Skip to main content

Unusual case of severe arrhythmia developed after acute intoxication with tosylchloramide



Drugs not commonly considered to be cardioactive agents may cause prolongation of the QT interval with resultant torsades de pointes and ventricular fibrillation. This form of drug toxicity often causes cardiac arrest or sudden death.

Case presentation

After accidental ingestion of tosylchloramide a caucasian 77-year-old woman, with a family history of cardiovascular disease and hypertension, was admitted to the intensive care unit following episodes of torsades de pointes with a prolonged QT/QTc interval (640/542 ms). The patient received an implantable cardioverter-defibrillator, was discharged from the hospital with normal QT/QTc interval and did not experience additional ventricular arrhythmias during one year of follow-up.


This is the first report concerning an unusual case of torsades de pointes after accidental intoxication by ingestion of tosylchloramide. The pronounced impact of the oxidyzing agent tosylchloramide on the activity of some of the ion channels regulating the QT interval was identified as a probable cause of the arrhythmia.

Peer Review reports


Because of its high activity against fungi and bacteria, tosylchloramide is a widely used disinfectant agent for common applications such household cleaning and swimming pool disinfection. Many case reports describing tosylchloramide intoxication have been already published in the past showing that the chronic exposure to this compound may cause hypersensitivity reactions, such as asthma [1, 2], conjunctivitis [3], whereas toxic pneumonitis [4], cardiovascular collapse and myocardial damage may occur in acutely intoxicated patients [5]. Here we report the first case of a severe arrhythmia developed in the context of acute oral intoxication with tosylchloramide.

Case presentation

A 77-year-old woman presenting shoulder girdle pain was admitted to our hospital with suspected coronary syndrome. She had a history of hypertension; treated since 5 years with Perindopril (5 mg once daily) and a family history of cardiovascular disease. Few hours after the admission at the Emergency Room (ER) the patient experienced a cardiac arrest due to a “Torsade de Pointes” (TdP) degenerated into ventricular fibrillation which required DC shock (200 J), as documented by electrocardiogram (ECG) (Figure 1). After specific questioning for drug intake, the patient revealed She had accidentally (non-intentionally) ingested an entire sachet of Euclorina (containing 2.5 g of tosylchloramide) between 5 and 6 hours before TdP.

Figure 1
figure 1

TDP with fast degeneration into Ventricular Fibrillation. The ECG-strip pre-TDP (Figure1A) shows a QT interval of 640 msec (QTc is 542 msec).

Surface ECG on admission in ER showed sinus rhythm with pre-existing left bundle branch block (LBBB). Serum potassium was in slightly lower normal range (3.3 mEq/l, before 3.8 mEq/l), while other haematological parameters were in their respective reference intervals (data not shown). On admission to the cardiology Intensive Care Unit (ICU) the ECG disclosed sinus bradycardia (55 bpm) with significant alteration in the QT interval (QT/QTc = 640/543 msec; Figure 2) that was significantly prolonged over a 24-hour period. Thereafter the patient underwent an echocardiography that revealed concentric left ventricle hypertrophy with a mild reduction in global systolic function (LVEF = 50%) due to LBBB-induced dyssynergy of the interventricular anterior septum wall.

Figure 2
figure 2

ECG at the admission to ICU shows a LBBB with a prolonged QT/QTc interval (640–542 msec).

The middle left anterior descending coronary artery (LAD) had a non-significant stenosis (< 50%) as revealed by coronary angiography and IVUS control (Figure 3). A not significant stenosis was detected in a non-dominant right coronary artery (Figure 3). According to the criteria defined in Thygesen et al. [6], myocardial infarction was excluded for the following reasons: a) no symptoms or electrocardiographic changes were detected; b) the peak CK-MB level was 8.1 ng/ml (the normal reference value in our laboratory is < 5 ng/ml) only after 6 h from DC shock, and normalized (3.2 ng/ml) within the following 6 h; c) the peak Troponin I level was 0.32 ng/ml (the normal reference value in our laboratory is < 0.08 ng/ml) 6 h after DC shock, and normalized (0.06 ng/ml) 6 h later. No signs of liver or kidney derangement were observed (data not shown).

Figure 3
figure 3

Coronary Angiography. No significant CAD is detected in right cororary artery. The middle left anterior descending coronary artery had a non-significant stenosis (< 50%), as confirmed by IVUS control.

The patient was discharged 7 days after admission, following the placement of an implantable cardioverter-defibrillator (ICD); the ECG at discharge showed a LBBB with a normal QT interval (QT/QTc = 400/430 msec; Figure 4). After 12 and 24 months of follow-up She has been clinically stable, no shock detected at ICD registration and her QT interval was normal (Figure 5).

Figure 4
figure 4

ECG at hospital discharge. QT interval measures 400 msec, the QTc interval 430 msec.

Figure 5
figure 5

ECG at 1-year follow-up shows stable LBBB and normal QT/QTc interval (405/432 msec).


The occurrence of TdP in our patient after tosylchloramide ingestion can be explained considering that this compound acts as a strong oxidant of methionines and cysteines residues in proteins [7]. The activity of some of the ion channels regulating the duration of the QT interval is, indeed, strongly influenced by oxydation of critical methionine residues in channel proteins. In particular, voltage-dependent inactivation of NaV channels is significantly slowed down when methionine residues located in the so called IMF domain, which is responsible for voltage-dependent channel inactivation, are oxydized [8]. Consistently, tosylchloramide, which has a strong preference in oxydizing methionine residues [9], is one of the most powerful oxydants affecting NaV channel inactivation [9, 10] and it has been used as a pharmacological tool to abolish voltage-dependent inactivation in studies aiming to determine its contribution in the activity of specific cardiovascular drugs [11]. Tosylchloramide-induced slowing of NaV channel inactivation is a quite general phenomenon being observed in the brain, muscle and, importantly, cardiac isoform of these channels [8]. Oxydant-induced impairment of NaV voltage-dependent inactivation may per se explain the appearance of TdP in our patient intoxicated with tosylchloramide since it causes a marked increase in persistent INa (INaP ) [12, 13], the inactivation-resistant Na+ current which persists in the presence of prolonged membrane depolarization [14]. An increase in INaP is, indeed, a well documented mechanism of QT prolongation and arrhythmogenesis and a potentailly relevant target for treatment and prevention of arrhythmias [15, 16]. In addition, an increase in INaP is considered responsible for arrhythmogenesis in patients affected with the LQT3 syndrome which bear specific mutations in the NaV1.5 channel gene [1719]. Confirming the involvement of INaP in oxydant-induced arrhythmogenesis, the INaP blocker ranolazine was effective in preventing QT prolongation and early afterdepolarzations induced by the strong oxydant agent H2O2 in cultured guinea pig cardiomyocytes [13]. Therefore, it is tempting to speculate that, in our patient, tosylchloramide exposure recapitulated the pathophysiological mechanism of cardiac arrhythmia in LQT3 patients.

hERG is another oxydation-sensitive ion channel that could have been involved in the genesis of TdP in our patient. hERG is the main K+ current responsible for rapid repolarization of cardiac myocytes in phase III of cardiac action potential [20] and its loss of function is one of the best characterized mechanisms of drug-induced or congenital LQT syndrome [21]. Specifically, mutations causing either loss of function or alterations in trafficking of hERG channels are responsible for the LQT2 syndrome [22, 23] whereas mutations in MiRP1, an accessory subunit that coassembles with hERG, have been found in LQT6 patients [24]. Intriguingly, by oxydizing critical methionine residues, tosylchloramide causes an almost complete loss of hERG channel activity in vitro[25] thus reproducing the effect of drugs or mutations known to cause TdP. Therefore, it is likely that hERG channel blockade could have played a role in the appearance of TdP in our patient.

Finally, it is worth to remind that several oxydants, including tosylchloramide, may also increase the activity of L-type voltage-gated Ca2+ channels (VGCC), even though, in this case, the specific inolvement of methionine residues has not been demonstrated [26, 27]. By increasing Ca2+ influx through L-type VGCC, tosylchloramide is expected to prolong the plateau phase of cardiac action potential thus delaying cardiomyocyte repolarization and promoting the appearance of TdP. Intriguingly, an increase in L-type VGCC activity represents the mechanistic base of arrhythmias in LQT8 patients [2830] bearing the Timothy syndrome mutations which cause an impairment in voltage-dependent CaV1.2 channel inactivation [31].


Oxidative stress has been proposed as one of the upstream events provoking clinical relevant arrhythmic responses [32] and several drugs used in therapy exert antiarrhythmic effects in part via their antioxidative property [33, 34]. Here we suggest that severe arrhythmia may occur in the form of TdP after massive exposure to the oxidizing agent tosylchloramide. In fact, tosylchloramide has a pronounced impact on the activity of some of the ion channels regulating the QT interval. Since our patient exhibited no evidence of QT interval alteration after 12 and 24 months of follow-up, this strongly suggests a causal role of tosylchloramide intoxication for the ECG abnormalities occurred during observation in the ICU. Therefore, a strict electrocardiographic monitoring is advised in patients intoxicated with this compound.


Written informed consent was obtained from the patient prior to publication of this case report and any accompanying images. A copy of the written consent is available for review by the Series Editor of this journal.

Authors’ information

Salvatore Amoroso and Gian Piero Perna equally contributed as senior authors.


  1. Blasco A, Joral A, Fuente R, Rodríguez M, García A, Domínguez A: Bronchial asthma due to sensitization to chloramine T. J Investig Allergol Clin Immunol. 1992, 2: 167-170.

    CAS  PubMed  Google Scholar 

  2. Kujala VM, Reijula KE, Ruotsalainen EM, Heikkinen K: Occupational asthma due to chloramine-T solution. Respir Med. 1995, 89: 693-695. 10.1016/0954-6111(95)90137-X.

    Article  CAS  PubMed  Google Scholar 

  3. Grant WM: Toxicology of the eye. 1974, Charles C. Thomas, Srpingfield

    Google Scholar 

  4. Pascuzzi TA, Storrow AB: Mass casualties from acute inhalation of chloramine gas. Mil Med. 1998, 163: 102-104.

    CAS  PubMed  Google Scholar 

  5. Gonzalez-Castro A, Holanda MS, Canas BS, Morlote JG, Minambres E, Prieto Solis JA: Myocardial damage after inhalation of chloramines. Eur J Emerg Med. 2006, 13: 108-110. 10.1097/01.mej.0000188229.67980.c7.

    Article  PubMed  Google Scholar 

  6. Thygesen K, Alpert JS, White HD: Universal definition of myocardial infarction. Eur Heart J. 2007, 28: 2525-2538.

    Article  PubMed  Google Scholar 

  7. Mihajlovic V, Cascone O, Biscoglio de Jiménez Bonino MJ: Oxidation of methionine residues in equine growth hormone by Chloramine-T. Int J Biochem. 1993, 25: 1189-1193. 10.1016/0020-711X(93)90598-9.

    Article  CAS  PubMed  Google Scholar 

  8. Kassmann M, Hansel A, Leipold E, Birkenbeil J, Lu SQ, Hoshi T, Heinemann SH: Oxidation of multiple methionine residues impairs rapid sodium channel inactivation. Pflugers Arch. 2008, 456: 1085-1095. 10.1007/s00424-008-0477-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wang GK: Irreversible modification of sodium channel inactivation in toad myelinated nerve fibres by the oxidant chloramine-T. J Physiol. 1984, 346: 127-141.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Quiñonez M, DiFranco M, González F: Involvement of methionine residues in the fast inactivation mechanism of the sodium current from toad skeletal muscle fibers. J Membr Biol. 1999, 169: 83-90. 10.1007/s002329900520.

    Article  PubMed  Google Scholar 

  11. Nawada T, Tanaka Y, Hisatome I, Sasaki N, Ohtahara A, Kotake H, Mashiba H, Sato R: Mechanism of inhibition of the sodium current by bepridil in guinea-pig isolated ventricular cells. Br J Pharmacol. 1995, 116: 1775-1780. 10.1111/j.1476-5381.1995.tb16662.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Niemann P, Schmidtmayer J, Ulbricht W: Chloramine-T effect on sodium conductance of neuroblastoma cells as studied by whole-cell clamp and single-channel analysis. Pflugers Arch. 1991, 418: 129-136. 10.1007/BF00370461.

    Article  CAS  PubMed  Google Scholar 

  13. Song Y, Shryock JC, Wagner S, Maier LS, Belardinelli L: Blocking late sodium current reduces hydrogen peroxide-induced arrhythmogenic activity and contractile dysfunction. J Pharmacol Exp Ther. 2006, 318: 214-222. 10.1124/jpet.106.101832.

    Article  CAS  PubMed  Google Scholar 

  14. Maltsev VA, Sabbah HN, Higgins RS, Silverman N, Lesch M, Undrovinas AI: Novel, ultraslow inactivating sodium current in human ventricular cardiomyocytes. Circulation. 1998, 98: 2545-2552. 10.1161/01.CIR.98.23.2545.

    Article  CAS  PubMed  Google Scholar 

  15. Hasenfuss G, Maier LS: Mechanism of action of the new anti-ischemia drug ranolazine. Clin Res Cardiol. 2008, 97: 222-226. 10.1007/s00392-007-0612-y.

    Article  CAS  PubMed  Google Scholar 

  16. Undrovinas A, Maltsev VA: Late sodium current is a new therapeutic target to improve contractility and rhythm in failing heart. Cardiovasc Hematol Agents Med Chem. 2008, 6: 348-359. 10.2174/187152508785909447.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bennett PB, Yazawa K, Makita N, George AL: Molecular mechanism for an inherited cardiac arrhythmia. Nature. 1995, 376: 683-685. 10.1038/376683a0.

    Article  CAS  PubMed  Google Scholar 

  18. Christé G, Chahine M, Chevalier P, Pásek M: Changes in action potentials and intracellular ionic homeostasis in a ventricular cell model related to a persistent sodium current in SCN5A mutations underlying LQT3. Prog Biophys Mol Biol. 2008, 96: 281-293. 10.1016/j.pbiomolbio.2007.07.023.

    Article  PubMed  Google Scholar 

  19. Tian XL, Yong SL, Wan X, Wu L, Chung MK, Tchou PJ: Mechanisms by which SCN5A mutation N1325S causes cardiac arrhythmias and sudden death in vivo. Cardiovasc Res. 2004, 61: 256-267. 10.1016/j.cardiores.2003.11.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tseng GN: I(Kr): the hERG channel. J Mol Cell Cardiol. 2001, 33: 835-849. 10.1006/jmcc.2000.1317.

    Article  CAS  PubMed  Google Scholar 

  21. Sanguinetti MC, Jiang C, Curran ME, Keating MT: A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell. 1995, 81: 299-307. 10.1016/0092-8674(95)90340-2.

    Article  CAS  PubMed  Google Scholar 

  22. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT: A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell. 1995, 80: 795-803. 10.1016/0092-8674(95)90358-5.

    Article  CAS  PubMed  Google Scholar 

  23. Chiang CE, Roden DM: The long QT syndromes: genetic basis and clinical implications. J Am Coll Cardiol. 2000, 36: 1-12. 10.1016/S0735-1097(00)00716-6.

    Article  CAS  PubMed  Google Scholar 

  24. Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA: MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell. 1999, 97: 175-187. 10.1016/S0092-8674(00)80728-X.

    Article  CAS  PubMed  Google Scholar 

  25. Su Z, Limberis J, Martin RL, Xu R, Kolbe K, Heinemann SH, Hoshi T, Cox BF, Gintant GA: Functional consequences of methionine oxidation of hERG potassium channels. Biochem Pharmacol. 2007, 74: 702-711. 10.1016/j.bcp.2007.06.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Campbell DL, Stamler JS, Strauss HC: Redox modulation of L-type calcium channels in ferret ventricular myocytes. Dual mechanism regulation by nitric oxide and S-nitrosothiols. J Gen Physiol. 1996, 108: 277-293. 10.1085/jgp.108.4.277.

    Article  CAS  PubMed  Google Scholar 

  27. Yamaoka K, Yakehiro M, Yuki T, Fujii H, Seyama I: Effect of sulfhydryl reagents on the regulatory system of the L-type Ca channel in frog ventricular myocytes. Pflugers Arch. 2000, 440: 207-215.

    Article  CAS  PubMed  Google Scholar 

  28. Jacobs A, Knight BP, McDonald KT, Burke MC: Verapamil decreases ventricular tachyarrhythmias in a patient with Timothy syndrome (LQT8). Hear Rhythm. 2006, 3: 967-970. 10.1016/j.hrthm.2006.04.024.

    Article  Google Scholar 

  29. Splawski I, Timothy KW, Sharpe LM, Decher N, Kumar P, Bloise R, Napolitano C, Schwartz PJ, Joseph RM, Condouris K, Tager-Flusberg H, Priori SG, Sanguinetti MC, Keating MT: Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell. 2004, 119: 19-31. 10.1016/j.cell.2004.09.011.

    Article  CAS  PubMed  Google Scholar 

  30. Splawski I, Timothy KW, Decher N, Kumar P, Sachse FB, Beggs AH, Sanguinetti MC, Keating MT: Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci USA. 2005, 102: 8089-8096. 10.1073/pnas.0502506102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Barrett CF, Tsien RW: The Timothy syndrome mutation differentially affects voltage- and calcium-dependent inactivation of CaV1.2 L-type calcium channels. Proc Natl Acad Sci USA. 2008, 105: 2157-2162. 10.1073/pnas.0710501105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Jeong EM, Liu M, Sturdy M, Gao G, Varghese ST, Sovari AA, Dudley SC: Metabolic stress, reactive oxygen species, and arrhythmia. J Mol Cell Cardiol. 2012, 52: 454-463. 10.1016/j.yjmcc.2011.09.018.

    Article  CAS  PubMed  Google Scholar 

  33. Liu T, Li G: Antioxidant interventions as novel preventive strategies for postoperative atrial fibrillation. Int J Cardiol. 2010, 145: 140-142. 10.1016/j.ijcard.2009.06.054.

    Article  PubMed  Google Scholar 

  34. Naccarelli GV, Lukas MA: Carvedilol’s antiarrhythmic properties: therapeutic implications in patients with left ventricular dysfunction. Clin Cardiol. 2005, 28: 165-173. 10.1002/clc.4960280403.

    Article  PubMed  Google Scholar 

Pre-publication history

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Salvatore Amoroso.

Additional information

Competing interest

The authors declare that they have no competing interest.

Authors’ contributions

AM identified and managed the case; GPP and SA analyzed the data, conceived of the study and helped to draft the manuscript; VL, MM, AAN and IB performed the literature search and wrote the article. All authors read and approved the final manuscript.

Vincenzo Lariccia, Alessandra Moraca contributed equally to this work.

Authors’ original submitted files for images

Rights and permissions

Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

Lariccia, V., Moraca, A., Marini, M. et al. Unusual case of severe arrhythmia developed after acute intoxication with tosylchloramide. BMC Pharmacol Toxicol 14, 8 (2013).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: