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Re: Authors' response

Dear Editor,

We note with interest the comments on our report made by David Wood and colleagues at the Guy’s Poisons Unit. Our response to these is as follows.

The evidence for our conclusion is obtained from the literature on troponins as well as the two case reports by Mullins and ourselves. As troponin testing is relatively new and colchicine overdose a rare event it will take many years to build up more evidence on the predictive value of troponin testing in this setting.

Troponin is the marker of choice for cardiac injury and the enzymes creatine kinase and aspartate transaminase are non-specific for cardiac injury and less sensitive for detecting minor damage.[1] Myocardial injury by anti-cancer drugs may be monitored using troponins.[2]

In our case report there were no clinical features of cardiovascular involvement during the first two days after overdose and hence the impending myocardial collapse was not suspected.

We agree that rising troponin concentrations are not specific for colchicine induced damage and may be due to myocardial ischaemia from any cause including myocardial under perfusion.

A review of troponin elevation in critically ill patients concludes that even minor elevations are specific for myocardial injury but not for myocardial infarction.[3] In another review, cardiac troponin I is regarded as a specific biomarker able to detect non-ischaemic cardiac damage in different clinical settings.[4] Serial measurements of troponins are used in cardiology to predict outcome,[5] a strategy we have illustrated is relevant in colchicine overdose and possibly other poisonings where cardiac toxicity is an issue.

We believe that our case report supports the conclusion reached by Mullins that early troponin testing in colchicine poisoning may be useful in alerting the clinician to impending cardiovascular collapse.

References

1. Malasky BR, Alpert JS. Diagnosis of myocardial injury by biochemical markers: problems and promises. Cardiol Rev. 2002 Sep-Oct;10(5):306-17. Review.

2. Sparano JA, Brown DL, Wolff AC. Predicting cancer therapy-induced cardiotoxicity: the role of troponins and other markers. Drug Saf.2002;25(5):301-11. Review.

3. Gunnewiek JM, Van der Hoeven JG. Cardiac Troponin elevations among critically ill patients. (Review) Curr Opin Crit Care. 2004, 342-6

4. Ni CY Cardiac Troponin I: a biomarker for detection and risk stratification of minor myocardiac damage. (Review) Clin Lab. 2001, 47, 483-92

5. Del Carlo CH, Pereira-Barretto AC, Cassaro- Strunz C, Latorre Mdo R, Ramires JA. Serial measure of cardiac troponin T levels for predication of clinical events in decompensated heart failure. J Card Fail. 2004 Feb;10(1):43-8.

Authors

Charles van Heyningen
Consultant Chemical Pathologist

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Re: Serial Troponin-I measurements are unlikely to be useful in acute colchicine toxicity

Dear Editor,

van Heyningen and Watson reported a case of acute colchicine poisoning, associated with significant cardiovascular compromise, with elevated troponin-I concentrations, resulting in death.[1] Elevation of cardiac troponin concentrations in acute colchicine toxicity has been previously reported.[2] The authors concluded that in future cases serial 12 hourly troponin measurements should be undertaken in acute colchicine toxicity to predict cardiovascular collapse; however they do not provide evidence for this conclusion.[1]

The basis for the author’s assumption for serial measurement of troponin-I concentrations in acute colchicine poisoning, is that troponin concentrations rose in line with clinical deterioration of their patient. However they report in Table 1 that creatinine kinase and aspartate transaminase, alternative markers of myocardial injury, were also elevated in line with the patients deterioration. In addition to elevation of other biochemical markers of myocardial injury, there is clear history of clinical deterioration and impending myocardial collapse

It seems unclear why the authors have focused on serial troponin-I measurements rather than other biochemical or clinical indicators of cardiovascular collapse. Elevated troponin concentrations not only reflect myocardial ischaemia in the context of underlying coronary artery disease.[3] The finding of raised troponin-I concentrations is not unique to colchicine poisoning and may be found in any patient subjected a severe systemic insult secondary to poisoning, trauma, sepsis, or any other condition causing poor myocardial perfusion.[3] In acute colchicine poisoning hypovolaemia, hypotension and poor myocardial perfusion can result from colchicine-induced nausea, vomiting, diarrhoea and cardiac arrhythmias. Elevation of troponin concentrations probably reflects these clinical features rather than direct colchicine toxicity itself.

Raised troponin-I concentrations may indicate a "sick heart" following overdose of colchicine, however this is neither unique in terms of severe poisoning, or likely to be clinically helpful in guiding provision of the meticulous supportive care indicated for these patients.

References

1.van Heyningen C, Watson ID. Troponin for prediction of cardiovascular collapse in acute colchicine overdose. Emerg Med J. 2005 Aug; 22(8): 599-600

2.Mullins ME, Robertson DG, Norton RL. Troponin I as a marker of cardiac toxicity in acute colchicine overdose. Am J Emerg Med. 2000 Oct; 18(6): 743-4

3.Jeremias A, Gibson CM. Narrative review: alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excluded. Ann Intern Med. 2005 May 3; 142(9): 786-91

Authors:

David M Wood
Specialist Registrar in Clinical Toxicology

Shaun L Greene
Associate Specialist in Clinical Toxicology

Paul I Dargan
Consultant Clinical Toxicologist

Alison L Jones
Director and Clinical Toxicologist