Overview

The response to burn injury occurs on a local and systemic level. Large burns (>20%) result in release of inflammatory mediators from damaged tissue that can exert their effects on the body as a whole. Predictable alterations of major organ systems are the result, leading to hypovolemic shock in the short term and multiple organ system dysfunction in the subacute setting.

In the first 24 hours after a massive burn, increased vascular permeability leads to migration of water into the interstitium. This decreases the intravascular fluid volume and necessitates replacement to maintain perfusion. If intravascular losses are not replaced, there is generalized and organ-specific hypoperfusion. Cardiac output (CO) is suppressed because of fluid shifts and changes in systemic vascular resistance as catecholamine release occurs on a large scale. Gastrointestinal and renal systems are the first to evidence dysfunction but eventually all organ systems are affected. Electrolyte imbalances are common and intercellular ion shifts occur from cellular death in thermally damaged tissues. Endocrine function is depressed, insulin and cortisol requirements increase, and hyperglycemia is common. The initial massive inflammatory response is followed by a period of immunosuppression. An effective therapeutic response requires knowing the physiologic changes that occur locally and systemically.

Local Response: Burn Wound Edema and Tissue Loss

Thermal injury to the skin results in cell death through coagulation, protein denaturation, and cell rupture. Cellular injury and death cause the release of many inflammatory mediators. Histamine, bradykinin, and prostaglandins act locally to promote tissue edema by altering connections in the basement membrane and increasing endothelial cell permeability. This results in transudation of large, osmotically active intravascular proteins out of the capillaries and into the burned tissues. Plasma oncotic pressure is reduced and water is leaked from the microvascular capillary circulation into burned tissue. Additionally, interstitial hydrostatic pressure is increased as integrins are broken and cell-to-cell adhesion is disrupted. This leads to exposure of hydrophilic proteoglycans, which further drive water into the interstitial space. The sum total of these interactions leads to profound and immediate edema in burn-injured tissue.

In addition, within thermally damaged tissue, the release of cytokines, such as interleukin-1, interleukin-8, and tumor necrosis factor-α, attracts leukocytes to the wound. Neutrophil degranulation results in release of proteases and reactive oxygen species. Although in small burns this serves as a useful microbicide, in large burns these are cytotoxic to normal tissue. Complement activation occurs, which furthers disruption of dermal microvasculature and perpetuates local tissue ischemia and necrosis.

Systemic Response: Burn Shock and Burn Edema

Burns greater than 20% of total body surface area cause a system-wide inflammatory response. The large volume release of inflammatory mediators and cytokines into the circulation leads to leaky microvasculature, vasodilation, and decreased CO. Simplistically, the local response overwhelms the microenvironment and becomes systemic.

As in burned tissue, capillary integrity becomes compromised systemically. Low-flow state coupled with osmotic pressure generated by transudate of proteins and electrolytes results in a profound efflux of intravascular volume into the interstitial space. Hematocrit increases as intravascular volume rapidly decreases. Changes in cell membrane integrity cause additional sequestration of fluid within the cellular space. The result is rapid onset total body edema, with maximal fluid shifts occurring at around 12 hours postburn.

In contrast to burned tissue, capillary integrity in nonburned tissue returns to near normal within 24 hours, and transudation of colloids out of the vascular space decreases. However, water continues to collect in the interstitial space in nonburned tissue even after capillary integrity has been restored because of loss of normal oncotic gradient. The loss of plasma proteins into burned tissue is significant enough to decrease vascular oncotic pressure, resulting in ongoing third spacing of water.

Burn shock is multifactorial because of the interplay between loss of intravascular volume, cardiac dysfunction, and vascular changes. Although hypovolemia is common early, vasodilatation also develops, caused by large volume release of inflammatory mediators. Cardiac dysfunction is common in large burns. This can be a primary cardiac dysfunction as a result of massive cytokine release or decreased circulating blood volume from serum loss. These changes in preload, contractility, and after-load can alone or in combination result in low CO and hypoperfusion. The kidney is most vulnerable to damage from burn shock. Increased blood viscosity from the elevated hematocrit and myoglobinemia from deeper tissue damage coupled with intravascular volume loss lead to poor perfusion and acute renal failure. Furthermore, injured tissue within the “zone of stasis” dies.

Crystalloids Alone

Proponents of crystalloid resuscitation argue that the solutions are inexpensive, readily available, and have a proven track record. Physiologically, capillaries in burned tissue remain leaky for more than 48 hours. Theoretically, colloids continue to leak into the burned tissue, which only perpetuates the osmotic drive of water into the interstitial space and worsens edema. Although logical, this thesis is not been proven to occur in human burn tissue.

There is no consensus statement regarding appropriate choice of crystalloid. LR solution is a balanced crystalloid and is the most popular, providing 130 mEq/L of sodium and 4 mEq of potassium. Although hypo-osmolar when compared with serum plasma it is effective at restoring extracellular sodium deficits. The lactate in the solution is metabolized by the liver to bicarbonate and thus the solution is alkalinizing. On the contrary, normal saline with 154 mEq of sodium and 154 mEq of chloride induces academia because of the dissociation of these ions in solution. In the setting of the lactic acidosis that accompanies burn injuries, this is undesirable and can potentiate the acidosis, rather than correct it. Our burn unit uses LR for crystalloid resuscitation. In the setting of hyperkalemia, sodium bicarbonate solution may be used. We never resuscitate with normal saline.

Hypertonic Saline

Hypertonic saline is a largely historic alternative to traditional crystalloid. In theory hypertonic saline acts osmotically to draw water from the interstitium into the intravascular space, thereby lessening fluid requirements. First popularized in the 1970s for use in the burn population, its use has been shown to reduce the amount of volume needed to maintain a target UOP. More recent reports suggest that increasing the intravascular osmolality by using hypertonic saline limits edema formation and reduces the incidence of abdominal compartment syndrome. Other authors, however, have reported that hypertonic saline does not reduce total fluid loads. Alarmingly, studies have also associated increased incidence of hypernatremia, renal failure, and mortality when hypertonic saline was used in burn resuscitation. Given these potentially devastating consequences, it is our opinion that hypertonic saline solutions have no role in the resuscitation of the burned patient and their use should be avoided. In 1996 Monafo recommended not using hypertonic as a burn resuscitation fluid.

Colloids and Starches

The use of colloids, starches, and plasma in burn resuscitation remains controversial. Proponents of colloids assert that these fluids are osmotically active intravascularly, require less volume to achieve a given end point, and may lead to less edema. In theory, the capillary beds in nonburned tissue return to baseline levels of permeability at 5 to 8 hours after initial thermal injury. Resuscitation after this time with colloids, such as albumin, fresh frozen plasma (FFP), or long chain polysaccharides, could provide circulating intravascular volume and lessen fluid needs. Decreased fluid volumes during initial resuscitation would lead to less global tissue edema and therefore decreased risks of compartment syndromes or other sequelae of overresuscitation.

The evidence for use of albumin or other colloids in burn resuscitation is plentiful and many burn institutions use them regularly in their resuscitation protocols. In a retrospective study, albumin use has been linked with decreased mortality when controlling for age, burn size, and inhalational injury. In another retrospective study specific to patients with large burns, albumin use has been demonstrated to decrease the incidence of extremity compartment syndrome and renal failure. A recent meta-analysis of albumin use in acute burn resuscitation found that its use was associated with decreased mortality and decreased incidence of compartment syndrome.

A prospective, randomized trial, comparing the use of LR alone against LR and FFP demonstrated that use of FFP was correlated with less total volume used and that patients had lower intra-abdominal pressures.

However, the evidence against use of colloids is equally plentiful. Cochrane systematic reviews have concluded that in resuscitation of critically ill patients, there is no improvement in mortality when using colloids over crystalloids alone. Similarly there is no difference in outcomes among the various colloid solutions. Moreover, in burned patients, colloid use has been associated with increased lung water after finishing resuscitation. A double blind, randomized clinical trial has demonstrated that hydroxyethyl starch is not superior to LR alone. FFP can cause transfusion-associated lung injury and allergic and anaphylactic reactions.

Given that colloids are more expensive and may have drawbacks when compared with iso-osmotic crystalloid solutions alone, the clinician should be judicious in their use. They may have a role in the patient with fluid-sensitive comorbidities, such as in chronic renal or heart failure.

In our burn unit albumin is used during resuscitation in two situations: symptomatic low oncotic pressure after massive crystalloid resuscitation, and when resuscitation is failing. With massive burn injuries, the volume of crystalloid needed to maintain tissue perfusion predictably dilutes the albumin remaining in the intravascular space. The result is an imbalance between intravascular and extracellular oncotic and hydrostatic pressures. This leads to ongoing loss of intravascular volume and excessive resuscitation. Depending on the patient, this occurs when albumin levels drop lower than 1.2 to 1.5 g/dL. In some patients with serious burns, standard Parkland formula resuscitation is not successful. In many patients the use of a 5% albumin solution results in restoration of effective perfusion. Although the mechanistic rationale for this treatment is not known, senior members of the burn community supported this algorithm at the National Institutes of Health state of the art consensus conference.

Adjuncts to Resuscitation

The massive inflammatory reaction to burn injury is acknowledged by all. A component of this is neutrophil degranulation, which releases large qualities of oxygen free radicals. Some have proposed this as a mechanism for burn wound progression in well-resuscitated patients. Antioxidants could therefore play a role in decreasing the effect of reactive oxygen species in burned tissue. The data for use of ascorbic acid (vitamin C) are clear in experimental models and are suggestive enough to support its use in the acutely burned patient. High-dose ascorbic acid delivered during the first 24 hours after a large burn has been shown to reduce fluid volume needed for adequate resuscitation. Although administration of vitamin C has been complicated by oxalate nephropathy, we believed the evidence is sufficient to recommend the use of ascorbic acid as an adjunct to resuscitation.