Richard A. Beers, M.D. Professor, Anesthesiology SUNY Upstate Medical Univ VA Medical Center Syracuse, NY

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1 Richard A. Beers, M.D. Professor, Anesthesiology SUNY Upstate Medical Univ VA Medical Center Syracuse, NY

2 2

3 Improvements in safety and advances in care are re-invested in older, sicker patients Rick Dutton, M.D Director, ASA s Anesthesia Quality Institute 3

4 Don t have a general anaesthetic once you re 50 it ll wipe out a quarter of your brain. Barbara Cartland, novelist (died aged 98) 4

5 the goal of research on ageing is not to increase human longevity regardless of the consequences, but to increase active longevity free from disability and functional dependence Hayflick L. The future of ageing. Nature 408:

6 accumulated effects molecular, cellular, and tissue Manifestations loss of functional units disruption of homeostatic processes reduced reserve during stress increased variability 6

7 age years years >85 years fitness fit frail 7

8 8

9 Mangoni AA, Jackson SHD. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol :6 14. Shafer SL. The Pharmacology of Anesthetic Drugs In Elderly Patients. Anesthesiol Clin N Amer 2000; 18:

10 increased sensitivity to hypnotics and opioids Depth of consciousness and EEG effects less sensitive to beta-adrenergic agents Jacobs JR, Reves JG, Marty J. et al. Aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam. Anesth Analg 1995; 80: Minto CF, Schnider TW, Egan TD. et al. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifenianil: I. Model development. Anesthesiol 1997; 86: Schnider TW, Minto CF. Shafer SL. et al. The influence of age on propofol pharmacodynamics. Anesthesiol 1999; 90:

11 stiffer, less compliant ventricle more dependence upon pre-load to increase contractility less reserve capacity to compensate for effects of anesthetic drugs Das S, Forrest K, Howell S. General Anaesthesia in Elderly Patients with Cardiovascular Disorders: Choice of Anaesthetic Agents. Drugs Aging 2010; 27 (4):

12 In general, decrease in reserve capacity Renal: Reduced GFR 12

13 principle role in drug metabolism biotransformation phase I CYP-dependent (e.g. oxidation, reduction) phase II (e.g. glucuronidation, acetylation) preserved in normal aging, frail, older elderly with critical illness Shi S, Klotz U. Age-Related Changes in Pharmacokinetics. Current Drug Metabolism 2011; 12:

14 α 1 - acid glycoprotein albumin e.g., midazolam and lidocaine 14

15 changes in the mechanism linking the receptor to the biologic response; receptor number and structure similar. 15

16 we are never more alike than the moment we are born and never so different than the day we die 16

17 Schnider TW, Minto CF, Shafer SL, et al: The influence of age on propofol pharmacodynamics. Anesthesiology 90: ,

18 Schnider TW, Minto CF, Shafer SL, et al: The influence of age on propofol pharmacodynamics. Anesthesiology 90: ,

19 elderly (66-85 y.o.) vs. young (25-39 y.o.) 20% reduction in induction dose Elderly require 30-50% reduction in infusion rate longer infusion rate longer 50% effect site decrement time 19

20 profound (75%) reduction in initial dose for sedation during endoscopic procedures reduction based upon pharmacokinetic differences (25% at most), but mostly due to increased sensitivity clearance reduced by 30% 20

21 6% decrease in MAC for each decade for age over 20 years; similar to increased sensitivity to all sedative/hypnotics; cardiovascular effects less well tolerated. 21

22 little difference in pharmacokinetics EEG 50% sensitivity to fentanyl effects; offset of effect similar if dose adjustment made 22

23 C50 for EEG effect decreases 30-50%; Longer equilibration plasma effect site More time to onset and offset of peak effect; Greater variability (more outliers); Less ability to compensate for abrupt changes in opioid effect Minto CF, Schnider TW, Shafer SL: The influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil: 11. Model application. Anesthesiology 86:24-33,

24 Reduce bolus by 50%; Reduce infusion rate by 30%; Greater probability of delay in expected time to emergence 24

25 reduced loading dose based upon body weight due to decreased muscle mass; Similar sensitivity; 30% decrease in clearance. 25

26 Tool to monitor depth of hypnosis; Useful during general anesthesia and sedation for regional anesthesia; Reduced incidence of postoperative delirium; Possible reduced incidence of postoperative cognitive dysfunction Chan MTV, Cheng BCP, Lee T, Gin T. BIS-guided Anesthesia Decreases Postoperative Delirium and Cognitive Decline. Journal of Neurosurgical Anesthesiology 2013; 25:

27 Optimize medical condition prior to surgery; Manage expectations. 27

28 Generally reduced initial dose; Longer wait for clinical effect; Titrate to response (variability) Depth of anesthesia monitoring? 28

29 Richard A. Beers, M.D. Professor, Anesthesiology SUNY Upstate Medical Univ VA Medical Center Syracuse, NY

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