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PARACETAMOL AND THE HEART
536 CYSTEAMINE FOR PARACETAMOL POISONING
SIR,-In view of the controversy over the efficacy of cysteamine in the treatment of paracetamol overdose,’2 we would like to make known our experience with this agent. We have treated thirteen patients within 10 h of ingestion of tablets, and so that we can compare our results directly with those given by Prescott et al.’ we have estimated tha plasmaparacetamol 4 h after the reported overdose by extrapolation on
semilogarithmic plots (see table).
-
COMPARABILITY AND BIOCHEMICAL INDICES IN PARACETAMOL OVERDOSE I
I
I
I
I
For normal term deliveries the risk of choriocarcinoma is ot the order of 1/50 000 whereas the risk for non-classic mole giving rise to trophoblastic tumour is of the order of 1/50 in our series. In our series classic moles account for 68% of all moles recorded whereas in that of Vassilakos and Kajii they account for only 29%, suggesting that the criteria for defining and following up partial or transitional moles are somewhat arbitrary. Minor degrees of molar change in aborted conceptions
and cases are registered for H.c.G. follow-up when vesicles are apparent to the naked eye or when trophoblastic proliferation is noted. The ability to predict which moles are likely to give rise to a trophoblastic tumour would be useful but it is unlikely to be clinically helpful unless comparable in reliability to follow-up by H.c.G. radioimmunoassay. The tradition of avoiding pregnancy for two years after mole may well be unnecessary in cases where H.c.G. values fall quickly to undetectable levels.
-
-
--
Department of Medical Oncology, Charing Cross Hospital (Fulham), London W6 8RF
M. STONE K. D. BAGSHAWE
the absence of liver necrosis but failed to find the abnormalities in the myocardium described by Pimstone and Uysl and Sanerkin.2 Dr Lesna and her colleagues (Jan. 24, p. 191) have never seen a cardiac arrest in the absence of liver failure, but the problem here is whether to attribute cardiac abnormalities to the severe metabolic derangement of liver failure or to the xtiological agent. In a survey of over 100 patients with fulminant hepatic failure we found cardiac arrhythmias in most. Although it was not possible to correlate the occurrence of these with the tetiology, the paracetamol group had more macroscopic abnormalities of the heart at necropsy. Asystolic arrests were common, and one patient with a paracetamol overdose arrested while still rousable. Since this study we have seen two similar episodes, one in a patient with paracetamol overdose and one with virus hepatitis, but both had biochemical evidence of severe liver-cell failure. Thus, in this series of selected patients it was not possible to attribute the cardiac abnormalities either to the liver failure or setiological agent. Further studies of cardiac function as early as possible after the ingestion of an overdose of paracetamol may elucidate any cardiotoxic effect of the drug, but in our own study of patients who had ingested insufficient paracetamol to develop hepatic encephalopathy, electrocardiographic and transaminase studies showed minor changes only. Unit,
Medical School, London SE5
1. Pimstone, B. C., Uys, C. J. S. Afr. med. J. 1968, 2. Sanerkin, N. G. Br. med. J. 1971, iii, 478. 3. Weston, M. J., Talbot, I. C., Howarth, P. J. N., Williams, R. Br. Heart J. (in the press).
M. J. WESTON ROGER WILLIAMS
A. K.,
--
I
Capildeo, R.,
_
---
I
--
I
-.
I
et
al. that the interval between in-
gestion of tablets and the administration of cysteamine is vitally important. It has been suggested that if this compound be administered within 8-10 h of the and there is evidence from animal studies reported overdose,’ which indicates that when given late cysteamine may be not only ineffectivebut also positively harmful.’ Taking all available evidence into account we would suggest that cysteamine may be effective in protecting against paracetamol-induced hepatic necrosis, although without a large-scale controlled trial one cannot be certain. Because of this, and in view of the known toxic effects of cysteamine, we feel it should only be used in patients with high plasma-paracetamol concentration who are at risk from hepatic damage, and certainly not more than 12 h after the overdose.
is
to
Liver
be effective it
must
Unit,
King’s College Hospital and Medical School, London SE5 8RX
R. D. HUGHES P. TREWBY ROGER WILLIAMS
MEASURING PLASMA-PARACETAMOL
SIR,--Glynn and Kendal6 have described a simple colorimetric method for paracetamol (acetaminophen) measure ment, based on the method of Chefetz et al. We compared the values obtained by’ their method with those of our usual methodS which measure the absorption at 268 nm after extracPrescott, L. F., Park, J., Proudfoot, A. T. Lancet, 1976, i, 357. Douglas, A. P., Hamlyn, A. N., James, O. ibid. p. 111. Prescott, L. F., Newton, R. W., Swainson, C. P., Wright, N., Forest, A. R. W., Matthew, H. ibid. 1974, i, 588. 4. Mitchell, J. R., Thorgeirsson, S. S., Potter, W. Z., Jollow, D. J., Keiser, H. Clin. Pharmac. Ther. 1974, 16, 676. 5. Labadarios, D., Davis, M., Williams, R. J. int. med. Res. suppl. (in the
1. 2. 3.
6. 7.
42, 259.
Mant,
-
We agree with Prescott
SiR,—We have read with interest the correspondence concerning the toxicity of paracetamol (acetaminophen) on organs other than the liver, including the heart. Dr Dixon (Jan. 7, p. 35) invoked cardiac arrest as an early cause of death even in
King’s College Hospital and
-
I
Despite high plasma-paracetamol levels no patient treated with cysteamine within 10 h of overdose developed hepatic encephalopathy or renal damage, no patient died, and subsequent liver histology did not show evidence of severe damage. However, as judged by abnormalities in liver-function tests, there was evidence of greater liver damage in our patients than in those treated by Prescott et al. This may be due to the fact that our patients received a lower dose of cysteamine (3.2g of cysteamine hydrochloride over 20 h) in an attempt to reduce the severity of side-effects, although despite this, there was a high incidence of nausea, profuse vomiting, and drowsiness.
PARACETAMOL AND THE HEART
Liver
_.
I
are common
press). Glynn, J. P., Kendal, S. E. Lancet, 1975, i, 1147. Chefetz, L., Daly, R. E., Schriftman, H., Lomner, J. J. J. pharm. Sci. 1971. 60, 463. J. I., Shane, N. A., Arredondo, E. G., Paul, W. D. Clin. Chem. 1968, 14, 882.
8. Routh,
SIR,-In view of the controversy over the efficacy of cysteamine in the treatment of paracetamol overdose,’2 we would like to make known our experience with this agent. We have treated thirteen patients within 10 h of ingestion of tablets, and so that we can compare our results directly with those given by Prescott et al.’ we have estimated tha plasmaparacetamol 4 h after the reported overdose by extrapolation on
semilogarithmic plots (see table).
-
COMPARABILITY AND BIOCHEMICAL INDICES IN PARACETAMOL OVERDOSE I
I
I
I
I
For normal term deliveries the risk of choriocarcinoma is ot the order of 1/50 000 whereas the risk for non-classic mole giving rise to trophoblastic tumour is of the order of 1/50 in our series. In our series classic moles account for 68% of all moles recorded whereas in that of Vassilakos and Kajii they account for only 29%, suggesting that the criteria for defining and following up partial or transitional moles are somewhat arbitrary. Minor degrees of molar change in aborted conceptions
and cases are registered for H.c.G. follow-up when vesicles are apparent to the naked eye or when trophoblastic proliferation is noted. The ability to predict which moles are likely to give rise to a trophoblastic tumour would be useful but it is unlikely to be clinically helpful unless comparable in reliability to follow-up by H.c.G. radioimmunoassay. The tradition of avoiding pregnancy for two years after mole may well be unnecessary in cases where H.c.G. values fall quickly to undetectable levels.
-
-
--
Department of Medical Oncology, Charing Cross Hospital (Fulham), London W6 8RF
M. STONE K. D. BAGSHAWE
the absence of liver necrosis but failed to find the abnormalities in the myocardium described by Pimstone and Uysl and Sanerkin.2 Dr Lesna and her colleagues (Jan. 24, p. 191) have never seen a cardiac arrest in the absence of liver failure, but the problem here is whether to attribute cardiac abnormalities to the severe metabolic derangement of liver failure or to the xtiological agent. In a survey of over 100 patients with fulminant hepatic failure we found cardiac arrhythmias in most. Although it was not possible to correlate the occurrence of these with the tetiology, the paracetamol group had more macroscopic abnormalities of the heart at necropsy. Asystolic arrests were common, and one patient with a paracetamol overdose arrested while still rousable. Since this study we have seen two similar episodes, one in a patient with paracetamol overdose and one with virus hepatitis, but both had biochemical evidence of severe liver-cell failure. Thus, in this series of selected patients it was not possible to attribute the cardiac abnormalities either to the liver failure or setiological agent. Further studies of cardiac function as early as possible after the ingestion of an overdose of paracetamol may elucidate any cardiotoxic effect of the drug, but in our own study of patients who had ingested insufficient paracetamol to develop hepatic encephalopathy, electrocardiographic and transaminase studies showed minor changes only. Unit,
Medical School, London SE5
1. Pimstone, B. C., Uys, C. J. S. Afr. med. J. 1968, 2. Sanerkin, N. G. Br. med. J. 1971, iii, 478. 3. Weston, M. J., Talbot, I. C., Howarth, P. J. N., Williams, R. Br. Heart J. (in the press).
M. J. WESTON ROGER WILLIAMS
A. K.,
--
I
Capildeo, R.,
_
---
I
--
I
-.
I
et
al. that the interval between in-
gestion of tablets and the administration of cysteamine is vitally important. It has been suggested that if this compound be administered within 8-10 h of the and there is evidence from animal studies reported overdose,’ which indicates that when given late cysteamine may be not only ineffectivebut also positively harmful.’ Taking all available evidence into account we would suggest that cysteamine may be effective in protecting against paracetamol-induced hepatic necrosis, although without a large-scale controlled trial one cannot be certain. Because of this, and in view of the known toxic effects of cysteamine, we feel it should only be used in patients with high plasma-paracetamol concentration who are at risk from hepatic damage, and certainly not more than 12 h after the overdose.
is
to
Liver
be effective it
must
Unit,
King’s College Hospital and Medical School, London SE5 8RX
R. D. HUGHES P. TREWBY ROGER WILLIAMS
MEASURING PLASMA-PARACETAMOL
SIR,--Glynn and Kendal6 have described a simple colorimetric method for paracetamol (acetaminophen) measure ment, based on the method of Chefetz et al. We compared the values obtained by’ their method with those of our usual methodS which measure the absorption at 268 nm after extracPrescott, L. F., Park, J., Proudfoot, A. T. Lancet, 1976, i, 357. Douglas, A. P., Hamlyn, A. N., James, O. ibid. p. 111. Prescott, L. F., Newton, R. W., Swainson, C. P., Wright, N., Forest, A. R. W., Matthew, H. ibid. 1974, i, 588. 4. Mitchell, J. R., Thorgeirsson, S. S., Potter, W. Z., Jollow, D. J., Keiser, H. Clin. Pharmac. Ther. 1974, 16, 676. 5. Labadarios, D., Davis, M., Williams, R. J. int. med. Res. suppl. (in the
1. 2. 3.
6. 7.
42, 259.
Mant,
-
We agree with Prescott
SiR,—We have read with interest the correspondence concerning the toxicity of paracetamol (acetaminophen) on organs other than the liver, including the heart. Dr Dixon (Jan. 7, p. 35) invoked cardiac arrest as an early cause of death even in
King’s College Hospital and
-
I
Despite high plasma-paracetamol levels no patient treated with cysteamine within 10 h of overdose developed hepatic encephalopathy or renal damage, no patient died, and subsequent liver histology did not show evidence of severe damage. However, as judged by abnormalities in liver-function tests, there was evidence of greater liver damage in our patients than in those treated by Prescott et al. This may be due to the fact that our patients received a lower dose of cysteamine (3.2g of cysteamine hydrochloride over 20 h) in an attempt to reduce the severity of side-effects, although despite this, there was a high incidence of nausea, profuse vomiting, and drowsiness.
PARACETAMOL AND THE HEART
Liver
_.
I
are common
press). Glynn, J. P., Kendal, S. E. Lancet, 1975, i, 1147. Chefetz, L., Daly, R. E., Schriftman, H., Lomner, J. J. J. pharm. Sci. 1971. 60, 463. J. I., Shane, N. A., Arredondo, E. G., Paul, W. D. Clin. Chem. 1968, 14, 882.
8. Routh,