Case report of pharmacokinetic analysis of continuous intravenous infusion of fentanyl in a patient with severe burn: burn shock stage complicates pain management.

BACKGROUND: Fentanyl is widely used as an analgesic and sedative for patients with severe burn injuries in intensive care units. However, pharmacokinetic (PK) data for fentanyl, particularly for continuous intravenous infusion during the acute phase of burn injuries, are limited. Here, we report the clinical course and changes in blood fentanyl concentrations during the acute phase in a patient with severe burns treated with continuous intravenous infusion of fentanyl. CASE PRESENTATION: A woman in her 40s, with burns caused by a gas cylinder explosion, was transported to our hospital. The patient had burn wounds on face, neck, shoulders, and all four extremities, with a total burn area of 39.0%. For pain relief, the patient received a continuous infusion of 0.01 mg/mL fentanyl (20-30 µg/h) with a target blood concentration of 1.0-1.5 ng/mL, but continued to suffer from pain due to burning during the acute phase. We measured the blood fentanyl concentrations and found that all concentrations obtained during the acute phase were subtherapeutic. Notably, during the burn shock stage, blood concentrations of fentanyl were 0.50 ng/mL on day 1 and 0.66 ng/mL on day 2, indicating that the blood concentration did not rise sufficiently for the dosage. From days 0 to 2, the patient was administered a massive fluid load for burn shock. After the burn shock stage resolved, fentanyl concentrations gradually approached the target range, and the pain rating scale improved, even though the fentanyl administration rate remained unchanged (30 µg/h). CONCLUSIONS: Major changes in the fluid volumes of body compartments that occur with large burns might increase the volume of fentanyl distribution, thereby lowering its concentration when a standard dose is administered. Our findings indicate that the PK of fentanyl in patients with severe burns can be substantially affected, especially during the shock phase, implying the importance of titrating analgesics for clinical efficacy in the acute phase.

Fluid Resuscitation and Cardiovascular Support in Acute Burn Care.

Acute burn injury creates a complex and multifactorial local response which may have systemic sequelae such as hypovolemia, hypothermia, cardiovascular collapse, hypercoagulability, and multi-system organ failure. Understanding the underlying pathophysiology of burn shock, the initial burn triage and assessment, calculation of fluid requirements, and the means of tailoring ongoing interventions to optimize resuscitation are critical for overcoming the wide spectrum of derangements which this condition creates. As a result, this article discusses the various key points in order to garner a greater understanding of these nuances and the optimal pathway to take when tackling these challenging issues.

Vital indicators in predicting burn mortality: A comparison of shock indices and burn shock indices.

Background/aim: In many studies, shock indices have proven to be good tools for predicting mortality. In the present study, burn shock index (BSI), percentage of total body surface area burned (TBSA%) multiplied by shock index; burn modified shock index (BMSI), TBSA% multiplied by modified shock index; burn age shock index (BASI), TBSA% multiplied by age shock index; burn rivers shock index (BrSI), TBSA% multiplied by rivers shock index; burn rivers shock index multiplied by Glasgow Coma Scale score (BrSIG) were examined in burn patients. We defined these burn shock indices for the first time. This study aimed to evaluate the effectiveness of shock indices and burn shock indices in predicting mortality in burn patients. Materials and methods: This study examines retrospectively of burn patients admitted to the emergency department of Dicle University Hospital between January 2010 and December 2022. The patients' vital signs were obtained at the time of presentation to the emergency department, and shock indices were calculated. The effectiveness of shock indices in predicting mortality was compared. Results: A total of 2445 patients were included in the study. Of the patients, 1793 were pediatric, and 652 were adults. BSI (AUC: 0.872, 95% confidence interval (CI): 0.812-0.931, p < 0.001) had the highest area under the curve (AUC) value in predicting mortality in children. The optimal cut-off value for BSI in children was 21.79 and its was sensitivity 83.05%, specificity 79.64%, positive predictive value (PPV) 12.19%, negative predictive value (NPV) 99.28%. In adults, BASI had the highest value of AUC (AUC: 0.936, 95% CI: 0.887-0.984, p < 0.001). The optimal cut-off value for BASI in adults was 62.5 and its sensitivity was 86.49%, specificity was 91.71%, PPV was 38.55%, and NPV was 99.12%. Conclusion: Shock indices are easy to calculate and effective in predicting mortality in burn patients admitted to the emergency department. Among the shock indices in the study, BSI was the best in predicting mortality in children, and BASI was the best in adults.

Current understanding of thermo(dys)regulation in severe burn injury and the pathophysiological influence of hypermetabolism, adrenergic stress and hypothalamic regulation-a systematic review.

Background: In this systematic review, we summarize the aetiology as well as the current knowledge regarding thermo(dys)regulation and hypothermia after severe burn trauma and aim to present key concepts of pathophysiology and treatment options. Severe burn injuries with >20% total body surface area (TBSA) affected commonly leave the patient requiring several surgical procedures, prolonged hospital stays and cause substantial changes to body composition and metabolism in the acute and long-term phase. Particularly in severely burned patients, the loss of intact skin and the dysregulation of peripheral and central thermoregulatory processes may lead to substantial complications. Methods: A systematic and protocol-based search for suitable publications was conducted following the PRISMA guidelines. Articles were screened and included if deemed eligible. This encompasses animal-based in vivo studies as well as clinical studies examining the control-loops of thermoregulation and metabolic stability within burn patients. Results: Both experimental animal studies and clinical studies examining thermoregulation and metabolic functions within burn patients have produced a general understanding of core concepts which are, nonetheless, lacking in detail. We describe the wide range of pathophysiological alterations observed after severe burn trauma and highlight the association between thermoregulation and hypermetabolism as well as the interactions between nearly all organ systems. Lastly, the current clinical standards of mitigating the negative effects of thermodysregulation and hypothermia are summarized, as a comprehensive understanding and implementation of the key concepts is critical for patient survival and long-term well-being. Conclusions: The available in vivo animal models have provided many insights into the interwoven pathophysiology of severe burn injury, especially concerning thermoregulation. We offer an outlook on concepts of altered central thermoregulation from non-burn research as potential areas of future research interest and aim to provide an overview of the clinical implications of temperature management in burn patients.

The Role of the Immune System in Pediatric Burns: A Systematic Review.

Burns are one of the most common causes of home injuries, characterized by serious damage to the skin and causing the death of affected tissues. In this review, we intended to collect information on the pathophysiological effects of burns in pediatric patients, with particular emphasis on local and systemic responses. A total of 92 articles were included in the review, and the time range of the searched articles was from 2000 to 2021. The occurrence of thermal injuries is a problem that requires special attention in pediatric patients who are still developing. Their exposure to various burns may cause disturbances in the immune response, not only in the area of tissue damage itself but also by disrupting the systemic immune response. The aspect of immunological mechanisms in burns requires further research, and in particular, it is important to focus on younger patients as the existence of subtle differences in wound healing between adults and children may significantly influence the treatment of pediatric patients.

Identification of Key Genes Associated with Changes in the Host Response to Severe Burn Shock: A Bioinformatics Analysis with Data from the Gene Expression Omnibus (GEO) Database.

BACKGROUND: Patients with severe burns continue to display a high mortality rate during the initial shock period. The precise molecular mechanism underlying the change in host response during severe burn shock remains unknown. This study aimed to identify key genes leading to the change in host response during burn shock. METHODS: The GSE77791 dataset, which was utilized in a previous study that compared hydrocortisone administration to placebo (NaCl 0.9%) in the inflammatory reaction of severe burn shock, was downloaded from the Gene Expression Omnibus (GEO) database and analyzed to identify the differentially expressed genes (DEGs). Functional enrichment analyses of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed. The protein-protein interaction (PPI) network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and then visualized in Cytoscape. In addition, important modules in this network were selected using the Molecular Complex Detection (MCODE) algorithm, and hub genes were identified in cytoHubba, a Cytoscape plugin. RESULTS: A total of 1059 DEGs (508 downregulated genes and 551 upregulated genes) were identified from the dataset. The DEGs enriched in GO terms and KEGG pathways were related to immune response. The PPI network contained 439 nodes and 2430 protein pairs. Finally, important modules and hub genes were identified using the different Cytoscape plugins. The key genes in burn shock were identified as arginase 1 (ARG1), cytoskeleton-associated protein (CKAP4), complement C3a receptor (C3AR1), neutrophil elastase (ELANE), gamma-glutamyl hydrolase (GGH), orosomucoid (ORM1), and quiescin sulfhydryl (QSOX1). CONCLUSION: The DEGs, functional terms and pathways, and hub genes identified in the present study can help shed light on the molecular mechanism underlying the changes in host response during burn shock and provide potential targets for early detection and treatment of burn shock.

[The use of reamberin in antishock therapy in severely burned patients]. / Ispol'zovanie reamberina pri provedenii protivoshokovoi terapii u tiazheloobozhzhennykh.

A 51-year-old severely burned woman had hospitalized at the Clinic of Thermal Injuries of the S.M. Kirov Military Medical Academy with a diagnosis: flame burn in a surface area of 40% (11%)/II-III b degrees of head, neck, trunk, limbs. Inhalation injury of moderate severity. The infusion drug of the combined action reamberin, which has a volemic and antihypoxic effect, had added to the complex antishock therapy. The presented clinical observation demonstrates the favorable course of burn shock: stopping of burn shock 28 hours after injury.

Systemic and Local Management of Burn Wounds.

Management of severe burn injury (SBI) requires prompt, complex, and aggressive care. Despite major advances in the management of SBI-including patient-targeted resuscitation, management of inhalation injuries, specific nutritional support, enhanced wound therapy, and infection control-the consequences of SBI often result in complex, multiorgan metabolic changes. Consensus guidelines and clinical evidence regarding specific management of small animal burn patients are lacking. This article aims to review updated therapeutic consideration for the systemic and local management of SBI that are proven effective to optimize outcomes in human burn patients and may translate to small animal patients.

Acute Fluid Management of Large Burns: Pathophysiology, Monitoring, and Resuscitation.

This article reviews the pathophysiology of large burn injury and the extreme fluid shifts that occur in the hours and days after this event. The authors focus on acute fluid management, monitoring of hemodynamic status, and end points of resuscitation. Understanding the need and causes for fluid resuscitation after burn injury helps the clinician develop an effective plan to balance the competing goals of normalized tissue perfusion and limited tissue edema. Thoughtful, individualized treatment is the best answer and the most effective compromise.

TRALI following fresh frozen plasma resuscitation from burn shock.

INTRODUCTION: Resuscitation from burn shock using fresh frozen plasma (FFP) has been described. Critics of FFP resuscitation cite the development of transfusion related acute lung injury (TRALI) as a deterrent to its use. This study examines the occurrence of TRALI with FFP resuscitation of critically ill burned patients. METHODS: A retrospective chart review was conducted of severely burned patients who received FFP resuscitation. Data points included age, TBSA, TBSA full thickness, presence of alternate etiologies of acute lung injury, total FFP administered, and signs and symptoms of TRALI as defined per the Canadian Blood Services Consensus Conference. RESULTS: Eighty-three patients met the definition of severe burn and received FFP resuscitation. Of those, 65 met exclusion criteria. Eighteen patients were left for analysis with only one found to have signs and symptoms of TRALI. That patient suffered a 53.5% TBSA burn, received a total of 6228ml FFP, had no competing etiologies of ALI, and was diagnosed with TRALI within 6h of completing the FFP transfusion. CONCLUSION: The possible occurrence of TRALI in burn patients receiving FFP resuscitation should be weighed against the reported benefits of such a resuscitation strategy.

Monitoring End Points of Burn Resuscitation.

This article discusses commonly used methods of monitoring and determining the end points of resuscitation. Each end point of resuscitation is examined as it relates to use in critically ill burn patients. Published medical literature, clinical trials, consensus trials, and expert opinion regarding end points of resuscitation were gathered and reviewed. Specific goals were a detailed examination of each method in the critical care population and how this methodology can be used in the burn patient. Although burn resuscitation is monitored and administered using the methodology as seen in medical/surgical intensive care settings, special consideration for excessive edema formation, metabolic derangements, and frequent operative interventions must be considered.

Burn Resuscitation in the Austere Environment.

Intravenous (IV) cannulation and sterile IV salt solutions may not be options in resource-limited settings (RLSs). This article presents recipes for fluid resuscitation in the aftermath of burns occurring in RLSs. Burns of 20% total body surface area (TBSA) can be resuscitated, and burns up to 40% TBSA can most likely be resuscitated, using oral resuscitation solutions (ORSs) with salt supplementation. Without IV therapy, fluid resuscitation for larger burns may only be possible with ORSs. Published global experience is limited, and the magnitude of burn injuries that successfully respond to World Health Organization ORSs is not well-described.

Burn resuscitation: is it straightforward or a challenge?

Burn shock resuscitation has been extensively studied over the past four decades. Many formulas exist and many parameters have been suggested to assess the adequacy of resuscitation. The most commonly used formula is the Parkland formula, the most commonly used fluids are crystalloids, and the most commonly used parameter is urine output. However, until now, no conclusive evidence has suggested that one formula is superior to another or that one parameter is a better predictor than another. In this article we will review the updated information about the subject and we will look into new advancements in this field. We will pose some questions at the end that will help researchers concentrate their future efforts to solve this important challenge in burn care.

Carbachol promotes gastrointestinal function during oral resuscitation of burn shock.

AIM: To investigate the effect of carbachol on gastrointestinal function in a dog model of oral resuscitation for burn shock. METHODS: Twenty Beagle dogs with intubation of the carotid artery, jugular vein and jejunum for 24 h were subjected to 35% total body surface area full-thickness burns, and were divided into three groups: no fluid resuscitation (NR, n = 10), in which animals did not receive fluid by any means in the first 24 h post-burn; oral fluid resuscitation (OR, n = 8), in which dogs were gavaged with glucose-electrolyte solution (GES) with volume and rate consistent with the Parkland formula; and oral fluid with carbachol group (OR/CAR, n = 8), in which dogs were gavaged with GES containing carbachol (20 µg/kg), with the same volume and rate as the OR group. Twenty-four hours after burns, all animals were given intravenous fluid replacement, and 72 h after injury, they received nutritional support. Hemodynamic and gastrointestinal parameters were measured serially with animals in conscious and cooperative state. RESULTS: The mean arterial pressure, cardiac output and plasma volume dropped markedly, and gastrointestinal tissue perfusion was reduced obviously after the burn injury in all the three groups. Hemodynamic parameters and gastrointestinal tissue perfusion in the OR and OR/CAR groups were promoted to pre-injury level at 48 and 72 h, respectively, while hemodynamic parameters in the NR group did not return to pre-injury level till 72 h, and gastrointestinal tissue perfusion remained lower than pre-injury level until 120 h post-burn. CO(2) of the gastric mucosa and intestinal mucosa blood flow of OR/CAR groups were 56.4 ± 4.7 mmHg and 157.7 ± 17.7 blood perfusion units (BPU) at 24 h post-burn, respectively, which were significantly superior to those in the OR group (65.8 ± 5.8 mmHg and 127.7 ± 11.9 BPU, respectively, all P < 0.05). Gastric emptying and intestinal absorption rates of GES were significantly reduced to the lowest level (52.8% and 23.7% of pre-injury levels) in the OR group at about 2 and 4 h post-burn, and did not return to 80% of pre-injury level until 24 h. In the first 24 h post-burn, the rate of gastric emptying and intestinal water absorption were elevated by a mean 15.7% and 11.5%, respectively, in the OR/CAR group compared with the OR group. At 5 days, the mortality in the NR group was 30% (3/10), 12.5% in the OR group (1/8), and none in the OR/CAR group. CONCLUSION: Carbachol had a beneficial effect on oral resuscitation of burn shock by promoting gastric emptying and intestinal absorption in our canine model.

Fluid management in major burn injuries.

It is a widely accepted fact that severe fluid loss is the greatest problem faced following major burn injuries. Therefore, effective fluid resuscitation is one of the cornerstones of modern burn treatment. The aim of this article is to review the current approaches available for modern trends in fluid management for major burn patients. As these current approaches are based on various experiences all over the world, the knowledge is essential to improve the status of this patient group.