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Perioperative Drug Therapy in Elderly Patients Richard Rivera, M.D.,* Joseph F

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Perioperative Drug Therapy in Elderly Patients Richard Rivera, M.D.,* Joseph F Ⅵ CLINICAL CONCEPTS AND COMMENTARY Bruno Riou, M.D., Ph.D., Editor Anesthesiology 2009; 110:1176–81 Copyright © 2009, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc. Perioperative Drug Therapy in Elderly Patients Richard Rivera, M.D.,* Joseph F. Antognini, M.D.† ADVANCES in modern medicine and public health have divide normally) and oxidative stress (inability to protect resulted in increased longevity, which in turn has re- against reactive metabolic molecules, e.g., free radicals).1 sulted in more elderly patients (arbitrarily defined as In addition, as humans age, protein structure is altered, Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/110/5/1176/247375/0000542-200905000-00035.pdf by guest on 30 September 2021 aged 65 yr or older) coming to the operating room for a and this likely accounts for physiologic changes of old variety of surgical procedures. Even in the absence of age.2 For example, blood vessel distensibility is drasti- comorbidities, these patients, as compared with their cally decreased in elderly patients and, combined with younger cohorts, respond differently to various peri- increased intimal thickness and endothelial dysfunction, operative physiologic trespasses and pharmacologic will increase systolic blood pressure, as well as left ven- interventions. In this clinical commentary, we focus tricular workload. Myocardial hypertrophy, along with on the altered pharmacologic responses elderly pa- increased collagen content, creates a stiff left ventricle tients have during the perioperative period. In many that depends on adequate preload to maintain cardiac instances, elderly patients are more sensitive to drugs, output. This makes elderly patients much more suscep- and for the purposes of this clinical commentary, we tible to fluid overload.3 In addition, blunted baroreflexes use the word sensitivity in its general clinical mean- make geriatric patients less able to respond normally to ing, i.e., an enhanced response for a given dose of hypovolemia and much more susceptible to orthostatic drug that might have a pharmacokinetic or pharmaco- 4 dynamic explanation. hypotension with drug therapy. Taken together, these alterations in the cardiovascular system can make elderly patients more sensitive to fluid shifts and blood loss. Normal Physiologic Function during Aging The pulmonary system also undergoes significant change during the aging process, with decreased forced expiratory As humans age, there is a general decline in organ volume, increased physiologic shunt, and increased closing function, although there is wide interindividual and in- volume. These pulmonary alterations increase the risk to traindividual variability (e.g., some organs might be af- elderly patients during the perioperative period.5 For ex- fected more than others). Most importantly, the cardio- ample, elderly patients are more likely to develop atelecta- vascular and pulmonary systems have reduced function sis, cough poorly, and develop pneumonia. Hypoxemia is that might impact patients’ physiologic responses during also more likely in these patients. surgery and anesthesia. Healthy elderly patients, how- Elderly patients, compared with younger ones, have ever, might not manifest this decreased function unless increased adipose tissue, decreased muscle mass, and de- stressed. That is, while they may have adequate function creased total body water (fig. 2 and table 1). Renal func- with normal activities, they have diminished reserves tion decreases over time, and this is manifested as de- that prevent them from tolerating moderate or severe creased glomerular filtration rate and impaired secretion. stress, such as major surgery and anesthesia. Chronic Creatinine clearance, which depends on the glomerular disease and acute exacerbation of chronic disease can filtration rate, can be estimated from the Cockroft–Gault further impact an elderly patient’s response to perioper- formula: ative stress (fig. 1). There are numerous theories of aging, including cellu- Creatinine clearance lar senescence (cells are unable to replicate DNA and ͑140 Ϫ age ͒ · Weight ͑kg͒ · ͑0.85 if female͒ ϭ ͑ ͒ * Associate Professor, † Professor. 72 · Serum Creatinine mg/ml Received from the Department of Anesthesiology and Pain Medicine, Univer- sity of California, Davis, California. Submitted for publication June 20, 2008. Changes in glomerular filtration rate are variable, with Accepted for publication December 11, 2008. Support was provided solely from some elderly patients having little change over time and institutional and/or departmental sources. others having a marked decrease. Because of decreased The tables and figures in this article have been prepared by Dimitri Karet- nikov, 7 Tennyson Drive, Plainsboro, New Jersey 08536. muscle mass, serum creatinine is usually in the normal Address correspondence to Dr. Antognini: Department of Anesthesiology and clinical range despite the lower glomerular filtration Pain Medicine, TB-170, University of California, Davis, California 95616. rate. All of these factors can impact how the elderly body [email protected]. This article may be accessed for personal use at no charge through the Journal Web site, www.anesthesiology.org. handles drugs. Added to this are changes in protein Anesthesiology, V 110, No 5, May 2009 1176 PERIOPERATIVE DRUG THERAPY IN THE ELDERLY 1177 Table 1. Age-related Changes in Physiological Parameters Downloaded from http://pubs.asahq.org/anesthesiology/article-pdf/110/5/1176/247375/0000542-200905000-00035.pdf by guest on 30 September 2021 Fig. 1. Organ function declines over time in normal healthy humans, as indicated by line 1. Chronic disease will accelerate this decline, as noted by line 2. Acute disease will cause tempo- rary rapid but reversible declines, as shown by lines 3. Regard- less of cause, reserve function is lost when organ function declines into the shaded area. Adapted from Bouchon22; used with permission. binding that alter free drug availability. This is important for drugs that have high protein binding. Elderly patients are particularly vulnerable to delirium and after surgery. Pharmacokinetics is often thought of and cognitive decline in the postoperative period, and as “what the body does to the drug”: The drug will be these complications are associated with increased mor- distributed to blood and various tissues and will be tality.6 For example, the incidences of postoperative metabolized, degraded, or secreted, thus decreasing the cognitive dysfunction at discharge and at 3 months after drug concentration over time. Pharmacodynamics is discharge are 41% and 13%, respectively, in elderly pa- “what the drug does to the body”: This is the set of tients.6 Preoperative memory complaints could signal pharmacologic actions produced by the drug, both de- early dementia and should be evaluated. Although the sired and undesired. In general, elderly patients will be etiology of these serious complications is unclear, there sensitive to drugs because of changes in pharmacokinet- are several potential risk factors, including advanced age, ics that lead to higher concentrations for a given dose, lower educational level, and history of cerebral stroke.6 because of pharmacodynamic changes (i.e., increased It behooves the anesthesiologist to minimize any possi- sensitivity for a given drug concentration), or because of ble contribution of excessive drug exposure to these both. outcomes. For a given drug dose, the plasma concentration and the volume of distribution of a drug are inversely related. Pharmacokinetics Total body water decreases as we age, and the use of diuretics exacerbates this change. Therefore, hydro- The aging process will affect the pharmacokinetics and philic drugs have a smaller volume of distribution and, pharmacodynamics of many drugs used before, during, for a given dose, a higher plasma concentration. This will generate a greater pharmacologic effect. Morphine, for example, has a volume of distribution in the elderly that is only half of that in younger patients. Ultimately, how- ever, the effect of a drug will depend in great part on the volume of distribution at the effect site (i.e., the site where the drug exerts its desired action). On the other hand, with the increase of body fat, the volume of distribution of lipid soluble drugs increases. This retards their elimination, as occurs with diaze- Fig. 2. Compared with young patients, elderly patients tend to pam—its elimination half-life is increased severalfold in have more adipose tissue, decreased body water, and less mus- the elderly. Although this prolonged half-life might not cle mass. These changes will cause water-soluble drugs to have be important after a single dose of diazepam, it would decreased volume of distribution (Vdwater), whereas lipid-solu- ble drugs may have increased volume of distribution (Vdlipid). have a more significant impact with repeated dosing. Clearance for most drugs is decreased in the elderly. Drug Most anesthetic drugs are, to one extent or another, sensitivity (especially to anesthetics) is usually increased in elderly patients but may be decreased for other drugs, such as ␤ protein bound. Albumin is decreased by up to 20% in the blockers. elderly, and perhaps more in the setting of poor nutri- Anesthesiology, V 110, No 5, May 2009 1178 R. RIVERA AND J. F. ANTOGNINI tion. Propofol is highly protein bound, and even mod- age 90 yr. Therefore, the clearance of drugs primarily estly decreased albumin levels might affect free-drug
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