Cimetidine and dapsone-mediated methaemoglobinaemia.
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ABSTRACT: Rasburicase is frequently used in tumor lysis syndrome (TLS). Although it is very well tolerated, it can cause severe oxidative hemolytic anemia and methemoglobinemia in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We report another case of rasburicase-induced methemoglobinemia in a patient with previously unrecognized G6PD deficiency and review the cases of methemoglobinemia and oxidative hemolysis reported in the literature to date. Patients from ethnicities in which G6PD deficiency is prevalent at high risk of TLS should be screened for G6PD deficiency prior to administration of rasburicase where practical. Asymptomatic decrease in oxygen saturation by oximetry and cyanosis are signs of methemoglobinemia; patients recover with conservative measures including supplemental oxygen and packed red cell transfusion.Acta Haematologica 07/2013; 130(4):254-259. · 0.89 Impact Factor
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Cimetidine and dapsone-
I read with interest the case report from
Choi et al.  relating to dapsone-
mediated methaemoglobinaemia. The
role of cimetidine in partially attenuat-
ing the haematological side-effects of
dapsone does not appear to have been
discussed in the anaesthesia literature.
I wish to suggest the possible therapeutic
benefit of peri-operative administration
of cimetidine in patients receiving
The oxidative metabolism of dapsone
leads to its toxicity. The majority of
dapsone undergoes reversible acetyla-
tion in liver followed by elimination as
N-hydroxylamine and to a lesser degree
monoacetylated hydroxylamine. Dap-
sone N- hydroxylation is responsible for
the haematological side-effects such as
methaemoglobinaemia and haemolysis.
Dapsone hydroxylamine depletes glu-
tathione within glucose-6-phosphate
dehydrogenase (G6PD)-deficient cells.
The nitroso derivative then causes per-
oxidation reactions, leading to rapid
haemolysis. Doses of 100 mg or less in
normal healthy persons and 50 mg or
less in G6PD-deficient individuals do
not cause haemolysis . A maximum
dose of 150–300 mg a day, in divided
doses, is recommended to minimise the
risk of methaemoglobinaemia .
Cimetidine, an H2-recector anta-
gonist, competes with dapsone for
cytochrome P 450
cimetidine may be used as a selective
decrease the quantity of methaemo-
globinaemia produced by dapsone [3, 4].
Cimetidine 400 mg three times daily has
been shown to lead to a significant
(> 25%) and sustained fall in methaemo-
globin in patients on chronic dapsone
therapy . This dose appears to be well
tolerated and not associated with adverse
effects. The peri-operative use of cimet-
idine is likely to benefit patients by
increasing the clinical safety margin,
minimising the incidence and severity
of methaemoglobinaemia and, possibly,
avoiding the complications associated
with treatment modalities such as meth-
ylene blue or ascorbic acid .
The mean elimination half-life of
dapsone is about 20–30 h. Sulphones
are retained in the circulation for long
periods because of intestinal re-absorp-
tion from bile, requiring periodic inter-
ruption of treatment in dermatological
diseases . It is imperative to discon-
tinue dapsone at least 4–7 days pre-
operatively in patients listed for elective
surgery. Furthermore, the G6PD level
should be checked in all patients receiv-
ing dapsone therapy to identify patients
at risk of peri-operative methaemoglo-
All India Institute of Medical Sciences
New Delhi, India
1 Choi A, Sarang A. Drug-induced met-
haemoglobinaemia following elective
coronary artery bypass grafting. Anaes-
thesia 2007; 62: 737–40.
2 Petri WA. Chemotherapy of tubercu-
losis, Mycobacterium avium complex
disease, and leprosy. In: Brunton LL,
Lazo JS, Parker KL, eds. Goodman and
Gilman’s the Pharmacological Basis of
Therapeutics, 11th edn. New York:
McGraw-Hill, 2006: 1203–23.
3 Fox LP, Merk HF, Bickers DR. Der-
matological pharmacology. In: Brunton
LL, Lazo JS, Parker KL, eds. Goodman
and Gilman’s the Pharmacological Basis of
Therapeutics, 11th edn. New York:
McGraw-Hill, 2006: 1679–706.
4 Beutler E. Methemoglobinemia and
other causes of cyanosis. In: Lichtman
MA, Beutler E, Kipps TJ, et al., eds.
Williams Hematology, 7th edn.
New York: McGraw-Hill, 2006:
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et al. The use of cimetidine to reduce
emia in dermatitis herpetiformis
patients. British Journal of Clinical Phar-
macology 1992; 34: 244–9.
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methaemoglobinaemia. Anaesthesia and
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We read with interest the letter about
machines. We, too, are concerned
resources in the hospital environment
decided, therefore, to repeat the audit
in our own theatre suite. First we
made some preliminary enquiries to
BOC and the local pharmacy depart-
ment about the cost of oxygen. BOC
deliver oxygen to the majority of
hospitals in the UK in cylinders of
various sizes (typically incurring rental
charges of £2–3 each, per month) and
as liquid oxygen, which has a cheaper
unit price. The costs that we were
given per litre of gaseous oxygen were
approximately 0.04 pence for oxygen
from a J-sized cylinder and 0.01 pence
for that evaporated from liquid oxygen.
Even allowing for a large degree of
wastage and ongoing costs, this is a
quoted in the letter.
We hesitated to write this letter as
we did not want to detract from the
resources and protection of the envi-
ronment. However, it may prove more
profitable to begin with the recycling of
resources such as glass and paper, which
certainly does not yet seem to be
widespread in hospitals in the UK.
Poole BH15 2JB, UK
Anaesthesia, 2007, 62, pages 1183–1192
? 2007 The Association of Anaesthetists of Great Britain and Ireland