor, did not have any effect on syncope frequency, we believe that NET inhibition and the consequent rise in blood pressure and heart rate is partially the mechanism of effect. Giza et al. [7] also reported successful prevention of syncope by the combination of carbamazepine and duloxetine in a patient with glossopharyngeal neuralgia. Therefore, SNRIs seem an advantageous choice in the treatment of neurally mediated syncope. However, since syncope is mainly sporadic, we may have a falsepositive effect with duloxetine. We believe that before recommending duloxetine for medical treatment of vasovagal syncope triggered by trauma-induced pain, a case series and further studies with larger sample size are required.
Corresponding address Dr. S.A. Kocaman Medical Faculty, Department of Cardiology, Rize University, Rize Education and Research Hospital 53020 Rize Turkey
[email protected] Conflict of interest. On behalf of all authors, the corresponding author states that there are no conflicts of interest.
Herz 2013 · [jvn]:[afp]–[alp] DOI 10.1007/s00059-012-3734-6 © Urban & Vogel 2013 C. Kaplan · S.A. Kocaman · M.E. Durakoğlugil · E. Kaya · M.G. Şenol
Cardiac syncope due to pain. Report of a case responsive to duloxetine treatment Abstract Neurocardiogenic syncope comprises situations triggered by neurological reflexes resulting in abnormal responses of the neurocardiovascular system that cause loss of consciousness. A vast number of clinical conditions may cause this disorder including pain, defecation, micturition, swallowing, cough, sudden fear or excitement, exercise, and long-time standing. Treatment options for syncope prevention are not satisfactory. Several agents were used for pharmacological treatment without success. Selective inhibi-
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Herz 2013
Keywords Cardiac syncope · Pain · Neurocardiovascular system · Treatment · Duloxetine
Schmerzbedingte kardiale Synkope. Bericht über einen auf Duloxetintherapie ansprechenden Fall Zusammenfassung Neurokardiogene Synkopen werden durch neurologische Reflexe getriggert, welche zu anomalen Reaktionen des neurokardiovaskulären Systems führen, die Bewusstseinsverlust verursachen. Diese Störung kann durch eine Vielzahl klinischer Bedingungen ausgelöst werden, einschließlich Schmerzen, Defäkation, Miktion, Schlucken, Husten, plötzlicher Angst oder Aufregung, Anstrengung und langem Stehen. Die Therapieoptionen zur Synkopenprävention sind nicht zufriedenstellend. Verschiedene Substanzen wurden erfolglos zur pharmakologischen Behandlung eingesetzt. Selektive Hemmer des neu-
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tors of neuronal norepinephrine transporter (NET) like duloxetine may play a role in neurally mediated syncope by increasing synaptic norepinephrine levels. Therefore, we report the effect of duloxetine in a patient with pain-induced syncope resistant to standard regimens.
5. Schroeder C, Birkenfeld AL, Mayer AF et al (2006) Norepinephrine transporter inhibition prevents tilt-induced pre-syncope. J Am Coll Cardiol 48(3):516–522 6. Smith TR (2006) Duloxetine in diabetic neuropathy. Expert Opin Pharmacother 7(2):215–223 7. Giza E, Kyriakou P, Liasides C, Dimakopoulou A (2008) Glossopharyngeal neuralgia with cardiac syncope: an idiopathic case treated with carbamazepine and duloxetine. Eur J Neurol 15(5):e38– e39
ronalen Norepinephrintransporters (NET)wie Duloxetin könnten eine Rolle bei der neural vermittelten Synkope durch steigende synaptische Norepinephrinspiegel spielen. Daher wird hier über die Wirkung von Duloxetin bei einer Patientin mit schmerzinduzierter Synkope berichtet, die gegenüber Standardtherapien resistent war. Schlüsselwörter Kardiale Synkope · Schmerzen · Neurokardiovaskuläres System · Behandlung · Duloxetin
