A Randomized Trial of Enteral Glutamine for Treatment of Burn Injuries.

BACKGROUND: Glutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. Clinical trials involving patients with burns and other critically ill patients have shown conflicting results regarding the benefits and risks of glutamine supplementation. METHODS: In a double-blind, randomized, placebo-controlled trial, we assigned patients with deep second- or third-degree burns (affecting ≥10% to ≥20% of total body-surface area, depending on age) within 72 hours after hospital admission to receive 0.5 g per kilogram of body weight per day of enterally delivered glutamine or placebo. Trial agents were given every 4 hours through a feeding tube or three or four times a day by mouth until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission, whichever came first. The primary outcome was the time to discharge alive from the hospital, with data censored at 90 days. We calculated subdistribution hazard ratios for discharge alive, which took into account death as a competing risk. RESULTS: A total of 1209 patients with severe burns (mean burn size, 33% of total body-surface area) underwent randomization, and 1200 were included in the analysis (596 patients in the glutamine group and 604 in the placebo group). The median time to discharge alive from the hospital was 40 days (interquartile range, 24 to 87) in the glutamine group and 38 days (interquartile range, 22 to 75) in the placebo group (subdistribution hazard ratio for discharge alive, 0.91; 95% confidence interval [CI], 0.80 to 1.04; P = 0.17). Mortality at 6 months was 17.2% in the glutamine group and 16.2% in the placebo group (hazard ratio for death, 1.06; 95% CI, 0.80 to 1.41). No substantial between-group differences in serious adverse events were observed. CONCLUSIONS: In patients with severe burns, supplemental glutamine did not reduce the time to discharge alive from the hospital. (Funded by the U.S. Department of Defense and the Canadian Institutes of Health Research; RE-ENERGIZE ClinicalTrials.gov number, NCT00985205.).

CytoSorb® in burn patients with septic shock and Acute Kidney Injury on Continuous Kidney Replacement Therapy is associated with improved clinical outcome and survival.

BACKGROUND: In burn patients, septic shock and acute kidney injury (AKI) with use of continuous renal replacement therapy (CRRT) severely increase morbidity and mortality. Sorbent therapies could be an adjunctive therapy to address the underlying metabolic changes in inflammatory and anti-inflammatory cytokines dysregulated production. METHODS: A retrospectively observational study of 35 severe burn patients admitted to the Burn Center (Turin, Italy, from January 2017 to December 2022), who underwent CRRT for AKI-associated septic shock. Out of 35 patients, 11 were treated with CytoSorb® as adjunctive therapy to CRRT (Sorbent group) and 24 patients only with CRRT (Control group). RESULTS: The application of CytoSorb® took place in a very dispersed way. Out of 11 patients, 7 started the CRRT together with the sorbent application. The patients of the sorbent group exhibited a significant reduction in norepinephrine use compared to that of the control group. A clinical improvement over the first 4 days of Cytosorb® was observed in both survivors and no survivors of the sorbent group, with significant norepinephrine decreased use on day 4 compared to day 1. In-hospital mortality was 45.4% and 70.8% in the sorbent and control group, respectively, and significantly better at Kaplan-Meier survival analysis at 270 days (p = 0.0445). In both groups, all survivor patients recovered renal function at discharge, whereas no survivors did not. CONCLUSIONS: Adjunctive treatment with CytoSorb® for burn patients with AKI-CRRT and septic shock poorly responsive to standard therapy led to a significant clinical improvement, and was associated with a lower mortality rate compared to CRRT alone.

Quality indicators in burn care: An international burn care professionals survey to define them.

INTRODUCTION: Quality indicators (QIs) are tools for improving and maintaining the standard of care. Although burn injuries are a major global health threat, requiring standardized management, there is a lack of worldwide accepted quality indicators for burn care. This study aims to identify the best burn care-specific QIs as perceived by worldwide burn practitioners. METHODS: The ISBI Burn Care Committee developed a survey to analyze which burn care- specific QIs were relevant to international burn care professionals. The questionnaire was based on the three dimensions of the Donabedian model (i.e., Structure, Process, and Outcome) to evaluate the quality of care. The study was conducted from April to September 2021 and analyzed and reported following the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). RESULTS: According to the 124 worldwide respondents, the most relevant QIs were: access to intensive care, burn surgeons, and dedicated burn care nurses (Structure category), 24-hours access to burn services, local protocols based on documented guidelines (Process category), and in-hospital mortality and incidence of severe infections (Outcome category). CONCLUSIONS: Specific QIs related to structures, clinical processes, and outcomes are needed to monitor the treatment of burn patients globally, assess the efficiency of the provided treatment, and harmonize the worldwide standard of burn care.

Renal replacement therapy for acute kidney injury in burn patients, an international survey and a qualitative review of current controversies.

BACKGROUND OF THE STUDY: Acute kidney injury (AKI) is a common complication in critically ill burn patients and is associated with a number of serious adverse outcomes. The clinical decision-making process related to the management of AKI in burn patients is complex and has not been sufficiently standardized. The main aim of this study was to explore the diagnostic approach and clinician's attitudes toward the management of AKI and RRT in burn patients around the world. METHODS: The questionnaire was widely distributed among the members of International Society for Burn Injury (ISBI), who were invited to complete the survey. Data collection and report was compliant with the the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) Web-survey guidelines. The survey form with multiple-choice questions was divided into 3 parts: a. physician and institutional demographics, b. AKI diagnostic information, c. technical aspects of RRT. RESULTS: A total of 44 respondents worldwide submitted valuable data in the 2-month period. Of all respondents, 43.2% were from Europe, 30% from North America, 7% from South-East Asia 2.3% from Africa and 18.2% from other regions. 93.1% of participants declare that they use specific definitions to detect AKI, while 11.4% declare the use of renal ultrasonography for AKI diagnosis. CRRT appeared to be the most preferred option by 43.2% of participants, followed by intermittent hemodialysis (25%), and prolonged intermittent RRT (6.8%). The expertise to deliver a modality and the availability of resources were considered important factors when selecting the optimal RRT modality by 20.5% and 29.6% of respondents. The use of specific serum biomarkers for AKI diagnosis are stated by 16% of respondents; 25% of specialists refer to the use of biomarkers of AKI as a criterium for discontinuing the RRT. Femoral vena and right jugular vena were the most frequently used location for RRT temporary catheter placement, 54.6% of respondents declared using ultrasound guidance for catheter placement. CONCLUSIONS: The majority of burn specialists use specific consensus classifications to detect acute kidney injury. Continuous renal replacement therapy appeared to be the most preferred option, while the expertise to deliver a particular modality and resources availability play a significant role in modality selection. The use of ultrasound and specific biomarkers for AKI evaluation is infrequent in routine clinical practice.

Colistin Therapy, Survival and Renal Replacement Therapy in Burn Patients: A 10-Year Single-Center Cohort Study.

Purpose: Colistin is still a therapeutic cornerstone against multidrug-resistant gram-negative bacteria (MDRGN), mostly when other antibiotics do not gain adequate activity on these strains. In the present study, we evaluated in a cohort of burn patients the relationship between colistin therapy, survival and requirement of renal replacement therapy (CRRT). Patients and Methods: Retrospective study of 133 burn patients treated with iv colistimethate sodium (loading dose 9.0 × 106 IU, maintenance dose 4.5 × 106 IU BID) and 35 treated with other antibiotics for MDRGN infection including Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae between January 2008 and December 2017. Multivariate analysis with logistic regression was used to determine the effect of the predictors such as age, total body surface area (TBSA), third-degree burn areas, Revised Baux score, Charlson comorbidity score, length of stay, colistin dose and duration of treatment, mechanical ventilation, and need of CRRT on in-hospital mortality. To investigate the relationship between colistin and renal function, we focused on survivor patients as the completion of the therapeutic course of colistin represented the basic requirement to analyze its impact on the kidney. Results: Out of 133 colistin- and 35 other antibiotics-treated patients, 83 (62.4%) and 31 (88.6%) survived, and 53 (39.8%) and 3 (9.7%) required CRRT, respectively. The severity of burns, as well as CRRT requirement and mortality, was significantly higher in colistin-treated patients than in other antibiotics-treated patients. Age and TBSA% were the significant predictors of mortality. Out of 83 colistin-treated survivors, 19 (22.9%) required CRRT (9 before and 10 after the start of colistin), and 64 (77.1%) had a normal renal function. No difference about the colistin dose and baseline characteristics, but the revised Baux score was found between the 9 patients requiring CRRT before the colistin course and the 10 patients after. Similarly, among the 64 patients not undergoing CRRT, no difference was found between the patients treated with the cumulative dose of colistin <99.0 × 106 IU (n = 33, median daily dose of 4.0 × 106 IU) and >99.0 × 106 IU (n = 31, median daily dose of 9.0 × 106 IU) about the baseline characteristics and the daily median plasma creatinine over 24 days of therapy. Conclusion: Colistin therapy was associated with more severe burns, mortality, and CRRT requirement. A short course therapy, at appropriate cumulative dosage, can lead to clinical success without a significant association with severe renal impairment.

Ventilation practices in burn patients-an international prospective observational cohort study.

BACKGROUND: It is unknown whether lung-protective ventilation is applied in burn patients and whether they benefit from it. This study aimed to determine ventilation practices in burn intensive care units (ICUs) and investigate the association between lung-protective ventilation and the number of ventilator-free days and alive at day 28 (VFD-28). METHODS: This is an international prospective observational cohort study including adult burn patients requiring mechanical ventilation. Low tidal volume (V T) was defined as V T ≤ 8 mL/kg predicted body weight (PBW). Levels of positive end-expiratory pressure (PEEP) and maximum airway pressures were collected. The association between V T and VFD-28 was analyzed using a competing risk model. Ventilation settings were presented for all patients, focusing on the first day of ventilation. We also compared ventilation settings between patients with and without inhalation trauma. RESULTS: A total of 160 patients from 28 ICUs in 16 countries were included. Low V T was used in 74% of patients, median V T size was 7.3 [interquartile range (IQR) 6.2-8.3] mL/kg PBW and did not differ between patients with and without inhalation trauma (p = 0.58). Median VFD-28 was 17 (IQR 0-26), without a difference between ventilation with low or high V T (p = 0.98). All patients were ventilated with PEEP levels ≥5 cmH2O; 80% of patients had maximum airway pressures <30 cmH2O. CONCLUSION: In this international cohort study we found that lung-protective ventilation is used in the majority of burn patients, irrespective of the presence of inhalation trauma. Use of low V T was not associated with a reduction in VFD-28. TRIAL REGISTRATION: Clinicaltrials.gov NCT02312869. Date of registration: 9 December 2014.

Coupled-plasma filtration and adsorption for severe burn patients with septic shock and acute kidney injury treated with renal replacement therapy.

BACKGROUND: Coupled-plasma filtration adsorption (CPFA) is a sorbent-based technology aimed at removing soluble mediators of septic shock. We present our experience on the use of CPFA in septic shock severe burn patients with acute kidney injury (AKI) needing renal replacement therapy (RRT) with the main goal to evaluate efficacy and safety of CPFA in this specific subset of septic shock patients. METHODS: In this observational study, we retrospectively reviewed the medical notes of all burn patients admitted to our adult Burn Center who received CPFA, as part of the septic shock treatment requiring RRT, between January 2001 and December 2017 (CPFA group). We compared CPFA group with all the burn patients admitted to our Center in the same period of time, with the same range of relevant clinical characteristics, who developed AKI and were treated with RRT, but not CPFA (control group). We collected demographic characteristics, burn size, Sequential Organ Assessment Failure (SOFA) score, microbiological data, and patient outcome, in terms of in-hospital mortality rate and the probability of survival calculated using the revised Baux score. We also collected data regarding CPFA safety (hemorrhagic episodes, catheter associated-complications, hypersensitivity reactions) and efficiency (number and duration of CPFA sessions, plasma treated amount, plasma processed dose). RESULTS: 39 severe burn patients were treated with CPFA (CPFA group) (mean age 46.0 years, range 40.0-56.0 years; mean burn size 48.0% TBSA, range 35.0-60.0% TBSA), and 87 patients treated with RRT, but not CPFA, who had similar clinical characteristics (control group). Observed mortality rate was 51.3% in the CPFA group and 77.1% in the control group (p 0.004). Regarding factors affecting survival in the CPFA group, SOFA score on the 1st day of CPFA resulted significant (OR 2.016, 95% CI, 1.221-3.326; p < 0.004) in the multivariate analysis logistic model. CONCLUSIONS: CPFA treatment for burn patients with AKI-RRT and septic shock, sustained by bacterial strains non or poorly responsive to therapy, was associated with a lower mortality rate, compared to RRT alone. However, further research, such as large prospective studies, is required to clarify the role of CPFA in the treatment of burns with septic shock and AKI-RRT.

Burn center function during the COVID-19 pandemic: An international multi-center report of strategy and experience.

The novel coronavirus, SARS-CO V2 responsible for COVID-19 pandemic is rapidly escalating across the globe. Burn centers gearing for the pandemic must strike a balance between contributing to the pandemic response and preserving ongoing burn care in a safe and ethical fashion. The authors of the present communication represent seven burn centers from China, Singapore, Japan, Italy, Spain, the United Kingdom (UK), and the United States (US). Each center is located at a different point along the pandemic curve and serves different patient populations within their healthcare systems. We review our experience with the virus to date, our strategic approach to burn center function under these circumstances, and lessons learned. The purpose of this communication is to share experiences that will assist with continued preparations to help burn centers advocate for optimum burn care and overcome challenges as this pandemic continues.

Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association.

This study aims to determine the presence of the components of the metabolic syndrome in primary nonalcoholic steatohepatitis (NASH) and to assess the role of liver disease in the genesis of peripheral hyperinsulinemia. Nineteen patients (18 men and 1 woman; mean age, +/- SD, 38 +/- 10 years; body mass index [BMI], 26 +/- 2 kg/m(2)) with histologic evidence of NASH were enrolled; 19 age- and sex-matched normal subjects were investigated as controls. Plasma glucose, insulin, and C-peptide levels were measured during an oral glucose tolerance test, and a frequently sampled intravenous glucose tolerance test (FSIGT), analyzed by minimal modeling technique, was performed. Compared with controls, the NASH group had lower insulin sensitivity (3.84 +/- 2.44 vs. 7.48 +/- 3.01 10(-4) x min(-1)/microU/mL; P =.0003) and higher total insulin secretion (21 +/- 13 vs. 10 +/- 3 nmol/L in 240 minutes; P =.001). Hepatic insulin extraction was similar in both groups (69.8% +/- 16.1% vs. 70.2% +/- 18.3%; P =.854). According to the results of the oral glucose tolerance test, no patient was classified as diabetic, 5 were classified as glucose intolerant, and 1 was classified as having impaired fasting glycemia. Nine patients (47%) had at least the 2 minimum criteria required to define the metabolic syndrome according to the European Group for the Study of Insulin Resistance (EGIR). In conclusion, hyperinsulinemia and insulin resistance occur frequently in patients with NASH; these conditions do not stem from a reduced hepatic insulin extraction but from an enhanced pancreatic insulin secretion compensatory to reduced insulin sensitivity. The derangement of insulin regulation, often associated with the metabolic syndrome, may play a causal role in the pathogenesis of NASH.