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The anthracycline chemotherapeutic agents, doxorubicin
(Adriamycin) and daunorubicin (Cerubidine) intercalate with DNA, affecting
DNA and RNA synthesis. The anthracyclines react with cytochrome P450 reductase
in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH)
to form semiquinone radical intermediates, which in turn react with oxygen
to produce superoxide anion radicals (OH). These radicals are highly destructive
to cells, including myocytes. Several clinical presentations of doxorubicin-induced
cardiotoxicity, including atrial and ventricular dysrhythmias, a pericarditis-myocarditis
syndrome, acute hypertensive reactions, cardiovascular collapse, and death
during and after administration of anesthetics, have been described. It is
probable that combined radiotherapy treatment that
passes through the heart increases the risk of ongoing myocardial dysfunction.
-Lipshultz SE, Lipstiz SR, Mone SM, Goorin AM, Sallan SE, Sanders SP, Orav
EJ, Gelber RD, Colan SD: Female sex and drug dose as risk factor for late cardiotoxic
effects of doxorubicin therapy for childhood cancer. N Eng J Med 1995; 332:
1738-43
Conclusions: Female sex and a higher rate of administration
of doxorubicin were independent risk factors for cardiac abnormalities
after treatment with doxorubicin for childhood cancer; the prevalence and
severity of abnormalities increased with longer follow-up.
-Burrows FA, Hickey PR, Colan S: Perioperative complications in patients with
anthracycline chemotherapeutic agents. Can Anaesth Soc J 1985; 32: 149-157
Anesthetic implications:
female gender, age at treatment (younger is worse), cumulative dose, thorax
radiation, and more time since treatment are risk factors for myocardial dysfunction
after these cardiotoxic agents. These factors, and the type of surgery, must
be taken into account when deciding whether to seek cardiac testing (MUGA,
echo) before anesthesia.
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