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ANESTHETIC PHARMACOLOGY

Autonomic Mechanisms in the Age-Related Hypotensive Effect of Propofol

Stavros G. Memtsoudis, MD, PhD^*,, Andrew H. S. The, BS^*, and Paul M. Heerdt, MD, PhD^*,

Departments of *Anesthesiology and Pharmacology, Weill Medical College of Cornell University, New York, NY.

Address correspondence to Stavros G. Memtsoudis, MD, PhD, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hopsital, 75 Francis Street, Boston, MA 02115. Address e-mail to smemtsoudis{at}partners.org

We hypothesized that age-related differences in cardiovascular regulatory processes play a role in the augmented vasodepressor response to anesthetic induction with propofol in older subjects. To test this hypothesis, differences in baroreceptor responsiveness (BR) were first demonstrated in young adult (6–12 mo, n = 12) and aged (>42 mo, n = 12) New Zealand rabbits, and then the vasodepressor effect of propofol was compared in both the absence and presence of ganglionic blockade. For each age group, half of the animals were pretreated with 20 mg/kg IV hexamethonium (HEX) with the remaining half designated as controls. BR was first assessed by plotting cardiac cycle length as a function of the decline in mean arterial blood pressure (MAP) produced by multiple IV boluses of tri-nitroglycerine. Propofol was then given as an IV bolus of 4.5, 6.4, or 8.4 mg/kg over 3 s. Each animal was studied three times, receiving a single dose in variable order with at least 7 days between injections. In control animals, marked age-related differences in BR were evident and propofol produced larger peak decreases in MAP in older rabbits at all doses. HEX pretreatment abolished BR for both young and aged rabbits. However, after HEX administration the vasodepressor response to propofol in young animals was enhanced by 150% at 4.5, 125% at 6.4, and 61% at 8.4 mg/kg, respectively, whereas the impact in aged animals was only 25%, 30%, and –10%, respectively. These data support the hypothesis that age-related enhancement of propofol-induced hypotension is largely a reflection of diminished BR.

IMPLICATIONS: Clinical experience suggests that aged individuals exhibit larger hypotensive effects after induction doses of propofol compared with young adults. The mechanism behind this observation remains largely unstudied. Our data gathered in a rabbit model suggest that age-related reduction in sensitivity of autonomic reflexes may contribute substantially to the increased hypotensive effect of propofol in the aged.

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