Cardiovascular Changes

Interrelated molecular and structural changes occur within the myocardium, aorta, and cardiac conduction system (Table 38.1). The breakdown of elastin and increased collagen deposition and cross-linking cause vascular stiffness, which increases impedance and peripheral vascular resistance. The aorta becomes more dilated, exhibiting decreased compliance associated with higher wall tension, as large elastic arteries become stiffer with an increase in pulse wave velocity and pulse pressure. This in turn is associated with an increase in left ventricular (LV) afterload with LV dilatation or reduced ejection fraction. Coronary arteries may develop plaques and calcified lesions, as well as fixed stenoses.⁸

Progressive myocyte hypertrophy, myocardial fibrosis, inflammation, valvular sclerosis, and calcification lead to increased LV mass over time and decreased compliance. Subcellular changes in myocyte calcium cycling occur that allow the ventricle to maintain tension against increased afterload,⁹ which can be helpful in some situations but maladaptive under other conditions, such as in the setting of tachycardia. In such a situation, delayed relaxation can impede chamber filling. Over time, there is an accumulation of misfolded proteins and dysfunctional mitochondria, as well as decreased in dysfunctional cell components removal by autophagy. Cardiac aging is characterized by the presence of hypertrophy, fibrosis, and accumulation of misfolded proteins and dysfunctional mitochondria. Autophagy may play an important role in combating the adverse effects of aging in the heart. Autophagy is a lysosome-dependent bulk degradation mechanism that is essential for intracellular protein and organelle quality control. Autophagic flux is generally decreased in aging hearts, with loss of function that develops exacerbated cardiac dysfunction that is accompanied by accumulation of misfolded proteins and dysfunctional organelles. Stimulation of autophagy generally improves cardiac function by removing accumulated misfolded proteins, dysfunctional mitochondria, and damaged deoxyribonucleic acid, thereby improving the overall cellular environment and alleviating aging-associated pathology in the heart.¹⁰ Increases in fatty infiltration, fibrosis, and amyloid content can result from altered collagen cross-linking that can increase the risk of conduction defects. Hypertrophic myocytes demand more energy and oxygen. As a result, cardiac performance may be maintained under normal circumstances, however, the diminished cardiac reserve may become apparent when the patient’s heart is subjected to increased workload or stressors.⁸

Homeostatic reflexes are dampened, which increases the impact of the age-related decline in cardiovascular reserve.⁹ Typical changes include decreased baroreceptor sensitivity, myocardial response to catecholamines, and autonomic control of peripheral vascular resistance. Maximal heart rate and cardiac output decrease as well.¹¹

Pulmonary Changes

Alterations in lung parenchyma, the chest wall, and central regulation of respiration that occur with aging can contribute to decreased respiratory function (Table 38.2). Fewer alveoli and lung capillaries, enlargement of alveolar air spaces, and decreased airway size and alveolar-capillary surface area become apparent with age. These changes result in decreased elastic recoil and less negative ­intrapleural pressure. Weakened musculature, a stiffer rib cage, kyphosis, and a greater anteroposterior diameter of the thorax lead to decreased chest wall compliance. The pulmonary physiologic changes of the aging lung may synergize with the pathologic changes of various lung diseases to affect lung structure and function. Such synergistic effects may lead to more severe manifestations of lung disease in the elderly. Loss of elastic recoil of the lung is a prominent feature of aging, similar to asthma and COPD. The presence of alveolar enlargement in the aged adult likely coexists with destruction of alveolar walls and the inflammatory infiltrate found in patients with emphysema. Aging leads to changes in the expression of transforming growth factor-β and extracellular matrix composition, which may lead to increased incidence of fibrotic lung disorders in the elderly. Although total lung capacity is characteristically maintained with normal aging, because the increased residual volume is counterbalanced by the decrease in vital capacity, this is not the case in the older individual with fibrotic lung disease, given the significant decrease in vital capacity (Fig. 38.1).

Aging is associated with changes in the pulmonary circulation that occur in response to increased dead space ventilation and ventilation/perfusion mismatch, as well as to general stiffening of the pulmonary vasculature, with an increase in pulmonary arterial systolic pressure particularly pertinent during exercise. The effects on the pulmonary circulation because of aging combined with severe lung disease may worsen gas exchange and increase the work of breathing¹² (Fig. 38.2).

Secretory and immune function also wane, resulting in less efficient mucociliary transport, less robust polymorphonuclear leukocyte function, blunted delayed-type hypersensitivity response to foreign antigens, and an increased response to autologous antigens.¹¹ Ventilatory response to hypoxia and hypercarbia is diminished, and periodic breathing during sleep may increase. Air trapping, work of breathing, closing capacity, dead space, and ventilation-perfusion mismatch increase. Forced expiratory volume exhaled in one second (FEV₁), forced vital capacity (FVC), diffusing capacity, and maximal voluntary ventilation (MVV) decrease.¹² The alveolar-arterial gradient for oxygen widens, and resting arterial oxygen partial pressure (PaO2) decreases. As a result of these changes, lung function can additionally be compromised after thoracic surgery, particularly in patients who have a history of COPD. Splinting for pain from chest incision exacerbates these effects. Conversely, opioids can further blunt the response to hypoxia and hypercarbia (Fig. 38.3).

Hepatorenal Changes

Changes in liver and kidney function as a result of the aging process can profoundly affect metabolism and clearance (Table 38.3). Liver size can decrease by 40%, as well as renal mass by the age of 80 years.¹³ Hepatic blood flow can decrease by 35% to 50%.¹⁴ Hepatic vascular resistance increases, and portal pressure increases. Hepatocyte function deteriorates, decreasing molecular biosynthesis and clearance of toxins.¹³ Decreased perfusion can affect the plasma clearance of drugs metabolized by the liver, such as opiates, benzodiazepines, propofol, etomidate, barbiturates, and most nondepolarizing neuromuscular blockers, which are commonly used during anesthesia.¹⁵ Decreased cytochrome P450 activity compounds this affect. Changes in immune function can predispose elderly patients to autoimmunity, while decreasing the immune response to pathogens and malignant cells.¹⁴

The number of functional glomeruli decrease with aging as a result of increased nephrosclerosis, increased arterial atherosclerosis, tubular atrophy, and interstitial fibrosis. Cortical volume decreases, and there may be other structural changes, such as an increased number of cysts or focal scars. Elderly patients possess diminished renal functional reserve, putting them at higher risk for ischemia and acute kidney injury. Glomerular filtration rate (GFR) declines at a rate of 6.3 mL/min/1.73 m² per decade. The lowest risk of mortality is at a GFR of more than or equal to 75 mL/min/1.73 m² for those under 55 years but at a lower GFR of 45 to 104 mL/min/1.73 m² for those 65 years and over.¹⁶ These patients experience prolonged elimination half-time of drugs, dependent on renal clearance. Reduced renal perfusion decreases GFR, creatinine clearance, and response to antidiuretic hormone aldosterone, renin, and vasopressin. Variability in individually calculated pharmacokinetic parameters increases with age, resulting in varying clearance of drugs across the geriatric population.¹⁷ Diminished sodium reabsorption, potassium secretion, and urine concentration ability puts the geriatric patient at higher risk of volume depletion and salt retention¹⁸ (Fig. 38.4).

Nervous System Changes

Changes in the brain that occur with age include a decrease in the number of dendrites and synapses, leading to decreased neuronal connectivity and brain volume. Older patients are at higher risk of experiencing dementia, sleep disorders, memory problems, movement disorders, and delirium.¹⁹ Cognitive function varies greatly among the elderly in terms of reserve and baseline deficit. An association between postoperative delirium and long-term outcome, as highlighted by recent data, suggests that short-term cognitiveimpairment may reflect systemic deficits. Using a series of functional and cognitive assessments, Robinson et al. found a 44% incidence of delirium in a study of 144 patients over 50 years old, of whom more than half underwent thoracic ­surgery.²⁰ Risk factors included increasing age, hypoalbuminemia, anemia, intraoperative hypotension, history of alcohol abuse, preexisting dementia, and impaired functional status. Delirium has been associated with increased length of hospital stay and a greater 6-month mortality.²¹

Medication choice and administration can have particular importance for geriatric patients. A recent study suggests that dexmedetomidine (DEX) may reduce the incidence and intensity of delirium in elderly patients after lung cancer surgery. Medical records of 346 lung cancer patients over 65 years post pulmonary resection for lung cancer were assigned to DEX or control group. Patients, care-providers, and investigators were all blinded to group assignment. DEX was administered in the preoperative and intraoperative periods. During postoperative day (POD) 1 to POD 7, delirium occurs in both groups. However, the incidence of delirium was lower in the DEX group than that in the control group, there were fewer moderate and severe delirium patients in the DEX group compared with the control group. Finally, patients in the DEX group had a shorter duration of delirium, a lower numeric pain rating scale during movement, and better sleep quality.²² Other data support the use of total intravenous anesthesia and epidural analgesia, citing an association between these techniques and a significant decrease in the number of unplanned admissions to intensive care for patients who underwent lung resection. A total of 253 out of 11,208 patients undergoing lung resection in the study period of 2 years that had an unplanned admission to intensive care in the postoperative period, were evaluated in the United Kingdom. The incidence of intensive care unit admission was 2.3% (95% confidence interval [CI], 2.0%–2.6%). Patients who had an unplanned admission to intensive care unit had a higher mortality (29.00% vs. 0.03%, P < .001), and hospital length of stay was increased (26 vs. 6 days, P < .001). Patients receiving total intravenous anesthesia [odds ratio [OR], 0.50 (95% CI, 0.34–0.70)], and patients receiving epidural analgesia (OR 0.56 (95% CI 0.41–0.78) were less likely to have an unplanned admission to intensive care after thoracic surgery.²³