these types of injuries are frequently under-reported [27]. Under-reporting of physical abuse and neglect occurs when the older adult is dependent on the abuser for care, feels shame or guilt from the event, or has impaired cognitive abilities. A British review of burns occurring in residential care facilities reported that inadequate staff supervision accounted for the majority of injuries, commonly from hot water scalds and contact with radiators [28]. In both types of injuries, residents with dementia and impaired mobility sustained burns because they were left unsupervised for variable periods of time. Appropriate recognition and management of non-acci- dental burns is challenging, as these injuries are associated with higher mortality rates when compared to accidental burns with similar characteristics [29, 30]. The recommended approach is to use a protocol for assessment, reporting and intervention in a multidisciplinary environment when elder abuse is suspected [31].

Pathophysiologic changes and implications for burn therapy

Aging

The aged skin is responsible for delayed wound healing in older adults. The dermis progressively thins with age, with a decrease in collagen content and extracellular matrix. The aging dermis has reduced microcirculation, macrophages and fibroblasts. In contrast, epidermal thickness is preserved with age, although there is flattening of the dermal-epidermal junction (rete ridges), making the epidermis more prone to shearing. Aging alters all phases of wound healing, from hemostasis and inflammation, to proliferation and resolution [32]. The rate of epidermal turnover is reduced by 50% after age 65, with fewer epidermal-lined skin appendages to permit re-epi- thelialization [33, 34]. Additionally, some environmental exposures can contribute to premature skin aging, such as tobacco smoking, sun exposure, and alcoholism-induced nutritional deficiencies [35]. Diabetes, chronic anticoagulation, and steroid immunosuppression are frequent comorbidities that predispose to premature skin aging and impaired wound healing. Clinically, burn providers often ob-

serve that even shallow-appearing partial thickness burn wounds in older adults can have significantly delayed re-epithelialization. In patients undergoing excision and grafting, delayed healing in donor sites and grafted wounds limits our ability to achieve early and complete wound closure.

Age-related changes in multiple organ systems contribute to the decreased physiologic reserve in older adults. Cardiac index decreases 1% per year whereas systemic vascular resistance rises 1% per year. Maximal heart rate and responses to adrenergic stimulation are also reduced with age [36]. Increased cardiovascular system stiffness (in the heart, arteries and arterioles) leads to an increased in pulse wave velocity and resetting of the baroreflex, thus causing the resting systolic pressure to rise. The aging cardiovascular system is more susceptible to the effects of hypovolemia, with a greater reduction in stroke volume and arterial systolic pressures. Respiratory performance decreases with age because of reduced chest wall compliance, decreased diaphragm strength, and alveolar airspace enlargement. Both forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) decrease over time [37]. Progressive renal deterioration is marked by a decrease in kidney size after age 50, with morphological changes often accelerated in the setting of diabetes and hypertension. Functionally, the age-dependent reduction in glomerular filtration rate (GFR) renders aging kidneys susceptible to second physiologic insults during critical illness [38]. Cognitive performance declines with age, although the underlying mechanisms are not fully characterized. Recent research indicates that brain tissue atrophy with aging may be concentrated in the loss of white matter fibers, resulting in altered relationships between cortical regions. This phenomenon has been termed “cortical disconnection”, a deficit in integration between different networks [39, 40].

Aging also causes progressive loss of lean body mass, weakened muscle strength and reduced physical function [41]. Frailty itself is an important risk factor for injuries from falls, and poor hospitalization outcomes [42, 43]. Post-burn hyperdynamic and hypermetabolic responses are relatively blunted in older adults, although these patients still suffer from persistent catabolism, and loss of lean body mass[44, 45] Together, these factors constitute an enormous

barrier to physical recovery in older patients. Early provision of nutritional support, maintenance of warm ambient temperatures, and control of infection are important strategies to mitigate the catabolic state. Pharmacologic agents to modulate hypermetabolism in older adults may achieve a similar benefit to those demonstrated in children with severe burns [46–49]. Oxandrolone, a testosterone analog with weak virilizing potential, is a promising agent for it induces anabolism in both older men and women after only two weeks of therapy [50]. The non-selective beta-blocker propranolol reduces tachycardia, energy expenditure, substrate cycling, and prevents fatty acid infiltration of the liver in severely burned children, but its application has not yet been reported in older adults with burns [45, 48]. This strategy is particularly appealing since aged patients do not tolerate tachycardia well. However, be- ta-adrenergic blockade must be balanced against the risks of inducing bradycardia and hypotension. The benefits of exercise regimens for older patients are numerous, including improved general health, faster hospitalization recovery in multiple conditions, and reduced repeat injuries [51–53]. The combination of anabolic agent supplementation and exercise should be a core component of a comprehensive rehabilitation plan, but thus far remains to be validated in older adults with burns.

Important changes in the aged host immune responses may partially account for post-injury complications and a higher susceptibility to infections. Aging alters antigen presentation, cytokine production, phagocyte activity and chemotaxis in multiple innate immune cells [54, 55]. Senescence also affects cell-mediated immunity with atrophy of the thymus, reduced naïve T-cells, and decreased T-cell memory [56]. At baseline, healthy older adults exhibit a chronic inflammatory state, characterized by higher circulating levels of pro-inflammatory mediators (TNF- , IL-1, IL-6). This condition has been termed “inflamm-aging”, and presumably arises from repeated exposure to antigens and other sources of cell stress [57]. After injury, early organ dysfunction develops more frequently in older adults with burns. It typically begins with acute lung and kidney injury, followed by deterioration in multiple organ systems [58]. Recent findings in a mouse burn injury model provide a potential mechanistic explanation for a

higher incidence of pulmonary dysfunction in the aged host: burn-injured aged mice have protracted neutrophil infiltration and chemokine production in the lung compared younger mice [59]. Animal models of aging and sepsis demonstrate that the aged host immune response to infectious challenges is markedly altered. Aged mice respond poorly to either endotoxin challenge or cecal ligation and puncture (CLP) [60]. Turnbull et al. reported that aged mice have 70% mortality with CLP compared to 20% in young mice, and that antibiotic therapy initiated 12 hours after CLP does not significantly improve survival in older mice [61]. Although a burn + sepsis model in aged animals has not yet been reported, patient outcomes data give ample evidence that this combination is a strong risk factor for late-onset multiple organ dysfunction syndrome (MODS) and death [62, 63].

Comorbidities

The relationship between injury and comorbidity is synergistic. Conditions such as smoking, physical disability, and altered sensorium are clear predisposing factors to burn injury [64, 65]. Additionally, the incidence of pre-injury comorbidities may be as high as 85% and frequently complicates the care of older burn patients [6]. Co-morbidities comprise a heterogeneous set of conditions, each with a different impact on burn management. Chronic obstructive lung disease and smoking strongly predict the development of pulmonary complications in older adults with burns [66]. Cardiac dysfunction may alter the timing of surgical procedures and can delay liberation from mechanical ventilation. The optimization of patients with systolic and diastolic heart dysfunction, or rhythm abnormalities may require additional diagnostic tests and invasive monitoring [67]. In contrast, well-managed comorbidities prior to injury may actually constitute a survival advantage: Arbabi et al. reported that older burn patients taking a beta-blocker prior to injury had better survival than those not treated with beta-blocker [68]. Whether this results from a biological effect of betablocker or simply better pre-injury care remains to be clarified. At the opposite end of the spectrum, patients on oxygen therapy who continue to smoke may be difficult to wean from mechanical ventilation