Ketamine exerts dual effects on the apoptosis of primary cultured hippocampal neurons from fetal rats in vitro.

Ketamine, a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist, is widely used in pediatric clinical practice. The neuroprotective and neurotoxic effects of ketamine on brain neurons during development remain controversial. The reason may be related to the different concentrations of ketamine used in practice and the small range of concentrations used in previous studies. In this study, cultured hippocampal neurons were treated with ketamine in a wide range of concentrations to comprehensively observe the effects of different concentrations of ketamine on neurons. We demonstrated that low concentrations of ketamine (10 µM, 100 µM and 1000 µM) promoted neuronal survival (p < 0.05) and reduced neuronal apoptosis (p < 0.05) compared with those of the control group. High concentrations of ketamine (2000 µM, 2500 µM and 3000 µM) reduced neuronal survival (p < 0.05) and promoted neuronal apoptosis (p < 0.05). The p38 MAPK inhibitor SB203580 reduced neuronal apoptosis induced by high concentrations of ketamine (2500 µM) (p < 0.05). Our findings indicate that ketamine exerts a dual effect on the apoptosis of primary cultured fetal rat hippocampal neurons in vitro and that the neurotoxic effects of ketamine are related to activation of the p38 MAPK signaling pathway.

Differences by age in the obesity paradox in severe burns.

BACKGROUND: Many studies show a "obesity paradox", which seems to protect against death. Whether an obesity paradox space is present in severe burn patients remains a matter of great debate. Most research on the obesity paradox of burn injuries is classified by body mass index (BMI) rather than by age. OBJECTIVE: To investigate whether the obesity paradox exists in severe burn patients stratified by age. METHODS: Retrospective analysis was performed on 490 patients with severe burns who were ≥ 18 years of age and were admitted to Fujian Medical University Union Hospital from January 2005 to December 2020. Demographic and clinical characteristics were collected, including age, BMI, total body surface area (TBSA), presence of inhalation injury, abbreviated burn severity index (ABSI) score, diabetes comorbidities, hypertension comorbidities, and in-hospital mortality. The patients were divided into the younger group (18 ≤ age<65 years) and the older group (age ≥ 65 years). The important variables of the two groups were compared. The predictive value of BMI stratified by age on in-hospital mortality was evaluated by binary logistic regression analysis and the Cochran's and Mantel-Haenszel statistics. RESULTS: A total of 490 patients were selected for this study, and were divided into the younger group (413) and the elderly group (77) according to their ages. In the younger group, logistic regression analyses indicated that high BMI remained significantly and independently associated with decreased in-hospital mortality (P = 0.021). That is, in-hospital mortality decreased by 17.8% when BMI increased by 1 kg/m2. In the older group, BMI was not associated with in-hospital mortality (P = 0.808). In the younger group, the results of Pearson's chi-square test was less than 0.05, indicating a correlation between BMI and prognosis. In the older group, the conclusion was contrary with, no correlation between BMI and prognosis. If the confounding factors of age were not considered, this results in no correlation between BMI and prognosis. In the younger group, the survival/death ratio of patients with overweight and obesity was 2.078 times that of patients with normal weight. CONCLUSION: In this study of patients with severe burns, overweight and obesity had protective effect on burn injury in the younger group (18 ≤ age<65 years), but not in the older group (age ≥ 65 years). Investigating the obesity paradox in burn patients needs to consider age differences. However, multicentre clinical trials are needed to verify the results.

Prognostic Values of Platelet Distribution Width and Platelet Distribution Width-to-Platelet Ratio in Severe Burns.

BACKGROUND: Platelet distribution width (PDW) and PDW-to-platelet ratio (PPR) have been proven to be good prognostic indicators for many diseases. However, their prognostic values in severe burns have not been reported. OBJECTIVE: To investigate the early time course of PDW and PPR in severe burn patients and investigate their prognostic values. METHODS: This is a 16-year, single-center retrospective study of 590 severe burn patients. The complete blood count parameters on day 1, day 3, and day 7 postburn, including PDW and PPR, were collected. Receiver operating characteristic curves (ROC) analysis, multiple logistic regression analysis and Kaplan-Meier survival analysis were performed to evaluate the prognostic values of PDW and PPR in severe burn patients. RESULTS: According to 120-day follow-up records, 96 patients were nonsurvivors and 494 patients were survivors. ROC and area under the curve (AUC) analysis showed that, for predicting 120-day prognosis, the AUC of PDW (0.782) and PPR (0.816) on day 3 was the highest, followed by the AUC of PDW (0.764) and PPR (0.750) on day 7. The ROC-AUC of PPR (0.816) on day 3 was very close to that of the ABSI score (0.818). Multiple logistic regression analysis showed that the PDW (P = 0.033 and P = 0.009) and PPR (P = 0.052 and P = 0.046) on day 3 and day 7 were all significantly independently positively associated with 120-day mortality. Kaplan-Meier survival analysis showed that high PDW and PPR were both significantly associated with a high 120-day mortality rate on day 3 and day 7. CONCLUSION: PDW and PPR on day 3 and day 7 were independent risk factors for 120-day mortality in severe burn patients. These objective and readily available prognostic indicators may be more clinically favored.

Association of the Circulating Supar Levels with Inflammation, Fibrinolysis, and Outcome in Severe Burn Patients.

BACKGROUND: Hyperfibrinolysis and pro/anti-inflammatory imbalance usually occur in the early stage of severe burns. Soluble urokinase-type plasminogen activator receptor (suPAR) is involved in fibrinolysis and inflammation. To date, the levels of circulating suPAR in non-survivors with severe burns remain unknown. This study aimed to investigate the early association between circulating suPAR levels and biomarkers of fibrinolysis, pro/anti-inflammatory, and prognosis. METHODS: Sixty-four consecutive Chinese patients with severe burns and 26 healthy volunteers were enrolled in a prospective observational cohort. Clinical characteristics and laboratory data were collected prospectively. Blood samples were collected at 48 h post-burn, and suPAR and biomarkers of pro/anti-inflammatory and fibrinolysis were detected by enzyme-linked immunosorbent assays. Important indicators between non-survivors and survivors were compared. Linear regression analysis was performed to screen variables associated with suPAR. Logistic regression analysis and receiver operating characteristic curve (ROC) analysis were performed to evaluate the prognostic value of suPAR. RESULT: Compared with the control group, the circulating suPAR levels in the survivors (P < 0.001) and non-survivors (P = 0.017) were higher. Compared with survivors, non-survivors had lower circulating suPAR levels at 48 h post-burn, and they showed a higher degree of fibrinolysis (higher D-dimer) and a lower TNF-α/IL-10 ratio. According to linear regression analysis, the variables independently associated with a lower suPAR level were lower platelet factor 4 (PF-4), urokinase-type plasminogen activator (uPA), and TNF-α/IL-10 levels and a higher D-dimer level. Logistic regression and ROC analyses indicated that a suPAR level ≤ 4.70 µg/L was independently associated with 30-day mortality. CONCLUSION: Low circulating suPAR levels at 48 h post-burn in severe burn patients may reflect decreased TNF-α/IL-10 ratio and increased hyperfibrinolysis. suPAR can predict 30-day mortality in patients with severe burn.

Low-soluble TREM-like transcript-1 levels early after severe burn reflect increased coagulation disorders and predict 30-day mortality.

BACKGROUND: Patients with severe burns often show systemic coagulation changes in the early stage and even develop extensive coagulopathy. Previous studies have confirmed that soluble TREM-like transcript-1 (sTLT-1) mediates a novel mechanism of haemostasis and thrombosis in inflammatory vascular injury. At present, the role of sTLT-1 in patients with severe burns is not well known. OBJECTIVE: To investigate the early association between sTLT-1 levels and markers of burn severity, coagulation disorders, endothelial permeability, shock and prognosis in patients with severe burns. METHODS: A prospective, observational study was conducted with 60 severe burn patients (divided into a death group and a survival group according to 30-day prognosis) admitted to our hospital. Twenty-eight healthy volunteers were recruited as the control group. Blood components at 48 h after burn were analysed for sTLT-1 and biomarkers reflecting platelet activation, shock, endothelial glycocalyx damage, capillary leakage, haemostasis, fibrinolytic activity, natural anticoagulation and blood cells. We compared the three groups, analysed the correlation between sTLT-1 and biomarkers, and investigated the predictive value of sTLT-1 for 30-day prognosis. RESULT: Compared with the surviving patients, the patients who died had a lower degree of platelet activation [lower sTLT-1, platelet factor 4 (PF-4) and platelet counts] and a higher degree of burn [higher abbreviated burn severity index score (ABSI score)], shock (higher lactate), endothelial glycocalyx damage [higher syndecan-1 and soluble thrombomodulin (sTM)] and capillary leakage [higher resuscitation fluid (0-48 h), lower albumin] as well as decreased haemostasis [higher activated partial prothrombin time (APTT), lower fibrinogen and thrombin-antithrombin III complex (TAT)], increased fibrinolytic activity [higher D-dimer and tissue-type plasminogen activator (tPA)] and decreased natural anticoagulation [lower protein C (PC) and protein S (PS)]. Higher D-dimer (P = 0.013) and lower PF-4 (P = 0.001) were significantly independently associated with lower sTLT-1. Low circulating sTLT-1 (a unit is 50 pg/mL) (odds ratio [OR] 2.08 [95% CI 1.11-3.92], P = 0.022) was an independent predictor of increased 30-day mortality. CONCLUSION: Low sTLT-1 levels at 48 h after burn in patients with severe burns is associated with increased coagulation disorders. Low circulating sTLT-1 levels were an independent predictor of increased 30-day mortality.

Circulating sFasL Levels Predict the Severity and Outcome of Burn Injury: A Prospective Observational Study.

BACKGROUND: Severe burn injury activates shock, inflammation, and blood cell system, but inappropriate reactions may lead to adverse outcomes. Soluble Fas ligand (sFasL) participates in apoptosis and inflammatory response. The circulating sFasL levels we investigated in association with the burn severity, shock, inflammation, blood cells, and mortality in patients with severe burns. METHODS: A total of 56 patients with severe burns were recruited. The levels of sFasL and the biomarkers reflecting shock, organ damage, inflammation, and blood cells at 48 h postburn were analyzed. We compared the practical situation of patients that stratified by median sFasL levels and investigated the predictive value of sFasL for mortality. RESULTS: High circulating sFasL levels were associated with the higher degrees of burn index, shock index, lactate, N-terminal probrain natriuretic peptide, total bilirubin, blood urea nitrogen, creatinine, tumor necrosis factor-α, interleukin-1ß, interleukin-8, intercellular adhesion molecule 1, and complement 3, and the lower degrees of oxygenation index, lymphocytes, and platelets. Multiple linear regression analysis showed that the higher tumor necrosis factor-α (P < 0.001) and the lower oxygenation index (P = 0.031) and lymphocytes (P = 0.043) were associated with the higher sFasL. High sFasL (a unit is 50 ng/L) (odds ratio [OR] 5.50 [95% CI 1.04-29.20], P = 0.045) was an independent predictor of increased mortality by multivariate logistic regression analysis. CONCLUSIONS: High circulating sFasL at 48 h postburn in patients with severe burns reflect shock, proinflammatory response, organ damage, and lymphocyte reductions and predict 30-day mortality.

Elevated serum procalcitonin predicts Gram-negative bloodstream infections in patients with burns.

BACKGROUND: Many studies have suggested that procalcitonin can predict bloodstream infection and also distinguish between Gram-negative, Gram-positive and fungal infections after burn. However, up to now, there is no literature on serum procalcitonin level of multidrug-resistant pathogens and non-multidrug-resistant pathogens among Gram-negative bloodstream infections after burn. The purpose of this study is to explore the value of serum procalcitonin in identifying Gram-negative bloodstream infection in patients with febrile critical burn and then to investigate the difference of serum procalcitonin level between multidrug-resistant pathogens and non-multidrug-resistant pathogens among Gram-negative bloodstream infections after burn. METHODS: Patients with febrile critical burn admitted to the burn department of our hospital from 1 January 2014 to 1 August 2018 were retrospectively analysed. Patients with positive blood culture whose blood samples were collected for simultaneous blood culture and procalcitonin testing were enrolled. All strains were identified by an automatic microorganism analyser, and procalcitonin was analysed by an automatic electrochemiluminescence immunoassay. RESULTS: Overall, a total of 119 patients with positive blood culture met the inclusion criteria. There were 64 Gram-negative bacilli, 38 Gram-positive bacteria, 8 C. albicans and 9 polymicrobial bloodstream infections. The median procalcitonin value in Gram-negative bloodstream infections (2.67 ng/mL, interquartile range (IQR) 1.58-6.08) was significantly higher than that in Gram-positive bloodstream infections (1.04 ng/mL, IQR 0.35-1.60, P < 0.01), or C. albicans bloodstream infections (1.09 ng/mL, IQR 0.82-2.30, P < 0.05). Receiver operating characteristic curve (ROC) analysis showed that in addition to polymicrobial bloodstream infections, the area of procalcitonin under the curve distinguishing Gram-negative bloodstream infections from all other blood culture-positive bloodstream infections was 0.761, the best critical value was 1.73 ng/mL, the sensitivity was 73%, the specificity was 74%, the positive predictive value was 80%, the negative predictive value was 67%, The level of procalcitonin was significantly higher in multidrug-resistant Gram-negative bacilli (A. baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa) (2.76 ng/mL, IQR 2.01-7.76) than in non-multidrug-resistant bacilli (1.01 ng/mL, IQR 0.58-1.56, P < 0.01). CONCLUSION: Elevated serum procalcitonin can identify Gram-negative bloodstream infections in patients with febrile critical burn. In Gram-negative bloodstream infections, high procalcitonin levels may be associated with multidrug-resistant Gram-negative bacilli (A. baumannii, K. pneumoniae and P. aeruginosa).

The application of early goal directed therapy in patients during burn shock stage.

Early goal directed therapy (EGDT) provided at the earliest stages of burn shock, has significant benefits for ordinary burn patients, however, its effect on patients with more than 80% of total surface area burned (TBSA) still remains unclear. In this study, 34 extensively burned patients with (87.3±5.6)% of total surface area burned were collected from January 2008 to January 2014. All burn patients here had similar monitoring or treatment modalities. Of these 34 burn patients, 13 patients were treated with EGDT under pulse indicator continuous cardiac output (PICCO) monitoring, and 21 patients were treated with conventional fluid management. Information obtained in the course of treatment included mean arterial pressure (MAP), central venous oxygen saturation (ScvO2), oxygenation index (PaO2/FiO2), blood lactic acid and urine volume, infusion volume (mL·1% TBSA-1·Kg-1), complications of over-resuscitation (hydrothorax or pulmonary edema), case rate of burn sepsis and fatality. Our results demonstrated that there existed significant difference between the two groups in parameters below: 1. Higher ScvO2 (%) after EGDT (EGDT: 78.1±8.6, CG: 65.5±11.2; t=-3.446, P<0.05), 2. Higher PaO2/FiO2 after EGDT (EGDT: 381.4±56.6, CG: 328.9±48.6; t=2-875, P<0.05), 3. Lower mean infusion volume after EGDT (mL·1% TBSA-1·Kg-1) (EGDT: 3.29±0.26, CG: 3.71±0.31; t=5.292, P<0.05), 4. Lower complications of over-resuscitation after EGDT (EGDT: 2/13, CG: 15/21; P<0.05); However, no statistical significance existed in parameters below: 1. MAP (EGDT: 76.2±13.1, CG: 74.3±15.6; t=-0.36, P>0.05), 2. Urine volume (EGDT: 0.83±0.12, CG: 0.85±0.17; t=0.370, P>0.05), 3. Case of burn sepsis (EGDT: 13/13, CG: 20/21; P=1), 4. Case fatality (EGDT: 1/13, CG: 3/21; P=1). The finding results showed that patients with more than 80% of total surface area burned during burn shock phase could get better outcome from EGDT.