External Validation of Mortality Prediction Models for Critical Illness Reveals Preserved Discrimination but Poor Calibration.

OBJECTIVES: In a recent scoping review, we identified 43 mortality prediction models for critically ill patients. We aimed to assess the performances of these models through external validation. DESIGN: Multicenter study. SETTING: External validation of models was performed in the Simple Intensive Care Studies-I (SICS-I) and the Finnish Acute Kidney Injury (FINNAKI) study. PATIENTS: The SICS-I study consisted of 1,075 patients, and the FINNAKI study consisted of 2,901 critically ill patients. MEASUREMENTS AND MAIN RESULTS: For each model, we assessed: 1) the original publications for the data needed for model reconstruction, 2) availability of the variables, 3) model performance in two independent cohorts, and 4) the effects of recalibration on model performance. The models were recalibrated using data of the SICS-I and subsequently validated using data of the FINNAKI study. We evaluated overall model performance using various indexes, including the (scaled) Brier score, discrimination (area under the curve of the receiver operating characteristics), calibration (intercepts and slopes), and decision curves. Eleven models (26%) could be externally validated. The Acute Physiology And Chronic Health Evaluation (APACHE) II, APACHE IV, Simplified Acute Physiology Score (SAPS)-Reduced (SAPS-R)' and Simplified Mortality Score for the ICU models showed the best scaled Brier scores of 0.11' 0.10' 0.10' and 0.06' respectively. SAPS II, APACHE II, and APACHE IV discriminated best; overall discrimination of models ranged from area under the curve of the receiver operating characteristics of 0.63 (0.61-0.66) to 0.83 (0.81-0.85). We observed poor calibration in most models, which improved to at least moderate after recalibration of intercepts and slopes. The decision curve showed a positive net benefit in the 0-60% threshold probability range for APACHE IV and SAPS-R. CONCLUSIONS: In only 11 out of 43 available mortality prediction models, the performance could be studied using two cohorts of critically ill patients. External validation showed that the discriminative ability of APACHE II, APACHE IV, and SAPS II was acceptable to excellent, whereas calibration was poor.

Right ventricular strain measurements in critically ill patients: an observational SICS sub-study.

BACKGROUND: Right ventricular (RV) dysfunction is common in critically ill patients and is associated with poor outcomes. RV function is usually evaluated by Tricuspid Annular Plane Systolic Excursion (TAPSE) which can be obtained using critical care echocardiography (CCE). Myocardial deformation imaging, measuring strain, is suitable for advanced RV function assessment and has widely been studied in cardiology. However, it is relatively new for the Intensive Care Unit (ICU) and little is known about RV strain in critically ill patients. Therefore, the objectives of this study were to evaluate the feasibility of RV strain in critically ill patients using tissue-Doppler imaging (TDI) and explore the association between RV strain and conventional CCE measurements representing RV function. METHODS: This is a single-center sub-study of two prospective observational cohorts (Simple Intensive Care Studies (SICS)-I and SICS-II). All acutely admitted adults with an expected ICU stay over 24 h were included. CCE was performed within 24 h of ICU admission. In patients in which CCE was performed, TAPSE, peak systolic velocity at the tricuspid annulus (RV s') and TDI images were obtained. RV free wall longitudinal strain (RVFWSL) and RV global four-chamber longitudinal strain (RV4CSL) were measured during offline analysis. RESULTS: A total of 171 patients were included. Feasibility of RVFWSL and RV4CSL was, respectively, 62% and 56% in our population; however, when measurements were performed, intra- and inter-rater reliability based on the intraclass correlation coefficient were good to excellent. RV dysfunction based on TAPSE or RV s' was found in 56 patients (33%) and 24 patients (14%) had RV dysfunction based on RVFWSL or RV4CSL. In 14 patients (8%), RVFWSL, RV4CSL, or both were reduced, despite conventional RV function measurements being preserved. These patients had significantly higher severity of illness scores. Sensitivity analysis with fractional area change showed similar results. CONCLUSIONS: TDI RV strain imaging in critically ill patients is challenging; however, good-to-excellent reproducibility was shown when measurements were adequately obtained. Future studies are needed to elucidate the diagnostic and prognostic value of RV strain in critically ill patients, especially to outweigh the difficulty and effort of imaging against the clinical value.

Calculated left ventricular outflow tract diameter for critically ill patients.

A fast and reliable left ventricular outflow diameter (LVOTd) estimation may aid in quickly estimating cardiac output. However, obtaining a correct LVOTd can be difficult in intensive care patients, potentially leading to errors and a cardiac output deviation. In this study, the measured LVOTd was compared with the expected LVOTd when estimated using an existing formula in 1177 critically ill patients. We show that estimated LVOTd based on baseline data can aid when obtaining LVOTd is difficult or impossible and simplified estimation based on a formula may allow for more reliable and accessible measurement of cardiac output.

The simple observational critical care studies: estimations by students, nurses, and physicians of in-hospital and 6-month mortality.

BACKGROUND: Prognostic assessments of the mortality of critically ill patients are frequently performed in daily clinical practice and provide prognostic guidance in treatment decisions. In contrast to several sophisticated tools, prognostic estimations made by healthcare providers are always available and accessible, are performed daily, and might have an additive value to guide clinical decision-making. The aim of this study was to evaluate the accuracy of students', nurses', and physicians' estimations and the association of their combined estimations with in-hospital mortality and 6-month follow-up. METHODS: The Simple Observational Critical Care Studies is a prospective observational single-center study in a tertiary teaching hospital in the Netherlands. All patients acutely admitted to the intensive care unit were included. Within 3 h of admission to the intensive care unit, a medical or nursing student, a nurse, and a physician independently predicted in-hospital and 6-month mortality. Logistic regression was used to assess the associations between predictions and the actual outcome; the area under the receiver operating characteristics (AUROC) was calculated to estimate the discriminative accuracy of the students, nurses, and physicians. RESULTS: In 827 out of 1,010 patients, in-hospital mortality rates were predicted to be 11%, 15%, and 17% by medical students, nurses, and physicians, respectively. The estimations of students, nurses, and physicians were all associated with in-hospital mortality (OR 5.8, 95% CI [3.7, 9.2], OR 4.7, 95% CI [3.0, 7.3], and OR 7.7 95% CI [4.7, 12.8], respectively). Discriminative accuracy was moderate for all students, nurses, and physicians (between 0.58 and 0.68). When more estimations were of non-survival, the odds of non-survival increased (OR 2.4 95% CI [1.9, 3.1]) per additional estimate, AUROC 0.70 (0.65, 0.76). For 6-month mortality predictions, similar results were observed. CONCLUSIONS: Based on the initial examination, students, nurses, and physicians can only moderately predict in-hospital and 6-month mortality in critically ill patients. Combined estimations led to more accurate predictions and may serve as an example of the benefit of multidisciplinary clinical care and future research efforts.

Fluid balance-adjusted creatinine in diagnosing acute kidney injury in the critically ill.

BACKGROUND: Acute kidney injury (AKI) is often diagnosed based on plasma creatinine (Cr) only. Adjustment of Cr for cumulative fluid balance due to potential dilution of Cr and subsequently missed Cr-based diagnosis of AKI has been suggested, albeit the physiological rationale for these adjustments is questionable. Furthermore, whether these adjustments lead to a different incidence of AKI when used in conjunction with urine output (UO) criteria is unknown. METHODS: This was a post hoc analysis of the Finnish Acute Kidney Injury study. Hourly UO and daily plasma Cr were measured during the first 5 days of intensive care unit admission. Cr values were adjusted following the previously used formula and combined with the UO criteria. Resulting incidences and mortality rates were compared with the results based on unadjusted values. RESULTS: In total, 2044 critically ill patients were analyzed. The mean difference between the adjusted and unadjusted Cr of all 7279 observations was 5 (±15) µmol/L. Using adjusted Cr in combination with UO and renal replacement therapy criteria resulted in the diagnosis of 19 (1%) additional AKI patients. The absolute difference in the incidence was 0.9% (95% confidence interval [CI]: 0.3%-1.6%). Mortality rates were not significantly different between the reclassified AKI patients using the full set of Kidney Disease: Improving Global Outcomes criteria. CONCLUSION: Fluid balance-adjusted Cr resulted in little change in AKI incidence, and only minor differences in mortality between patients who changed category after adjustment and those who did not. Using adjusted Cr values to diagnose AKI does not seem worthwhile in critically ill patients.

Fluid management in patients with acute kidney injury - A post-hoc analysis of the FINNAKI study.

PURPOSE: Whether positive fluid balance among patients with acute kidney injury (AKI) stems from decreased urine output, overzealous fluid administration, or both is poorly characterized. MATERIALS AND METHODS: This was a post hoc analysis of the prospective multicenter observational Finnish Acute Kidney Injury study including 824 AKI and 1162 non-AKI critically ill patients. RESULTS: We matched 616 AKI (diagnosed during the three first intensive care unit (ICU) days) and non-AKI patients using propensity score. During the three first ICU days, AKI patients received median [IQR] of 11.4 L [8.0-15.2]L fluids and non-AKI patients 10.2 L [7.5-13.7]L, p < 0.001 while the fluid output among AKI patients was 4.7 L [3.0-7.2]L and among non-AKI patients 5.8 L [4.1-8.0]L, p < 0.001. In AKI patients, the median [IQR] cumulative fluid balance was 2.5 L [-0.2-6.0]L compared to 0.9 L [-1.4-3.6]L among non-AKI patients, p < 0.001. Among the 824 AKI patients, smaller volumes of fluid input with a multivariable OR of 0.90 (0.88-0.93) and better fluid output (multivariable OR 1.12 (1.07-1.18)) associated with enhanced change of resolution of AKI. CONCLUSIONS: AKI patients received more fluids albeit having lower fluid output compared to matched critically ill non-AKI patients. Smaller volumes of fluid input and higher fluid output were associated with better AKI recovery.

Incidence, prognostic factors, and outcomes of venous thromboembolism in critically ill patients: data from two prospective cohort studies.

BACKGROUND: The objective of this study was to describe the prevalence, incidence, prognostic factors, and outcomes of venous thromboembolism in critically ill patients receiving contemporary thrombosis prophylaxis. METHODS: We conducted a pooled analysis of two prospective cohort studies. The outcomes of interest were in-hospital pulmonary embolism or lower extremity deep vein thrombosis (PE-LDVT), in-hospital nonleg deep vein thrombosis (NLDVT), and 90-day mortality. Multivariable logistic regression analysis was used to evaluate the association between predefined baseline prognostic factors and PE-LDVT or NLDVT. Cox regression analysis was used to evaluate the association between PE-LDVT or NLDVT and 90-day mortality. RESULTS: A total of 2208 patients were included. The prevalence of any venous thromboembolism during 3 months before ICU admission was 3.6% (95% CI 2.8-4.4%). Out of 2166 patients, 47 (2.2%; 95% CI 1.6-2.9%) developed PE-LDVT and 38 patients (1.8%; 95% CI 1.2-2.4%) developed NLDVT. Renal replacement therapy (OR 3.5 95% CI 1.4-8.6), respiratory failure (OR 2.0; 95% CI 1.1-3.8), and previous VTE (OR 3.6; 95% CI 1.7-7.7) were associated with PE-LDVT. Central venous catheters (OR 5.4; 95% CI 1.7-17.8) and infection (OR 2.2; 95% CI 1.1-4.3) were associated with NLDVT. Occurrence of PE-LDVT but not NLDVT was associated with increased 90-day mortality (HR 2.7; 95% CI 1.6-4.6, respectively, 0.92; 95% CI 0.41-2.1). CONCLUSION: Thrombotic events are common in critically ill patients, both before and after ICU admittance. Development of PE-LDVT but not NLDVT was associated with increased mortality. Prognostic factors for developing PE-LDVT or NLDVT despite prophylaxis can be identified at ICU admission and may be used to select patients at higher risk in future randomized clinical trials. TRIAL REGISTRATION: NCT03773939.

Temporal artery temperature measurements versus bladder temperature in critically ill patients, a prospective observational study.

PURPOSE: Accurate measurement of body temperature is important for the timely detection of fever or hypothermia in critically ill patients. In this prospective study, we evaluated whether the agreement between temperature measurements obtained with TAT (test method) and bladder catheter-derived temperature measurements (BT; reference method) is sufficient for clinical practice in critically ill patients. METHODS: Patients acutely admitted to the Intensive Care Unit were included. After BT was recorded TAT measurements were performed by two independent researchers (TAT1; TAT2). The agreement between TAT and BT was assessed using Bland-Altman plots. Clinical acceptable limits of agreement (LOA) were defined a priori (<0.5°C). Subgroup analysis was performed in patients receiving norepinephrine. RESULTS: In total, 90 critically ill patients (64 males; mean age 62 years) were included. The observed mean difference (TAT-BT; ±SD, 95% LOA) between TAT and BT was 0.12°C (-1.08°C to +1.32°C) for TAT1 and 0.14°C (-1.05°C to +1.33°C) for TAT2. 36% (TAT1) and 42% (TAT2) of all paired measurements failed to meet the acceptable LOA of 0.5°C. Subgroup analysis showed that when patients were receiving intravenous norepinephrine, the measurements of the test method deviated more from the reference method (p = NS). CONCLUSION: The TAT is not sufficient for clinical practice in critically ill adults.

Bundled care in acute kidney injury in critically ill patients, a before-after educational intervention study.

BACKGROUND: Acute kidney injury (AKI) often occurs in critically ill patients. AKI is associated with mortality and morbidity. Interventions focusing on the reduction of AKI are suggested by the Kidney Disease: Improving Global Outcomes guideline. We hypothesized that these educational interventions would improve outcome in patients admitted to the Intensive Care Unit (ICU). METHODS: This was a pragmatic single-centre prospective observational before-after study design in an ICU in a tertiary referral hospital. All consecutive patients admitted to the ICU irrespective their illness were included. A 'Save the Kidney' (STK) bundle was encouraged via an educational intervention targeting health care providers. The educational STK bundle consisted of optimizing the fluid balance (based on urine output, serum lactate levels and/or central venous oxygen saturation), discontinuation of diuretics, maintaining a mean arterial pressure of at least 65 mmHg with the potential use of vasopressors and critical evaluation of the indication and dose of nephrotoxic drugs. The primary outcome was the composite of mortality, renal replacement therapy (RRT), and progression of AKI. Secondary outcomes were the components of the composite outcome the severity of AKI, ICU length of stay and in-hospital mortality. MAIN RESULTS: The primary outcome occurred in 451 patients (33%) in the STK group versus 375 patients (29%) in the usual care group, relative risk (RR) 1.16, 95% confidence interval (CI) 1.03-1.3, p < 0.001. Secondary outcomes were, ICU mortality in 6.8% versus 5.6%, (RR 1.22, 95% CI 0.90-1.64, p = 0.068), RRT in 1.6% versus 3.6% (RR 0.46, 95% CI 0.28-0.76, p = 0.002), and AKI progression in 28% versus 24% (RR 1.18, 95% CI 1.04-1.35, p = 0.001). CONCLUSIONS: Providing education to uniformly apply an AKI care bundle, without measurement of the implementation in a non-selected ICU population, targeted at prevention of AKI progression was not beneficial.

Diagnostic accuracy of arterial and venous renal Doppler assessment for acute kidney injury in critically ill patients: A prospective study.

BACKGROUND AND PURPOSE: Renal Resistive Index (RRI) and Venous Impedance Index (VII) might be of additional value for diagnosing Acute Kidney Injury (AKI). The purpose of this study was to assess the diagnostic accuracy of RRI and VII for AKI. MATERIALS AND METHODS: In the prospective Simple Intensive Care Studies-II (NCT03577405), we measured RRI and VII in acutely admitted adult intensive care patients within 24 h of admission. AKI was defined by the Kidney Disease Improving Global Outcome (KDIGO) criteria. The primary outcome was persistent AKI, defined as non-resolved AKI on day three. We tested specificity, sensitivity and diagnostic accuracy of both RRI and VII for persistent AKI. RESULTS: In total, 371 patients were included of whom 123 patients (33%) had persistent AKI. RRI and VII did not differ between patients with and those without persistent AKI (p = .08 and p = .59). RRI had a moderate specificity (72%, 95%CI 66-78%) and low sensitivity (32%, 95%CI 24-41%) and VII had high sensitivity (93%, 95%CI 85-98%) and low specificity (11%, 95%CI 6-16%) for persistent AKI. Overall diagnostic accuracy of RRI and VII was moderate. CONCLUSIONS: In acutely admitted critically ill patients, measures of renal perfusion by renal ultrasound were not different between patients with and without AKI, and show limited diagnostic accuracy for AKI. Registered:NCT03577405.

Different applications of the KDIGO criteria for AKI lead to different incidences in critically ill patients: a post hoc analysis from the prospective observational SICS-II study.

BACKGROUND: Acute kidney injury (AKI) is a frequent and clinically relevant problem in critically ill patients. Various randomized controlled trials (RCT) have attempted to assess potentially beneficial treatments for AKI. Different approaches to applying the Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI make a comparison of studies difficult. The objective of this study was to assess how different approaches may impact estimates of AKI incidence and whether the association between AKI and 90-day mortality varied by the approach used. METHODS: Consecutive acutely admitted adult intensive care patients were included in a prospective observational study. AKI was determined following the KDIGO criteria during the first 7 days of ICU admission. In this post hoc analysis, we assessed whether AKI incidence differed when applying the KDIGO criteria in 30 different possible methods, varying in (A) serum creatinine (sCr), (B) urine output (UO), and (C) the method of combining these two into an outcome, e.g., severe AKI. We assessed point estimates and 95% confidence intervals for each incidence. Univariable regression was used to assess the associations between AKI and 90-day mortality. RESULTS: A total of 1010 patients were included. Baseline creatinine was available in 449 (44%) patients. The incidence of any AKI ranged from 28% (95%CI 25-31%) to 75% (95%CI 72-77%) depending on the approach used. Methods to estimate missing baseline sCr caused a variation in AKI incidence up to 15%. Different methods of handling UO caused a variation of up to 35%. At 90 days, 263 patients (26%) had died, and all 30 variations were associated with 90-day mortality. CONCLUSIONS: In this cohort of critically ill patients, AKI incidence varied from 28 to 75%, depending on the method used of applying the KDIGO criteria. A tighter adherence to KDIGO definitions is warranted to decrease the heterogeneity of AKI and increase the comparability of future studies.

Two subphenotypes of septic acute kidney injury are associated with different 90-day mortality and renal recovery.

BACKGROUND: The pathophysiology of septic acute kidney injury is inadequately understood. Recently, subphenotypes for sepsis and AKI have been derived. The objective of this study was to assess whether a combination of comorbidities, baseline clinical data, and biomarkers could classify meaningful subphenotypes in septic AKI with different outcomes. METHODS: We performed a post hoc analysis of the prospective Finnish Acute Kidney Injury (FINNAKI) study cohort. We included patients admitted with sepsis and acute kidney injury during the first 48 h from admission to intensive care (according to Kidney Disease Improving Global Outcome criteria). Primary outcomes were 90-day mortality and renal recovery on day 5. We performed latent class analysis using 30 variables obtained on admission to classify subphenotypes. Second, we used logistic regression to assess the association of derived subphenotypes with 90-day mortality and renal recovery on day 5. RESULTS: In total, 301 patients with septic acute kidney injury were included. Based on the latent class analysis, a two-class model was chosen. Subphenotype 1 was assigned to 133 patients (44%) and subphenotype 2 to 168 patients (56%). Increased levels of inflammatory and endothelial injury markers characterized subphenotype 2. At 90 days, 29% of patients in subphenotype 1 and 41% of patients in subphenotype 2 had died. Subphenotype 2 was associated with a lower probability of short-term renal recovery and increased 90-day mortality. CONCLUSIONS: In this post hoc analysis, we identified two subphenotypes of septic acute kidney injury with different clinical outcomes. Future studies are warranted to validate the suggested subphenotypes of septic acute kidney injury.

Non-invasive oscillometric versus invasive arterial blood pressure measurements in critically ill patients: A post hoc analysis of a prospective observational study.

PURPOSE: The aim was to compare non-invasive blood pressure measurements with invasive blood pressure measurements in critically ill patients. METHODS: Non-invasive blood pressure was measured via automated brachial cuff oscillometry, and simultaneously the radial arterial catheter-derived measurement was recorded as part of a prospective observational study. Measurements of systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and mean arterial pressure (MAP) were compared using Bland-Altman and error grid analyses. RESULTS: Paired measurements of blood pressure were available for 736 patients. Observed mean difference (±SD, 95% limits of agreement) between oscillometrically and invasively measured blood pressure was 0.8 mmHg (±15.7 mmHg, -30.2 to 31.7 mmHg) for SAP, -2.9 mmHg (±11.0 mmHg, -24.5 to 18.6 mmHg) for DAP, and -1.0 mmHg (±10.2 mmHg, -21.0 to 18.9 mmHg) for MAP. Error grid analysis showed that the proportions of measurements in risk zones A to E were 78.3%, 20.7%, 1.0%, 0%, and 0.1% for MAP. CONCLUSION: Non-invasive blood pressure measurements using brachial cuff oscillometry showed large limits of agreement compared to invasive measurements in critically ill patients. Error grid analysis showed that measurement differences between oscillometry and the arterial catheter would potentially have triggered at least low-risk treatment decisions in one in five patients.

Should the ultrasound probe replace your stethoscope? A SICS-I sub-study comparing lung ultrasound and pulmonary auscultation in the critically ill.

BACKGROUND: In critically ill patients, auscultation might be challenging as dorsal lung fields are difficult to reach in supine-positioned patients, and the environment is often noisy. In recent years, clinicians have started to consider lung ultrasound as a useful diagnostic tool for a variety of pulmonary pathologies, including pulmonary edema. The aim of this study was to compare lung ultrasound and pulmonary auscultation for detecting pulmonary edema in critically ill patients. METHODS: This study was a planned sub-study of the Simple Intensive Care Studies-I, a single-center, prospective observational study. All acutely admitted patients who were 18 years and older with an expected ICU stay of at least 24 h were eligible for inclusion. All patients underwent clinical examination combined with lung ultrasound, conducted by researchers not involved in patient care. Clinical examination included auscultation of the bilateral regions for crepitations and rhonchi. Lung ultrasound was conducted according to the Bedside Lung Ultrasound in Emergency protocol. Pulmonary edema was defined as three or more B lines in at least two (bilateral) scan sites. An agreement was described by using the Cohen κ coefficient, sensitivity, specificity, negative predictive value, positive predictive value, and overall accuracy. Subgroup analysis were performed in patients who were not mechanically ventilated. RESULTS: The Simple Intensive Care Studies-I cohort included 1075 patients, of whom 926 (86%) were eligible for inclusion in this analysis. Three hundred seven of the 926 patients (33%) fulfilled the criteria for pulmonary edema on lung ultrasound. In 156 (51%) of these patients, auscultation was normal. A total of 302 patients (32%) had audible crepitations or rhonchi upon auscultation. From 130 patients with crepitations, 86 patients (66%) had pulmonary edema on lung ultrasound, and from 209 patients with rhonchi, 96 patients (46%) had pulmonary edema on lung ultrasound. The agreement between auscultation findings and lung ultrasound diagnosis was poor (κ statistic 0.25). Subgroup analysis showed that the diagnostic accuracy of auscultation was better in non-ventilated than in ventilated patients. CONCLUSION: The agreement between lung ultrasound and auscultation is poor. TRIAL REGISTRATION: NCT02912624. Registered on September 23, 2016.

Feasibility of cardiac output measurements in critically ill patients by medical students.

BACKGROUND: Critical care ultrasonography (CCUS) is increasingly applied also in the intensive care unit (ICU) and performed by non-experts, including even medical students. There is limited data on the training efforts necessary for novices to attain images of sufficient quality. There is no data on medical students performing CCUS for the measurement of cardiac output (CO), a hemodynamic variable of importance for daily critical care. OBJECTIVE: The aim of this study was to explore the agreement of cardiac output measurements as well as the quality of images obtained by medical students in critically ill patients compared to the measurements obtained by experts in these images. METHODS: In a prospective observational cohort study, all acutely admitted adults with an expected ICU stay over 24 h were included. CCUS was performed by students within 24 h of admission. CCUS included the images required to measure the CO, i.e., the left ventricular outflow tract (LVOT) diameter and the velocity time integral (VTI) in the LVOT. Echocardiography experts were involved in the evaluation of the quality of images obtained and the quality of the CO measurements. RESULTS: There was an opportunity for a CCUS attempt in 1155 of the 1212 eligible patients (95%) and in 1075 of the 1212 patients (89%) CCUS examination was performed by medical students. In 871 out of 1075 patients (81%) medical students measured CO. Experts measured CO in 783 patients (73%). In 760 patients (71%) CO was measured by both which allowed for comparison; bias of CO was 0.0 L min-1 with limits of agreement of - 2.6 L min-1 to 2.7 L min-1. The percentage error was 50%, reflecting poor agreement of the CO measurement by students compared with the experts CO measurement. CONCLUSIONS: Medical students seem capable of obtaining sufficient quality CCUS images for CO measurement in the majority of critically ill patients. Measurements of CO by medical students, however, had poor agreement with expert measurements. Experts remain indispensable for reliable CO measurements. Trial registration Clinicaltrials.gov; http://www.clinicaltrials.gov; registration number NCT02912624.

Plasma neutrophil gelatinase-associated lipocalin at intensive care unit admission as a predictor of acute kidney injury progression.

BACKGROUND: Acute kidney injury (AKI) is a common complication in patients during intensive care unit (ICU) admission. AKI is defined as an increase in serum creatinine (SCr) and/or a reduction in urine output. SCr is a marker of renal function with several limitations, which led to the search for biomarkers for earlier AKI detection. Our aim was to study the predictive value of plasma neutrophil gelatinase-associated lipocalin (NGAL) at admission as a biomarker for AKI progression during the first 48 h of ICU admission in an unselected, heterogeneous ICU patient population. METHODS: We conducted a prospective observational study in an academic tertiary referral ICU population. We recorded AKI progression in all ICU patients during the first 48 h of ICU admission in a 6-week period. Plasma NGAL was measured at admission but levels were not reported to the attending clinicians. As possible predictors of AKI progression, pre-existing AKI risk factors were recorded. We examined the association of clinical parameters and plasma NGAL levels at ICU admission with the incidence and progression of AKI within the first 48 h of the ICU stay. RESULTS: A total of 361 patients were included. Patients without AKI progression during the first 48 h of ICU admission had median NGAL levels at admission of 115 ng/mL [interquartile range (IQR) 81-201]. Patients with AKI progression during the first 48 h of ICU admission had median NGAL levels at admission of 156 ng/mL (IQR 97-267). To predict AKI progression, a multivariant model with age, sex, diabetes mellitus, body mass index, admission type, Acute Physiology and Chronic Health Evaluation score and SCr at admission had an area under the receiver operating characteristics (ROC) curve of 0.765. Adding NGAL to this model showed a small increase in the area under the ROC curve to 0.783 (95% confidence interval 0.714-0.853). CONCLUSIONS: NGAL levels at admission were higher in patients with progression of AKI during the first 48 h of ICU admission, but adding NGAL levels at admission to a model predicting this AKI progression showed no significant additive value.

Clinical examination findings as predictors of acute kidney injury in critically ill patients.

BACKGROUND: Acute Kidney Injury (AKI) in critically ill patients is associated with a markedly increased morbidity and mortality. The aim of this study was to establish the predictive value of clinical examination for AKI in critically ill patients. METHODS: This was a sub-study of the SICS-I, a prospective observational cohort study of critically ill patients acutely admitted to the Intensive Care Unit (ICU). Clinical examination was performed within 24 hours of ICU admission. The occurrence of AKI was determined at day two and three after admission according to the KDIGO definition including serum creatinine and urine output. Multivariable regression modeling was used to assess the value of clinical examination for predicting AKI, adjusted for age, comorbidities and the use of vasopressors. RESULTS: A total of 1003 of 1075 SICS-I patients (93%) were included in this sub-study. 414 of 1003 patients (41%) fulfilled the criteria for AKI. Increased heart rate (OR 1.12 per 10 beats per minute increase, 98.5% CI 1.04-1.22), subjectively cold extremities (OR 1.52, 98.5% CI 1.07-2.16) and a prolonged capillary refill time on the sternum (OR 1.89, 98.5% CI 1.01-3.55) were associated with AKI. This multivariable analysis yielded an area under the receiver-operating curve (AUROC) of 0.70 (98.5% CI 0.66-0.74). The model performed better when lactate was included (AUROC of 0.72, 95%CI 0.69-0.75), P = .04. CONCLUSION: Clinical examination findings were able to predict AKI with moderate accuracy in a large cohort of critically ill patients. Findings of clinical examination on ICU admission may trigger further efforts to help predict developing AKI.

Mortality prediction models in the adult critically ill: A scoping review.

BACKGROUND: Mortality prediction models are applied in the intensive care unit (ICU) to stratify patients into different risk categories and to facilitate benchmarking. To ensure that the correct prediction models are applied for these purposes, the best performing models must be identified. As a first step, we aimed to establish a systematic review of mortality prediction models in critically ill patients. METHODS: Mortality prediction models were searched in four databases using the following criteria: developed for use in adult ICU patients in high-income countries, with mortality as primary or secondary outcome. Characteristics and performance measures of the models were summarized. Performance was presented in terms of discrimination, calibration and overall performance measures presented in the original publication. RESULTS: In total, 43 mortality prediction models were included in the final analysis. In all, 15 models were only internally validated (35%), 13 externally (30%) and 10 (23%) were both internally and externally validated by the original researchers. Discrimination was assessed in 42 models (98%). Commonly used calibration measures were the Hosmer-Lemeshow test (60%) and the calibration plot (28%). Calibration was not assessed in 11 models (26%). Overall performance was assessed in the Brier score (19%) and the Nagelkerke's R2 (4.7%). CONCLUSIONS: Mortality prediction models have varying methodology, and validation and performance of individual models differ. External validation by the original researchers is often lacking and head-to-head comparisons are urgently needed to identify the best performing mortality prediction models for guiding clinical care and research in different settings and populations.

Clinical Examination for the Prediction of Mortality in the Critically Ill: The Simple Intensive Care Studies-I.

OBJECTIVES: Caregivers use clinical examination to timely recognize deterioration of a patient, yet data on the prognostic value of clinical examination are inconsistent. In the Simple Intensive Care Studies-I, we evaluated the association of clinical examination findings with 90-day mortality in critically ill patients. DESIGN: Prospective single-center cohort study. SETTING: ICU of a single tertiary care level hospital between March 27, 2015, and July 22, 2017. PATIENTS: All consecutive adults acutely admitted to the ICU and expected to stay for at least 24 hours. INTERVENTIONS: A protocolized clinical examination of 19 clinical signs conducted within 24 hours of admission. MEASUREMENTS MAIN RESULTS: Independent predictors of 90-day mortality were identified using multivariable logistic regression analyses. Model performance was compared with established prognostic risk scores using area under the receiver operating characteristic curves. Robustness of our findings was tested by internal bootstrap validation and adjustment of the threshold for statistical significance. A total of 1,075 patients were included, of whom 298 patients (28%) had died at 90-day follow-up. Multivariable analyses adjusted for age and norepinephrine infusion rate demonstrated that the combination of higher respiratory rate, higher systolic blood pressure, lower central temperature, altered consciousness, and decreased urine output was independently associated with 90-day mortality (area under the receiver operating characteristic curves = 0.74; 95% CI, 0.71-0.78). Clinical examination had a similar discriminative value as compared with the Simplified Acute Physiology Score-II (area under the receiver operating characteristic curves = 0.76; 95% CI, 0.73-0.79; p = 0.29) and Acute Physiology and Chronic Health Evaluation-IV (using area under the receiver operating characteristic curves = 0.77; 95% CI, 0.74-0.80; p = 0.16) and was significantly better than the Sequential Organ Failure Assessment (using area under the receiver operating characteristic curves = 0.67; 95% CI, 0.64-0.71; p < 0.001). CONCLUSIONS: Clinical examination has reasonable discriminative value for assessing 90-day mortality in acutely admitted ICU patients. In our study population, a single, protocolized clinical examination had similar prognostic abilities compared with the Simplified Acute Physiology Score-II and Acute Physiology and Chronic Health Evaluation-IV and outperformed the Sequential Organ Failure Assessment score.