Organ responses and organ support

Introduction

Over the past fifty years, goal-directed resuscitation [1–3], early burn wound excision and grafting [4–7], and recognition of burn hypercatabolism[8 –10] have dramatically reduced mortality rates after burn injury [11–15]. Despite this progress, end-organ dysfunction remains a threat throughout a patient’s clinical course. Recent studies approximate the incidence of multiple organ dysfunction as 40–60% among patients with greater than 20% total body surface area (TBSA) burns, with associated mortality rates from 22–100% [16–19]. These mortality rates increase in proportion to the number of failed systems [19]. The link between multi-organ failure and patient mortality highlights the necessity for practitioners to cultivate an understanding of burn pathophysiology, as well as critical care principles of organ support.

Burn shock and resuscitation

The primary step toward management of multiorgan failure is prevention. In burn patients, this originates with adequate resuscitation during the first 24 hours after injury. Thermal injury covering greater than 20% TBSA induces massive capillary leak and autonomic dysfunction, with resultant distributive and hypovolemic shock. On the cellular level,

Marc G. Jeschke et al. (eds.), Handbook of Burns

burn injury disrupts transmembrane sodium-AT- Pase activity, with resultant intracellular sodium retention, osmotic shifts, and cellular edema [20]. Mast cells aggregate to burn wounds and secrete histamine, which disrupts inter-cellular junctions at the venules and allows for extravasation of plasma fluid and proteins from the intravascular space into the tissues [21]. This efflux of protein from the capillaries decreases plasma oncotic pressure, and worsens hypovolemia and tissue edema. Large burns also trigger the release of inflammatory mediators, including but not limited to bradykinin, vasoactive amines, prostaglandins, leukotrienes, activated complement, and catecholamines [20–22]. This outpouring of cytokines induces local vasoconstriction, systemic vasodilatation, and massive capillary leak, yielding hypovolemia and hemoconcentration that peaks at 12 hours post-burn [20]. Without adequate resuscitation, plasma volume becomes insufficient to maintain preload, cardiac output decreases, and end-organ hypoperfusion and ischemia ensue, with ultimate multi-organ failure and death [20–24].

Early burn wound excision – within the first 72 hours post-burn – has been shown to modulate the inflammatory response to burn injury by reducing levels of pro-inflammatory mediators, and is now considered standard of care [25]. Additionally, maintenance of organ perfusion during burn shock depends upon restoration of intravascular volume. Toward this end, burn surgeons have adopted resus-

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citation algorithms to guide the appropriate infusion rates of crystalloid in the first 24 hours after burn injury. The most popular of these algorithms in the United States, the Parkland formula, calculates a total volume of crystalloid based upon the patient’s weight and an estimation of the percentage of body surface area burned. According to the American Burn Association (ABA), these formulas provide guidelines, not absolute protocols, for resuscitation in burn shock [20]. Burn depth, inhalation injury, patient age, delays in resuscitation, and alcohol and drug use may increase fluid requirements during burn resuscitation [24]. In these scenarios, the Parkland formula may underestimate patient’s fluid needs, leading to under-resuscitation and organ failure.

Unfortunately, specific titration endpoints for fluid resuscitation remains a topic of fervent debate. To avoid under-resuscitation, the ABA recommends titrating crystalloid infusions to normotension (MAP > 65), and to urine output greater than 0.5 cc/ kg/hr in adults [20]. Although urine output values less than this amount are correlated with higher complication rates at 48 hours, hourly urine output is a nonspecific measure, with scant data linking it to tissue hypoxia. Glycosuria and polyuric renal failure can falsely elevate rates, and several studies highlight the failure of urine output to reflect adequate global perfusion [23]. Similarly, blood pressure and heart rate may be normal in states of compensated shock, and normal values can mask occult cellular hypoperfusion.

Concerns over the specificity of resuscitation endpoints have prompted a paradigm shift in burns care over the past ten years. In 2001, Rivers et al. published results of a randomized control trial that demonstrated improved outcomes among septic patients resuscitated to meet to pre-defined goals of preload, contractility, and oxygen delivery [26]. Further studies substantiated this approach, and in 2008 the Surviving Sepsis Campaign incorporated goaldirected therapy into their international guidelines [27]. Current sepsis management includes optimization of preload and oxygen delivery according to invasive hemodynamic monitoring, base deficit, lactate, and central venous saturation measurements, and enhancement of contractility with inotropic support.

The paradigm shift in sepsis care has prompted efforts toward a goal-directed resuscitation strategy in burn patients. Recent studies suggest that lactic acid and base deficit, both reliable measures of hypoperfusion in the trauma setting, correlate with burn size and with mortality [28 – 31]. Experience with invasive hemodynamic monitoring, i. e., esophageal Doppler [32–34] and transpulmonary thermodilution systems [35], reveals that the Parkland formula frequently underestimates a patient’s fluid requirements. Unfortunately, efforts to optimize resuscitation with new strategies have unveiled new dangers. Patients with severe burns often receive crystalloid volumes significantly in excess of Parkland predictions, a phenomenon the burn community has termed “fluid creep.”[36] The result has been an resurgence in complications of overresuscitation, including pulmonary edema, myocardial edema with atrial arrhythmias, conversion of superficial to deep burns, and compartment syndromes of the extremities [24]. Studies in trauma patients have described the immuno-modulatory effects of massive crystalloid resuscitation, including upregulation of the neutrophil oxidative burst, increased expression of neutrophil adhesion molecules, and cellular injury [37]. Researchers have hypothesized that inappropriate neutrophil activation from crystalloid infusion triggers ARDS and end-organ injury. Results from a recent multicenter trial mirror these concerns, and reveal a link in burn patients between massive resuscitation and mortality. In 2007, Klein et al. published their findings that increasing fluid requirements in burn patients significantly increased the risk of developing ARDS, pneumonia, bloodstream infections, multiorgan failure, and death [38]. Even after adjustment for patient and injury characteristics that might confound the relationship between fluid administration and outcome, there was a trend toward increased risk of adverse outcome, including death, when fluid received exceeded predicted requirements by more than 25 %. Additional studies have established an increased risk of abdominal compartment syndrome among patients who receive more than 250 cc/kg of crystalloid within 24 hours, with resultant renal failure, mesenteric ischemia, coronary malperfusion, and impairment in pulmonary compliance [39, 40].