June 2021 - Burn Surgery

June 2021
EAST Monthly Literature Review

"Keeping You Up-to-Date with Current Literature"
Brought to you by the EAST Manuscript and Literature Review Committee

This issue was prepared by EAST Burn Surgery Committee Members Robel Beyene, MD and Mack D. Drake, DO, FACS.

In This Issue: Burn Surgery

Scroll down to see summaries of these articles

Article 1 reviewed by Robel Beyene, MD
The use of vasopressors during acute burn resuscitation. Adibfar A, Camacho F, Rogers AD, Cartotto R. Burns. 2021 Feb;47(1):58-66.

Article 2 reviewed by Robel Beyene, MD
Circulating Syndecan-1 and Tissue Factor Pathway Inhibitor, Biomarkers of Endothelial Dysfunction, Predict Mortality in Burn Patients. Keyloun JW, Le TD, Pusateri AE, Ball RL, Carney BC, Orfeo T, et al. Shock. 2020 Dec 23.

Article 3 reviewed by Mack D. Drake, MD
The Effect of Transfer on Outcomes in Burns. Bodily NE, Bruenderman EH, Bhutiani N, The S, Schucht JE, Bozeman MC. Journal of Burn Care & Research. 2021 Jun 4.

Article 4 reviewed by Mack D. Drake, MD
High Dose Ascorbic Acid During Acute Resuscitation in Critically Burn Patients. Flores E, Sanchez M, Gutierrez C, Estebanez B, Millan P, Gutierrez C, et al. Journal of Burn Care & Research. 2021 June 3.

Article 1
The use of vasopressors during acute burn resuscitation. Adibfar A, Camacho F, Rogers AD, Cartotto R. Burns. 2021 Feb;47(1):58-66.

Acute burn resuscitations do not traditionally include use of vasoactive medications within the first 24 to 48 hours after injury. Instead, tissue perfusion which is diminished due to the vasodilatory inflammatory state and insensible losses is maintained primarily through fluid resuscitation and the use of adjuncts, such as colloids or high-dose vitamin C (HDVC). In fact, the use of early vasoactive medications in an acute burn resuscitation is seen as a morbidity due to the presumed deleterious effect on the burn wound bed, potentially leading to burn progression and other sequelae of end-organ malperfusion.  Despite this, many burn centers will use vasoactives early in resuscitation to avoid over-resuscitation and support tissue perfusion by maintaining an adequate mean arterial pressure. This study sought to better identify factors associated with initiation of vasoactive medications during an acute burn resuscitation.

The authors performed a retrospective single-institution review examining nearly 3 years’ worth of their severe burn (≥20% total body surface area - TBSA) admissions to see what factors led to vasoactive infusions in the subset that ultimately required it. Patients who were under 16, had vasoactives started before arrival to the burn center, or were placed on palliative comfort care measures within 24 hours of injury were excluded. Only infusions (not single injections) of vasoactive medications that lasted longer than 30 minutes in duration were considered relevant. Of the 52 patients that met the criteria, 16 received vasoactive medications (“PRESSOR”) and 36 did not 9”NO PRESSOR”). The PRESSOR group was older (mean age 55.3 vs 42.3), had greater TBSA and full thickness TBSA (44% vs 25% and 33.8% vs. 14.5%, respectively). Everyone in the PRESSOR group required mechanical ventilation. Multivariate logistic regression for mortality found that vasopressor use was NOT independently associated with increased mortality, when controlling for covariates traditionally used to predict mortality, including age, TBSA, and presence of inhalation injury. Mean volume of resuscitation at 24 hours and hourly urine output over the first 24 hours was not significantly different between the two groups. More PRESSOR patients received HDVC frequently (68.8% vs 16.7%) and in multivariable regression analysis, only that and age were independently associated with greater use of vasoactive medications during an acute burn resuscitation. Inverse propensity weighted analysis showed the HDVC was associated with increased vasoactive medication use (OR 6.902) while 5% albumin administration was significantly associated with less (OR0.310).
In summary, this retrospective suggests that vasoactive medications are used with moderate frequency in the acute resuscitation of severe burns. In this group, greater 30% of those patients who met inclusion criteria, and 20% of all severe burn patients, received an infusion of vasoactives within the first 48 hours after injury. Vasoactive initiation in this time was at provider discretion. The PRESSOR group had larger and deeper burns, suggesting that they were sicker, but neither group was clearly under-resuscitated, as both had higher volumes of resuscitation than would be predicted by the Parkland formula. Furthermore, when controlling for TBSA, along with age and presence of inhalation injury, the PRESSOR group did not have a worse mortality though it is unclear that this study was powered to determine such differences.  One of the biggest concerns with pressor use during acute resuscitation is end-organ damage such as acute kidney injury, which was not addressed in this paper. HDVC was identified as a risk factor for vasoactive administration, but this may be linked to the known osmotic diuresis frequently linked to HDVC. This effect may suggest adequate resuscitation by falsely elevating urine output while simultaneously decreasing preload, and thus cardiac output and blood pressure, ultimately leading to hypovolemic shock and early use of vasoactive medications. However, this study was not designed to answer this questions.

Article 2
Circulating Syndecan-1 and Tissue Factor Pathway Inhibitor, Biomarkers of Endothelial Dysfunction, Predict Mortality in Burn Patients. Keyloun JW, Le TD, Pusateri AE, Ball RL, Carney BC, Orfeo T, et al. Shock. 2020 Dec 23.

The understanding of burn shock continues to evolve beyond the model of hypovolemia due to insensible loss to a more complex derangement of physiology that includes endothelial dysfunction. The endothelium is a complex system of cells involved in multiple regulatory functions; dysfunction in this system can have several negative effects. This endotheliopathy has been described in other acute disease states and is of increasing interest in burn critical care. Two specific areas of interest are the endothelial proteoglycan Syndecan-1 (SDC-1), which has been shown to be shed from the endothelium after injury, and tissue factor pathway inhibitor (TFPI), a coagulation inhibitor made by the endothelium. Serum levels of these biomarkers have been studied as biomarkers of endotheliopathy.
This study is a cohort controlled, observational study performed at a single center over 5 years in order to investigate the association between burn injury severity, the biomarkers SDC-1 and TFPI, and burn outcomes. 158 patients were enrolled within 4 hours of thermal injury and 74 of them had biomarker data to analyze. SCD-1 and TFBP samples were taken. The patients were mostly male (75.7%). Admission SCD-1 and TFPI were higher in patients that died than in survivors, with median interquartile range (IQR) of 58.0 ng/mL vs. 20.9 ng/mL and 78.6 ng/mL vs. 70 ng/mL, respectively. ROC analysis for 30-day in-hospital mortality showed an area under the curve of 0.92 for SDC-1, which is similar to that of both total body surface area (TBSA) and the revised BAUX (rBAUX) score. A cutoff of SDC-1 >34ng/mL at admission was found to maximize the sensitivity (93%) and sensitivity (83%) of predicting 30-day in-hospital mortality. After adjusting for confounders, SDC-1 above this cutoff was significantly associated with mortality (OR 32.65) and a reduction in time to death (HR 14.08). Higher levels of SDC-1 and TFPI at admission were associated with burn size, but also ICU admission, intubation, and mechanical ventilation.
In summary, this study found that circulating SDC-1, which is shed in settings of endothelial dysfunction, may be an adequate predictor of 30-day in-hospital mortality when compared to predictors in practice presently, such as the rBAUX score. Unlike the rBAUX, however, serum SDC-1 is a completely objective measure that does not rely on TBSA estimates and the presence of inhalation injury, which are prone to intra-operator discrepancies and error. These findings suggest that patients with clinically significant, burn-induced endothelial dysfunction may be identifiable in the early stages of their resuscitation and could potentially benefit from targeted treatment. While no treatment is studied directly in this study, and it is observational in design, it suggests an intriguing area of possible future research, whose implications could range beyond burn to other acute disease states.

Article 3
The Effect of Transfer on Outcomes in Burns. Bodily NE, Bruenderman EH, Bhutiani N, The S, Schucht JE, Bozeman MC. Journal of Burn Care & Research. 2021 Jun 4.

Burn injured patients are often initially treated at a non-burn center prior to transfer to definitive care. The American Burn Association maintains a criteria list of injury characteristics necessitating specialized burn care to serve as a general guide to healthcare personnel less familiar with the nature of the complex injuries given that optimal outcomes are provided to these patients when cared for by a burn center’s multidisciplinary team and comprehensive infrastructure. With approximately 40,000 patients requiring inpatient acute burn care per year in the United States the effect of the inherent delay in definitive treatment for those patients meeting American Burn Association transfer criteria is not fully realized in the literature. One might surmise that outcomes would be negatively affected by this potential delay compared to patients who are transferred directly from scene to a facility with specialized burn care capability.
This paper represents a single center retrospective evaluation of adult patients transferred to a regional burn center between 2016 and 2019. Cohorts were separated into patients transferred directly from scene or site of injury to the burn center and those first treated at a referring facility prior to transfer to the author’s center. Specific outcomes examined included demographics, rate of infectious complications, ventilator days, need for emergency operative procedure (defined as <24 hours after admission), total operative procedures performed, hospital length of stay, and mortality. Of the 122 patients included, half were direct presentation to the burn center’s facility and half were transferred from a referring facility (n = 61 each). The median age was 48 years and patients were 72% male with similar other demographics. Patients transferred from other facilities prior to burn center arrival traveled a median of 42 miles (0.2 to 266 miles) and had a significantly increased time from injury to burn center admission (1 vs 8 hours, p<0.01). Patients presenting directly to the burn center had higher rates of inhalation injury (30% vs 6.6%, P < 0.01) and were more likely to require intubation after admission (16.4% vs 3.3%, p = 0.03). Rates of emergent procedures required and infectious complications were higher in the direct admission cohort (p = 0.03 and p < 0.01, respectively) which was later confirmed with multivariate analysis when controlling for age, associated trauma, and Total Body Surface Area (TBSA). Median TBSA of burn did not significantly differ between the groups (10% in each, p = 0.08) nor did the relative proportion of patients who had thermal + traumatic injury (0% vs 6.6%, p = 0.012) nor did patients in the transfer group have higher rate of intubation prior to arrival (8.2% vs 11.5%, p = 0.76). Similarities comparing the cohorts existed with regards to ventilator days (9 vs 3 days, p = 0.37), operative procedures performed (0 in each, p = 0.16), length of stay (3 vs 3 days, p = 0.44), disposition, and mortality (10% vs 5%, p = 0.50). Subgroup analysis of patients with > 15% TBSA was performed (n = 26 direct admit, n = 23 transfer). In this subgroup of larger TBSA burns transfer patients were confirmed to have prolonged time from injury to burn center admission (1.4 vs 10 hours, p = 0.03) and direct admissions were more likely to have inhalation injury (p = 0.02) and require emergent surgical procedures (p < 0.01).
In conclusion, this single center retrospective experience found that burn patients with more severe injuries such as those with inhalation injury or early mechanical ventilation requirements were more likely to be transported from the site/scene of injury directly to the burn center thus eliminating delay in reaching definitive care. Seemingly, patients with less serious injuries often were transferred from referring facilities lending prolonged time to burn center admission but this occurred without deleterious effect on examined outcomes. This study did not examine fluid administration nor did it consider the effects of prolonged delays in transfer of > 24 hours. Pitfalls common to delays in transfer to definitive care of burn injured patients must be identified and avoided to avoid poor outcomes. Less severe burn injuries may be adequately triaged at referring facilities, possibly avoiding unnecessary transfer without sacrificing patient outcomes.

Article 4
High Dose Ascorbic Acid During Acute Resuscitation in Critically Burn Patients. Flores E, Sanchez M, Gutierrez C, Estebanez B, Millan P, Gutierrez C, et al. Journal of Burn Care & Research. 2021 June 3.

High dose ascorbic acid (HDAA) is an oxygen free radical scavenger that has been shown to decrease fluid requirements during acute burn resuscitation. The role of HDAA in acute burn resuscitation and its implications with regards to reduction of organ dysfunction and associated adverse effects are the subject of debate. The exact timing, dosing, and utility of HDAA in acute burn resuscitation has yet to be completely characterized. The authors hypothesize that the addition of HDAA to severely injured burn patients may both significantly reduce fluid resuscitation requirements and also prevent organ dysfunction.
This retrospective study in a single center European burn unit included 75 adult patients between 2018 and 2019. 25 patients were identified with > 30% Total Body Surface Area burn (TBSA) who received HDAA during resuscitation. The remaining 50 patients received similar resuscitation minus HDAA from the same database but were randomly selected between years 2014-2017 thus creating a non-formal case control study. Specific matching of Abbreviated Burn Severity Index (ABSI), modified Baux score, age, and TBSA of patients was performed. In the HDAA arm of the study, patients were treated with the same fluid resuscitation protocol but in addition received HDAA at 66 mg/kg/hr started at admission and concluded at 36 hours post-injury. Average time of infusion was 31 hours. Patients who were pregnant, suffered pre-existing heart failure or liver failure, acute kidney injury with serum creatinine > 2mg/dL, had contraindications to central venous and arterial access, or had life expectancy < 24 hours were excluded.  Transpulmonary thermodilution (TPDT) and lactate were utilized as markers of resuscitation in addition to the resuscitation protocol set goals of a Cardiac Index of > 2.2l/min/m2, intrathoracic blood volume index of at least 600 ml/m2, and extravascular water lung index (EVLW) < 10mL/kg. Vasoactive agents were used to maintain MAP > 65mmHg. Colloids were added at 12 hours post-injury if vasopressors were required. When comparing the HDAA vs non-HDAA cohorts, the HDAA group required less volume in the initial 24 hours of resuscitation (3.06ml/kg/%TBSA vs 4.32, p < 0.05) but this was not significant at 72-hour requirements. Urine output was higher initially in the HDAA group but this did not hold throughout the 72 hours of the HDAA infusion. The HDAA group had higher overall TBSA therefore subgroup analysis was performed. When specifically examining patients with 30-55% TBSA burns, the HDAA group (n=14) favored similarity with the non-HDAA matched group for demographics, APACHE II, ABSI, and Baux scores. Measured lactate levels, SOFA scores, thermodilution parameters, and EVLW values demonstrated no statistical difference between the HDAA and non-HDAA cohorts. There was no identified difference in the need for mechanical ventilation, incidence of acute kidney injury, compartment syndrome, or mortality.
This center’s experience indicates that though HDAA administration initially decreased required volume of resuscitation it did not affect the total requirements within the first 72 hours. Variability in resuscitation approaches and algorithms makes the utility of HDAA administration difficult to characterize at best; however, this study lends support to the experience of others, indicating that the fluid reducing effects of HDAA within the early phase of burn resuscitation do not persist after the 72-hour mark post-injury. Though hyperosmolar effects of HDAA may lead to transient diuretic effect this is short lived. In the absence of effect on 72-hour total fluid requirements lent by HDAA administration this study highlights the need to risk stratify the usefulness of HDAA versus its identified negative effects, particularly its interference with serum glucose measurement and its potential for acute kidney injury, during acute burn resuscitation.

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This Literature Review is being brought to you by the EAST Manuscript and Literature Review Committee. Have a suggestion for a review or an additional comment on articles reviewed? Please email litreview@east.orgPrevious issues available on the EAST website.