DURING the past few decades, much has been learned about the physiology and pharmacology of aging, including the way aging alters the response to drugs used during anesthesia. The literature generally supports the notion that older patients should receive lower doses of opioids. Several rigorous pharmacokinetic–pharmacodynamic (PK–PD) modeling studies have shown that elderly subjects have increased sensitivity to opioids. 1,2This is partly due to changes in opioid disposition with aging (decreased clearance, decreased volumes of distribution), but the primary difference appears to be a true increase in pharmacodynamic sensitivity. This means that lower opioid concentrations are needed to produce the same effect in elderly patients. The article by Aubrun et al.  3in this issue of Anesthesiology seems to be inconsistent with these PK–PD data. The authors conclude that treating postoperative pain by incrementally titrating a fixed morphine dose (2–3 mg every 5 min) is equally effective and safe for adults of all ages. This conclusion is valid, but not because old and young are equally opioid sensitive. We must be clear about what this trial has and has not shown.

Aubrun et al.  have shown us a good way to provide postoperative analgesia. All patients had the same incremental dose of morphine, but it was titrated carefully using visual analog pain scales and frequent observation for side effects. The fact that no patient was hurt probably reflects the frequency of clinical assessments. It does not mean that all patients needed or tolerated the same treatment. In fact, there is good evidence that older patients were being treated differently. The study was unblinded, so all clinical decision makers knew whether they were treating older or younger patients. We do not know whether this affected intraoperative treatment (different premedication, lower doses of anesthetics, analgesics, and so forth), but we do know that postanesthesia care unit nurses waited 45 min longer to give morphine to older patients, and they kept the patients in postanesthesia care unit for observation nearly 2 h longer. If one considers all patients studied (as one should), the absolute morphine dose (in milligrams) was slightly but significantly lower in the elderly. The difference in total morphine dose only disappeared when a post hoc  adjustment to milligrams per kilogram was made, but this is not how postanesthesia care unit nurses were actually dosing.

Even if the study had been blinded, the results might have been the same. In carefully controlled experimental situations, there can still be 5- to 10-fold individual variability in intraoperative 4and postoperative 5opioid requirements. In an unselected postoperative population such as that studied by Aubrun et al. , morphine dose could have been affected by numerous factors, including sex, duration of anesthesia, intraoperative analgesics, opioid tolerance, organ dysfunction, severity of pain, and so forth. This study did not control for sources of variability other than age and weight, and this makes it highly unlikely that any true age effect could be detected through the clinical “noise.” Of course, that is exactly the point the authors are trying to make. Under normal clinical conditions, we can never adjust for all of these factors, so we titrate to effect. Creating an analgesic “recipe” that incorporates only one or two factors, such as age and weight, does not account for sufficient variability to make a meaningful difference in pain relief or side effects.

Despite these limitations, the results suggest that if care is taken, the incremental administration of morphine may not need to be radically modified for age. This novel observation could change our approach to the postoperative treatment of the elderly. Older patients are often treated empirically with less drug and may therefore be undermedicated in the immediate (postanesthesia care unit) postoperative period. These results indicated that such undermedication is not warranted because of a fear of adverse events.

The importance of knowing how to manage the elderly patient safely cannot be ignored. The 2000 census figures affirm the predictions for growth in the population of older Americans. 6By 2050, there are expected to be 31 million citizens aged older than 80 yr. In just the past decade, those over 75 have gone from 5.3 to 6.1% of the US population. Given that the elderly have surgery four times more often than the rest of the population, anesthesiologists can look to the future and see a time when the majority of our patients will be aged older than 65 yr, and many will be older than 80 yr.

The implications of this change in demographics are enormous and require action now. Schneider made a plea in 1999 that scientists and granting agencies around the world commit resources to better understand the implication of aging on our future. 7For anesthesiologists, there is a pressing need to learn the differences and similarities between young and old as they relate to the entire continuum of the perioperative period. This is one reason a group of anesthesiologists started the Society for the Advancement of Geriatric Anesthesia last fall. *Research should take a broad, integrative approach via  systematic clinical trials that test the hypothesis that age alters the physiologic and pharmacologic response of patients. The article by Aubrun et al.  is an example of a useful, albeit isolated, investigation that needs companion studies looking at pain management throughout the hospital stay. Many postoperative complications, such as cognitive impairment, are directly related to age, 8and it is imperative that a carefully planned research program be crafted and presented to funding agencies so that complications and their mechanism are identified and methods to prevent them are tested.

Successful research by anesthesiologists will benefit practitioners of other concerned specialties if there is an effective mechanism to exchange the information. The perioperative care of the elderly has not been extensively examined from a multidisciplinary perspective. Furthermore, available knowledge has not been adequately disseminated. In recognition of these deficiencies, the American Geriatrics Society (AGS) has for several years now been bringing physicians of many specialties together to exchange information and provide ideas on how to correct these problems. The AGS has targeted 10 specialties: emergency medicine, anesthesiology, general surgery, gynecology, ophthalmology, orthopedic surgery, otolaryngology, thoracic surgery, urology, and physical medicine and rehabilitation. With funding from the Hartford Foundation, the AGS has encouraged each specialty to develop its own educational programs in geriatrics †and has supported symposia, faculty development for individuals and departments, and production of written materials. 9Our specialty has received money to support anesthesiology research through the Foundation for Anesthesia Education and Research, the biannual (1997–2001) Duke Conference on Surgery and the Elderly, and faculty development and resident education at the Universities of California-San Francisco (San Francisco, CA), Duke (Durham, NC), Pennsylvania (Philadelphia, PA), and Washington (Seattle, WA).

The AGS has also held meetings with an Interdisciplinary Leadership Group made up of geriatricians and representatives of the 10 specialties. The initial task was to define what must happen in organized medicine to provide good care for the elderly outside of internal medicine. Their conclusions were summarized in a Statement of Principles. ‡10The Statement enumerated a number of complications from hospitalization common to the elderly, including delirium, thromboembolism, adverse drug events, dehydration, infection, and inadequate pain management. The Statement set goals for the future, including increased geriatric education of medical students, residents, and practitioners, elimination of historical disinterest in geriatrics, better remuneration for the care of the elderly, and of course, more research.

The next phase of AGS-funded programs will create further opportunities for the various specialties to interact with one another and to expand their geriatric programs. The Interdisciplinary Leadership Group will expand in size and scope into the Executive Committee of the Section on Surgical and Related Medical Specialties of the AGS. Representatives from each specialty are currently reviewing the literature, from which a research agenda will be constructed by determining the most important issues common to the specialties. A significant opportunity to promote individual academic careers will be provided through the Jahnigen Career Development Annoucements ($100,000 per year for 2 yr, five per cohort, so applicants from anesthesiology will also compete with those from the other specialties). Institutional grants of $32,000 over 2 yr are available to enhance faculty development and resident education in the geriatric aspects of the specialties. In the first round of these grants, 2 of the 15 awards went to anesthesiology programs (Johns Hopkins University [Baltimore, MD] and University of California-San Francisco). Other programs include the Geriatrics Syllabus for Specialists, discretionary grants of $10,000 per year per specialty, and expansion of a clearinghouse and Web site for information regarding the aging aspects of the specialties. In short, the AGS encourages the involvement of anesthesiology and recognizes our specialty's scientific and clinical contributions to the care of the elderly. The future direction of these AGS initiatives is to devise strategies and test protocols to reduce specific complications common to the elderly. It is important that anesthesiologists seize the opportunities that lie ahead in research and education and join with the other specialties to make the future a safer place for our geriatric patients.

Scott JC, Stanski DR: Decreased fentanyl and alfentanil dose requirements with age: A simultaneous pharmacokinetic and pharmacodynamic evaluation. J Pharmacol Exp Ther 1987; 240: 159–66
Minto CF, Schnider TW, Egan TD, Youngs E, Lemmens HJM, Gambus PL, Billard V, Hoke JF, Moore KHP, Hermann DJ, Muir KT, Mandema JW, Shafer SL: Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil, I: Model development. A nesthesiology 1997; 86: 10–23
Aubrun F, Monsel S, Langeron O, Coriat P, Riou B: Postoperative titration of intravenous morphine in the elderly patient. A nesthesiology 2002; 96: 17–23
Ausems ME, Hug CC, Stanski DR, Burm AGL: Plasma concentrations of alfentanil required to supplement nitrous oxide anesthesia for general surgery. A nesthesiology 1986; 65: 362–73
Austin KL, Stapleton JV, Mather LE: Relationship between blood meperidine concentrations and analgesic response: A preliminary report. A nesthesiology 1980; 53: 460–6
Day JC: Population projections of the United States by age, sex, race, and Hispanic origin: 1995 to 2050, Current Population Reports, Bureau of the Census. Washington, DC, US Printing Office, 1996, p 25
Schneider EL: Aging in the third millennium. Science 1999; 283: 796–7
Newman MF, Kirchner JL, Phillips-Bute B, Gaver V, Grocott H, Jones RH, Reves JG, Blumenthal JA, Neurological Outcome Research Group of the Duke Heart Center: Longitudinal assessment of neurocognitive function after coronary artery bypass surgery: Perioperative decline predicts long-term (5-year) neurocognitive deterioration. N Engl J Med: 2001; 344: 395–402
Neurological Outcome Research Group of the Duke Heart Center:
Solomon DH, Burton JR, Lundebjerg NE, Eisner J: The new frontier: Increasing geriatrics expertise in surgical and medical specialties. J Am Geriatr Soc 2000; 48: 702–4
Interdisciplinary Leadership Group of the American Geriatrics Society: A statement of principles: Toward improved care of older patients in surgical and medical specialties. J Am Geriatr Soc 2000; 48: 699–701
Interdisciplinary Leadership Group of the American Geriatrics Society: