Introduction: About one-third of critically ill patients with acute kidney injury (AKI) develop persistently decreased kidney function, known as acute kidney disease (AKD), which may progress to chronic kidney disease (CKD). Although sepsis is the most common cause of AKI, little is known about sepsis-associated AKD.Methods: Using data from a large randomized trial including 1341 patients with septic shock, we studied patients with stage 2 or 3 AKI on day 1 of hospitalization. We defined AKD as a persistently reduced glomerular filtration rate for >7 days. In addition to clinical data, we measured several urinary biomarkers (tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 [TIMP-2*IGFBP7], neutrophil gelatinase-associated lipocalin [NGAL], kidney injury molecule-1 [KIM-1], liver-type fatty acid binding protein, and type 4 collagen) at 0, 6, and 24 hours, to predict AKD.Results: Of 598 patients, 119 (19.9%) died within 7 days, 318 (53.2%) had early reversal of AKI within the first 7 days, whereas 161 (26.9%) developed AKD. In patients with early reversal, 45 (14.2%) had relapsed AKI after early reversal, and only about one-third of these recovered. Among patients developing AKD, only 15 (9.3%) recovered renal function prior to discharge. Male sex, African American race, and underlying CKD were more predominant in patients developing AKD. None of the biomarkers tested performed well for prediction of AKD, although NGAL modestly increased the performance of a clinical model. Conclusions: AKD is common in patients with septic shock, especially among African American males and those with underlying CKD. Existing AKI biomarkers have limited utility for predicting AKD but might be useful together with clinical variables. Novel predictive biomarkers for renal recovery are needed.
BackgroundWe sought to determine the effects of alternative resuscitation strategies on microcirculatory perfusion and examine any association between microcirculatory perfusion and mortality in sepsis.MethodsThis was a prospective, formally designed substudy of participants in the Protocolized Care in Early Septic Shock (ProCESS) trial. We recruited from six sites with the equipment and training to perform these study procedures. All subjects were adults with septic shock, and each was assigned to alternative resuscitation strategies. The two main analyses assessed (1) the impact of resuscitation strategies on microcirculatory perfusion parameters and (2) the association of microcirculatory perfusion with 60-day in-hospital mortality. We measured sublingual microcirculatory perfusion using sidestream dark field in vivo video microscopy at the completion of the 6-h ProCESS resuscitation protocol and then again at 24 and 72 h.ResultsWe enrolled 207 subjects (demographics were similar to the overall ProCESS cohort) and observed 40 (19.3%) deaths. There were no differences in average perfusion characteristics between treatment arms. Analyzing the relationship between microcirculatory perfusion and mortality, we found an association between vascular density parameters and mortality. Total vascular density (beta = 0.006, p < 0.003), perfused vascular density (beta = 0.005, p < 0.04), and De Backer score (beta = 0.009, p < 0.01) were higher overall in survivors in a generalized estimating equation model, and this association was significant at the 72-h time point (p < 0.05 for each parameter).ConclusionsMicrocirculatory perfusion did not differ between three early septic shock treatment arms. We found an association between microcirculatory perfusion parameters of vascular density at 72 h and mortality.Trial registrationClinicalTrials.gov, NCT00510835. Registered on August 2, 2007.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2240-5) contains supplementary material, which is available to authorized users.
Background Esophageal thermal injury can occur after radiofrequency (RF) ablation in the left atrium to treat atrial fibrillation. Existing methods to prevent esophageal injury have various limitations in deployment and uncertainty in efficacy. A new esophageal heat transfer device currently available for whole-body cooling or warming may offer an additional option to prevent esophageal injury. We sought to develop a mathematical model of this process to guide further studies and clinical investigations and compare results to real-world clinical data. Results The model predicts that the esophageal cooling device, even with body-temperature water flow (37 °C) provides a reduction in esophageal thermal injury compared to the case of the non-protected esophagus, with a non-linear direct relationship between lesion depth and the cooling water temperature. Ablation power and cooling water temperature have a significant influence on the peak temperature and the esophageal lesion depth, but even at high RF power up to 50 W, over durations up to 20 s, the cooling device can reduce thermal impact on the esophagus. The model concurs with recent clinical data showing an 83% reduction in transmural thermal injury when using typical operating parameters. Conclusions An esophageal cooling device appears effective for esophageal protection during atrial fibrillation, with model output supporting clinical data. Analysis of the impact of ablation power and heart wall dimensions suggests that cooling water temperature can be adjusted for specific ablation parameters to assure the desired myocardial tissue ablation while keeping the esophagus protected.
Traumatic brain injury (TBI) is a leading cause of death in the United States, and represents 2.5 million Emergency Department attendances, admissions into hospital, and deaths. A range of temperature modulating devices have been used to proactively cool TBI patients; however, there are currently no uniform targeted temperature management (TTM) guidelines in this patient population. Esophageal temperature management (ETM) is a relatively new TTM modality and the purpose of this study is to determine whether ETM is effective in controlling core temperature in TBI cases. This prospective interventional trial was a single-site study that enrolled 12 patients who received a TTM protocol using ETM. Eleven out of 12 patients reached target temperature during the first 10 hours of treatment. A total of 480 temperature measurements were recorded; 85% of the total measurements were within-1°C of target temperature (408 measurements) and 75% were within-0.5°C of target temperature (360 measurements). The average time to target was 5.83-5.01 hours (range 1-20), with an average cooling rate of 0.58°C/h (range 0.15-1.5°C/h). This prospective interventional trial supports that ETM is a feasible TTM modality for severe TBI cases. The esophageal heat transfer device used in this study demonstrated comparable or superior performance to other commercially available TTM modalities, and the low adverse event rate may offer advantages over more invasive methods with reported higher complication rates.
Purpose: We sought to quantify the capabilities of a commercially available cooling device to protect the esophagus from RF injury in an animal model and develop a mathematical model to describe the system and provide a framework from which to advance this technology.Methods: A series of ablations (10 W, duration 30-45 seconds) were performed directly on exposed swine esophagus. Control ablations were performed with static 37°C water, and treatment ablations were performed with water (range 5°C-37°C) circulating within the device. Mucosal lesions were evaluated visually and with target tissue histology. A mathematical model was then developed and compared against the experimental data.Results: All 23 ablations (100%) performed under control conditions produced visible external esophageal lesions; 12 of these (52%) were transmural. Under treatment conditions, only 5 of 23 ablations (22%) produced visible external lesions; none (0%) were transmural. Transmurality of lesions decreased as circulating water temperature decreased, with absolute reduction ranging from 5.1% with the use of 37°C water (p=0.7) to 44.5% with the use of 5°C water (p<0.001). Comparison to the mathematical model showed an R^2 of 0.75, representing good agreement.Conclusions: Under worst-case conditions, with RF energy applied directly to the adventitial side of the esophagus, internal esophageal cooling with an esophageal cooling device provides significant protective effect from thermal injury. A mathematical model of the process provides a means to further investigate this approach to preventing esophageal injury during RF ablation and can serve to guide ongoing clinical investigations currently in progress.
Background:New scoring systems, including the Rapid Emergency Medicine Score (REMS), the Mortality in Emergency Department Sepsis (MEDS) score, and the confusion, urea nitrogen, respiratory rate, blood pressure, 65 years and older (CURB-65) score, have been developed for emergency department (ED) use in various patient populations. Increasing use of early goal directed therapy (EGDT) for the emergent treatment of sepsis introduces a growing population of patients in which the accuracy of these scoring systems has not been widely examined.Objectives:To evaluate the ability of the REMS, MEDS score, and CURB-65 score to predict mortality in septic patients treated with modified EGDT.Materials and Methods:Secondary analysis of data from prospectively identified patients treated with modified EGDT in a large tertiary care suburban community hospital with over 85,000 ED visits annually and 700 inpatient beds, from May 2007 through May 2008. We included all patients with severe sepsis or septic shock, who were treated with our modified EGDT protocol. Our major outcome was in-hospital mortality. The performance of the scores was compared by area under the ROC curves (AUCs).Results:A total of 216 patients with severe sepsis or septic shock were treated with modified EGDT during the study period. Overall mortality was 32.9%. Calculated AUCs were 0.74 [95% confidence interval (CI): 0.67–0.81] for the MEDS score, 0.62 (95% CI: 0.54–0.69) for the REMS, and 0.59 (95% CI: 0.51–0.67) for the CURB-65 score.Conclusion:We found that all three ED-based systems for scoring severity of illness had low to moderate predictive capability. The MEDS score demonstrated the largest AUC of the studied scoring systems for the outcome of mortality, although the CIs on point estimates of the AUC of the REMS and CURB-65 scores all overlap.
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