Pharmacokinetics in burned patients

Burned patients experience a hyperdynamic circulation, fluid shifts, altered serum protein levels, and unusual fluid losses which often complicate the dosing of medications including antibiotics, analgesics, etc. Such alterations in clearance, distribution, and protein binding may not be critical for drugs with wide margins between therapeutic and toxic levels; however, where the margin is narrow, these effects must be taken into account and combined with frequent monitoring.

Higher than expected drug levels during the hypodynamic or resuscitation phase may result from decreased volume of distribution or because clearance is prolonged by decreased hepatic and renal blood flow. Decreased blood flow to organs and tissues may result in decreased absorption from the gastrintestinal tract or from subcutaneous or intramuscular sites. Therefore the safest approach is frequent small intravenous doses with regular monitoring of their effects.

A supranormal cardiac output, with increased blood flow to the splanchnic and renal beds, elevated temperature, hypoproteinemia, and major fluid shifts are common during the hypermetabolic phase of burn injury. Renal blood flow is significantly increased, but renal tubular function is depressed. Drugs cleared primarily by filtration may show accelerated elimination, while those secreted by the tubules may accumulate. Hepatic drug metabolism is more complex, but some generalizations are possible. Drug elimination by oxidation or reduction, hydroxylation, etc. will often be impaired, while conjugation reactions are preserved. Plasma protein levels are significantly altered during this period. Even when nutrition is well maintained, albumin synthesis is depressed as a component of the acute phase response, while synthesis of aracid glycoprotein is increased. Drugs with significant albumin binding usually show an increase in the free drug, but the free fraction of drugs binding to aracid glycoprotein will be reduced. Such changes in drug binding also lead to changes in renal clearance, since only the free component is readily filtered at the glomerulus. Drugs with a narrow therapeutic window should not be used in burned patients unless no other agent will achieve similar therapeutic goals, in which case the frequency of monitoring of both drug levels and effects must be increased.

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