It is critical to appreciate that while burn injury patients share many physiologic and interventional commonalities with other forms or presentations of major traumatic injuries, burn injury patients manifest a unique set of pathophysiologic insults. This appreciation helped justify and promote the establishment of specialized burn units.

Many burn centres currently employ and rely upon individually defined protocols, which are derived from current and established guidelines, tempered by experience, training, practice, and logistical considerations. These protocols allow for the uniform and efficient translation of care amongst personnel, in an effort to efficiently and methodically guide care.

In an effort to further diminish morbidity and mortality rates among this unique patient population, it is imperative to introduce new data and developments in re-examining and re-establishing treatment protocols and guidelines, as well as the critical timing of therapeutic interventions. Lessons learned from evolving orthopaedic and surgical trauma efforts may similarly prove beneficial for burn patients. It is only through future objective study that thwe researchers ccan improve our patients’ survival and subsequent quality of life.

Damage control surgery complements this practice and could potentially further improve outcomes. There is, however, only spare evidence as to which burn patients would benefit from deferred early total care and gain from damage control surgery. Discussions of what exactly constitutes early excisional approaches continue to be argued and challenged.

Hypothermia has been identified as a major responsible factor for mortality in burned patients: Muthukumar et al. ^[1][12] identified a 4.27-fold risk of death in patients presenting with a mean hypothermia of 34.8 °C, and Hostler et al. ^[2][13] reported that hypothermia was independently associated with mortality. Ziegler et al. ^[3][14] described a positive influence of normothermia (≥36 °C) on survival. In contrast, Sherren et al. ^[4][11] reported that the lethal triad in burn patients was associated with the severity of the injury as measured by the Abbreviated Burn Severity Index (ABSI) but did not reflect the patients’ outcomes. Similarly, Ehrl et al. ^[5][15] could not identify a significant difference in mortality between normothermic and hypothermic patients; however, time until death was shorter in hypothermic patients. Regarding intraoperative hypothermia, an increased risk of infectious complications by a rate of 1.4 was reported ^[6][16]. In summary, hypothermia seems to be a critical parameter that correlates with morbidity and mortality. Thus, hypothermic patients may benefit from the concept of damage control surgery in combination with warming measures, rather than early total care ^[7][17].

The second factor of the lethal triad, namely coagulopathy, is certainly reported and appreciated in thermally injured patients ^[4][8][11,18]. Fibrinolytic dysfunction has been identified as early as 1 to 2 hrs post insult. Garcia-Avello et al. ^[9][19] reported that burn patients exhibited hypercoagulability and hyperfibrinolysis beginning as early as post-burn day 1 and persisted until post-burn day 7. This derangement of coagulation factors was more pronounced in non-survivors and appears to be related to organ failure. Pusateri et al. ^[10][20] and Sherren et al. ^[11][21] reported that early fibrinolytic dysfunction as measured by thromboelastography was associated with increased mortality in burn patients. Huzar et al. ^[12][22] noted that hypocoagulability was negatively associated with mortality. Taken in concert, these reports demonstrate that analysing coagulation parameters in burn patients may identify patients at risk for deleterious outcomes.

Acidaemia has also been shown to correlate with a poorer outcome in severe burn injury ^[13][14][23,24], thereby establishing all three factors of the lethal triad in severe burn injury.

Orthopaedic traumatologists have increasingly recognized the importance of soft tissue injury in overall patient morbidity and mortality. As a result, injury scoring measures have added soft tissue injury as a fourth parameter when assessing orthopaedic trauma patients who have suffered concomitant injuries to extremities, lungs, the abdomen, and the pelvis ^{[15][16][17][18]}[4,25,26,27]. Cutaneous soft tissue loss is a hallmark of burn injury and has been identified as an independent risk factor in burn lethality ^[19][20][28,29]. While fundamental questions as to the optimal time to perform debridement and even definitive skin grafting persist, burn patients with critical findings of the lethal triad and extensive TBSA burns may well benefit from DC surgery, and this in turn may improve survival.

Pape et al. ^[17][26] described four classes of orthopaedic trauma patients, according distinct parameters from the following categories: shock, coagulation, temperature, and soft tissue injury, as either “stable”, “borderline”, “unstable”, or “in extremis” (see Table 3 in ^[17][26]). The authors recognized that immediate surgery would significantly and negatively impact patients in the latter two groups, leading to organ failure or even death. “Borderline” patients who are initially stable may worsen after surgery ^[17][26]. In an effort to better define this subset, several negative prognostic factors have been described for “borderliners”. To date, similar clear or identifying characterizations for burn patients at risk have not been fully established and described; however, detrimental prognostic factors, such as inhalation injury and the total body surface area of burned skin, are well-recognized for burn patients, which, in like manner, justify pursuing a DC surgical approach.

To achieve the goals of both timely debridement and safe grafting in severely burned patients, a precise knowledge about the patient’s status seems crucial. Several scoring systems on mortality or survivability have been reported for burn patients. Most of these burn injury-related scores (Baux score, revised Baux score, Abbreviated Burn Severity Index (ABSI) score, Ryan score, and Belgium Outcome Burn Injury (BOBI) score) are based on total body surface area (TBSA), age, and inhalational trauma (IHT) ^[19][20][28,29], but do not specifically respect pathophysiological data of the lethal triad ^[21][30]. Currently, none of the prognostic burn scores are utilized for strategic planning of surgical procedures in burn patients.

2. Burn Toxins and Debridement of Bburn Eeschar — Wwhat is the Cclinical Eevidence?

Our innate immune system has the capacity to detect and respond to a variety of critical stimuli such as 'non-self' molecules derived from pathogens and other insults. Burn eschar, a reservoir of damaged and dying cells release endogenous host-derived molecules termed damage-associated molecular patterns DAMPs which bind to receptors expressed on innate immune cells, notably Toll-like receptors (TLRs) promoting an inflammatory response ^[22][23][24][58,59,60] . In cases of significant burn injury the collective DAMP associated response, as introduced above, results in a cascade of deleterious systemic effects, specifically a dysregulated sterile inflammatory state which when severe culminates in a profound state of immunosuppression. In the last century Allgöwer et al. ^[25][26][61,62] identified burn tissue derived toxins responsible for severe immunosuppression and mortality. An elegant set of experiments by Hansbrough et al. ^[27][63] demonstrated that burn tissue was at least one causal source for the detrimental immunological effects observed in burn injury. These clinicians and others strongly advocated elimination of burn toxins from the skin either by primary excision of the burns ^[28][29][30][64,65,66] or local application of a protein-complex-binding substance such as cerium nitrate ^{[31][32][33][34]}[67,68,69,70]. In concert with this direction, clinical evidence has repeatedly demonstrated that patients with extensive burns (>30% TBSA), whose eschars were excised early, showed reductions in circulating cytokines, hypermetabolism, and mortality. Data derived from a variety of early versus late (> day 6) eschar removal performed in animal studies concluded that early debridement prevented the often seen profound inflammatory state and immunologic dysfunction associated with such injuries, as well as promoting an accelerated reepithelialization and reduction in scarring. A 2006 meta-analysis ^[35][46] reviewed prospective studies comparing early excision and grafting with delayed grafting after eschar separation (historical approach) in burn patients without inhalation injury. In this meta-analysis survival was improved in the early excision group with a shortened length of stay (LOS). Of particular note, early excision was reported as spanning a period of as early as < 24 hrs post burn to the 6th post burn day making a recommendation on exact timing difficult. In contrast, a very recent review on regrouped data ^[36][71] described that mortality was lower in late excision (>7 days) compared to early excision (<6 days), while early excision reduced septic episodes and LOS. In an experimental burn model thwe researchers were able to demonstrate that very early debridement of the burn wound led to an exaggerated sequestration of polymorphonuclear leucocytes (PMNs) in the lung ^[37][72] . The impact or “second hit” of surgical debridement may explain the subsequent cascade of effects resulting from early excision of the burn eschar. In line with this assumption, data from the German Burn Registry ^[38][73] confirmed the negative impact of full thickness burns on survival possibly indicating that the impact of surgical intervention may have a negative effect on outcome. These results underscore the relevance and importance of a second hit phenomenon and ask for an individualized damage control surgical approach in order to reduce DAMP and improve outcome.

Allogenic blood transfusion is well recognized as an independent factor for immunosuppression in trauma patients ^[39][40][74,75]. It is extremely important to appreciate that in the aforementioned metanalysis ^[35][46], early excision was accompanied by increase blood transfusion requirements. In order to achieve a timely debridement with reduced blood transfusion requirements, enzymatic debridement has been advocated ^[41][42][76,77]. Several forms of enzymatic debriding agents have been developed and promoted expressing differing potencies and efficiencies. At least one randomized controlled clinical study has demonstrated that enzymatic debridement of up to 15% TBSA can safely be performed accompanied by a reduced blood transfusion rate in the enzymatically debrided group as compared to the conventional surgically debrided burn patients ^[43][44][78, 79]. It is hypothesized that in severely burned patients this evolving technique may reduce the second hit. At present further study and proof is needed, still timely debridement remains the clinical standard for full thickness burns.

The burn eschar is at considerable risk of becoming a nidus for pathogenic bacterial and fungal growth with subsequent systemic complications such as sepsis, particularly as tissue and cellular integrity and vitality are compromised. Further complicating the clinical challenge of caring for severely injured patients and particularly burn injured patients is the contribution of their premorbid and morbid medical status which may not always allow for safe, early surgical debridement. A very recent report described the binding of DAMPs from eschar by topical cerium nitrate, leading to a reduced systemic inflammatory response and modulating over-activation of PMNs and immunologic dysfunction ^[45][37] . Interestingly, as early as 1976 ^[46][80], topically applied cerium nitrate, a potent antiseptic was clinically reported to reduce mortality in burn patients. Dutch burn surgeons have shown that the introduction of topical cerium nitrate may allow for safe serial surgical debridement in the compromised burn patient ^[23][69]. Further studies will have to show the precise role of topical cerium nitrate in damage control burn treatment.

3. Future Aspects of Damage Control (DC) Burn Management and Safe Definitive Surgery (SDS) in Burns

Burn injuries alone or in combination with inhalation injury constitute one of the most complex pathophysiologic systemic insults, with dynamic and rapidly evolving effects transpiring over a very short period of time. As a result of this injury pattern and despite tireless efforts and lessons learned, mortality remains high. Effective burn treatment requires a profound knowledge of this rather unique pathophysiology in order to execute safe, timely, and optimal care. The patient’s status or severity of injury is primarily defined by age and burn size. It is accepted that burn trauma is a “first hit”, with a resultant dramatic inflammatory response accompanied by changes in the innate immune system (e.g., neutrophils). There is evidence that additional surgery, such as that seen with burn wound excision, leads to a “second hit phenomenon”, which may further compromise the burn patient. Excision of the burned tissue followed by skin transplantation remains the standard of care for the treatment of deep burn injuries. This course has definitively been shown to reduce morbidity and mortality. Excising the burn eschar removes dead and dying tissue from local and systemic interaction; the concomitant reduction of DAMPs seems a rational approach. The extent of excision, timing of the procedures, and applied debridement techniques are not generally standardized among burn centres, leaving much room for improvement and unfortunately adverse events. Enzymatic debridement and topical application of cerium nitrate are just a few examples of techniques currently available that may alter current burn management. Knowledge of which patients might benefit from such strategies unfortunately remains lacking, further bolstering the need for a comprehensive methodology to establish optimal damage control management. Up to now, several burn-related scores and single soluble parameters have been described to either classify the severity of burns or predict survival. While these efforts have certainly shown promise and aid in care, these scores and combinations of parameters have not been applied to identify patients who may benefit from a broader damage control approach. Orthopaedic trauma surgeons concluded that multiple scores in combination with additional parameters such as lactate clearance must be employed to categorize patients for either safe definitive surgery or a damage control approach. A polytraumatized patient classification system indicating who may benefit from definitive surgery or damage control surgery has been published ^[19](see Table 3 in [28]). A consensus among burn surgeons to adapt this classification may prove helpful and, in theour estimation, necessary if the researchers  are we are to continue to advance and execute ever safer and effective burn surgery and care. For pure burn injuries, i.e., those who did not suffer additional multitrauma, such as head injury, long bone injury, etc., the researchers we propose replacement of the variable “blood units” by “amount of resuscitation volume”, “chest trauma” by “inhalation injury”, and “pelvic fracture classification” by “TBSA” or a burn-related score. Additional advances in technical developments, such as point-of-care flow cytometry (FACS) analysis, may allow for analysis of PMN subsets and their functions, such as respiratory burst capacity. These findings will be helpful in defining patients at risk for extensive or prolonged surgical procedures. While general guidelines exist for identifying and addressing inhalation injury, no clear recommendation is afforded to us as to how and when to execute safe surgery in this complex condition that is so well-known to profoundly and negatively affect survival. In the future, well-designed prospective studies are warranted to evaluate the benefit of damage control management versus definitive surgery for burn patients. Assessment of patient immune status is needed to more accurately and better categorize and address dynamic burn patient risk profiles, as well as the evolving physiologic state of injury response, as opposed to solely relying on extent of injury (TBSA) and accompanied diseases such as inhalation injury. In theour lifetime, the researchers hwe have seen and participated in the development and application of significant improvements in theour ability to treat and care for burn patients. This process deserves continued reflection and attention. Damage control resuscitation and point-of-care measurements to direct and correct this incredibly complex pathophysiologic disease demands it. It is likely that establishing more comprehensive guidelines, addressing the our rapidly evolving understanding of coagulation pathology and lactate clearance, will further improve the quality and efficacy of theour burn care efforts and make burn surgery safer.