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GPs will lead UK’s swine flu vaccination campaign

BMJ 2009; 339 doi: https://doi.org/10.1136/bmj.b2879 (Published 15 July 2009) Cite this as: BMJ 2009;339:b2879

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Antipyretic treatment: double-edged sword.

"The most sensitive method for detecting malignant hyperthermia [a
potentially fatal complication of anaesthesia] is measuring end-tidal CO2
which increases at constant ventilation" (1).

CO2 is, of course, the end-product of oxidative phosphorylation and
is a direct function of oxygen consumption which rises some 10% for ever
degree rise in body temperature [the Q10 effect] which occurs in
proportion with the rise in metabolic rate. The rise in pCO2 inhibits
oxidative phosphorylation by mass action unless compensated by a rise in
bicarbonate that limits the magnitude of the fall in pH also induced by
the rise in pCO2. This compensatory effect of bicarbonate is limited and
respiratory failure, evidence of cellular dysfunction, occurs when the
pCO2 rises much above 45mmHg. Further rises in pCO2 cause unconsciousness,
and can be used for anaesthesia, and ultimately death, hypercarbia being
the preferred method of euthanasia in small animals.

The rise in temperature increases ATP yield needed to meet the
metabolic demands of the inflammatory response including cytokine
synthesis and release unless the pCO2 rises to levels that inhibit
oxidative phosphorylation. Antipyretics may decrease the demand for ATP by
decreasing metabolic rate but may also impair oxidative phosphorylation
by, for example, uncoupling (2). If, however, administered when the pCO2
is elevated they can be expected to compound the severity of the
inhibition of oxidative phosphorylation. Hence the adverse effects upon
outcomes.

Giving antipyretics without the means of establishing whether tissue
energetics are adequate or not, improving or getting worse, would seem to
be a hazardous exercise except in the majority of patients who are not
seriously ill.

1. Malignant Hyperthermia Gerald A. Gronert, MD Professor of
Anesthesiology University
of California-Davis School of Medicine Davis, California 95616. ASA
Refresher Courses in Anesthesiology, 1989.

2.THEODORE M. BRODY. THE UNCOUPLING OF OXIDATIVE PHOSPHORYLATION AS A
MECHANISM OF DRUG ACTION. Pharmacological Reviews, 1955;7:335-363,

Competing interests:
None declared

Competing interests: No competing interests

25 July 2009
Richard G Fiddian-Green
FRCS, FACS
None