Age-related changes in skin contribute to poor wound healing after surgical procedures. Changes in skin with age include a decline in thickness and composition, a decrease in the number of most cell types, and diminished microcirculation, the process that provides tissue perfusion, fluid homeostasis, and delivery of oxygen and other nutrients. It also controls temperature and the inflammatory response. Surgical incisions cause further disruption of the microvasculature of aged skin; however, perioperative management can be modified to minimize damage to aged tissues. Judicious use of fluids, maintenance of normal body temperature, pain control, and increased tissue oxygen tension are examples of adjustable variables that support microcirculation. Anesthetic agents influence microcirculation in a number of ways, including cardiac output, arterial pressure, and local microvascular changes. The authors examined the role of anesthetic management in optimizing microcirculation and potentially improving postoperative wound repair in older persons.
Aged skin is at increased risk of poor postoperative wound healing. Changes in the cutaneous microcirculation with aging contribute to this risk. This review examines the role of anesthesia management in microcirculatory function.
SURGICAL wound repair is a major problem in the older population, who are at increased risk of wound dehiscence and infection. As a specific example, surgical site infections (SSIs) are common (approximately 500,000 cases annually in the United States), lead to worse patient outcome (patients who develop SSI are twice as likely to die), and are an enormous economic burden (1–10 billion dollars annually). Many factors contribute to age-related changes in skin5 and subsequent vulnerability to impaired wound healing and infection. Changes in skin with age (fig. 1) include a decline in epidermal and dermal thickness and composition, as well as a decrease in the number of most resident cell types. The dermal–epidermal junction is flattened and the microcirculation is diminished. The latter is defined as blood flow through arterioles, capillaries, and venules and is the key system that affects the entire skin surface. In the aging patient, the microcirculation in the skin is reduced by 40% between the ages of 20 and 70 yr. The microcirculation provides tissue perfusion, fluid hemostasis, and delivery of oxygen and other nutrients. It also controls temperature and the inflammatory response. Surgical incisions cause disruption of the microcirculation in the skin as manifested by local edema resulting from vasodilation and increased vascular permeability.
Numerous changes in skin with age contribute to impaired wound healing.
Perioperative management can be modified to optimize the microcirculation. Measures that support the microcirculation include careful use of fluids, normothermia, pain control, and smoking cessation. Factors that can be influenced by intraoperative management (judicious use of fluids, maintenance of normal body temperature, pain control, and increased tissue oxygen tension) have been suggested to be beneficial as well. Most anesthetic agents also influence the microcirculation: a reduction in cardiac output and arterial pressure decreases flow in the microcirculation, whereas anesthetic-induced local microvascular changes and vasodilatation can increase perfusion. Optimization of these variables plays an important role in enhancing the microcirculation in all patients, but is especially relevant if modifications could improve postoperative wound healing in the older population.
In this review, we will use skin as a representative organ to describe age-related changes that negatively affect the microcirculation and have subsequent impacts on wound healing and the incidence of postoperative infection. We will then examine the role of anesthesia management in minimizing detrimental effects on the microcirculation. A greater understanding of these variables could promote improvements that lead to better outcomes with respect to wound repair in older patients.
Summary of Wound Repair and Aging
It has been nearly a century since it was noted that the rate of cutaneous scar formation after a wound is inversely related to the age of the patient. Four decades ago, it was observed that older age was associated with an increased risk of postoperative disruption of the surgical wound, leading to higher mortality. Recent data suggest that in patients older than 65 yr, development of SSI is associated with a two-fold increase in cost and a staggering four-fold increase in mortality.
Wound healing ensues via a sequential chain of events (with variable overlap) that includes inflammation, tissue formation, and remodeling (fig. 2). Circulating factors have a pivotal role in each of these phases. Accordingly, as we will discuss below, immediate changes in the microcirculation influence each stages of the wound-healing response in aging. As human data is lacking, we have taken data from established animal models of aging. Although animal models are not uniformly predictive of responses in human tissues, several animal models of wound healing are generally accepted.
The stages of wound healing are a sequential chain of events that include: (A) inflammation, (B) proliferation and granulation tissue formation, and (C) extracellular matrix (ECM) deposition and tissue remodeling. PDGF = platelet-derived growth factor; TGF-β1 = transforming growth factor-β1; TNF-α = tumor necrosis factor-α; VEGF = vascular endothelial growth factor.
Nearly every anesthesiologist who provides care to adults will participate in the care of geriatric patients. A growing older population is undergoing surgical procedures that are increasing in number and complexity. Poor healing of surgical wounds is a major cause of morbidity, mortality, and substantial economic burden. Wound healing is dependent on the microcirculation that supplies the incision area. Measures that support the microcirculation during the perioperative period have a profound effect on wound healing. Some measures such as maintenance of normal body temperature and control of postoperative pain are supported by ample evidence and have been implemented in routine clinical care. Other measures, for example, the choice of anesthesia technique and use of opioids are supported by basic research but need further clinical studies. A better understanding of the effect of aging and anesthesia on the microcirculation can potentially assist in improving postoperative wound repair, thereby benefiting a growing older population.
The Surgical Context of Wound Repair and Aging
Measures that support the microcirculation improve wound repair, thereby reducing the risk of postoperative dehiscence and infection.52 General preoperative measures such as smoking cessation and optimal management of comorbid medical conditions have been reviewed in other contexts.53,54 For the purpose of this review, we will focus on interventions in the perioperative setting.
Wound healing is dependent upon adequate levels of oxygen.55 Oxygen interacts with growth factor signaling and regulates numerous transduction pathways necessary for cell proliferation and migration.56 It is also an indispensable factor for oxidative killing of microbes.57 Consequently, the effects of oxygen tension on the outcome of surgical wounds have been best studied in the context of postoperative infection. Resistance to surgical wound infection is presumed to be oxygen dependent—with low oxygen tension viewed as a predictor of the development of infection,56 particularly when subcutaneous tissue oxygenation (measured by a polarographic electrode) decreases to less than 40 mmHg.58
In two recent meta-analyses, one found that perioperative supplemental oxygen therapy exerts a significant beneficial effect on the prevention of SSIs,59 whereas the other suggested a benefit only for specific subpopulations.60 Although most authors suggest that supplemental oxygen during surgery is associated with a reduction in infection risk,61,62 others propose it may be associated with an increased incidence of postoperative wound infection.63 Notably, in the latter report, the sample size was small and there was a difference in the baseline characteristics of the groups. A prospective trial randomizing patients to either 30 or 80% supplemental oxygen during and 2 h after surgery did not find any difference in several outcome measures including death, pulmonary complications, and wound healing.64 Of note, the administration of oxygen to aged subjects may be limited by the finding that although arterial oxygen tension did not decrease with age, there was reduced steady-state transfer of carbon monoxide in the lungs.65 This indicates that oxygen transport could be diffusion-limited in older subjects, especially when oxygen consumption is increased. Furthermore, longitudinal studies of five healthy men over 3 decades showed impaired efficiency of maximal peripheral oxygen extraction,66 suggesting that tissue oxygen uptake is reduced in the aged subjects.67 This likely reflects a decrease in the number of capillaries as well as a reduction in mitochondrial enzyme activity.68 Animal models (rabbit69 and mouse69,70 ) have suggested that aging and ischemia have an additive effect on disruption of wound healing. Consequently, the potential benefit of increasing tissue oxygen tension during surgical wound repair in older patients should be further evaluated.