Trajectories of longitudinal biomarkers for mortality in severely burned patients
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ABSTRACT:
SUBMITTER: Yoon J
PROVIDER: S-EPMC7530734 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:PurposeBurn injury has high clinical heterogeneity and worse prognosis in severely burned patients. Clustering algorithms using unsupervised methods to identify groups with similar trajectories in heterogeneous disease patients can provide insight into mechanisms of disease pathogenesis. This study analyzed routinely collected biomarkers to evaluate mortality prediction, find clinical meanings for these or their subtypes, and evaluate patterns.MethodsThis retrospective cohort study included patients aged >18 years, between July 2012 and June 2021. All eligible patients received fluid resuscitation and survived for at least 7 days. Characteristics of clinical interest to the physician at 4 clinically important time points were evaluated.ResultsEligible patients were divided into 4 subgroups according to these time points: from 1st week to 4th week. Total of 1,249 patients admitted within 2 days after burns and receiving fluid resuscitation were included. Mean Harrell's C-index of pH was the highest (0.816), followed by platelets (0.807), creatinine (0.796), red cell distribution width (RDW, 0.778), and lactate (0.759). Longitudinal profiles among biomarkers were different.ConclusionThe main predictors were pH, platelets, creatinine, RDW, and lactate. Creatinine and RDW showed consistent patterns. The other markers varied according to patient condition. Thus, these markers could provide clues into underlying mechanisms and predict mortality.
| S-EPMC9929432 | biostudies-literature
Project description:Hypernatremia is common in critical care, especially in severely burned patients. Its occurrence has been linked to increased mortality. Causes of hypernatremia involve a net gain of sodium or a loss of free water. Renal loss of electrolyte-free water due to urea-induced osmotic diuresis has been described as causative in up to 10% of hypernatremic critical ill patients. In this context, excessive urea production due to protein catabolism acts as major contributor. In severe burn injury, muscle wasting occurs as result of hypermetabolism triggered by ongoing systemic inflammation. In this retrospective study, severely burned patients were analysed for the occurrence of hypernatremia and subsequent signs of hypermetabolism. The urea: creatinine ratio-as a surrogate for hypermetabolism-sufficiently discriminated between two groups. Four of nine hypernatremic burn patients (44%) had a highly elevated urea: creatinine ratio, which was clearly associated with an increased urea production and catabolic index. This hypermetabolism was linked to hypernatremia via an elevated urea- and reduced electrolyte-fraction in renal osmole excretion, which resulted in an increased renal loss of electrolyte-free water. In hypermetabolic severely burned patients, the electrolyte-free water clearance is a major contributor to hypernatremia. A positive correlation to serum sodium concentration was shown.
| S-EPMC7146173 | biostudies-literature
Project description:BACKGROUND This study evaluated factors influencing early and late occurrence of AKI in severely burned patients and assessed the relationship between time of occurrence of AKI and mortality of AKI patients. MATERIAL AND METHODS Renal function was evaluated at 3 time points: at admission, at the critical point or middle point of hospitalization, and at the endpoint for which death or a discharge from the center was considered. AKI criteria were: decrease in GFR of less than 60 ml/min at admission, decrease in GFR of more than 75% compared to baseline, and decrease in the daily diuresis of less than 500 ml/24 h. RESULTS At admission, 15.1% of the patients had eGFR <60 ml/min. AKI occurred in 38.5% of cases. The occurrence of AKI was associated with: elderly age (p<0.001), female sex (p=0.017), overweight and obesity (p=0.055); extent and depth of burns, respiratory failure, low protein concentration (for all p<0.001), low blood pressure (p=0.014), and high WBC (p=0.010). Early AKI was detected in 28% of patients. Mortality was 100% with the initial GFR ?60, 100% with the initial GFR <60 and early deterioration of renal function, 80% with the initial GFR <60 and late worsening, and 60% with the initial GFR <60 and no worsening. Late AKI was observed in 10% of patients and mortality in this group was 79.2%. Mortality in the entire group with AKI was 88.0% versus 24.5%. CONCLUSIONS The frequent occurrence of AKI, especially early, worsens the prognosis for survival. Assessment of renal function should be included in the prognostic scales for burned patients.
| S-EPMC5070618 | biostudies-other
Project description:Continuous renal replacement therapy (CRRT) is administered to critically ill patients with renal injuries as renal replacement or renal support. We aimed to identify predictors of mortality among burn patients receiving CRRT, and to investigate clinical differences according to acute kidney injury (AKI) status. This retrospective observational study evaluated 216 Korean burn patients who received CRRT at a burn intensive care unit. Patients were categorized by AKI status. Data were collected regarding arterial pH, laboratory results, ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF ratio), and urine production. Among surviving patients, CRRT duration and the sequential organ failure assessment score were 6.5 days and 4.7 in the non-AKI group and 23.4 days and 7.4 in the AKI group, respectively (p = 0.003 and p = 0.008). On logistic regression analyses, mortality was significantly associated with a pH of <7.2 (p = 0.004), potassium levels of >5.0 mEg/L (p = 0.045), creatinine levels of >2.0 mg/dL (p = 0.011), lactate levels of >2 mmol/L (p<0.001), a PF ratio of <200 (p = 0.042), and a platelet count of <100,000/μL (p<0.001). In the AKI group, poor outcomes were associated with a pH of <7.2, potassium levels of <5.0 mEg/L, lactate levels of >2 mmol/L, and a platelet count of <100,000/μL, while good outcomes were associated with creatinine levels of >2 mg/dL. In the non-AKI group, poor outcomes were associated with lactate levels of >1.5 mmol/L, a PF ratio of <200, and a platelet count of <100,000/μL, while good outcomes were associated with creatinine levels of >1.2 mg/dL. Duration of the CRRT application and the requirement for either renal replacement or renal support at the initiation of CRRT application are important considerations depending on its application.
| S-EPMC5708827 | biostudies-literature
Project description:INTRODUCTION: Extensive burn injury has systemic consequences due to capillary leak. After restoration of cellular integrity, infused fluid volume has to be removed partially. This can provoke electrolyte disorders. PURPOSE: We investigated the effect of progressive fluid removal on serum sodium level. METHOD: Retrospective study. Patients admitted to a burn unit were analyzed and separated in two groups without (Group A) or with (Group B) prolonged hypernatremia. Daily infusion-diuresis-ratio (IDR) was analyzed. RESULTS: Fourty (12 female; 28 male) patients with a mean age of 47±19 years, a total burn surface area (TBSA) of 26±12%, and a mean abbreviated burned severity index (ABSI) score of 7.3±2 were included. In Group A 25 patients with a mean age of 47±18 years, a mean TBSA of 23±11%, and a mean ABSI score of 6.9±2.1 were summarized. In Group B 15 patients with a mean age of 47±22 years, a mean TBSA of 30±13%, and a mean ABSI score of 8.1±1.7 were included. Hypernatremia occurred on day 5±1.4. There was no significant difference between both groups for fluid resuscitation amount within the first 24 hours. Statistical analysis of the first 7 days after burn injury showed a significantly higher percentage of removed fluid in Group B for day 3, day 4, day 5, day 6 and day 7. CONCLUSIONS: Amount and velocity of fluid removal regimen after burn injury can provoke electrolyte disorders. Serum sodium concentration can be used to calculate need of fluid resuscitation for fluid maintenance. There is a need of an established fluid removal strategy.
| S-EPMC3118691 | biostudies-other
Project description:Elevated fibroblast growth factor 23 (FGF23) levels, measured at a single time, are strongly associated with increased risk of mortality in patients with CKD. There are minimal data on serial FGF23 measurements in CKD. In a prospective case-cohort study of the Chronic Renal Insufficiency Cohort, we measured FGF23 at two to five annual time points (mean 4.0±1.2) in a randomly selected subcohort of 1135 participants, of whom 203 died, and all remaining 390 participants who died through mid-2013. Higher FGF23 was independently associated with increased risk of death in multivariable-adjusted analyses of time-varying FGF23 (hazard ratio per 1-SD increase in ln-transformed FGF23, 1.84; 95% CI, 1.67 to 2.03). Median FGF23 was stable over 5 years of follow-up, but its gradually right-skewed distribution suggested a subpopulation with markedly elevated FGF23. Trajectory analysis revealed three distinct trajectories: stable FGF23 in the majority of participants (slope of lnFGF23 per year =0.03, 95% CI, 0.02 to 0.04, n=724) and smaller subpopulations with slowly (slope=0.14, 95% CI, 0.12 to 0.16, n=486) or rapidly (slope=0.46, 95% CI, 0.38 to 0.54, n=99) rising levels. Compared with stable FGF23, participants with slowly rising FGF23 trajectories were at 4.49-fold higher risk of death (95% CI, 3.17 to 6.35) and individuals with rapidly rising FGF23 trajectories were at 15.23-fold higher risk of death (95% CI, 8.24 to 28.14) in fully adjusted analyses. Trajectory analyses that used four or three annual FGF23 measurements yielded qualitatively similar results. In conclusion, FGF23 levels are stable over time in the majority of patients with CKD, but serial measurements identify subpopulations with rising levels and exceptionally high risk of death.
| S-EPMC5791067 | biostudies-literature
Project description:RationaleHyperglycemia and insulin resistance have been shown to increase morbidity and mortality in severely burned patients, and glycemic control appears essential to improve clinical outcomes. However, to date no prospective randomized study exists that determines whether intensive insulin therapy is associated with improved post-burn morbidity and mortality.ObjectivesTo determine whether intensive insulin therapy is associated with improved post-burn morbidity.MethodsA total of 239 severely burned pediatric patients with burns over greater than 30% of their total body surface area were randomized (block randomization 1:3) to intensive insulin treatment (n = 60) or control (n = 179).Measurements and main resultsDemographics, clinical outcomes, sepsis, glucose metabolism, organ function, and inflammatory, acute-phase, and hypermetabolic responses were determined. Demographics were similar in both groups. Intensive insulin treatment significantly decreased the incidence of infections and sepsis compared with controls (P < 0.05). Furthermore, intensive insulin therapy improved organ function as indicated by improved serum markers, DENVER2 scores, and ultrasound (P < 0.05). Intensive insulin therapy alleviated post-burn insulin resistance and the vast catabolic response of the body (P < 0.05). Intensive insulin treatment dampened inflammatory and acute-phase responses by deceasing IL-6 and acute-phase proteins compared with controls (P < 0.05). Mortality was 4% in the intensive insulin therapy group and 11% in the control group (P = 0.14).ConclusionsIn this prospective randomized clinical trial, we showed that intensive insulin therapy improves post-burn morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00673309).
| S-EPMC2921599 | biostudies-literature
Project description:ObjectivesThe aim of this study was to determine the appropriate propranolol dosing strategy for reducing heart rate in severely burned adults.MethodsA total of 26 patients (≥18 years) with burns covering ≥30% of the total body surface area were included in this IRB-approved study. Plasma propranolol concentrations were determined in a placebo group (n=10) or following one of three dosing strategies: Q6 (n=4), Q8 (n=6), and Q24 (n=6). Blood was collected just before dosing and at regular intervals over two dosing periods with corresponding heart rate and blood pressure recordings. Statistical significance was determined by one-way ANOVA followed by the appropriate post-hoc test.ResultsHeart rate was 86±2 bpm for Q6, 93±3 bpm for Q8, and 90±4 bpm for Q24. The Q8 group had a significantly higher heart rate than the Q6 group (p=0.0001). Plasma propranolol concentrations were significantly higher in the Q6 dosing strategy than in the Q8 dosing strategy (p=0.02).ConclusionsHeart rate can be decreased to a similar degree with Q6 and Q24 dosing strategies, with the Q8 dosing strategy being less effective. Q6 dosing is recommended to maintain reduced heart rate throughout dosing periods.
| S-EPMC8173765 | biostudies-literature
Project description:To determine the safety and efficacy of propranolol given for 1 year on cardiac function, resting energy expenditure, and body composition in a prospective, randomized, single-center, controlled study in pediatric patients with large burns.Severe burns trigger a hypermetabolic response that persists for up to 2 years postburn. Propranolol given for 1 month postburn blunts this response. Whether propranolol administration for 1 year after injury provides a continued benefit is currently unclear.One-hundred seventy-nine pediatric patients with more than 30% total body surface area burns were randomized to control (n = 89) or 4 mg/kg/d propranolol (n = 90) for 12 months postburn. Changes in resting energy expenditure, cardiac function, and body composition were measured acutely at 3, 6, 9, and 12 months postburn. Statistical analyses included techniques that adjusted for non-normality, repeated-measures, and regression analyses. P < 0.05 was considered significant.Long-term propranolol treatment significantly reduced the percentage of the predicted heart rate and percentage of the predicted resting energy expenditure, decreased accumulation of central mass and central fat, prevented bone loss, and improved lean body mass accretion. There were very few adverse effects from the dose of propranolol used.Propranolol treatment for 12 months after thermal injury, ameliorates the hyperdynamic, hypermetabolic, hypercatabolic, and osteopenic responses in pediatric patients. This study is registered at clinicaltrials.gov: NCT00675714.
| S-EPMC3505887 | biostudies-literature
Project description:The systemic impact of severe burn injury results in a variety of disorders that require therapeutic intervention. Propranolol, a nonselective β1, β2-adrenergic receptor antagonist, reduces resting heart rate and cardiac work caused by elevated circulating catecholamines. Oxandrolone, a testosterone mimetic, promotes protein synthesis and anabolism to counter muscle wasting. Coadministration of these drugs is expected to synergistically improve patient outcomes. Testosterone administration is known to alter β-adrenergic receptor-mediated signaling. Here, we determined whether the coadministration of oxandrolone alters plasma propranolol concentrations. Ninety-two pediatric patients with burns covering ≥30% of the TBSA were enrolled in this institutional review board-approved study and randomized to receive propranolol (n = 49) or oxandrolone + propranolol (n = 43). Plasma propranolol concentrations were determined following two dosing strategies: Q6 (liquid formulation; n = 86) and Q24 (extended-release capsule; n = 22). Samples were drawn before drug administration and at regular intervals throughout the next two dosing periods. Heart rate and blood pressure were recorded throughout the study. Propranolol half-life was 3.3 hours for the Q6 drug dosing frequency (P < .0001) and 11.2 hours for the Q24 strategy (P < .0001). Percentage of predicted heart rate declined by 2.8% for each doubling of the propranolol concentration in the Q6 dosing schedule (P < .0001). Percentage of predicted heart rate declined by 2.5% for each doubling of propranolol concentration on the Q24 dosing schedule (P < .0001). Maximum and minimum propranolol plasma concentrations were similar with either dosing regimen. The addition of oxandrolone did not affect any of the measured parameters. Oxandrolone coadministration does not alter propranolol's plasma concentration, half-life, or effect on heart rate. This study is registered at clincialtrials.gov: NCT00675714.
| S-EPMC5507814 | biostudies-literature