Anesthesia Drug Metabolism in the Elderly

By July 13, 2018Uncategorized

Anesthesia providers are likely to see increasing numbers of geriatric patients in their practice. By 2030, 20% of the US population will be greater than 65 years old, and elderly patients are four times more likely to require surgery than younger individuals. It is beneficial to review pharmacologic considerations and dose adjustments for this patient population.

First of all, body composition changes with age, with a loss of lean muscle and an increase in adipose tissue. Hydrophilic drugs therefore see a decreased volume of distribution, while lipophilic drugs have a larger volume of distribution, leading to prolonged action of fat soluble agents such as propofol infusions. There is a 20-30% decrease in plasma volume and intracellular volume by the age of 75, causing a smaller volume of distribution in the central compartment and reduced bolus doses needed for the same effect.

Next, neurologic changes to the geriatric population include a reduction in brain volume by 5% per decade after age 40, decreased nerve conduction velocities, and altered neurotransmitter level and activity – all of which increase sensitivity to anesthetic agents. Decreasing presynaptic release of GABA may explain the increased sensitivity to benzodiazepines in elderly patients. They are also more likely to have baseline cognitive impairment, and are at higher risk for postoperative cognitive dysfunction and delirium.

elder patient

Cardiovascularly, the decline of cardiac output with age leads to higher initial peak drug concentrations but longer time to reach the target site; this results in smaller doses of IVĀ agents needed for induction, but the onset of action is slower. Inhalational agents have a faster onset due to decreased anesthetic washout from the lungs into the blood, leading to a faster equilibration of blood, brain and lung partial pressures of volatile gas.

Renal blood flow also decreases by 10% per decade after the age of 40, and renal cortical mass is reduced by 25% by age 80. The resultant 50% decrease in glomerular filtration rate by age 80 necessitates a dose reduction on any agent that depends on renal metabolism and elimination.

Furthermore, hepatic blood flow declines by 10% per decade. Decreased hepatic function primarily affects phase I reactions, and drugs dependent on this pathway for metabolism are considered to be flow-limited. Drugs that are metabolized by phase II reactions are not affected by declining hepatic function and are considered capacity-limited. More than 90% of patients older than 65 years take more than one drug regularly, 40% take 5 or more per week, and 12% use 10 or more per week. This polypharmacy may increase the likelihood of drug interactions, particularly with agents metabolized by the cytochrome P450 pathway.

In summary, anesthesia providers will often need to make dose adjustments based on altered drug metabolism in the elderly. Guidelines include reducing bolus and infusion rates for propofol by 20-50%, and fentanyl and remifentanil by 50% after age 80. Morphine, hydromorphone, and meperidine have active metabolites that may not be efficiently cleared with age, so their doses should also be reduced. Midazolam, though not recommended given increased risk of delirium in the geriatric population, should have a 25-75% dose reduction if necessary. Succinylcholine and cisatracurium are not affected by aging, though rocuronium doses should be reduced. Inhalational agents dosages should be reduced as MAC decreases by 6% per decade after age 40. A BIS monitor is often helpful to measure anesthetic depth.

 

References:

Rana MV, Bonasera LK, Bordelon GJ. Pharmacologic Considerations of Anesthetic Agents in Geriatric Patients. Anesthesioly Clin. 2017 Jun;35(2):259-271.

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