Thermal injuries have been a phenomenon intertwined with the human condition since the dawn of our species. Autologous skin translocation, also known as skin grafting, has played an important role in burn wound management and has a rich history of its own. In fact, some of the oldest known medical texts describe ancient methods of skin translocation. In this article, we examine how skin grafting has evolved from its origins of necessity in the ancient world to the well-calibrated tool utilized in modern medicine. The popularity of skin grafting has ebbed and flowed multiple times throughout history, often suppressed for cultural, religious, pseudo-scientific, or anecdotal reasons. It was not until the 1800s, that skin grafting was widely accepted as a safe and effective treatment for wound management, and shortly thereafter for burn injuries. In the nineteenth and twentieth centuries skin grafting advanced considerably, accelerated by exponential medical progress and the occurrence of man-made disasters and global warfare. The introduction of surgical instruments specifically designed for skin grafting gave surgeons more control over the depth and consistency of harvested tissues, vastly improving outcomes. The invention of powered surgical instruments, such as the electric dermatome, reduced technical barriers for many surgeons, allowing the practice of skin grafting to be extended ubiquitously from a small group of technically gifted reconstructive surgeons to nearly all interested sub-specialists. The subsequent development of biologic and synthetic skin substitutes have been spurred onward by the clinical challenges unique to burn care: recurrent graft failure, microbial wound colonization, and limited donor site availability. These improvements have laid the framework for more advanced forms of tissue engineering including micrografts, cultured skin grafts, aerosolized skin cell application, and stem-cell impregnated dermal matrices. In this article, we will explore the convoluted journey that modern skin grafting has taken and potential future directions the procedure may yet go.
C-reactive protein (CRP) is an acute-phase protein produced in response to inflammation after traumatic injury. We posit that C-reactive protein (CRP) is reliable in predicting morbidity and mortality following severe burn. In this study, we explored the relationship between serum CRP values and clinical outcomes in the severely burned. Using the Research Network within the TriNetX database, we queried de-identified burn patient data across the United States and enrolled 36,556 burn patients with reported CRP values from 2006 to 2020. Circulating CRP levels were elevated significantly in patients ≥60 years as well as in males and African Americans (p < 0.05). CRP levels reached the zenith on the first day after burn, and were highest when burn size reached 60% total body surface area (TBSA). After bisecting the data at 10 mg/L of CRP, we compared clinical findings between patient groups (n = 16,284/18,647 in high/low CRP levels). The risk of patient death doubled in the high CRP group from 4.687% to 9.313%, with higher incidences of sepsis, skin infection, and myocardial infarction (p < 0.05). Moreover, mortality increased from 0.9% to 1.926% in those younger than 20 years when comparing the low and high CRP groups, whereas mortality significantly increased from 8.84% to 15.818% in those ≥60 years old (p < 0.05). Both elderly and paediatric groups had significant increases in the diagnosis of sepsis-associated with increased CRP expression. However, incidences of skin infection, pneumonia, and acute kidney injury increased significantly only in the elderly group (p < 0.05). Elevated CRP expression is common in burn patients. The factor of age influenced the association of CRP expression to clinical outcomes.
Burn patients are prone to infections, which often warrants broad-spectrum antibiotic coverage. Vancomycin is a common antibiotic used at burn centers and is administered alone, or in combination with other agents such as piperacillin-tazobactam (Pip/Tazo). A recent study showed that this combination therapy was associated with increased rates of acute kidney injury (AKI) in adult and pediatric burn patients when compared to vancomycin in combination with other antibiotics. However, other studies failed to demonstrate these findings. The degree of nephrotoxic effect of the combination therapy relative to its drug components has not been demonstrated in burn patients. Using a large national database encompassing 41 health care organizations, we sought to determine whether a combination of vancomycin and Pip/Tazo exacerbates AKI in burn patients. Using the TriNetX Global Health Research Network, we identified the population of burn patients with ICD-10 codes T20-T25 and T30-T32 between 2000–2020. We then grouped this population into 4 cohorts based on the administration of broad-spectrum antibiotics they received after the burn incident: vancomycin, Pip/Tazo alone, combination, and neither vancomycin nor Pip/Tazo. All cohorts were balanced for age, gender, and race. We explored the distribution of these cohorts and conducted comparative outcome analysis to determine the relative risk of developing AKI using the ICD10 code N17. Comparative analysis showed burn patients who received vancomycin had a 4.81% increased associated risk with AKI compared to those who did not receive either vancomycin or Pip/Tazo (p< 0.0001, RR =3.35, 95%CI= 2.63–4.26). Patients who received Pip/Tazo monotherapy had a 5.1% increased association with AKI compared to those who did not receive either drug (p< 0.0001, RR =3.57, 95%CI: 2.33–5.45). The combination of vancomycin with Pip/Tazo increased the association with AKI by 9.49% compared to patients who did not receive either drug (p< 0.00001, RR=5.65, 95%CI: 4.40–7.26). Combination therapy also increased the risk of AKI when compared to the vancomycin monotherapy (5.01%, p< 0.00001, RR= 1.69, 95%CI: 1.42–2.00) and Pip/Tazo monotherapy (4.85%, p< 0.00002, RR= 1.62, 95%CI: 4.40–7.26). The use of broad-spectrum antibiotics in burn patients is associated with a higher risk of AKI. The combination of these drugs affords an increased relative risk of AKI when compared to monotherapy with the respective component drugs. Whether this is associated with selection bias or drug-effect warrants further investigation.
Older adult patients often present with malnutrition, which is associated with increased morbidity and mortality after burn injury. This multicenter retrospective cohort study assessed outcomes in older adult burn patients (≥60 years) presenting to 12 burn centers in the US and Canada. Patients were stratified by nutritional status (nourished: admission albumin ≥3.0 g/dL; malnourished: admission albumin <3 g/dL) with further subgrouping by albumin level (1-1.9, 2-2.9, 3-3.9, 4+). A mixed effect generalized linear model controlling for admitting center was fit to assess the adjusted odds of in-hospital mortality and complications. About 712 patients met inclusion criteria, 442 in the nourished cohort and 270 in the malnourished cohort. On multivariable analysis, the binary classification of albumin was not significantly associated with morbidity or mortality. However, when treating albumin as continuous, levels were highly associated with mortality and select complications, with every one point increase in admission albumin lowering the odds of death by 54% (aOR 0.46, 95% CI, 0.26, 0.81), the odds of multiple organ failure by 59% (aOR 0.41, 95% CI, 0.20, 0.85) and the odds of intensive care unit delirium by 54% (aOR 0.46, 95% CI, 0.23, 0.95). Admission albumin levels are highly associated with morbidity and mortality in older adult burn patients and appear to be a readily available useful indicator of outcomes.