Clinical review: Biomarkers of acute kidney injury: where are we now?

The recognition that acute kidney injury (AKI) is a significant independent risk factor for morbidity and mortality has resulted in a substantial number of publications over the past 5 years or more. In no small part these have, to a degree, highlighted the inadequacy of conventional markers of renal insufficiency in the acute setting. Much effort has been invested in the identification of early, specific AKI markers in order to aid early diagnosis of AKI and hopefully improve outcome. The search for a 'biomarker' of AKI has seen early promise replaced by a degree of pessimism due to the lack of a clear candidate molecule and variability of results. We outline the major studies described to date as well as discuss potential reasons for the discrepancies observed and suggest that evolution of the field may result in success with ultimately an improvement in patient outcomes

Prognostic value of serial score measurements of the national early warning score, the quick sequential organ failure assessment and the systemic inflammatory response syndrome to predict clinical outcome in early sepsis

BACKGROUND AND IMPORTANCE: Sepsis is a common and potentially lethal syndrome, and early recognition is critical to prevent deterioration. Yet, currently available scores to facilitate recognition of sepsis lack prognostic accuracy. OBJECTIVE: To identify the optimal time-point to determine NEWS, qSOFA and SIRS for the prediction of clinical deterioration in early sepsis and to determine whether the change in these scores over time improves their prognostic accuracy. DESIGN: Post hoc analysis of prospectively collected data. SETTINGS AND PARTICIPANTS: This study was performed in the emergency department (ED) of a tertiary-care teaching hospital. Adult medical patients with (potential) sepsis were included. OUTCOME MEASURES AND ANALYSIS: The primary outcome was clinical deterioration within 72 h after admission, defined as organ failure development, the composite outcome of ICU-admission and death. Secondary outcomes were the composite of ICU-admission/death and a rise in SOFA at least 2. Scores were calculated at the ED with 30-min intervals. ROC analyses were constructed to compare the prognostic accuracy of the scores. RESULTS: In total, 1750 patients were included, of which 360 (20.6%) deteriorated and 79 (4.5%) went to the ICU or died within 72 h. The NEWS at triage (AUC, 0.62; 95% CI, 0.59-0.65) had a higher accuracy than qSOFA (AUC, 0.60; 95% CI, 0.56-0.63) and SIRS (AUC, 0.59; 95% CI, 0.56-0.63) for predicting deterioration. The AUC of the NEWS at 1 h (0.65; 95% CI, 0.63-0.69) and 150 min after triage (0.64; 95% CI, 0.61-0.68) was higher than the AUC of the NEWS at triage. The qSOFA had the highest AUC at 90 min after triage (0.62; 95% CI, 0.58-0.65), whereas the SIRS had the highest AUC at 60 min after triage (0.60; 95% CI, 0.56-0.63); both are not significantly different from triage. The NEWS had a better accuracy to predict ICU-admission/death <72 h compared with qSOFA (AUC difference, 0.092) and SIRS (AUC difference, 0.137). No differences were found for the prediction of a rise in SOFA at least 2 within 72 h between the scores. Patients with the largest improvement in any of the scores were more prone to deteriorate. CONCLUSION: NEWS had a higher prognostic accuracy to predict deterioration compared with SIRS and qSOFA; the highest accuracy was reached at 1 h after triage

Acute lung injury in paediatric intensive care: course and outcome

Introduction: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) carry a high morbidity and mortality (10-90%). ALI is characterised by non-cardiogenic pulmonary oedema and refractory hypoxaemia of multifactorial aetiology [1]. There is limited data about outcome particularly in children. Methods This retrospective cohort study of 85 randomly selected patients with respiratory failure recruited from a prospectively collected database represents 7.1% of 1187 admissions. They include those treated with High Frequency Oscillation Ventilation (HFOV). The patients were admitted between 1 November 1998 and 31 October 2000. Results: Of the 85, 49 developed acute lung injury and 47 had ARDS. There were 26 males and 23 females with a median age and weight of 7.7 months (range 1 day-12.8 years) and 8 kg (range 0.8-40 kg). There were 7 deaths giving a crude mortality of 14.3%, all of which fulfilled the Consensus I [1] criteria for ARDS. Pulmonary occlusion pressures were not routinely measured. The A-a gradient and PaO2/FiO2 ratio (median + [95% CI]) were 37.46 [31.82-43.1] kPa and 19.12 [15.26-22.98] kPa respectively. The non-survivors had a significantly lower PaO2/FiO2 ratio (13 [6.07-19.93] kPa) compared to survivors (23.85 [19.57-28.13] kPa) (P = 0.03) and had a higher A-a gradient (51.05 [35.68-66.42] kPa) compared to survivors (36.07 [30.2-41.94]) kPa though not significant (P = 0.06). Twenty-nine patients (59.2%) were oscillated (Sensormedics 3100A) including all 7 non-survivors. There was no difference in ventilation requirements for CMV prior to oscillation. Seventeen of the 49 (34.7%) were treated with Nitric Oxide including 5 out of 7 non-survivors (71.4%). The median (95% CI) number of failed organs was 3 (1.96-4.04) for non-survivors compared to 1 (0.62-1.62) for survivors (P = 0.03). There were 27 patients with isolated respiratory failure all of whom survived. Six (85.7%) of the non-survivors also required cardiovascular support.Conclusion: A crude mortality of 14.3% compares favourably to published data. The A-a gradient and PaO2/FiO2 ratio may be of help in morbidity scoring in paediatric ARDS. Use of Nitric Oxide and HFOV is associated with increased mortality, which probably relates to the severity of disease. Multiple organ failure particularly respiratory and cardiac disease is associated with increased mortality. ARDS with isolated respiratory failure carries a good prognosis in children

An investigation into the effects of commencing haemodialysis in the critically ill

&lt;b&gt;Introduction:&lt;/b&gt; We have aimed to describe haemodynamic changes when haemodialysis is instituted in the critically ill. 3 hypotheses are tested: 1)The initial session is associated with cardiovascular instability, 2)The initial session is associated with more cardiovascular instability compared to subsequent sessions, and 3)Looking at unstable sessions alone, there will be a greater proportion of potentially harmful changes in the initial sessions compared to subsequent ones. &lt;b&gt;Methods:&lt;/b&gt; Data was collected for 209 patients, identifying 1605 dialysis sessions. Analysis was performed on hourly records, classifying sessions as stable/unstable by a cutoff of &gt;+/-20% change in baseline physiology (HR/MAP). Data from 3 hours prior, and 4 hours after dialysis was included, and average and minimum values derived. 3 time comparisons were made (pre-HD:during, during HD:post, pre-HD:post). Initial sessions were analysed separately from subsequent sessions to derive 2 groups. If a session was identified as being unstable, then the nature of instability was examined by recording whether changes crossed defined physiological ranges. The changes seen in unstable sessions could be described as to their effects: being harmful/potentially harmful, or beneficial/potentially beneficial. &lt;b&gt;Results:&lt;/b&gt; Discarding incomplete data, 181 initial and 1382 subsequent sessions were analysed. A session was deemed to be stable if there was no significant change (&gt;+/-20%) in the time-averaged or minimum MAP/HR across time comparisons. By this definition 85/181 initial sessions were unstable (47%, 95% CI SEM 39.8-54.2). Therefore Hypothesis 1 is accepted. This compares to 44% of subsequent sessions (95% CI 41.1-46.3). Comparing these proportions and their respective CI gives a 95% CI for the standard error of the difference of -4% to 10%. Therefore Hypothesis 2 is rejected. In initial sessions there were 92/1020 harmful changes. This gives a proportion of 9.0% (95% CI SEM 7.4-10.9). In the subsequent sessions there were 712/7248 harmful changes. This gives a proportion of 9.8% (95% CI SEM 9.1-10.5). Comparing the two unpaired proportions gives a difference of -0.08% with a 95% CI of the SE of the difference of -2.5 to +1.2. Hypothesis 3 is rejected. Fisher’s exact test gives a result of p=0.68, reinforcing the lack of significant variance. &lt;b&gt;Conclusions:&lt;/b&gt; Our results reject the claims that using haemodialysis is an inherently unstable choice of therapy. Although proportionally more of the initial sessions are classed as unstable, the majority of MAP and HR changes are beneficial in nature

Machine Learning Methods for Septic Shock Prediction

Sepsis is an organ dysfunction life-threatening disease that is caused by a dysregulated body response to infection. Sepsis is difficult to detect at an early stage, and when not detected early, is difficult to treat and results in high mortality rates. Developing improved methods for identifying patients in high risk of suffering septic shock has been the focus of much research in recent years. Building on this body of literature, this dissertation develops an improved method for septic shock prediction. Using the data from the MMIC-III database, an ensemble classifier is trained to identify high-risk patients. A robust prediction model is built by obtaining a risk score from fitting the Cox Hazard model on multiple input features. The score is added to the list of features and the Random Forest ensemble classifier is trained to produce the model. The Cox Enhanced Random Forest (CERF) proposed method is evaluated by comparing its predictive accuracy to those of extant methods

Shock index predicts outcome in patients with suspected sepsis or community acquired pneumonia : a systematic review

Supplementary Materials: The following are available online at www.mdpi.com/xxx/s1, Table S1: Medline search strategy, Table S2: Downs and Black quality assessment for included studies. Table S3: CURASI score as a predictor of mortality in CAP.Peer reviewedPublisher PD

Evaluation Of A 5-Group Classification System For Severe Sepsis By Ed Vasopressor Use And Initial Serum Lactate

HYPOTHESIS AND SPECIFIC AIMS: The aim of this study is to characterize the incidence and outcomes of various groups within a novel classification system of severe sepsis and septic shock, for the purpose of informing more accurate risk prediction in the proximal phases of care. Our primary hypothesis is that an early classification system of septic patients categorized by organ dysfunction, initial emergency department (ED) serum lactate, and ED vasopressor utilization will offer accurate mortality prognostication in patients with severe sepsis and septic shock. METHODS: We performed a retrospective analysis of a prospectively- gathered registry of severe sepsis and septic shock patients presenting to a dual-site academic emergency department (ED). In the primary analysis, registry subjects were categorized into five groups by initial ED serum lactate level and vasopressor requirement in the ED: dysoxic shock (vasopressor use + lactate \u3e4 mmol/L), vasoplegic shock (vasopressor use + lactate \u3c4 mmol/L), cryptic shock major (no vasopressor use + lactate \u3e4 mmol/L), cryptic shock minor (no vasopressor use + lactate \u3e2 and \u3c4 mmol/L), and severe sepsis without lactate elevation (no vasopressor use + lactate \u3c2 mmol/L + evidence of organ dysfunction). For each group, the 28-day mortality rate was evaluated by logistic regression controlling for specific factors associated with sepsis severity. RESULTS: Of 521 registry subjects, 85.6% (n=446) met inclusion criteria. 4.9% (n=22) subjects presented in dysoxic shock, 11.7% (n=52) in vasoplegic shock, 12.1% (n=54) in cryptic shock major, 30.9% (n=138) in cryptic shock minor, and 40.4% (n=180) in severe sepsis without lactate elevation. The 28-day mortality rates for these groups were 50.0%, 21.1%, 18.5%, 12.3%, and 7.2%, respectively; this stepwise trend was paralleled by metrics of critical care utilization such as ICU admission, mechanical ventilation, and vasopressor use within 72 hours of admission. After controlling for known risk factors for sepsis severity, the odds ratios for death before 28 days were 15.06 for dysoxic shock, 3.61 for vasoplegic shock, 3.77 for cryptic shock major, and 1.93 for cryptic shock minor, as compared to severe sepsis without lactate elevation. CONCLUSION: This study suggests that high-risk subgroups of severe sepsis and septic shock patients can be identified at presentation and during the emergency department stay. We show that in severe sepsis and septic shock, a proximal-phase classification system based on vasopressor requirement in the ED and initial ED lactate level predicts 28-day in-hospital mortality and may inform prognostication, triage decisions and future sepsis clinical trial design

Clinical examination, critical care ultrasonography and outcomes in the critically ill : cohort profile of the Simple Intensive Care Studies-I

Purpose In the Simple Intensive Care Studies-I (SICS-I), we aim to unravel the value of clinical and haemodynamic variables obtained by physical examination and critical care ultrasound (CCUS) that currently guide daily practice in critically ill patients. We intend to (1) measure all available clinical and haemodynamic variables, (2) train novices in obtaining values for advanced variables based on CCUS in the intensive care unit (ICU) and (3) create an infrastructure for a registry with the flexibility of temporarily incorporating specific (haemodynamic) research questions and variables. The overall purpose is to investigate the diagnostic and prognostic value of clinical and haemodynamic variables. Participants The SICS-I includes all patients acutely admitted to the ICU of a tertiary teaching hospital in the Netherlands with an ICU stay expected to last beyond 24 hours. Inclusion started on 27 March 2015. Findings to date On 31 December 2016, 791 eligible patients fulfilled our inclusion criteria of whom 704 were included. So far 11 substudies with additional variables have been designed, of which six were feasible to implement in the basic study, and two are planned and awaiting initiation. All researchers received focused training for obtaining specific CCUS images. An independent Core laboratory judged that 632 patients had CCUS images of sufficient quality. Future plans We intend to optimise the set of variables for assessment of the haemodynamic status of the critically ill patient used for guiding diagnostics, prognosis and interventions. Repeated evaluations of these sets of variables are needed for continuous improvement of the diagnostic and prognostic models. Future plans include: (1) more advanced imaging; (2) repeated clinical and haemodynamic measurements; (3) expansion of the registry to other departments or centres; and (4) exploring possibilities of integration of a randomised clinical trial superimposed on the registry. Study registration number NCT02912624; Pre-results.Peer reviewe