An aging population carries profound implications for the practice of anesthesiology. Geriatric issues impact every aspect of anesthesiology. First, the preoperative evaluation of the geriatric patient is typically more complex than that of the younger patient because of the heterogeneity of this patient group and the greater number and complexity of comorbid conditions that usually accumulate with age. Perioperative functional status can be difficult to predict because many elderly patients have reduced preoperative function as a consequence of deconditioning, age-related disease, or cognitive impairment. This makes it difficult to adequately assess the patient's ability to respond to the specific stresses associated with surgery. A common example is trying to determine cardiopulmonary reserve in a patient very limited by osteoarthritis. Physiologic heterogeneity and decreased functional reserve are also manifested perioperatively. Normal aging results in changes in cardiac, respiratory, and renal physiology, and the response of the elderly patient to surgical stress is often unpredictable. The pharmacokinetics and pharmacodynamics of elderly and younger patients also differ; moreover, the elderly patient's use of multiple medications may alter homeostatic mechanisms.

Numerous changes in cardiovascular function with aging have implications for anesthetic care. With aging, the progressive decrease in the elasticity of the arterial vasculature leads to an increase in systolic blood pressure. Diastolic blood pressure increases through middle age and typically declines after age 60. ¹ The cross-sectional area of the peripheral vascular bed also decreases, resulting in a higher peripheral vascular resistance. ² A decrease in the peripheral vasodilatory response to Β-adrenergic stimulation may also contribute to the hypertension of aging. ³

  Progressive ventricular hypertrophy develops in response to increased afterload, resulting in both cellular hypertrophy and deposition of fibrotic tissue. Ventricular hypertrophy increases both wall stress and myocardial oxygen demand and makes the ventricle more prone to ischemia.

  Although intrinsic contractility and resting cardiac output are unaltered with aging, the practical effect of ventricular hypertrophy and stiffening is that they limit the ability of the heart to adjust stroke volume. ⁴ Ventricular hypertrophy impairs the passive filling phase of diastole, making ventricular preload more dependent on the contribution of atrial contraction. At the same time, fatty infiltration and fibrosis of the heart increases the incidence of sinus, atrioventricular, and ventricular conduction defects. ^5,6 Myocardial responsiveness to catecholamines also decreases with age; maximal heart rate response is correspondingly decreased. ^4,7,8 The reduction in ventricular compliance and the attenuated response to catecholamines compromise the heart's ability to buffer increases in circulatory volume, which results in a predisposition to congestive heart failure. Similarly, even modest decreases in circulatory volume produce hypotension.

The pulmonary system also undergoes age-related changes in both mechanics and control mechanisms independently of comorbid disease processes. Functionally, there are remarkable parallels with changes in the heart. With aging, the thorax becomes stiffer. ^14,15 This may not be evident in the sedentary patient, but reduced chest wall compliance increases the work of breathing and reduces maximal minute ventilation. ^14-16 Loss of thoracic skeletal muscle mass aggravates this process. ¹⁷ Because of a decrease in elastic lung recoil, the closing volume increases such that by age 65 it exceeds functional residual capacity. ¹⁸ Inspiratory and expiratory functional reserve decrease with aging, and the normal matching of ventilation and perfusion decreases. ^19,20 The latter process increases the alveolar-arterial O₂ gradient and decreases the resting Pao₂. ^18,21 The respiratory response to hypoxia also diminishes in the aged patient. ²² (See Figure 2.2.) In addition, ciliary function is decreased and cough is reduced. ¹⁵ Finally, pharyngeal sensation and the motor function required for swallowing are diminished. ^23,24

Pulmonary and cardiac complications, respectively, account for most morbidity and mortality in older surgical patients. However, neurologic morbidity affects a large number of patients, and age-related degenerative changes in the central and peripheral nervous systems contribute to a variety of other morbidities. In themselves, neurologic complications have a dramatic impact on length of stay and discharge disposition, translating directly into altered functional status and quality of life.

  Independently of any comorbid process, both the central and peripheral nervous systems are affected by aging. ³¹ There is a loss of cortical gray matter beginning in middle age, resulting in cerebral atrophy, ³² although how much of this is attributable to aging itself or to degenerative diseases is a subject of ongoing investigation. ³³ At the level of the neuron, the complexity of neuronal connections decreases, the synthesis of neurotransmitters decreases, and the enzymes responsible for their postsynaptic degradation increase. ^32,34,35 While cerebral metabolism, blood flow, and autoregulation generally remain intact, ³² neuronal loss and the deficiency of neurotransmitters limit the ability of the older brain to integrate multiple neural inputs. This has been described as a loss of "fluid" intelligence. Neuronal loss and demyelinization also occur in the spinal cord. ³⁶ Functionally, spinal cord reflexes change and proprioception is reduced. There are also important decreases in hypoxic and hypercarbic drive. ^22,37 Declines in visual and auditory function further complicate the ability of the nervous system to acquire and process information. This combination of changes can limit the ability of the older patient to understand and process information in the perioperative period. These changes are probably important contributors to postoperative delirium, drug toxicity, and falls.

  Aging is also associated with neuronal loss in the autonomic nervous system. Both sympathetic and parasympathetic ganglia lose neurons, and fibrosis of peripheral sympathetic neurons occurs. This peripheral neuronal adrenergic loss is associated withimpairment of cardiovascular reflexes. At the same time, decreases in adrenoceptor responsiveness result in increased adrenomedullary output and plasma catecholamine concentrations. ^11,13,36

Aging is accompanied by a progressive decrease in renal blood flow and loss of renal parenchyma. ^49,50 By age 80, half of all older persons may have reduced renal blood flow. This is accompanied by renal cortical atrophy, resulting in a 30% decrease in nephrons by the end of middle age. ^49,51 Furthermore, aging is associated with sclerosis of remaining nephrons so that some of those remaining are dysfunctional. ^50,52 Together, these processes result in a progressive decrease in glomerular capillary surface area and glomerular filtration rate. ^50,52-54 However, because of loss of muscle mass, aging is not associated with an increase in serum creatinine. This physiologic, and often occult, aspect of senescence has practical implications in the perioperative period.

  The old kidney has difficulty in maintaining circulating blood volume and sodium homeostasis in the perioperative period. ^11,53-55 Sodium conservation and excretion are both impaired by aging. Fluid homeostasis is further complicated by alterations in thirst mechanisms and antidiuretic hormone release that frequently result in dehydration. ^53-56 In the perioperative period, metabolic acidosis is also relatively common, particularly in elderly patients who are less efficient in the renal excretion of acid. ⁵⁷

Aging is associated with multiple physiologic changes that may affect drug pharmaco-kinetics. ⁵⁸ Decreased lean body mass and total body water and an increased proportion of body fat alter the volume of distribution of drugs, their redistribution among body compartments, and subsequently their rates of clearance and elimination. ^59-61 The effect of changes in body composition on drug distribution and action varies, depending on the lipid or aqueous solubility of the drug. Water-soluble drugs can have higher serum concentration and lower redistribution, whereas fat-soluble drugs tend to undergo wider distribution and accumulation, followed by delayed release.

The preoperative assessment of the elderly surgical patient is determined by the underlying health of the patient and influenced by the urgency of the procedure. That said, preoperative evaluation could serve several purposes in most patients. Historically, it has served two primary functions: One is to alert the surgical care providers to physiologic conditions that may alter perioperative management, and the other is to determine if medical intervention is indicated before proceeding. Two more contemporary uses of the preoperative assessment are to provide an index of risk and therefore contribute to decisions about the most appropriate intervention, and to provide baseline data on which the success of a surgical intervention might be judged.

  Physiologic studies of aging and clinical experience with the elderly population yield three important conclusions that bear on preoperative assessment. First, the geriatric population is tremendously heterogeneous. This concept was superbly expressed by Muravchick, who noted that humans are never so similar as at birth, and never so dissimilar as in old age. ⁷¹ The second conclusion is that basal function in most elderly patients is sufficient to meet daily needs, but that under conditions of physiologic stress, impairment in functional reserve becomes evident. Third, it is evident that most older surgical patients have significant comorbidities. Up to 80% of elderly surgical patients have at least one comorbid condition, and one third have three or more pre-existing conditions. ^72,73

  In spite of these limitations, even extreme age is not a contraindication to surgery. Acceptable outcomes are reported for operations even in very old patients. ^74-78 What is less clear is how to identify which patients will do well and which will do poorly. Even though this has been the subject of considerable research, no area of perioperative anesthetic care and management requires more investigation. The preoperative assessment of the individual patient is composed of four interrelated functions:

• risk assessment that is based on a stratification of risk derived from population-based studies,
• the history and physical examination to determine health and functional status,
• preoperative testing, and
• in some cases, preoperative optimization.

Because age itself adds very little additional risk in the absence of comorbid disease, ⁷⁹ most risk-factor identification and risk-predictive indices have been disease oriented. ^80-84 Typically, these investigations have studied a broad age range of patients and in multivariate analyses identified the relative contribution of age and comorbid conditions to surgical morbidity and mortality. ^81,82,85-88 Others have looked at the predictive value of the number of comorbid diseases independently of the operative condition or have evaluated the impact of ASA (American Society of Anesthesiologists) status, specific surgical factors, and intra-operative management. ^82,88-93

The efficacy of preoperative functional evaluation in elderly surgical patients requires investigation. This is important for several reasons. The evaluation of the "resting" patient does not indicate how the patient will respond to the cardiac, pulmonary, and metabolic demands of the perioperative period. This approach is emphasized in the guidelines of the American College of Cardiology and the American Heart Association for preoperative cardiac evaluation, in which the patient's activity level, expressed in metabolic units, is a primary determinant of the need for subsequent evaluation. ⁸⁰ However, this concept must be expanded because the geriatric population has a unique need for functional evaluation in more areas than just cardiopulmonary capacity. Because of patient heterogeneity, functional assessments may be indicated to better characterize patient differences, whether it is for activities of daily living (ADLs), instrumental activities of daily living (IADLs), cognitive and emotional status, or urologic function. ^94,95 Scales like the Medical Outcomes Study Short Form-36 (SF-36) ⁹⁶ have multiple domains that are particularly useful in assessing older patients. Although these metrics have been applied successfully in orthopedic and thoracic surgery ^97-99 and can have predictive value for longer term outcomes, ^100-104 multidimensional assessment and perioperative functional assessment are largely absent from the surgical literature. ^98,105,106

The third dimension of the preoperative evaluation of the elderly surgical patient is preoperative testing. Work in this area has been done for large populations of mixed-age groups. However, it is not clear whether selected preoperative screening tests have a different yield in the elderly age group or, more likely, if specific testing is indicated for elderly patient populations undergoing certain types of surgical procedures.

  In the general population there is agreement that most routine tests are not indicated. ^125-128 In an evaluation of preoperative screening in 1010 persons undergoing cholecystectomy, abnormal results were found in only 4.5% of tests. ¹²⁵ In another investigation of 3131 patients aged 0 to 98 years who underwent 38,286 tests, unexpected abnormal results were found in 15% of patients. ¹²⁶ However, only 3% had a change in their anesthetic or surgical plan that was based on those results. Unfortunately, in neither report was age-specific data provided, so it is unclear if the results can be applied to an elderly surgical population.

The fourth dimension of preoperative evaluation determines whether medical intervention is indicated before proceeding with surgery. To some extent, this dimension has been lost with the foreshortening of the preoperative period, the "AM admit," and a progressive elimination of preoperative testing.

  If we are going to define research agendas for the care of elderly surgery patients, preoperative optimization of medical status must be revisited. This is an area where relatively little work has been done. Again, in specific populations undergoing high-risk surgery, the value of preoperative optimization, particularly of cardiac and pulmonary status, can be demonstrated. Examples where the data are compelling include intervention for coronary disease before vascular surgery; pulmonary toilet, antibiotics, and corticosteroid therapy for some types of thoracic surgery; and preoperative Β-blockade. ^{143,144,146-150} Nevertheless, many areas have not been evaluated, particularly in the elderly population. Improving nutritional status before major elective surgery, preoperative hydration, and optimization of renal function in those with chronic or acute insufficiency could have broad impact. Preoperative management of antibiotic therapy, anticoagulation, antiplatelet therapy, and anemia are other obvious areas to examine. There are also suggestions that preoperative education, psychologic support, and physical therapy might facilitate pain management and rehabilitation following some types of surgery, ^151,152 but these have not been adequately assessed.

Anes 2 (Level B): Once better understanding of characteristic outcomes of specific types of surgery for older patients is attained, patient- and surgery-specific risk factors for geriatric complications should be identified by multivariate analysis that would stratify surgical risk as low, intermediate, or high, depending on type of surgery.

Anes 3 (Level B): The positive predictive value of preoperative assessment instruments should be determined in prospective nonrandomized or prospective cohort trials.

Anes 4 (Level A): Following evaluation of preoperative assessment instruments (Anes 3), prospective randomized trials should be performed to determine whether the application of these metrics could improve outcomes for elderly surgical patients by altering perioperative intervention, surgical timing, the type or extent of surgery, or postoperative management.

Anes 5 (Level B): Prospective cohort studies are needed to determine whether assessment of the older surgical patient's preoperative functional status affects surgical decision making or perioperative care.

Anes 6 (Level A): Depending on findings of prospective cohort studies (Anes 5), randomized trials should be performed to determine whether preoperative functional status assessment of elderly patients changes decisions about type or timing of surgery, or pre- or postoperative care strategies and outcomes.

Anes 7 (Level B): Cross-sectional or prospective cohort studies are needed to determine by multivariate analysis whether there is an association between pre-existing cognitive impairment, depression, or alcohol abuse and adverse outcomes in geriatric patients.

Anes 8 (Level A): For any association that is established by cross-sectional cohort studies between cognitive impairment, depression, or alcohol abuse and adverse outcomes in elderly surgical patients (Anes 7), prospective randomized trials should be performed to determine the effect of pre- or postoperative interventions on these adverse outcomes.

Anesthetic care is episodic, so most of the criteria to judge the success of anesthetic interventions are short-term. Studies of anesthetic drugs and techniques typically address hemodynamic stability, time to awakening, extubation time, postoperative nausea and vomiting, recovery room time, and length of stay. Awareness of the physiologic and pharmacokinetic changes characteristic of the elderly patient have led investigators to examine the effects of a host of anesthetic agents and adjuncts in this population. The effects on elderly patients of intravenous induction agents, narcotics, benzodiazepines, volatile anesthetics, neuromuscular blocking agents, and various types of local anesthetics have all been evaluated. Studies have included the use of these agents for inpatient surgical procedures, outpatient procedures, premedication, sedation, and their administration by bolus and infusion techniques. Because there is a theoretical advantage to shortening recovery time in patients for whom awakening, ambulation, and discharge might otherwise be delayed (ie, elderly patients), much of the more recent work focusing on elderly patients has been devoted to the ultra-short-acting agents.

Most general anesthetic agents depress cardiovascular and pulmonary function as well as alter consciousness, which is why it is often advocated that regional anesthesia be used for geriatric patients whenever possible. A major area of research has been to compare the risks and benefits of regional versus general anesthesia in elderly surgical patients. Elderly patients undergoing orthopedic procedures have been the focus of such research. These comparative studies have examined intraoperative cardiovascular stability; cardiac, pulmonary, and thrombotic complications; pain control; and cognitive outcomes. This subject was reviewed recently by Roy. ¹⁵⁴

  A few early studies reported that regional anesthesia for hip surgery was associated with better outcomes. Reduced mortality, higher postoperative Pao₂, and fewer mental changes have been reported in patients receiving regional anesthesia. ^155,156 However, these studies were very small, and their assessment of cognitive function would not meet current standards for reliability or validity. ¹⁵⁷

  Subsequent investigations of elderly patients undergoing hip surgery found that intra-operative hypotension is more common with regional anesthesia, and although the incidence of deep-vein thrombosis (DVT) and blood loss were typically lower with regional techniques, no difference in major morbidity or mortality could be identified. ^85,158-163 Because most of these studies are underpowered for rare events, meta-analysis has been used to help address statistical limitations.

In addition to establishing a surgical plane of anesthesia, the anesthesiologist maintains physiologic stability. Although numerous studies have examined the relationship between intraoperative physiologic management and outcome, outside of relatively rare catastrophic events, such as loss of the airway or uncontrolled hemorrhage, it appears that physiologic management plays a modulatory rather than a primary role in outcomes. The best example is in cardiac surgery, where the acute changes in blood pressure, hematocrit, and temperature typically exceed those seen with any other type of surgery. Additionally, most of the patients are older. In spite of that, it has been difficult to demonstrate a direct relationship between physiologic management and outcome. ^184-186 Rather, it appears that technical issues during surgery and the comorbidities that the patient brings to the operating room primarily determine outcome. ^187,188

  There is a role for specific studies of physiologic or pharmacologic management in elderly surgical patients, but those investigations are likely to have a smaller yield than risk stratification based on population studies and tailoring the surgical procedure to the patient on the basis of preoperative assessment.

  It is important to note that these conclusions are not an indictment of anesthetic practice or the role of the anesthesiologist in the operating room. Just the opposite is true. Over the past three decades, anesthesiology has made tremendous strides in patient safety, monitoring, drugs, and education that have made the intraoperative period extraordinarily safe. Those advances will continue to expand what is possible surgically. At the same time, it is because the advances in intraoperative care have been so great that the greatest needs for research lie in the preoperative assessment and the postoperative management of patients.

  There are also broad areas related to intraoperative management (rather than the specifics of anesthetic choice) where research focused on the elderly patient would be productive. It is clear that anesthetics and alterations in autonomic function make it more difficult for older patients to maintain their body temperature, and postoperative hypothermia increases the risk of adverse outcomes. ^189-193 Studies of temperature control in older patients could be expanded. The appropriate place for prophylactic Β-blockade, antiplatelet agents, and H₂ blockers in elderly surgical patients needs to be examined. Given that the immune response may be attenuated in elderly persons and that infectious complications are very common, the appropriate dosage and scheduling for perioperative antibiotics may be a useful area of research. Furthermore, elderly patients receive most of blood given in the perioperative period, so investigation of the immunosuppressive effects of homologous blood transfusion would be instructive. Elderly patients are also at increased risk for musculoskeletal and nerve injury, as well as thrombotic complications. Therefore, documenting the relationship between patient positioning, nerve and skin injury, and thrombotic complications is indicated. Similarly, the appropriateness of nothing-by-mouth (NPO) status, its relationship to hypovolemia, and aspiration risk in the elderly patient would be an area of research with a large potential impact on practice and patient satisfaction.

Anes 9 (Level B): Cross-sectional or retrospective case-control studies are needed to identify the incidence of adverse cardiac or thrombotic-embolic complications in elderly patients undergoing surgery with and without preoperative Β-blockade, antithrombotic or antiplatelet therapy, or with a hematocrit above a target value. These studies should be in surgeries identified as having an intermediate or high risk for related complications.

Anes 10 (Level A): For any association in elderly patients of cardiac thrombotic-embolic complications with a specific preoperative therapy or hematocrit level, prospective cohort or randomized studies are needed to determine if pre- or intraoperative therapies would reduce the complications.

Anes 11 (Level D): Prospective nonrandomized investigation of the effect of perioperative temperature management on surgical morbidity in the geriatric population is needed. These investigations should be conducted under conditions where either the surgery is physiologically very challenging or the older patient carries a high burden of comorbidity. Cardiac, respiratory, bleeding, and renal outcomes would be the primary focus of these investigations.

Anes 12 (Level D): Retrospective or cross-sectional research studies should be conducted to identify any relationship between the use or timing of perioperative antibiotic therapy and postoperative pneumonia or wound infection. Differences, if any, between younger and older patients undergoing the same type of surgery should also be examined.

Anes 13 (Level C): Depending on the findings in Anes 12, prospective randomized studies should be used to determine whether preoperative or postoperative antibiotic therapies reduce complications related to infections in elderly surgical patients.

Anes 14 (Level D): Multicenter case-control or prospective cohort studies should be performed to determine whether receiving or not receiving blood in the perioperative period affects the incidence of perioperative infection and immunosuppression in elderly patients. Multivariate analysis would be required to separate the effect of homologous blood transfusion from the comorbid conditions making transfusion more likely.

Anes 15 (Level C): If perioperative infection and immunosuppression in older surgical patients are shown to be associated with receiving blood in the preoperative period (Anes 14), alternative strategies such as delaying surgery or erythropoietin therapy should then be compared with blood transfusion in prospective cohort studies, because a randomized trial could not be justified.

Anes 16 (Level D): Cohort or case-control studies are needed to determine the relationship in older surgical patients between perioperative termination of anticoagulation and thromboembolic or bleeding risk.

Anes 17 (Level C): The effect of timing of termination and resumption as well as the temporizing use of antiplatelet agents in older surgical patients should be compared in case-control or prospective cohort studies.

Anes 18 (Level B): In prospective cohort studies the incidence of perioperative hypotension, aspiration, and renal insufficiency should be compared in elderly patients undergoing standard nothing-by-mouth orders before surgery and in elderly patientswho would be allowed clear liquids closer to the time of surgery. This study would need to be conducted in:

patients undergoing specific types of procedures where liberalization of fluid intake is not contraindicated for surgical reasons,

patients undergoing procedures that place them at greater risk for developing hypovolemia (bowel prep), and

instances where preoperative hypovolemia may contribute to complications (angiographic procedures).

The most common morbidity following noncardiac surgery is respiratory. A Veterans Administration study of 84,000 patients (97% male, mean age of 60) found that 17% of patients experienced complications, with pneumonia in 3.6%, ventilatory failure in 3.2%, and unplanned intubation in 2.4%. ⁸⁸ In a study of 288 general surgical patients aged 65 and over, Seymour and Vaz reported that 17% of patients had atelectasis, 12% had acute bronchitis, and 10% developed pneumonia. ¹⁹⁷

  For many reasons, postoperative hypoxia may occur in 20% to 60% of elderly surgical patients. ^28,29 As highlighted previously, elderly patients have an increased alveolar-arterial gradient, reduced respiratory muscle strength, and hypoxic and hypercarbic drives at baseline. ^14,20,27 Additionally, there is a progressive loss of airway reflexes with age, and apnea and periodic breathing following administration of narcotics are more common. ^18,25,198 Postoperative pain, atelectasis, and fluid shifts further increase the likelihood of respiratory complications, as do reductions in cardiac output, hemoglobin concentration, and shivering. ^19,191 The supine position during recovery increases the transpulmonary shunt and makes hypoxia more likely. ¹⁸ Finally, orthopedic and upper abdominal surgeries, which are common in elderly persons, have an independent effect in increasing postoperative hypoxia and respiratory complications. ^26,197,199

  In spite of the frequency of postoperative hypoxia and hypercarbia in elderly surgical patients, clear guidelines for oxygen therapy, pulse oximetry, and capnography in older patients have been poorly defined. ^200,201 This issue is of pressing importance, as "day surgery" has increased and continued efforts are made to abbreviate the time to discharge. Further, more and more patients, most of them elderly, undergo conscious sedation outside the operating room environment. Even though the study by Bailey et al is more than 10 years old, its implications are unchanged. ²⁰² In a study of hypoxemia and apnea after sedation with fentanyl and midazolam, they describe deaths associated with the use of these drugs. Of 86 reported U.S. deaths, "All but three . . . occurred outside the operating room . . . where patients are typically unattended by anesthesia personnel." Determination of the requirements for oxygen therapy, pulse oximetry, and capnography in elderly patients undergoing inpatient and outpatient surgery, including procedures with conscious sedation, is indicated.

  The risk of postoperative aspiration for the elderly surgical patient also requires attention. Because of alterations in pharyngeal function, diminished cough, and an increased incidence of gastroesophageal reflux, elderly patients are at increased risk of aspiration. ^23,24 This risk is accentuated by the effect of anesthesia, sedatives, and narcotics as well as by endotracheal intubation, nasogastric tube placement, and upper abdominal or neck surgery. ^30,203,204 Even though the incidence of aspiration in the operative period is low and is uncommonly associated with clinically important pneumonitis or pneumonia, ²⁰⁵ the risk for aspiration extends well beyond the acute operative period.

  It is likely that instrumentation of the pharynx, whether from an endotracheal tube, ³⁰ nasogastric tube, ²⁰⁴ or a transesophageal echocardiography probe, ²⁰³ alters sensation, motor function, and the protective reflexes preventing aspiration. For patients with prolonged endotracheal intubation (> 24 hours), this effect is persistent for at least 48 hours following extubation. ³⁰ Nasogastric tubes may also contribute to aspiration by increasing the incompetence of the gastroesophageal junction. Pharyngeal dysfunction and aspiration may be related to a greater acuity of illness, but sufficient evidence suggests pharyngeal trespass itself has independent effects.

The perioperative period results in stress and inflammatory responses that peak postoperatively when cardiopulmonary and neurologic complications occur. Therefore, efforts have been made to link the adequacy of analgesia with the magnitude of the stress response. In particular, it has been proposed that inadequate postoperative analgesia may be associated with myocardial ischemia and pulmonary failure. Researchers have examined the effect of the intraoperative anesthetic ^207-210 and postoperative epidural analgesia on plasma levels of cortisol, epinephrine, norepinephrine, leucocyte counts, and acute phase proteins and have tried to relate these to cardiopulmonary outcomes. ^{173,207,211-215} Both negative and positive conclusions have been reached.

  When this subject was reviewed by Liu, Carpenter, and Neal, ²¹⁶ they concluded that intensive analgesia using regional techniques has a limited impact on cardiopulmonary outcomes or the stress response in a general population of surgical patients. They also concluded that pain and the stress response are not directly coupled because the neuroendocrine response is still demonstrated (although blunted) in the presence of intense surgical analgesia with local anesthetics or opioids. However, studies in the groups with highest risk suggest a possible improvement in outcome with intense analgesia that uses regional techniques. ^173,217 Intensive pain management strategies may be indicated in high-risk elderly patients or in low-risk elderly patients undergoing high-risk surgery. Defining the circumstances under which epidural analgesia or any other pain management strategy can improve outcomes is an important area for future research.

  In addition to the stress response typically associated with the sympathetic-adrenal axis, most types of surgery initiate a significant catabolic state. An inhibitory effect of analgesia on protein wasting has been suggested, ^218-220 but a more pressing area for research is to understand postsurgical catabolism in elderly patients. The relationship between preoperative nutritional status and postoperative catabolism must be better understood. Experience with some critically ill patients suggests that catabolism may become dissociated from the initial surgical stress. Because elderly patients have decreased nutritional and metabolic reserve, they are most challenged by the postoperative catabolic state. Basic investigation into postoperative catabolism in the elderly person is important, as are investigations of interventions that might attenuate catabolism or facilitate the transition back to an anabolism.

  The adequacy of postoperative analgesia does not appear to be an independent determinant of outcomes in the general population of surgical patients; however, a variety of other issues related to postoperative analgesia require attention. The relative benefit of patient-controlled analgesia (PCA) ²²¹ versus an as-needed or scheduled analgesic administration is of special importance for the elderly surgical patient. Because of the physiologic and psychologic heterogeneity in the geriatric population, it is unlikely that fixed formulae for age-appropriate drug dosing can be identified. Thus, the administration of narcotics on a set schedule in the elderly person is fraught with the potential for both over- and underdosing. These considerations potentially make PCA analgesia an ideal choice. Nevertheless, the issue is complicated. The side-effect profile for PCA analgesics in elderly patients has not been established. ^222,223 It has also been suggested that many elderly patients may struggle with the technology. Similarly, the application of PCA for patients with altered mental status is troubling. Outcomes with PCA in the elderly patient must be compared with fixed and as-needed dosing techniques, as well as with postoperative pain control by regional blockade.

  The same is true regarding route of administration for analgesic agents. Is there a clear advantage or disadvantage to the use of the intravenous, epidural, or intrathecal routes for analgesic administration in the elderly patient? The elderly person is unusually susceptible to drug interactions and has an increased incidence of respiratory depression, urinary retention, ileus, constipation, and postoperative falls. These are influenced by choices in postoperative analgesia and may differ by route of administration. ^222-225 Investigations of analgesic strategies for elderly surgical patients will need to determine not only the quality of analgesia but also the risks and benefits specific to that population. Additionally, because narcotics are commonly associated with side effects in the elderly population, the use of analgesic adjuncts in postoperative pain management requires further investigation. Drugs like ketorolac, clonidine, dexmedetomidine, and COX-2 inhibitors have the potential to achieve adequate analgesia with lower doses of opioids, potentially reducing side effects. ^226-230

  A final reason why studies of acute pain management in the elderly person are required is that acute pain management may bear on rehabilitation and subsequently on functional status on discharge. ²³¹ This has been shown with analgesic programs for continuous passive motion machines used following knee replacement. ^231-233 Research is required following other types of surgical procedures to determine whether facilitating rehabilitation by effectively managing acute pain can improve other functional outcomes.

  Another opportunity for research in the postoperative care of hospitalized elderly patients is related to polypharmacy and adverse drug events. Elderly patients tend to accumulate drug prescriptions over time, and there is a clear relationship between the number of drugs taken and the incidence of adverse drug-related events. ^66-70 This problem will be compounded during the surgical period when even more medications are added.

  A study by Cullen et al prospectively compared adverse drug events among surgical and medical hospitalized patients in intensive care (ICU) and in general units. ²³⁴ The researchers found that the rate of preventable and potential adverse drug events is related to the number of drugs administered rather than to the type of care delivered (ICU or non-ICU, surgical or medical). The earlier report of the same data on 4031 adult hospital admissions identified, among other things, the incidence of adverse drug events, their preventability, and the classes of drugs that caused most events. Those results have particular bearing on the perioperative care of the elderly person. ⁶⁸

  In the investigation by Bates et al, analgesics were found to be the class of drug that is associated with the highest number of adverse drug events. ⁶⁸ Antibiotics were found to cause the second greatest number of adverse reactions. Analgesics are also the leading class of drug associated with preventable adverse drug events, followed by sedatives and then antibiotics (see Table 2.2). In the 20 preventable adverse events related to analgesics, 40% were found to be caused by overmedication.

Postoperative delirium or cognitive decline affect 5% to 50% of elderly patients; both disorders have similar predisposing factors, but the syndromes are not equiva-lent. ^{111,196,235-237} Disordered thinking and confusion that waxes and wanes characterize postoperative delirium. The onset is typically on the first to third postoperative day, may be sustained for more than a week, and is associated with other medical complications, prolonged hospitalization, and decreased functional status on discharge. ^{114,121,196,236,238-240} To date, much of the research has centered on the impact of regional versus general anesthesia in orthopedic surgery. ^{117,118,157,170-172,241} Cognitive dysfunction, a deterioration of such capacities as memory, central processing time, and acquisition of new information, has been well described in both cardiac and noncardiac surgical patients. ^242-245

  In anesthesia, the effect of differing anesthetics on postoperative delirium has been studied, ^{118,157,172,246-249} and a leading hypothesis has been that offending agents aggravate an age-associated central cholinergic insufficiency. ^117,250,251 However, from review of the literature it becomes evident that delirium is a syndrome that can be triggered by many different perioperative events, so no single cause is identifiable and no single intervention is likely to be successful.

  In addition to being linked to narcotics, sedatives, and anticholinergics, delirium has been associated with urinary tract infection, pneumonia, hypoxia or hypercarbia, fever, blood loss, and electrolyte disturbances. ^{196,235,236,252-254} Chronic patient factors such as pre-existing frank or subclinical dementia, other organic brain disease, and vision and hearing loss are also predictors of postoperative delirium and cognitive decline. ^{103,111,114,196,235,255,256} Finally, in the elderly patient it has been suggested that pain, sleep deprivation, sensory deprivation, and an unfamiliar environment may contribute to delirium. ^{113,196,235,257,258}

  Most of the research in the anesthesia literature has focused on the effect of anesthetic and analgesic agents, but the literature in medical patients suggests that the yield for those studies will be low. Studies of the type conducted by Inouye might serve as a model for research in anesthesia. ^{104,109,254-256,259-261} Inouye describes a multifactorial model for delirium involving the interrelationship between a vulnerable patient and acute insults. ^254,259 In a study of elderly medical patients, multivariate modeling identified four risk factors for developing hospitalization delirium: vision impairment, severe illness, pre-existing cognitive impairment, and a blood urea nitrogen-creatinine ratio ≥ 18. ^259,262 Patients were then divided into low-, intermediate-, and high-risk groups, depending on the number of risk factors. In a subsequent validation cohort, the rates of delirium in the low-, intermediate-, and high-risk groups were 3%, 16%, and 32%, respectively. ²⁵⁹ In those patients the rate of death or nursing-home placement was 3%, 14%, and 26%, respectively, an eightfold increase from the lowest to highest risk group. ²⁶²

  Precipitating factors for delirium in hospitalized medical patients have also been described by Inouye and Charpentier ²⁵⁴ Twenty-five factors occurring at least 24 hours before the onset of delirium were considered. Of those, a multivariate model identified five as predictive: use of physical restraints, malnutrition, more than three medications added, use of a bladder catheter, and any iatrogenic event (eg, volume overload, urinary tract infection, pressure ulcer). Even though the precipitating factors were independent of each other, the authors note that "baseline and precipitating factors are highly interrelated and contribute to delirium in a cumulative fashion."

  In a subsequent publication, Inouye et al ²⁶⁰ determined the effect of interventions that were based on their predictive model. Four hundred and twenty-six elderly medical patients in an intervention group were matched to an equal number in a usual care group. In the intervention group, six risk factors for delirium were targeted for intervention: cognitive impairment, sleep deprivation, immobility, visual and hearing impairment, and dehydration. The group receiving intervention by an interdisciplinary team had a 9.9% incidence of delirium versus 15% in the usual care group (a 34% difference). Subdivision of patients into intermediate- or high-risk groups demonstrated that intervention reduced delirium diagnosed by the Confusion Assessment Method (CAM) ²⁶³ in intermediate-risk patients, but the tendency to reduce delirium in the high-risk group was not found to be statistically significant.

  These studies indicate that presence and severity of cognitive deficit is a strong predictor of the likelihood of delirium during the hospitalization. ²⁵⁹ The same effect has been identified in surgical patients. ^111-114 This brings us back to the recurring theme: Subclinical decrements in functional status may become evident during the perioperative period. These findings are extended by the observation that postoperative delirium or cognitive decline may be a harbinger of a potentially permanent decrease in mental status. ^242,264

  Together, the data on the predictive value of preoperative cognitive status ²⁵⁹ and the effect of that assessment on the success of intervention ²⁶⁰ provide a compelling rationale to conduct a simple, short mental status examination as part of the preoperative interview. Short functional scales have been designed that might be applicable in the preoperative interview. ^116,265,266 The practicality of using such metrics in elderly surgical patients must be established. Following that, the incidence of preoperative cognitive impairment, and its severity, could be identified in populations of elderly patients undergoing different types of procedures. Research into the effectiveness of differing prevention strategies could follow. Those investigations could also examine whether reductions in delirium translate into reduced medical complications or improved functional status on discharge.

Anes 19 (Level B): Prospective studies that better identify patient and procedural risk factors for respiratory failure, aspiration, and pneumonia in elderly surgical patients are needed.

Anes 20 (Level A): Randomized trials are needed to determine if respiratory monitoring or O₂ therapy can reduce the incidence of respiratory failure in elderly surgical patients.

Anes 21 (Level A): Randomized studies of prophylactic antibiotics, changes in pharyngeal instrumentation, or the way feeding is advanced are needed to determine whether practice changes reduce aspiration and postoperative pneumonia in elderly surgical patients. (See also Key Research Questions in Geriatric Anesthesia, end of chapter.)

Anes 22 (Level B): Cross-sectional studies capable of identifying any relationship in elderly surgical patients between intensive nutritional support in high-risk surgery and functional status on discharge (eg, chronic respiratory failure, ambulation, independent living) are needed.

Anes 23 (Level A): Data from studies of associations between nutritional support and postoperative functional status after high-risk surgery in elderly patients (Anes 22) should be used to design prospective cohort or randomized controlled trials comparing feeding strategies in elderly patients at risk for malnutrition and muscle wasting following major surgery.

Anes 24 (Level C): Randomized trials of interventions that might attenuate postoperative catabolism or facilitate the transition to anabolism in the elderly patient are needed.

Anes 25 (Level D): Large cross-sectional studies describing analgesic practice and its complications in the elderly surgical patient are needed.

Anes 26 (Level B): Depending in part on findings of large, descriptive studies of analgesia in elderly patients (Anes 25), prospective cohort studies are needed to determine the effect of analgesic modes (patient-controlled versus as-needed versus scheduled dosing), route of administration, the role of nonopioid adjunctive drugs, and nonpharmacologic interventions. These investigations must define a balance between adequate analgesia and reduction of the incidence of adverse drug events in the elderly patient.

Anes 27 (Level A): Prospective randomized controlled trials comparing outcomes with analgesic programs specific to types of surgery are needed to determine whether analgesic regimes designed for the elderly patient reduce in-hospital morbidity or improve functional status on discharge. (See also Key Research Questions in Geriatric Anesthesia, end of chapter.)

Anes 28 (Level D): Improved tools for the assessment of pain in the cognitively impaired elderly patient should be developed.

Anes 29 (Level C): Improved tools for assessing pain in cognitively impaired elderly patients (Anes 28) should be used to determine the adequacy of pain management strategies in this group of patients.

Anes 30 (Level D): A retrospective review is needed to determine the incidence of polypharmacy with combinations of drugs that might contribute to complications (hypotension, bradycardia, falls, confusion, bleeding diathesis, constipation, and urinary retention) in geriatric surgical patients.

Anes 31 (Level A): The effect on outcomes for elderly surgical patients of simplifying drug regimens in hospital or of communicating that information to primary care physicians should be examined in a randomized controlled trial.

Anes 32 (Level B): Cross-sectional studies, with multivariate analysis, are needed to determine whether the risk factors for delirium in elderly surgical patients are the same as those for elderly medical patients.

Anes 33 (Level B): Studies are needed on the utility of the Confusion Assessment Method (CAM) for serial testing of elderly patients before and after surgery to facilitate the diagnosis of postoperative delirium. The CAM should be compared with other tests of cognitive function and with the clinical diagnosis for delirium. At the same time, since dementia is the leading predisposing factor for delirium, the utility of short mental status tests to make the preoperative diagnosis of early dementia should be tested, using a full psychiatric examination as the gold standard.

Anes 34 (Level A): Prospective controlled (nonrandomized; ie, by ward or unit) trials in patients at moderate to high risk for delirium should be performed to determine the effect of preoperative or postoperative interventions on the incidence of delirium.

A significant proportion of the geriatric population suffers from chronic pain conditions. ^46,47 Much of this is related to osteoarthritis; other neuropathic pain disorders that afflict older patients include postherpetic neuralgia (PHN), diabetic neuropathies, and causalgias. ²⁶⁷ Care of these patients is complex, and for many of these painful conditions, therapy is inadequate.

  A number of factors limit success in treating chronic pain in elderly persons. First, unlike acute postoperative pain, chronic pain is caused by conditions that typically are not reversible. Second, pain conditions in the elderly person may have a central nervous system component. Third, effective treatment of chronic pain is hampered by the side effects of medications and complications from polypharmacy. Fourth, depression and behavioral changes commonly complicate therapy. ²⁶⁸ Fifth, assessment of pain in older patients can be difficult, ⁴⁶ and, finally, chronic pain in the elderly person is often associated with unrelated comorbid conditions that may alter treatment plans. ^43,269 In spite of these limitations, geriatric patients benefit, as do younger patients, from chronic pain therapy. ^43,270,271

  As described by the American Geriatric Society Panel on Persistent Pain in Older Persons, most pain syndromes can be classified into one of four types: nociceptive, neuropathic, mixed or unspecified, and psychogenic. ⁴⁷ The usefulness of different classes of analgesic agents in these types of syndromes is reasonably well described. Nociceptive pain includes the pain typically associated with arthropathies, myalgias, and ischemic disorders; the mainstays of analgesia are initially acetaminophen and nonsteroidal anti-inflammatory drugs, followed later by narcotics. ^46,47,267 In contrast, narcotics are thought to have a lesser place in the treatment of neuropathies such as diabetic neuropathy, PHN, and complex regional pain syndromes. ^267,272,273 Instead, the primary pharma-cologic therapies are tricyclic antidepressants and anticonvulsant agents. ^{46,267,274-276} Antiarrhythmic drugs are second-tier agents for neuropathic conditions. Treatment of mixed or unspecified pain syndromes is challenging, as the mechanisms are unknown and treatment may require trials of differing analgesic approaches. ⁴⁷ For patients whose pain has been classified as psychogenic, psychiatric intervention rather than analgesic agents is indicated. ⁴⁷

  In addition to familiar analgesics and adjuncts, there is a need for a multidimensional approach to chronic pain in elderly persons. Neuraxial opioids, local anesthetics, and corticosteroids have a role for some patients, as do peripheral or central neuromodulatory techniques and a host of physical, physiatric, and cognitive-behavioral strategies. ^43,46,47

  Defining research priorities for anesthesiologists in such a broad and complex area is difficult. The first priority is that chronic pain trials must have sufficient control groups and statistical power. As pointed out by Stanton-Hicks et al regarding neuropathic pain conditions, studies are typically small and anecdotal with few experimental findings, and "without adequate predictors for the choice of therapy, current practice is chaotic, and continues to use the trial-and-error approach." ²⁷⁵

  After design issues are addressed, probably the most basic research recommendation for any of these types of pain conditions is that outcomes should emphasize functional status ^271,277 rather than a change in a pain score per se. This is superbly outlined in the consensus report on complex regional pain syndromes. ²⁷⁵ Though quantifying pain is relevant, ultimately the determination of which interventions facilitate rehabilitation, maintain or increase mobility, and support ADLs is a priority. ^271,277

  The second broad area requiring further investigation relates to prevention. One of the best examples is in PHN. The rash of acute herpes zoster is very common in elderly persons; a lesser but significant percentage of those affected develop the chronic debilitating pain condition of PHN. ²⁷⁸ Because zoster is chronic and recurring, the percentage of the population affected with PHN increases with age. ²⁷⁸ Although PHN may develop in less than 5% of younger patients with zoster, it may develop in half of patients aged 60 and over. ²⁷⁹ Once established, PHN is difficult to treat. Further research is indicated to determine whether antiviral, analgesic, or anti-inflammatory therapies during acute zoster can prevent the development of chronic PHN. ^280-283 A better understanding of precipitating events for other chronic pain conditions, as in PHN, ²⁸⁴ might allow the introduction of preventive measures.

  In addition to directing research efforts toward functional effects and trying to define opportunities for prevention of chronic pain conditions, for any strategy it is important to examine the risk-benefit ratio, emphasizing adverse outcomes that are more likely to occur in a geriatric population. As in acute pain management, the effect of chronic therapy on the incidence of complications like confusion, postural hypotension, falls, urinary retention, and constipation must be reported.

Anes 35 (Level B): The first priority in chronic pain trials is large cross-sectional studies that are powered to identify any relationship between pain intervention and functional outcomes.

Anes 36 (Level A): With the establishment of any relationship between intervention for chronic pain and functional outcomes in elderly patients (Anes 35), it must be determined prospectively if specific chronic pain therapies can improve functional outcomes in treatment groups relative to a historical or concurrent, nonrandomized control.

Anes 37 (Level C): Given the high incidence rate of herpes zoster in the geriatric population, further prospective studies are needed to determine if antiviral, analgesic, or anti-inflammatory therapies during acute zoster can reduce, relative to standard care, the devel-opment of chronic post-herpetic neuralgia.

Anes 38 (Level D): Cross-sectional studies documenting the association of chronic pain therapy with the incidence of complications like confusion, postural hypotension, falls, urinary retention, and constipation in the elderly population are needed.

Anes 39 (Level D): Cross-sectional studies that describe pain management in cognitively impaired patients, relative to a nonimpaired population, are needed.

Anes 40 (Level D): Pain assessment tools for chronic pain in the cognitively impaired elderly patient must be compared prospectively with standard assessment methods.

Anes 41 (Level C): Prospective trials comparing different analgesic strategies with regard to clinical and functional outcomes are needed.

The perioperative care of the geriatric patient is complex. Older patients are at increased risk for a host of complications, and it is probably easier to precipitate these complications than to directly prevent them. This precarious state is a function of decreased functional reserve, variable response to stress, and the number of comorbidities in older patients

  Nevertheless, we have learned a great deal that can guide future research. Rather than continuing to focus attention on the choice of anesthetic technique or on short-term outcomes, such as time to extubation or recovery room stay, we should focus attention on better risk stratification of elderly patients in order to better serve the goal of improving patient outcomes. If identified risk factors are amenable to therapy, it should be determined whether improvement in patient status leads to improved outcome. An essential element of both types of investigations will be a focus on preoperative functional status and outcomes appropriate to the geriatric population, rather than just major cardiopulmonary morbidity and mortality.

Anes KQ1: What preoperative assessments are useful in developing patient management plans for surgeries common in the elderly population?

Hypothesis-generating: Large observational studies are needed to identify preoperative risk factors for adverse geriatric outcomes following common surgeries. These will identify both patient- and surgery-dependent factors. Assessment tools for mental status, nutrition, hydration, thrombotic risk, and ADLs must be applied or developed when necessary. It then should be determined which risk factors are potentially modifiable.

Hypothesis-testing: Randomized controlled trials are needed to determine if preoperative or postoperative intervention against modifiable risk factors will decrease perioperative geriatric complications. The adverse effects of such interventions, such as delay of surgery or postoperative bleeding, must be examined along with the potential benefits of interventions.

Examples of interventions that could reasonably be attempted include intensive nourishment for malnutrition and precise management of hydration, multifactorial interventions to prevent postoperative delirium, pre- or postoperative rehabilitation programs to maintain or improve functional status (ADLs, exercise capacity), and antiplatelet therapy for thrombotic and embolic complications.

Anes KQ2: Can proper choice of postoperative analgesic techniques reduce postoperative morbidity or improve functional status at discharge?

Hypothesis-generating: Large prospective studies describing analgesic practice and its complications in the elderly patient are needed. The efficacy and complications of regional analgesic techniques, nonopioid adjunctive drugs, and physiatric interventions must be investigated. These investigations must emphasize the type and incidence of adverse drug events in the elderly population.

Hypothesis-testing: Prospective randomized trials are needed to determine if perioperative intensive analgesic techniques (including traditional narcotic, regional, nonopioid adjunctive drugs and physiatric interventions) designed for the elderly patient reduce in-hospital morbidity or improve functional status on discharge.

Anes KQ3: How can postoperative pulmonary complications in the elderly patient be reduced?

Hypothesis-generating: Cross-sectional or cohort studies that better identify high-risk procedures or perioperative periods of vulnerability for postoperative hypoxia, respiratory failure, and pneumonia in the elderly surgical patient are needed. These investigations should identify both patient and procedure risk factors, as well as their interaction, for these complications.

Hypothesis-testing: Randomized trials are needed to determine if respiratory monitoring, prophylactic antibiotics, changes in pharyngeal instrumentation, or the way feeding is advanced will reduce respiratory failure, aspiration, and postoperative pneumonia among elderly patients.

1. Franklin SS, Gustin WT, Wong ND, et al. Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. Circulation 1997;96:308-315.
2. Landahl S, Bengtsson C, Sigurdsson JA, et al. Age-related changes in blood pressure. Hypertension 1986;8:1044-1049.
3. Pan HY, Hoffman BB, Pershe RA, Blaschke TF. Decline in beta adrenergic receptor-mediated vascular relaxation with aging in man. J Pharmacol Exp Ther 1986;239:802-807.
4. Folkow B, Svanborg A. Physiology of cardiovascular aging. Physiol Rev 1993;73:725-764.
5. Falk RH. Etiology and complications of atrial fibrillation: insights from pathology studies. Am J Cardiol 1998;82:10N-17N.
6. Mackstaller LL, Alpert JS. Atrial fibrillation: a review of mechanism, etiology, and therapy. Clin Cardiol 1997;20:640-650.
7. Lakatta EG. Age-related alterations in the cardiovascular response to adrenergic mediated stress. Fed Proc 1980;39:3173-3177.
8. Rodeheffer RJ, Gerstenblith G, Becker LC, et al. Exercise cardiac output is maintained with advancing age in healthy human subjects: cardiac dilatation and increased stroke volume compensate for a diminished heart rate. Circulation 1984;69:203-213.
9. Collins KJ, Exton-Smith AN, James MH, Oliver DJ. Functional changes in autonomic nervous responses with ageing. Age Ageing 1980;9:17-24.
10. McGarry K, Laher M, Fitzgerald D, et al. Baroreflex function in elderly hypertensives. Hypertension 1983;5:763-766.
11. Phillips PA, Hodsman GP, Johnston CI. Neuroendocrine mechanisms and cardiovascular homeostasis in the elderly. Cardiovasc Drugs Ther 1991;4 Suppl 6:1209-1213.
12. Cleroux J, Giannattasio C, Bolla G, et al. Decreased cardiopulmonary reflexes with aging in normotensive humans. Am J Physiol 1989;257:H961-H968.
13. Rowe JW, Troen BR. Sympathetic nervous system and aging in man. Endocr Rev 1980;1:167-179.
14. Wahba WM. Influence of aging on lung function-clinical significance of changes from age twenty. Anesth Analg 1983;62:764-776.
15. Zaugg M, Lucchinetti E. Respiratory function in the elderly. Anesthesiol Clin North America 2000;18:47-58, vi.
16. Fowler RW. Ageing and lung function. Age Ageing 1985;14:209-215.
17. Tolep K, Kelsen SG. Effect of aging on respiratory skeletal muscles. Clin Chest Med 1993;14:363-378.
18. Pontoppidan H, Geffin B, Lowenstein E. Acute respiratory failure in the adult. 1. N Engl J Med 1972;287:690-698.
19. Kitamura H, Sawa T, Ikezono E. Postoperative hypoxemia: The contribution of age to the maldistribution of ventilation. Anesthesiology 1972;36:244-252.
20. Lynne-Davies P. Influence of age on the respiratory system. Geriatrics 1977;32:57-60.
21. Cerveri I, Zoia MC, Fanfulla F, et al. Reference values of arterial oxygen tension in the middle-aged and elderly. Am J Respir Crit Care Med 1995;152:934-941.
22. Kronenberg RS, Drage CW. Attenuation of the ventilatory and heart rate responses to hypoxia and hypercapnia with aging in normal men. J Clin Invest 1973;52:1812-1819.
23. Aviv JE. Effects of aging on sensitivity of the pharyngeal and supraglottic areas. Am J Med 1997;103:74S-76S.
24. Marik PE. Aspiration pneumonitis and aspiration pneumonia. N Engl J Med 2001;344:665-671.
25. Arunasalam K, Davenport HT, Painter S, Jones JG. Ventilatory response to morphine in young and old subjects. Anaesthesia 1983;38:529-533.
26. Sari A, Miyauchi Y, Yamashita S, et al. The magnitude of hypoxemia in elderly patients with fractures of the femoral neck. Anesth Analg 1986;65:892-894.
27. Kronenberg RS, Drage CW, Ponto RA, Williams LE. The effect of age on the distribution of ventilation and perfusion in the lung. Am Rev Respir Dis 1973;108:576-586.
28. Clayer M, Bruckner J. Occult hypoxia after femoral neck fracture and elective hip surgery. Clin Orthop 2000:265-271.
29. Moller JT, Wittrup M, Johansen SH. Hypoxemia in the postanesthesia care unit: an observer study. Anesthesiology 1990;73:890-895.
30. de Larminat V, Montravers P, Dureuil B, Desmonts JM. Alteration in swallowing reflex after extubation in intensive care unit patients. Crit Care Med 1995;23:486-490.
31. Morris JC, McManus DQ. The neurology of aging: normal versus pathologic change. Geriatrics 1991;46:47-48, 51-44.
32. Creasey H, Rapoport SI. The aging human brain. Ann Neurol 1985;17:2-10.
33. Morrison JH, Hof PR. Life and death of neurons in the aging brain. Science 1997;278:412-419.
34. Severson JA. Neurotransmitter receptors and aging. J Am Geriatr Soc 1984;32:24-27.
35. Wong DF, Wagner HN, Jr., Dannals RF, et al. Effects of age on dopamine and serotonin receptors measured by positron tomography in the living human brain. Science 1984;226:1393-1396.
36. Muravchick S. Central nervous system. Geroanesthesia: Principles for Management of the Elderly Patient. St. Louis: Mosby-Year Book, Inc., 1997:78-113.
37. Peterson DD, Pack AI, Silage DA, Fishman AP. Effects of aging on ventilatory and occlusion pressure responses to hypoxia and hypercapnia. Am Rev Respir Dis 1981;124:387-391.
38. Muravchick S. Peripheral and autonomic nervous system. Geroanesthesia: Principles for Management of the Elderly Patient. St. Louis: Mosby-Year Book, Inc., 1997:114-148.
39. Gibson SJ, Helme RD. Age differences in pain perception and report: a review of physiological, psychological, laboratory and clinical studies. Pain Rev 1995;2:111-137.
40. Tucker MA, Andrew MF, Ogle SJ, Davison JG. Age-associated change in pain threshold measured by transcutaneous neuronal electrical stimulation. Age Ageing 1989;18:241-246.
41. Potvin AR, Syndulko K, Tourtellotte WW, et al. Human neurologic function and the aging process. J Am Geriatr Soc 1980;28:1-9.
42. Chakour MC, Gibson SJ, Bradbeer M, Helme RD. The effect of age on A delta- and C-fibre thermal pain perception. Pain 1996;64:143-152.
43. Helme RD, Gibson SJ. Pain in the elderly. In Jensen TS, Turner JA, Wiesenfeld-Hallin Z (eds): 8th World Congress on Pain. Parkville, Australia: IASP Press, 1997:919-944.
44. Harkins SW. Geriatric pain. Pain perceptions in the old. Clin Geriatr Med 1996;12:435-459.
45. Harkins SW, Davis MD, Bush FM, Kasberger J. Suppression of first pain and slow temporal summation of second pain in relation to age. J Gerontol A Biol Sci Med Sci 1996;51:M260-M265.
46. Ferrell BA. Pain management in elderly people. J Am Geriatr Soc 1991;39:64-73.
47. American Geriatrics Society Panel on Persistent Pain in Older Persons. The management of persistent pain in older persons. J Am Geriatr Soc 2002;50:S205-S224.
48. Jones JS, Johnson K, McNinch M. Age as a risk factor for inadequate emergency department analgesia. Am J Emerg Med 1996;14:157-160.
49. McLachlan MS. The ageing kidney. Lancet 1978;2:143-145.
50. Anderson S, Brenner BM. The aging kidney: structure, function, mechanisms, and therapeutic implications. J Am Geriatr Soc 1987;35:590-593.
51. Epstein M. Aging and the kidney. J Am Soc Nephrol 1996;7:1106-1122.
52. Anderson S, Brenner BM. Effects of aging on the renal glomerulus. Am J Med 1986;80:435-442.
53. Shannon RP, Minaker KL, Rowe JW. Aging and water balance in humans. Semin Nephrol 1984;4:346-353.
54. Miller M. Fluid and electrolyte balance in the elderly. Geriatrics 1987;42:65-68, 71, 75-66.
55. Phillips PA, Rolls BJ, Ledingham JG, et al. Reduced thirst after water deprivation in healthy elderly men. N Engl J Med 1984;311:753-759.
56. Rowe JW, Minaker KL, Sparrow D, Robertson GL. Age-related failure of volume-pressure-mediated vasopressin release. J Clin Endocrinol Metab 1982;54:661-664.
57. Kliger AS. The role of the kidney in fluid, electrolyte, and acid-base disorders. Int Anesthesiol Clin 1984;22:65-82.
58. Lamy PP, Wiser TH. Geriatric anesthesia. In Katlic MR (ed): Pharmacotherapeutic considerations in the elderly surgical patient. Baltimore: Urban & Schwarzenberg, Inc., 1990:209-239.
59. Greenblatt DJ, Sellers EM, Shader RI. Drug therapy: drug disposition in old age. N Engl J Med 1982;306:1081-1088.
60. Shafer SL. The pharmacology of anesthetic drugs in elderly patients. Anesthesiol Clin North America 2000;18:1-29, v.
61. Matteo RS, Ornstein E. Pharmacokinetics and pharmacodynamics of injected drugs in the elderly. Adv Anesthesia 1988;5:25-52.
62. Silverstein JH, Bloom HG, Cassel CK. New challenges in anesthesia: new practice opportunities. Anesthesiol Clin North America 1999;17:453-465.
63. Dundee JW, Robinson FP, McCollum JS, Patterson CC. Sensitivity to propofol in the elderly. Anaesthesia 1986;41:482-485.
64. Jacobs JR, Reves JG, Marty J, et al. Aging increases pharmacodynamic sensitivity to the hypnotic effects of midazolam. Anesth Analg 1995;80:143-148.
65. Homer TD, Stanski DR. The effect of increasing age on thiopental disposition and anesthetic requirement. Anesthesiology 1985;62:714-724.
66. Hurwitz N. Predisposing factors in adverse reactions to drugs. Br Med J 1969;1:536-539.
67. Hurwitz N, Wade OL. Intensive hospital monitoring of adverse reactions to drugs. Br Med J 1969;1:531-536.
68. Bates DW, Cullen DJ, Laird N, et al. Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group. JAMA 1995;274:29-34.
69. Patterson C. Iatrogenic disease in late life. Clin Geriatr Med 1986;2:121-136.
70. Williamson J, Chopin JM. Adverse reactions to prescribed drugs in the elderly: a multicentre investigation. Age Ageing 1980;9:73-80.
71. Muravchick S. The biology of aging and preoperative evaluation. Geroanesthesia: Principles for Management of the Elderly Patient. St. Louis: Mosby-Year Book, Inc., 1997:1-34.
72. Thomas DR, Ritchie CS. Preoperative assessment of older adults. J Am Geriatr Soc 1995;43:811-821.
73. Vaz FG, Seymour DG. A prospective study of elderly general surgical patients: I. Pre-operative medical problems. Age Ageing 1989;18:309-315.
74. Schneider JR, Droste JS, Schindler N, Golan JF. Carotid endarterectomy in octogenarians: comparison with patient characteristics and outcomes in younger patients. J Vasc Surg 2000;31:927-935.
75. Hoballah JJ, Nazzal MM, Jacobovicz C, et al. Entering the ninth decade is not a contraindication for carotid endarterectomy. Angiology 1998;49:275-278.
76. Hosking MP, Warner MA, Lobdell CM, et al. Outcomes of surgery in patients 90 years of age and older [see comments]. JAMA 1989;261:1909-1915.
77. Warner MA, Saletel RA, Schroeder DR, et al. Outcomes of anesthesia and surgery in people 100 years of age and older. J Am Geriatr Soc 1998;46:988-993.
78. Laskin RS. Total knee replacement in patients older than 85 years. Clin Orthop 1999:43-49.
79. Tiret L, Desmonts JM, Hatton F, Vourc'h G. Complications associated with anaesthesia-a prospective survey in France. Can Anaesth Soc J 1986;33:336-344.
80. Eagle KA, Brundage BH, Chaitman BR, et al. Guidelines for perioperative cardiovascular evaluation for noncardiac surgery. Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Committee on Perioperative Cardiovascular Evaluation for Noncardiac Surgery. Circulation 1996;93:1278-1317.
81. Goldman L. Cardiac risks and complications of noncardiac surgery. Ann Intern Med 1983;98:504-513.
82. Liu LL, Leung JM. Predicting adverse postoperative outcomes in patients aged 80 years or older. J Am Geriatr Soc 2000;48:405-412.
83. Arvidsson S, Ouchterlony J, Sjostedt L, Svardsudd K. Predicting postoperative adverse events. Clinical efficiency of four general classification systems. The project perioperative risk. Acta Anaesthesiol Scand 1996;40:783-791.
84. Detsky AS, Abrams HB, Forbath N, et al. Cardiac assessment for patients undergoing noncardiac surgery. A multifactorial clinical risk index. Arch Intern Med 1986;146:2131-2134.
85. Pedersen T, Eliasen K, Henriksen E. A prospective study of risk factors and cardiopulmonary complications associated with anaesthesia and surgery: risk indicators of cardiopulmonary morbidity. Acta Anaesthesiol Scand 1990;34:144-155.
86. Pedersen T, Eliasen K, Henriksen E. A prospective study of mortality associated with anaesthesia and surgery: risk indicators of mortality in hospital. Acta Anaesthesiol Scand 1990;34:176-182.
87. Browner WS, Li J, Mangano DT. In-hospital and long-term mortality in male veterans following noncardiac surgery. The Study of Perioperative Ischemia Research Group. JAMA 1992;268:228-232.
88. Khuri SF, Daley J, Henderson W, et al. The National Veterans Administration Surgical Risk Study: risk adjustment for the comparative assessment of the quality of surgical care. J Am Coll Surg 1995;180:519-531.
89. Arvidsson S, Ouchterlony J, Nilsson S, et al. The Gothenburg study of perioperative risk. I. Preoperative findings, postoperative complications. Acta Anaesthesiol Scand 1994;38:679-690.
90. Mohr DN. Estimation of surgical risk in the elderly: a correlative review. J Am Geriatr Soc 1983;31:99-102.
91. Cheng KW, Wang CH, Ho RT, et al. Outcome of surgery and anesthesia in patients 80 years of age and older. Acta Anaesthesiol Sin 1994;32:37-43.
92. Cohen MM, Duncan PG, Tate RB. Does anesthesia contribute to operative mortality? JAMA 1988;260:2859-2863.
93. Cohen MM, Duncan PG. Physical status score and trends in anesthetic complications. J Clin Epidemiol 1988;41:83-90.
94. Goldman L, Hashimoto B, Cook EF, Loscalzo A. Comparative reproducibility and validity of systems for assessing cardiovascular functional class: advantages of a new specific activity scale. Circulation 1981;64:1227-1234.
95. Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 1969;9:179-186.
96. Ware JE, Jr., Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992;30:473-483.
97. Moy ML, Ingenito EP, Mentzer SJ, et al. Health-related quality of life improves following pulmonary rehabilitation and lung volume reduction surgery. Chest 1999;115:383-389.
98. Mangione CM, Goldman L, Orav EJ, et al. Health-related quality of life after elective surgery: measurement of longitudinal changes. J Gen Intern Med 1997;12:686-697.
99. Hannan EL, Magaziner J, Wang JJ, et al. Mortality and locomotion 6 months after hospitalization for hip fracture: risk factors and risk-adjusted hospital outcomes. JAMA 2001;285:2736-2742.
100. Tammela T, Kontturi M, Lukkarinen O. Postoperative urinary retention. I. Incidence and predisposing factors. Scand J Urol Nephrol 1986;20:197-201.
101. Duits AA, Boeke S, Taams MA, et al. Prediction of quality of life after coronary artery bypass graft surgery: a review and evaluation of multiple, recent studies. Psychosom Med 1997;59:257-268.
102. Keene JS, Anderson CA. Hip fractures in the elderly. Discharge predictions with a functional rating scale. JAMA 1982;248:564-567.
103. McCartney JR, Palmateer LM. Assessment of cognitive deficit in geriatric patients. A study of physician behavior. J Am Geriatr Soc 1985;33:467-471.
104. Inouye SK, Peduzzi PN, Robison JT, et al. Importance of functional measures in predicting mortality among older hospitalized patients. JAMA 1998;279:1187-1193.
105. Raja SN, Haythornthwaite JA. Anesthetic management of the elderly: measuring function beyond the immediate perioperative horizon. Anesthesiology 1999;91:909-911.
106. Heyland DK, Guyatt G, Cook DJ, et al. Frequency and methodologic rigor of quality-of-life assessments in the critical care literature. Crit Care Med 1998;26:591-598.
107. Holmes J, House A. Psychiatric illness predicts poor outcome after surgery for hip fracture: a prospective cohort study. Psychol Med 2000;30:921-929.
108. Dolan MM, Hawkes WG, Zimmerman SI, et al. Delirium on hospital admission in aged hip fracture patients: prediction of mortality and 2-year functional outcomes. J Gerontol A Biol Sci Med Sci 2000;55:M527-M534.
109. Inouye SK, Schlesinger MJ, Lydon TJ. Delirium: a symptom of how hospital care is failing older persons and a window to improve quality of hospital care. Am J Med 1999;106:565-573.
110. Millar K, Asbury AJ, Murray GD. Pre-existing cognitive impairment as a factor influencing outcome after cardiac surgery. Br J Anaesth 2001;86:63-67.
111. Dyer CB, Ashton CM, Teasdale TA. Postoperative delirium. A review of 80 primary data-collection studies. Arch Intern Med 1995;155:461-465.
112. Ni Chonchubhair A, Valacio R, Kelly J, O'Keefe S. Use of the abbreviated mental test to detect postoperative delirium in elderly people. Br J Anaesth 1995;75:481-482.
113. Kaneko T, Takahashi S, Naka T, et al. Postoperative delirium following gastrointestinal surgery in elderly patients. Surg Today 1997;27:107-111.
114. Gustafson Y, Berggren D, Brannstrom B, et al. Acute confusional states in elderly patients treated for femoral neck fracture. J Am Geriatr Soc 1988;36:525-530.
115. McDowell I, Kristjansson B, Hill GB, Hebert R. Community screening for dementia: the Mini Mental State Exam (MMSE) and Modified Mini-Mental State Exam (3MS) compared. J Clin Epidemiol 1997;50:377-383.
116. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198.
117. Berggren D, Gustafson Y, Eriksson B, et al. Postoperative confusion after anesthesia in elderly patients with femoral neck fractures. Anesth Analg 1987;66:497-504.
118. Williams-Russo P, Urquhart BL, Sharrock NE, Charlson ME. Post-operative delirium: predictors and prognosis in elderly orthopedic patients [see comments]. J Am Geriatr Soc 1992;40:759-767.
119. de Graeff A, de Leeuw JR, Ros WJ, et al. Pretreatment factors predicting quality of life after treatment for head and neck cancer. Head Neck 2000;22:398-407.
120. Lyness JM, Noel TK, Cox C, et al. Screening for depression in elderly primary care patients. A comparison of the Center for Epidemiologic Studies-Depression Scale and the Geriatric Depression Scale. Arch Intern Med 1997;157:449-454.
121. Roca R. Psychosocial aspects of surgical care in the elderly patient. Surg Clin North Am 1994;74:223-243.
122. Bradley EH, Bogardus ST, Jr., van Doorn C, et al. Goals in geriatric assessment: are we measuring the right outcomes? Gerontologist 2000;40:191-196.
123. Heijmeriks JA, Pourrier S, Dassen P, et al. Comparison of quality of life after coronary and/or valvular cardiac surgery in patients > or = 75 years of age with younger patients. Am J Cardiol 1999;83:1129-1132, A1129.
124. Katz S. Assessing self-maintenance: activities of daily living, mobility, and instrumental activities of daily living. J Am Geriatr Soc 1983;31:721-727.
125. Turnbull JM, Buck C. The value of preoperative screening investigations in otherwise healthy individuals. Arch Intern Med 1987;147:1101-1105.
126. Perez A, Planell J, Bacardaz C, et al. Value of routine preoperative tests: a multicentre study in four general hospitals. Br J Anaesth 1995;74:250-256.
127. Kaplan EB, Sheiner LB, Boeckmann AJ, et al. The usefulness of preoperative laboratory screening. JAMA 1985;253:3576-3581.
128. Narr BJ, Warner ME, Schroeder DR, Warner MA. Outcomes of patients with no laboratory assessment before anesthesia and a surgical procedure. Mayo Clin Proc 1997;72:505-509.
129. Seymour DG, Pringle R, Shaw JW. The role of the routine pre-operative chest X-ray in the elderly general surgical patient. Postgrad Med J 1982;58:741-745.
130. Seymour DG, Pringle R, MacLennan WJ. The role of the routine pre-operative electrocardiogram in the elderly surgical patient. Age Ageing 1983;12:97-104.
131. Sewell JM, Spooner LL, Dixon AK, Rubenstein D. Screening investigations in the elderly. Age Ageing 1981;10:165-168.
132. Sanders DP, McKinney FW, Harris WH. Clinical evaluation and cost effectiveness of preoperative laboratory assessment on patients undergoing total hip arthroplasty. Orthopedics 1989;12:1449-1453.
133. Grimes CJ, Younathan MT, Lee WC. The effect of preoperative total parenteral nutrition on surgery outcomes. J Am Diet Assoc 1987;87:1202-1206.
134. Gibbs J, Cull W, Henderson W, et al. Preoperative serum albumin level as a predictor of operative mortality and morbidity: results from the National VA Surgical Risk Study. Arch Surg 1999;134:36-42.
135. Baker JP, Detsky AS, Wesson DE, et al. Nutritional assessment: a comparison of clinical judgement and objective measurements. N Engl J Med 1982;306:969-972.
136. Covinsky KE, Martin GE, Beyth RJ, et al. The relationship between clinical assessments of nutritional status and adverse outcomes in older hospitalized medical patients. J Am Geriatr Soc 1999;47:532-538.
137. Mazolewski P, Turner JF, Baker M, et al. The impact of nutritional status on the outcome of lung volume reduction surgery: a prospective study. Chest 1999;116:693-696.
138. Cohendy R, Gros T, Arnaud-Battandier F, et al. Preoperative nutritional evaluation of elderly patients: the Mini Nutritional Assessment as a practical tool. Clin Nutr 1999;18:345-348.
139. McClave SA, Snider HL, Spain DA. Preoperative issues in clinical nutrition. Chest 1999;115:64S-70S.
140. Moore AA, Siu AL. Screening for common problems in ambulatory elderly: clinical confirmation of a screening instrument. Am J Med 1996;100:438-443.
141. Schein OD, Katz J, Bass EB, et al. The value of routine preoperative medical testing before cataract surgery. Study of Medical Testing for Cataract Surgery. N Engl J Med 2000;342:168-175.
142. Dzankic S, Pastor D, Gonzalez C, Leung JM. The prevalence and predictive value of abnormal preoperative laboratory tests in elderly surgical patients. Anesth Analg 2001;93:301-308.
143. Berlauk JF, Abrams JH, Gilmour IJ, et al. Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial. Ann Surg 1991;214:289-297; discussion 298-289.
144. Leppo JA. Preoperative cardiac risk assessment for noncardiac surgery. Am J Cardiol 1995;75:42D-51D.
145. Roubenoff R, Roubenoff RA, Preto J, Balke CW. Malnutrition among hospitalized patients. A problem of physician awareness. Arch Intern Med 1987;147:1462-1465.
146. Del Guercio LR, Cohn JD. Monitoring operative risk in the elderly. JAMA 1980;243:1350-1355.
147. Smith MS, Muir H, Hall R. Perioperative management of drug therapy, clinical considerations. Drugs 1996;51:238-259.
148. Zaugg M, Tagliente T, Lucchinetti E, et al. Beneficial effects from beta-adrenergic blockade in elderly patients undergoing noncardiac surgery. Anesthesiology 1999;91:1674-1686.
149. Yeager RA, Moneta GL, Edwards JM, et al. Reducing perioperative myocardial infarction following vascular surgery. The potential role of beta-blockade. Arch Surg 1995;130:869-872; discussion 872-863.
150. Bisson A, Stern M, Caubarrere I. Preparation of high-risk patients for major thoracic surgery. Chest Surg Clin N Am 1998;8:541-555, viii.
151. Debigare R, Maltais F, Whittom F, et al. Feasibility and efficacy of home exercise training before lung volume reduction. J Cardiopulm Rehabil 1999;19:235-241.
152. Arthur HM, Daniels C, McKelvie R, et al. Effect of a preoperative intervention on preoperative and postoperative outcomes in low-risk patients awaiting elective coronary artery bypass graft surgery. A randomized, controlled trial. Ann Intern Med 2000;133:253-262.
153. Fisher DA, Trimble S, Clapp B, Dorsett K. Effect of a patient management system on outcomes of total hip and knee arthroplasty. Clin Orthop 1997:155-160.
154. Roy RC. Choosing general versus regional anesthesia for the elderly. Anesthesiol Clin North America 2000;18:91-104, vii.
155. McLaren AD, Stockwell MC, Reid VT. Anaesthetic techniques for surgical correction of fractured neck of femur. A comparative study of spinal and general anaesthesia in the elderly. Anaesthesia 1978;33:10-14.
156. Hole A, Terjesen T, Breivik H. Epidural versus general anaesthesia for total hip arthroplasty in elderly patients. Acta Anaesthesiol Scand 1980;24:279-287.
157. Nielson WR, Gelb AW, Casey JE, et al. Long-term cognitive and social sequelae of general versus regional anesthesia during arthroplasty in the elderly. Anesthesiology 1990;73:1103-1109.
158. Davis FM, Woolner DF, Frampton C, et al. Prospective, multi-centre trial of mortality following general or spinal anaesthesia for hip fracture surgery in the elderly. Br J Anaesth 1987;59:1080-1088.
159. McKenzie PJ, Wishart HY, Dewar KM, et al. Comparison of the effects of spinal anaesthesia and general anaesthesia on postoperative oxygenation and perioperative mortality. Br J Anaesth 1980;52:49-54.
160. McKenzie PJ, Wishart HY, Gray I, Smith G. Effects of anaesthetic technique on deep vein thrombosis. A comparison of subarachnoid and general anaesthesia. Br J Anaesth 1985;57:853-857.
161. Hendolin H, Mattila MA, Poikolainen E. The effect of lumbar epidural analgesia on the development of deep vein thrombosis of the legs after open prostatectomy. Acta Chir Scand 1981;147:425-429.
162. White IW, Chappell WA. Anaesthesia for surgical correction of fractured femoral neck. A comparison of three techniques. Anaesthesia 1980;35:1107-1110.
163. Valentin N, Lomholt B, Jensen JS, et al. Spinal or general anaesthesia for surgery of the fractured hip? A prospective study of mortality in 578 patients. Br J Anaesth 1986;58:284-291.
164. Sorenson RM, Pace NL. Anesthetic techniques during surgical repair of femoral neck fractures. A meta-analysis. Anesthesiology 1992;77:1095-1104.
165. Urwin SC, Parker MJ, Griffiths R. General versus regional anaesthesia for hip fracture surgery: a meta-analysis of randomized trials. Br J Anaesth 2000;84:450-455.
166. Gilbert TB, Hawkes WG, Hebel JR, et al. Spinal anesthesia versus general anesthesia for hip fracture repair: a longitudinal observation of 741 elderly patients during 2-year follow-up. Am J Orthop 2000;29:25-35.
167. Sutcliffe AJ, Parker M. Mortality after spinal and general anaesthesia for surgical fixation of hip fractures. Anaesthesia 1994;49:237-240.
168. O'Hara DA, Duff A, Berlin JA, et al. The effect of anesthetic technique on postoperative outcomes in hip fracture repair. Anesthesiology 2000;92:947-957.
169. Rodgers A, Walker N, Schug S, et al. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials. BMJ 2000;321:1493.
170. Riis J, Lomholt B, Haxholdt O, et al. Immediate and long-term mental recovery from general versus epidural anesthesia in elderly patients. Acta Anaesthesiol Scand 1983;27:44-49.
171. Bigler D, Adelhoj B, Petring OU, et al. Mental function and morbidity after acute hip surgery during spinal and general anaesthesia. Anaesthesia 1985;40:672-676.
172. Ghoneim MM, Hinrichs JV, O'Hara MW, et al. Comparison of psychologic and cognitive functions after general or regional anesthesia. Anesthesiology 1988;69:507-515.
173. Yeager MP, Glass DD, Neff RK, Brinck-Johnsen T. Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology 1987;66:729-736.
174. Chung F, Meier R, Lautenschlager E, et al. General or spinal anesthesia: which is better in the elderly? Anesthesiology 1987;67:422-427.
175. Asbjorn J, Jakobsen BW, Pilegaard HK, et al. Mental function in elderly men after surgery during epidural analgesia. Acta Anaesthesiol Scand 1989;33:369-373.
176. Edwards ND, Callaghan LC, White T, Reilly CS. Perioperative myocardial ischaemia in patients undergoing transurethral surgery: a pilot study comparing general with spinal anaesthesia. Br J Anaesth 1995;74:368-372.
177. Bode RH, Lewis KP, Zarich SW, et al. Cardiac outcome after peripheral vascular surgery. Comparison of general and regional anesthesia. Anesthesiology 1996;84:3-13.
178. Christopherson R, Beattie C, Frank SM, et al. Perioperative morbidity in patients randomized to epidural or general anesthesia for lower extremity vascular surgery. Perioperative Ischemia Randomized Anesthesia Trial Study Group. Anesthesiology 1993;79:422-434.
179. Corson JD, Chang BB, Shah DM, et al. The influence of anesthetic choice on carotid endarterectomy outcome. Arch Surg 1987;122:807-812.
180. Papavasiliou AK, Magnadottir HB, Gonda T, et al. Clinical outcomes after carotid endarterectomy: comparison of the use of regional and general anesthetics. J Neurosurg 2000;92:291-296.
181. Fiorani P, Sbarigia E, Speziale F, et al. General anaesthesia versus cervical block and perioperative complications in carotid artery surgery. Eur J Vasc Endovasc Surg 1997;13:37-42.
182. Bowyer MW, Zierold D, Loftus JP, et al. Carotid endarterectomy: a comparison of regional versus general anesthesia in 500 operations. Ann Vasc Surg 2000;14:145-151.
183. Ferguson GG, Eliasziw M, Barr HW, et al. The North American Symptomatic Carotid Endarterectomy Trial: surgical results in 1415 patients. Stroke 1999;30:1751-1758.
184. Slogoff S, Reul GJ, Keats AS, et al. Role of perfusion pressure and flow in major organ dysfunction after cardiopulmonary bypass. Ann Thorac Surg 1990;50:911-918.
185. Wong BI, McLean RF, Naylor CD, et al. Central-nervous-system dysfunction after warm or hypothermic cardiopulmonary bypass. Lancet 1992;339:1383-1384.
186. Gold JP, Charlson ME, Williams-Russo P, et al. Improvement of outcomes after coronary artery bypass. A randomized trial comparing intraoperative high versus low mean arterial pressure. J Thorac Cardiovasc Surg 1995;110:1302-1311; discussion 1311-1304.
187. Roach GW, Kanchuger M, Mangano CM, et al. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med 1996;335:1857-1863.
188. Cook DJ. Neurologic effects. In Gravlee GP, Davis RF, Kurusz M, Utley JR (eds): Cardiopulmonary Bypass: Principles and Practice, 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2000:403-431.
189. Frank SM, Beattie C, Christopherson R, et al. Unintentional hypothermia is associated with postoperative myocardial ischemia. The Perioperative Ischemia Randomized Anesthesia Trial Study Group. Anesthesiology 1993;78:468-476.
190. Frank SM, El-Rahmany HK, Cattaneo CG, Barnes RA. Predictors of hypothermia during spinal anesthesia. Anesthesiology 2000;92:1330-1334.
191. Frank SM, Fleisher LA, Breslow MJ, et al. Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events. A randomized clinical trial. JAMA 1997;277:1127-1134.
192. Frank SM, Fleisher LA, Olson KF, et al. Multivariate determinants of early postoperative oxygen consumption in elderly patients. Effects of shivering, body temperature, and gender. Anesthesiology 1995;83:241-249.
193. Frank SM, Higgins MS, Breslow MJ, et al. The catecholamine, cortisol, and hemodynamic responses to mild perioperative hypothermia. A randomized clinical trial. Anesthesiology 1995;82:83-93.
194. Cohen MM, Duncan PG, Pope WD, et al. The Canadian four-centre study of anaesthetic outcomes: II. Can outcomes be used to assess the quality of anaesthesia care? Can J Anaesth 1992;39:430-439.
195. Rao TL, Jacobs KH, El-Etr AA. Reinfarction following anesthesia in patients with myocardial infarction. Anesthesiology 1983;59:499-505.
196. O'Keeffe ST, Ni Chonchubhair A. Postoperative delirium in the elderly. Br J Anaesth 1994;73:673-687.
197. Seymour DG, Vaz FG. A prospective study of elderly general surgical patients: II. Post-operative complications. Age Ageing 1989;18:316-326.
198. Pontoppidan H, Beecher HK. Progressive loss of protective reflexes in the airway with the advance of age. JAMA 1960;174:2209-2213.
199. Pedersen T, Viby-Mogensen J, Ringsted C. Anaesthetic practice and postoperative pulmonary complications. Acta Anaesthesiol Scand 1992;36:812-818.
200. Moller JT, Johannessen NW, Espersen K, et al. Randomized evaluation of pulse oximetry in 20,802 patients: II. Perioperative events and postoperative complications. Anesthesiology 1993;78:445-453.
201. Moller JT, Svennild I, Johannessen NW, et al. Perioperative monitoring with pulse oximetry and late postoperative cognitive dysfunction. Br J Anaesth 1993;71:340-347.
202. Bailey PL, Pace NL, Ashburn MA, et al. Frequent hypoxemia and apnea after sedation with midazolam and fentanyl. Anesthesiology 1990;73:826-830.
203. Hogue CW, Jr., Lappas GD, Creswell LL, et al. Swallowing dysfunction after cardiac operations. Associated adverse outcomes and risk factors including intraoperative transesophageal echocardiography. J Thorac Cardiovasc Surg 1995;110:517-522.
204. Mitchell CK, Smoger SH, Pfeifer MP, et al. Multivariate analysis of factors associated with postoperative pulmonary complications following general elective surgery. Arch Surg 1998;133:194-198.
205. Warner MA, Warner ME, Weber JG. Clinical significance of pulmonary aspiration during the perioperative period. Anesthesiology 1993;78:56-62.
206. Roberts JR, Shyr Y, Christian KR, et al. Preemptive gastrointestinal tract management reduces aspiration and respiratory failure after thoracic operations. J Thorac Cardiovasc Surg 2000;119:449-452.
207. Breslow MJ, Parker SD, Frank SM, et al. Determinants of catecholamine and cortisol responses to lower extremity revascularization. The PIRAT Study Group. Anesthesiology 1993;79:1202-1209.
208. Rem J, Nielsen OS, Brandt MR, Kehlet H. Release mechanisms of postoperative changes in various acute phase proteins and immunoglobulins. Acta Chir Scand Suppl 1980;502:51-56.
209. Kilickan L, Toker K. The effects of preemptive intravenous versus preemptive epidural morphine on postoperative analgesia and surgical stress response after orthopaedic procedures. Minerva Anestesiol 2000;66:649-655.
210. Schulze S, Schierbeck J, Sparso BH, et al. Influence of neural blockade and indomethacin on leucocyte, temperature, and acute-phase protein response to surgery. Acta Chir Scand 1987;153:255-259.
211. Klasen JA, Opitz SA, Melzer C, et al. Intraarticular, epidural, and intravenous analgesia after total knee arthroplasty. Acta Anaesthesiol Scand 1999;43:1021-1026.
212. Schulze S, Sommer P, Bigler D, et al. Effect of combined prednisolone, epidural analgesia, and indomethacin on the systemic response after colonic surgery. Arch Surg 1992;127:325-331.
213. Rem J, Brandt MR, Kehlet H. Prevention of postoperative lymphopenia and granulocytosis by epidural analgesia. Lancet 1980;1:283-284.
214. Hjortso NC, Andersen T, Frosig F, et al. Failure of epidural analgesia to modify postoperative depression of delayed hypersensitivity. Acta Anaesthesiol Scand 1984;28:128-131.
215. Rutberg H, Hakanson E, Anderberg B, et al. Effects of the extradural administration of morphine, or bupivacaine, on the endocrine response to upper abdominal surgery. Br J Anaesth 1984;56:233-238.
216. Liu S, Carpenter RL, Neal JM. Epidural anesthesia and analgesia. Their role in postoperative outcome. Anesthesiology 1995;82:1474-1506.
217. Tuman KJ, McCarthy RJ, March RJ, et al. Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesth Analg 1991;73:696-704.
218. Giesecke K, Klingstedt C, Ljungqvist O, Hagenfeldt L. The modifying influence of anaesthesia on postoperative protein catabolism. Br J Anaesth 1994;72:697-699.
219. Heindorff H, Schulze S, Mogensen T, et al. Hormonal and neural blockade prevents the postoperative increase in amino acid clearance and urea synthesis. Surgery 1992;111:543-550.
220. Carli F, Halliday D. Continuous epidural blockade arrests the postoperative decrease in muscle protein fractional synthetic rate in surgical patients. Anesthesiology 1997;86:1033-1040.
221. Wasylak TJ, Abbott FV, English MJ, Jeans ME. Reduction of postoperative morbidity following patient-controlled morphine. Can J Anaesth 1990;37:726-731.
222. Petros JG, Alameddine F, Testa E, et al. Patient-controlled analgesia and postoperative urinary retention after hysterectomy for benign disease. J Am Coll Surg 1994;179:663-667.
223. Petros JG, Mallen JK, Howe K, et al. Patient-controlled analgesia and postoperative urinary retention after open appendectomy. Surg Gynecol Obstet 1993;177:172-175.
224. Carpenter RL, Abram SE, Bromage PR, Rauck RL. Consensus statement on acute pain management. Reg Anesth 1996;21:152-156.
225. Carpenter RL. Gastrointestinal benefits of regional anesthesia/analgesia. Reg Anesth 1996;21:13-17.
226. Kumar A, Bose S, Bhattacharya A, et al. Oral clonidine premedication for elderly patients undergoing intraocular surgery. Acta Anaesthesiol Scand 1992;36:159-164.
227. Singelyn FJ, Gouverneur JM. Extended "three-in-one" block after total knee arthroplasty: continuous versus patient-controlled techniques. Anesth Analg 2000;91:176-180.
228. De Kock MF, Pichon G, Scholtes JL. Intraoperative clonidine enhances postoperative morphine patient-controlled analgesia. Can J Anaesth 1992;39:537-544.
229. Wong HY, Carpenter RL, Kopacz DJ, et al. A randomized, double-blind evaluation of ketorolac tromethamine for postoperative analgesia in ambulatory surgery patients. Anesthesiology 1993;78:6-14.
230. Milligan KR, Convery PN, Weir P, et al. The efficacy and safety of epidural infusions of levobupivacaine with and without clonidine for postoperative pain relief in patients undergoing total hip replacement. Anesth Analg 2000;91:393-397.
231. Capdevila X, Barthelet Y, Biboulet P, et al. Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology 1999;91:8-15.
232. Mahoney OM, Noble PC, Davidson J, Tullos HS. The effect of continuous epidural analgesia on postoperative pain, rehabilitation, and duration of hospitalization in total knee arthroplasty. Clin Orthop 1990:30-37.
233. Williams-Russo P, Sharrock NE, Haas SB, et al. Randomized trial of epidural versus general anesthesia: outcomes after primary total knee replacement. Clin Orthop 1996:199-208.
234. Cullen DJ, Sweitzer BJ, Bates DW, et al. Preventable adverse drug events in hospitalized patients: a comparative study of intensive care and general care units. Crit Care Med 1997;25:1289-1297.
235. Parikh SS, Chung F. Postoperative delirium in the elderly. Anesth Analg 1995;80:1223-1232.
236. Ritchie K, Polge C, de Roquefeuil G, et al. Impact of anesthesia on the cognitive functioning of the elderly. Int Psychogeriatr 1997;9:309-326.
237. Grichnik KP, Ijsselmuiden AJ, D'Amico TA, et al. Cognitive decline after major noncardiac operations: a preliminary prospective study. Ann Thorac Surg 1999;68:1786-1791.
238. Billig N, Stockton P, Cohen-Mansfield J. Cognitive and affective changes after cataract surgery in an elderly population. Am J Geriatr Psychiatry 1995;4:29-38.
239. Goldstein MZ, Young BL, Fogel BS, Benedict RH. Occurrence and predictors of short-term mental and functional changes in older adults undergoing elective surgery under general anesthesia. Am J Geriatr Psychiatry 1998;6:42-52.
240. Rogers MP, Liang MH, Daltroy LH, et al. Delirium after elective orthopedic surgery: risk factors and natural history. Int J Psychiatry Med 1989;19:109-121.
241. Williams-Russo P, Sharrock NE, Mattis S, et al. Cognitive effects after epidural vs general anesthesia in older adults. A randomized trial. JAMA 1995;274:44-50.
242. Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet 1998;351:857-861.
243. McKhann GM, Goldsborough MA, Borowicz LM, Jr., et al. Cognitive outcome after coronary artery bypass: a one-year prospective study. Ann Thorac Surg 1997;63:510-515.
244. Newman MF, Kramer D, Croughwell ND, et al. Differential age effects of mean arterial pressure and rewarming on cognitive dysfunction after cardiac surgery. Anesth Analg 1995;81:236-242.
245. Selnes OA, Goldsborough MA, Borowicz LM, et al. Determinants of cognitive change after coronary artery bypass surgery: a multifactorial problem. Ann Thorac Surg 1999;67:1669-1676.
246. Chung FF, Chung A, Meier RH, et al. Comparison of perioperative mental function after general anaesthesia and spinal anaesthesia with intravenous sedation. Can J Anaesth 1989;36:382-387.
247. Marcantonio ER, Juarez G, Goldman L, et al. The relationship of postoperative delirium with psychoactive medications. JAMA 1994;272:1518-1522.
248. Herrick IA, Ganapathy S, Komar W, et al. Postoperative cognitive impairment in the elderly. Choice of patient-controlled analgesia opioid. Anaesthesia 1996;51:356-360.
249. Crul BJ, Hulstijn W, Burger IC. Influence of the type of anaesthesia on post-operative subjective physical well-being and mental function in elderly patients. Acta Anaesthesiol Scand 1992;36:615-620.
250. Tune LE, Damlouji NF, Holland A, et al. Association of postoperative delirium with raised serum levels of anticholinergic drugs. Lancet 1981;2:651-653.
251. Brebner J, Hadley L. Experiences with physostigmine in the reversal of adverse post-anaesthetic effects. Can Anaesth Soc J 1976;23:574-581.
252. Marcantonio ER, Goldman L, Orav EJ, et al. The association of intraoperative factors with the development of postoperative delirium. Am J Med 1998;105:380-384.
253. Dodds C, Allison J. Postoperative cognitive deficit in the elderly surgical patient. Br J Anaesth 1998;81:449-462.
254. Inouye SK, Charpentier PA. Precipitating factors for delirium in hospitalized elderly persons. Predictive model and interrelationship with baseline vulnerability. JAMA 1996;275:852-857.
255. Inouye SK. Delirium in hospitalized older patients: recognition and risk factors. J Geriatr Psychiatry Neurol 1998;11:118-125; discussion 157-118.
256. Inouye SK. Delirium in hospitalized older patients. Clin Geriatr Med 1998;14:745-764.
257. Lynch EP, Lazor MA, Gellis JE, et al. The impact of postoperative pain on the development of postoperative delirium. Anesth Analg 1998;86:781-785.
258. Koenig HG, George LK, Stangl D, Tweed DL. Hospital stressors experienced by elderly medical inpatients: developing a Hospital Stress Index. Int J Psychiatry Med 1995;25:103-122.
259. Inouye SK. Predisposing and precipitating factors for delirium in hospitalized older patients. Dement Geriatr Cogn Disord 1999;10:393-400.
260. Inouye SK, Bogardus ST, Jr., Charpentier PA, et al. A multicomponent intervention to prevent delirium in hospitalized older patients [see comments]. N Engl J Med 1999;340:669-676.
261. Inouye SK, Rushing JT, Foreman MD, et al. Does delirium contribute to poor hospital outcomes? A three-site epidemiologic study. J Gen Intern Med 1998;13:234-242.
262. Inouye SK, Viscoli CM, Horwitz RI, et al. A predictive model for delirium in hospitalized elderly medical patients based on admission characteristics. Ann Intern Med 1993;119:474-481.
263. Inouye SK, van Dyck CH, Alessi CA, et al. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med 1990;113:941-948.
264. Goldstein MZ. Cognitive change after elective surgery in nondemented older adults. Am J Geriatr Psychiatry 1993;1:118-125.
265. McDowell I, Newell C. Measuring Health: A Guide to Rating Scales and Questionnaires, 2nd ed. New York: Oxford University Press, Inc., 1996.
266. Froehlich TE, Robison JT, Inouye SK. Screening for dementia in the outpatient setting: the time and change test [see comments]. J Am Geriatr Soc 1998;46:1506-1511.
267. Freedman GM, Peruvemba R. Geriatric pain management. The anesthesiologist's perspective. Anesthesiol Clin North America 2000;18:123-141, vii.
268. Parmelee PA, Katz IR, Lawton MP. The relation of pain to depression among institutionalized aged. J Gerontol 1991;46:15-21.
269. Farrell MJ, Gerontol M, Gibson SJ, Helme RD. The effect of medical status on the activity level of older pain clinic patients. J Am Geriatr Soc 1995;43:102-107.
270. Sorkin BA, Rudy TE, Hanlon RB, et al. Chronic pain in old and young patients: differences appear less important than similarities. J Gerontol 1990;45:64-68.
271. Cutler RB, Fishbain DA, Rosomoff RS, Rosomoff HL. Outcomes in treatment of pain in geriatric and younger age groups. Arch Phys Med Rehabil 1994;75:457-464.
272. Lipman AG. Analgesic drugs for neuropathic and sympathetically maintained pain. Clin Geriatr Med 1996;12:501-515.
273. Arner S, Meyerson BA. Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain 1988;33:11-23.
274. Swerdlow M. Anticonvulsants in the therapy of neuralgic pain. In The Pain Clinic. Utrecht: VNU Science Press, 1986:9-19.
275. Stanton-Hicks M, Baron R, Boas R, et al. Complex Regional Pain Syndromes: guidelines for therapy. Clin J Pain 1998;14:155-166.
276. Max MB, Kishore-Kumar R, Schafer SC, et al. Efficacy of desipramine in painful diabetic neuropathy: a placebo-controlled trial. Pain 1991;45:3-9; discussion 1-2.
277. Cutler RB, Fishbain DA, Lu Y, et al. Prediction of pain center treatment outcome for geriatric chronic pain patients. Clin J Pain 1994;10:10-17.
278. Carmichael JK. Treatment of herpes zoster and postherpetic neuralgia. Am Fam Physician 1991;44:203-210.
279. Watson CP, Evans RJ, Watt VR. Post-herpetic neuralgia and topical capsaicin. Pain 1988;33:333-340.
280. Hwang SM, Kang YC, Lee YB, et al. The effects of epidural blockade on the acute pain in herpes zoster. Arch Dermatol 1999;135:1359-1364.
281. Chiarello SE. Tumescent infiltration of corticosteroids, lidocaine, and epinephrine into dermatomes of acute herpetic pain or postherpetic neuralgia. Arch Dermatol 1998;134:279-281.
282. Alper BS, Lewis PR. Does treatment of acute herpes zoster prevent or shorten postherpetic neuralgia? J Fam Pract 2000;49:255-264.
283. Kost RG, Straus SE. Postherpetic neuralgia. Predicting and preventing risk. Arch Intern Med 1997;157:1166-1167.
284. Byrd JC, McGrail LH, Hospenthal DR, et al. Herpes virus infections occur frequently following treatment with fludarabine: results of a prospective natural history study. Br J Haematol 1999;105:445-447.
285. Sengstaken EA, King SA. The problems of pain and its detection among geriatric nursing home residents. J Am Geriatr Soc 1993;41:541-544.