Initial lactate levels linked to oliguria in term neonates with perinatal asphyxia.

BACKGROUND: Oliguria is a sign of impaired kidney function and has been shown to be an early predictor of adverse prognoses in patients with acute kidney injury. The relationship between urine output (UOP) and early lactate levels in neonates with perinatal asphyxia (PA) has not been extensively explored. This study aimed to investigate the link between oliguria during the first 24 h of life and early lactate levels in neonates with PA. METHODS: The medical records of 293 term neonates with asphyxia from 9216 hospitalized newborns were retrospectively analyzed, including 127 cases designated as the oliguria group and 166 cases as controls. Peripheral arterial blood gas after PA and UOP within 24 h after birth were analyzed. Logistic regression analyses and receiver operating characteristic curve analysis were conducted. RESULTS: Oliguria occurred in 43.34% of neonates with PA. The median UOP of the oliguria and control groups were 0.65 and 1.46 mL/kg/h, respectively. Elevated lactate levels after PA are an independent risk factor for oliguria in the following 24 h (p = 0.01; OR: 1.19; 95%CI: 1.04-1.35) and show a moderate discriminatory power for oliguria (AUC = 0.62). Using a cut off value of 8.15 mmol/L, the positive and negative predictive values and the specificity were 59.34%, 63.86%, and 78.30%, respectively. CONCLUSION: Neonates with elevated lactate levels after PA face a risk of oliguria in the following 24 h. Based on early elevated lactate levels after resuscitation, especially ≥ 8.15 mmol/L, meticulously monitoring UOP will allow this vulnerable population to receive early, tailored fluid management and medical intervention.

CCL14 Predicts Oliguria and Dialysis Requirement in Patients with Moderate to Severe Acute Kidney Injury.

INTRODUCTION: AKI is a frequent complication of critical illness and portends poor outcome. CCL14 is a validated predictor of persistent severe AKI in critically ill patients. We examined the association of CCL14 with urine output within 48 h. METHODS: In pooled data from 2 studies of critically ill patients with KDIGO stage 2-3 AKI, CCL14 was measured by NEPHROCLEAR™ CCL14 Test on the Astute 140® Meter (low, intermediate, and high categories [1.3 and 13 ng/mL]). Average hourly urine output over 48 h, stage 3 AKI per urine output criterion on day 2, and composite of dialysis or death within 7 days were examined using multivariable mixed and logistic regression models. RESULTS: Of the 497 subjects with median age of 65 (56-74) years, 49% (242/497) were on diuretics. CCL14 concentration was low in 219 (44%), intermediate in 217 (44%), and high in 61 (12%) patients. In mixed regression analysis, hourly urine output over time was different within each CCL14 risk category based on diuretic use due to significant three-way interaction (p < 0.001). In logistic regression analysis, CCL14 risk category was independently associated with low urine output on day 2 per KDIGO stage 3 (adjusted for diuretic use and baseline clinical variables), and composite of dialysis or death within 7 days (adjusted for urine output within 48 h of CCL14 measurement). CONCLUSIONS: CCL14 measured in patients with moderate to severe AKI is associated with urine output trajectory within 48 h, oliguria on day 2, and dialysis within 7 days.

Focus on oliguria during renal replacement therapy.

Oliguria is a clinical symptom characterized by decreased urine output, which can occur at any stage of acute kidney injury and also during renal replacement therapy. In some cases, oliguria may resolve with adjustment of blood purification dose or fluid management, while in others, it may suggest a need for further evaluation and intervention. It is important to determine the underlying cause of oliguria during renal replacement therapy and to develop an appropriate treatment plan. This review looks into the mechanisms of urine production to investigate the mechanism of oliguria during renal replacement therapy from two aspects: diminished glomerular filtration rate and tubular abnormalities. The above conditions all implying a renal oxygen supply-demand imbalance, which is the signal of worsening kidney injury. It also proposes a viable clinical pathway for the treatment and management of patients with acute kidney injury receiving renal replacement therapy.

The role of the bladder diary in phenotyping men with LUTS.

AIMS: The aim of this study was to compare the clinical characteristics of men with lower urinary tract symptoms (LUTS) grouped by 24-h urine output determined from a bladder voiding diary. METHODS: An online database was queried to identify men who completed a 24-hour bladder diary (24HBD), and the Lower Urinary Tract Symptom Score (LUTSS) questionnaire from 2015 to 2019 using a mobile app. Data from the bladder diary and questionnaire were contemporaneously matched within a 2-week period. Additional data, including maximum uroflow (Qmax ) and postvoid residual urine (PVR), were obtained from the electronic medical record (EMR). The cohort was divided into three groups: normal, oliguria, and polyuria based on their 24-hour voided volume (24HVV). The LUTSS, 24HVV, maximum voided volume (MVV), maximum flow rate (Qmax ), and PVR were compared between those with oliguria and polyuria. RESULTS: A total of 327 men (mean age 62, SD: 19) completed the LUTSS questionnaire and contemporaneous 24HBD. Of these, 61% had a normal 24HVV, 13% had oliguria, and 26% had polyuria. A total of 147 patients from the study cohort had contemporaneous Qmax and PVR abstracted from the EMR. There was no difference in symptom severity, bother, or PVR among the three patient groups. However, several objective metrics were significantly correlated with urine output. Men with oliguria, as compared to men with polyuria were older (65 vs. 55 years) and had lower MVV (260 vs. 470 mL), fewer voids/24 h (8 vs. 13), and lower Qmax (8.5 vs. 18.3 mL/s). CONCLUSIONS: These observations suggest that men with oliguria or polyuria and LUTS constitute easily distinguished phenotypes that might require different diagnostic and therapeutic algorithms. Those with oliguria were older, and had lower MVVs and much lower uroflows, suggesting that they are more likely to have underlying disorders such as bladder outlet obstruction and detrusor underactivity or may be patients with overactive bladder who reduced fluid intake to improve symptoms.

Identification of an optimal threshold to define oliguria in critically ill patients: an observational study.

BACKGROUND: The relevance of current consensus threshold to define oliguria has been challenged by small observational studies. We aimed to determine the optimal threshold to define oliguria in critically-ill patients. METHODS: Cohort study including adult patients admitted within a multi-disciplinary intensive care unit between January 1st 2010 and June 15th 2020. Patients on chronic dialysis or who declined consent were excluded. We extracted hourly urinary output (UO) measurements along with patient's characteristics from electronic medical records and 90-day mortality from the Swiss national death registry. We randomly split our data into a training (80%) and a validation (20%) set. In the training set, we developed multivariable models to assess the relationship between 90-day mortality and the minimum average UO calculated over time windows of 3, 6, 12 and 24 h. Optimal thresholds were determined by visually identifying cut-off values for the minimum average UO below which predicted mortality increased substantially. We tested models' discrimination and calibration on the entire validation set as well as on a subset of patients with oliguria according to proposed thresholds. RESULTS: Among the 15,500 patients included in this analysis (training set: 12,440, validation set: 3110), 73.0% (95% CI [72.3-73.8]) presented an episode of oliguria as defined by consensus criteria (UO < 0.5 ml/kg/h for 6 h). Our models had excellent (AUC > 85% for all time windows) discrimination and calibration. The relationship between minimum average UO and predicted 90-day mortality was nonlinear with an inflexion point at 0.2 ml/kg/h for 3 and 6 h windows and 0.3 ml/kg/h for 12 and 24 h windows. Considering a threshold of < 0.2 ml/kg/h over 6 h, the proportion of patients with an episode of oliguria decreased substantially to 24.7% (95% CI [24.0-25.4]). Contrary to consensus definition, this threshold identified a population with a higher predicted 90-day mortality. CONCLUSIONS: The widely used cut-off for oliguria of 0.5 ml/kg/h over 6 h may be too conservative. A cut-off of 0.2 ml/kg/h over 3 or 6 h is supported by the data and should be considered in further definitions of oliguria.

Tocilizumab Associated With Survival in Patients Hospitalized for COVID-19 Acute Respiratory Distress Syndrome and Low Urine Output.

BACKGROUND: Acute respiratory distress syndrome (ARDS) with oliguria is associated with increased mortality. Interleukin-6 (IL-6) plays an integral role in the pathophysiology of both disease processes. Patients who experience severe COVID-19 have demonstrated higher IL-6 levels compared to baseline, and use of tocilizumab has demonstrated efficacy in such cohorts. We set out to investigate the relationship between tocilizumab use, COVID-19 ARDS, low urine output, and mortality. METHODS: Retrospective cohort review of adult patients aged ≥ 18 years with COVID-19 and moderate or severe ARDS, admitted to the intensive care unit (ICU) of a tertiary referral center in metropolitan Detroit. Patients were analyzed based on presence of oliguria (defined as ≤ 0.7 mL/kg/h) on the day of intubation and exposure to tocilizumab while inpatient. The primary outcome was inpatient mortality. RESULTS: One hundred and twenty-eight patients were analyzed, 103 (80%) with low urine output, of whom 30 (29%) received tocilizumab. In patients with low urine output, risk factors associated with mortality on univariate analysis included Black race (P = .028), lower static compliance (P = .015), and tocilizumab administration (P = .002). Tocilizumab (odds ratio 0.245, 95% confidence interval 0.079-0.764, P = .015) was the only risk factor independently associated with survival on multivariate logistic regression analysis. CONCLUSION: In this retrospective cohort review of patients hospitalized with COVID-19 and moderate or severe ARDS, tocilizumab administration was independently associated with survival in patients with low urine output ≤ 0.7 mL/kg/h on the day of intubation. Prospective studies are needed to investigate the impact of urine output on efficacy of interleukin-targeted therapies in the management of ARDS.

Early detection of oliguric events in critically ill patients in the ICU with a novel continuous urine flow measurement device: results of an initial validation study.

OBJECTIVES: Urine output is used to evaluate fluid status and is an important marker for acute kidney injury (AKI). Our primary aim was to validate a new automatic urine output monitoring device by comparison to the current practice - the standard urometer. METHODS: We conducted a prospective observational study in three ICUs. Urine flow measurements by Serenno Medical Automatic urine output measuring device (Serenno Medical, Yokneam, Israel) were compared to standard urometer readings taken automatically at 5-minutes intervals by a camera, and to hourly urometer readings by the nurses, both over 1 to 7 days. Our primary outcome was the difference between urine flow assessed by the Serenno device and reference camera-derived measurements (Camera). Our secondary outcome was the difference between urine flow assessed by the Serenno device and hourly nursing assessments (Nurse), and detection of oliguria. RESULTS: Thirty-seven patients completed the study, with 1,306 h of recording and a median of 25 measurement hours per patient. Bland and Altman analysis comparing the study device to camera measurements demonstrated good agreement, with a bias of -0.4 ml/h and 95% confidence intervals ranging from - 28 to 27ml/h. Concordance was 92%. The correlation between Camera and hourly nursing assessment of urine output was distinctly worse with a bias of 7.2 ml and limits of agreement extending from - 75 to + 107 ml. Severe oliguria (urine output < 0.3 ml/kg/h) lasting 2 h or more was common and observed in 8 (21%) of patients. Among the severe oliguric events lasting more than 3 consecutive hours, 6 (41%) were not detected or documented by the nursing staff. There were no device-related complications. CONCLUSION: The Serenno Medical Automatic urine output measuring device required minimal supervision, little ICU nursing staff attention, and is sufficiently accurate and precise. In addition to providing continuous assessments of urine output, it was considerably more accurate than hourly nursing assessments.

Association between intraoperative oliguria and postoperative acute kidney injury in non-cardiac surgical patients: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the association between intraoperative oliguria and the risk of postoperative acute kidney injury (AKI) in patients undergoing non-cardiac surgery. METHODS: The MEDLINE and EMBASE databases were searched up to August 2022 for studies in adult patients undergoing non-cardiac surgery, where the association between intraoperative urine output and the risk of postoperative AKI was assessed. Both randomised and non-randomised studies were eligible for inclusion. Study selection and risk of bias assessment were independently performed by two investigators. The risk of bias was evaluated using the Newcastle-Ottawa scale. We performed meta-analysis of the reported multivariate adjusted odds ratios for the association between intraoperative oliguria (defined as urine output < 0.5 mL/kg/hr) and the risk of postoperative AKI using the inverse-variance method with random effects models. We conducted sensitivity analyses using varying definitions of oliguria as well as by pooling unadjusted odds ratios to establish the robustness of the primary meta-analysis. We also conducted subgroup analyses according to surgery type and definition of AKI to explore potential sources of clinical or methodological heterogeneity. RESULTS: Eleven studies (total 49,252 patients from 11 observational studies including a post hoc analysis of a randomised controlled trial) met the selection criteria. Seven of these studies contributed data from a total 17,148 patients to the primary meta-analysis. Intraoperative oliguria was associated with a significantly elevated risk of postoperative AKI (pooled adjusted odds ratio [OR] 1.74; 95% confidence interval [CI] 1.36-2.23, p < 0.0001, 8 studies). Sensitivity analyses supported the robustness of the primary meta-analysis. There was no evidence of any significant subgroup differences according to surgery type or definition of AKI. CONCLUSIONS: This study demonstrated a significant association between intraoperative oliguria and the risk of postoperative AKI, regardless of the definitions of oliguria or AKI used. Further prospective and multi-centre studies using standardised definitions of intraoperative oliguria are required to define the thresholds of oliguria and establish strategies to minimise the risk of AKI.

Clinical algorithms for the management of intrapartum maternal urine abnormalities.

AIM: To develop evidence-based clinical algorithms for management of common intrapartum urinary abnormalities. POPULATION: Women with singleton, term pregnancies in active labour and immediate postnatal period, at low risk of complications. SETTING: Healthcare facilities in low- and middle-income countries. SEARCH STRATEGY: A systematic search and review were conducted on the current guidelines from WHO, NICE, ACOG and RCOG. Additional search was done on PubMed and The Cochrane Database of Systematic Reviews up to May 2020. CASE SCENARIOS: Four common intrapartum urinary abnormalities were selected: proteinuria, ketonuria, glycosuria and oliguria. Using reagent strip testing, glycosuria was defined as ≥2+ on one occasion or of ≥1+ on two or more occasions. Proteinuria was defined as ≥2+ and presence of ketone indicated ketonuria. Oliguria was defined as hourly urine output ≤30 ml. Thorough initial assessment using history, physical examination and basic investigations helped differentiate most of the underlying causes, which include diabetes mellitus, dehydration, sepsis, pre-eclampsia, shock, anaemia, obstructed labour, underlying cardiac or renal problems. A clinical algorithm was developed for each urinary abnormality to facilitate intrapartum management and referral of complicated cases for specialised care. CONCLUSIONS: Four simple, user-friendly and evidence-based clinical algorithms were developed to enhance intrapartum care of commonly encountered maternal urine abnormalities. These algorithms may be used to support healthcare professionals in clinical decision-making when handling normal and potentially complicated labour, especially in low resource countries. TWEETABLE ABSTRACT: Evidence-based clinical algorithms developed to guide intrapartum management of commonly encountered urinary abnormalities.

Non-interventional follow-up versus fluid bolus in RESPONSE to oliguria in hemodynamically stable critically ill patients: a randomized controlled pilot trial.

BACKGROUND: Fluid bolus therapy is a common intervention to improve urine output. Data concerning the effect of a fluid bolus on oliguria originate mainly from observational studies and remain controversial regarding the actual benefit of such therapy. We compared the effect of a follow-up approach without fluid bolus to a 500 mL fluid bolus on urine output in hemodynamically stable critically ill patients with oliguria at least for 2 h (urine output < 0.5 mL/kg/h) in randomized setting. METHODS: We randomized 130 patients in 1:1 fashion to receive either (1) non-interventional follow-up (FU) for 2 h or (2) 500 mL crystalloid fluid bolus (FB) administered over 30 min. The primary outcome was the proportion of patients who doubled their urine output, defined as 2-h urine output post-randomization divided by urine output 2 h pre-randomization. The outcomes were adjusted for the stratification variables (presence of sepsis or AKI) using two-tailed regression. Obtained odds ratios were converted to risk ratios (RR) with 95% confidence intervals (CI). The between-group difference in the continuous variables was compared using mean or median regression and expressed with 95% CIs. RESULTS: Altogether 10 (15.9%) of 63 patients in the FU group and 22 (32.8%) of 67 patients in FB group doubled their urine output during the 2-h period, RR (95% CI) 0.49 (0.23-0.71), P = 0.026. Median [IQR] change in individual urine output 2 h post-randomization compared to 2 h pre-randomization was - 7 [- 19 to 17] mL in the FU group and 19[0-53] mL in the FB group, median difference (95% CI) - 23 (- 36 to - 10) mL, P = 0.001. Median [IQR] duration of oliguria in the FU group was 4 [2-8] h and in the FB group 2 [0-6] h, median difference (95%CI) 2 (0-4) h, P = 0.038. Median [IQR] cumulative fluid balance on study day was lower in the FU group compared to FB group, 678 [518-1029] mL versus 1071 [822-1505] mL, respectively, median difference (95%CI) - 387 (- 635 to - 213) mL, P < 0.001. CONCLUSIONS: Follow-up approach to oliguria compared to administering a fluid bolus of 500 mL crystalloid in oliguric patients improved urine output less frequently but lead to lower cumulative fluid balance. Trial registration clinical. TRIALS: gov, NCT02860572. Registered 9 August 2016.

Improving awareness of kidney function through electronic urine output monitoring: a comparative study.

BACKGROUND: The current classification for acute kidney injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria integrates both serum creatinine (SCr) and urine output (UO). Most reports on AKI claim to use KDIGO guidelines but fail to include the UO criterion. It has been shown that patients who had intensive UO monitoring, with or without AKI, had significantly less cumulative fluid volume and fluid overload, reduced vasopressor use, and improved 30-day mortality. We examined whether real-time monitoring of this simple, sensitive, and easy-to-use biomarker in the ICU led to more appropriate intervention by healthcare providers and better outcomes.  METHODS: RenalSense Clarity RMS Consoles were installed in the General ICU at the Hadassah Medical Center, Israel, from December 2019 to November 2020. The Clarity RMS system continuously and electronically monitors UO in real-time. 100 patients were randomly selected from this period as the study group (UOelec) and compared to a matched control group (UOmanual) from the same period two years earlier. To test whether there was an association between oliguric hours and fluid treatment in each group, the correlation was calculated and analyzed for each of the different UO monitoring methods. RESULTS: Therapeutic intervention: The correlation of the sum of all oliguric hours on Day 1 and 2 with the sum of any therapeutic intervention (fluid bolus or furosemide) showed a significant correlation for the study group UOelec (P = 0.017). The matched control group UOmanual showed no such correlation (P = 0.932). Length of Stay (LOS): Median LOS [IQR] in the ICU of UOelec versus UOmanual was 69.46 [44.7, 125.9] hours and 116.5 [62.46, 281.3] hours, respectively (P = 0.0002). CONCLUSIONS: The results of our study strongly suggest that ICU patients had more meaningful and better medical intervention, and improved outcomes, with electronic UO monitoring than with manual monitoring.

Assessment of prognostic value of intraoperative oliguria for postoperative acute kidney injury: a retrospective cohort study.

BACKGROUND: Oliguria is often viewed as a sign of renal hypoperfusion and an indicator for volume expansion during surgery. However, the prognostic association and the predictive utility of intraoperative oliguria for postoperative acute kidney injury (AKI) are unclear. METHODS: We conducted a retrospective cohort study on patients undergoing major thoracic surgery in an academic hospital to assess the association of intraoperative oliguria with postoperative AKI and its predictive value. To contextualise our findings, we included our results in a meta-analysis of observational studies on the importance of oliguria during noncardiac surgery. RESULTS: In our cohort study, 3862 patients were included; 205 (5.3%) developed AKI after surgery. Intraoperative urine output of 0.3 ml kg-1 h-1 was the optimal threshold for oliguria in multivariable analysis. Patients with oliguria had an increased risk of AKI (adjusted odds ratio: 2.60; 95% confidence interval: 1.24-5.05). However, intraoperative oliguria had a sensitivity of 5.9%, specificity of 98%, positive likelihood ratio of 2.74, and negative likelihood ratio of 0.96, suggesting poor predictive ability. Moreover, it did not improve upon the predictive performance of a multivariable model, based on discrimination and reclassification indices. Our findings were generally consistent with the results of a systematic review and meta-analysis, including six additional studies. CONCLUSIONS: Intraoperative oliguria has moderate association with, but poor predictive ability for, postoperative AKI. It remains of clinical interest as a risk factor potentially modifiable to interventions.

Hemodynamic disturbances and oliguria during continuous kidney replacement therapy in critically ill children.

BACKGROUND: About 1.5% of patients admitted to the Pediatric Intensive Care Unit (PICU) will require continuous kidney replacement therapy (CKRT)/renal replacement therapy (CRRT). Mortality of these patients ranges from 30 to 60%. CKRT-related hypotension (CKRT-RHI) can occur in 19-45% of patients. Oliguria after onset of CKRT is also common, but to date has not been addressed directly in the scientific literature. METHODS: A prospective observational study was conducted to define factors involved in the hemodynamic changes that take place during the first hours of CKRT, and their relationship with urinary output. RESULTS: Twenty-five patients who were admitted to a single-center PICU requiring CKRT between January 1, 2014, and December 31, 2018, were included, of whom 56.3% developed CKRT-RHI. This drop in blood pressure was transient and rapidly restored to baseline, and significantly improved after the third hour of CKRT, as core temperature and heart rate decreased. Urine output significantly decreased after starting CKRT, and 72% of patients were oliguric after 6 h of therapy. Duration of CKRT was significantly longer in patients presenting with oliguria than in non-oliguric patients (28.7 vs. 7.9 days, p = 0.013). CONCLUSIONS: The initiation of CKRT caused hemodynamic instability immediately after initial connection in most patients, but had a beneficial effect on the patient's hemodynamic status after 3 h of therapy, presumably owing to decreases in body temperature and heart rate. Urine output significantly decreased in all patients and was not related to negative fluid balance, patient's hemodynamic status, CKRT settings, or kidney function parameters.

Perioperative acute kidney injury and urine output in lower limb arthroplasties.

BACKGROUND: This study aimed to evaluate the occurrence and perioperative risk factors of acute kidney injury (AKI) in primary elective hip and knee and emergency hip arthroplasty patients. We also aimed to assess the effect of urine output (UOP) as a diagnostic criterion in addition to serum creatinine (sCr) levels. We hypothesized that emergency arthroplasties are prone to AKI and that UOP is an underrated marker of AKI. METHODS: This retrospective, register-based study assessed 731 patients who underwent primary elective knee or hip arthroplasty and 170 patients who underwent emergency hip arthroplasty at Oulu University Hospital, Finland, between January 2016 and February 2017. RESULTS: Of the elective patients, 18 (2.5%) developed AKI. The 1-year mortality rate was 1.5% in elective patients without AKI and 11.1% in those with AKI (P = .038). Of the emergency patients, 24 (14.1%) developed AKI. The mortality rate was 16.4% and 37.5% in emergency patients without and with AKI, respectively (P = .024). In an AKI subgroup analysis of the combined elective and emergency patients, the mortality rate was 31.3% (n = 5) in the sCr group (n = 16), 23.5% (n = 4) in the UOP group (n = 17), and 22.2% (n = 2) in AKI patients who met both the sCr and UOP criteria (n = 9). CONCLUSION: Emergency hip arthroplasty is associated with an increased risk of AKI. Since AKI increases mortality in both elective and emergency arthroplasty, perioperative oliguria should also be considered as a diagnostic criterion for AKI. Focusing solely on sCr may overlook many cases of AKI.

Early identification of acute kidney injury in the ICU with real-time urine output monitoring: a clinical investigation.

BACKGROUND: KDIGO (Kidney Disease: Improving Global Outcomes) provides two sets of criteria to identify and classify acute kidney injury (AKI): serum creatinine (SCr) and urine output (UO). Inconsistencies in the application of KDIGO UO criteria, as well as collecting and classifying UO data, have prevented an accurate assessment of the role this easily available biomarker can play in the early identification of AKI. STUDY GOAL: To assess and compare the performance of the two KDIGO criteria (SCr and UO) for identification of AKI in the intensive care unit (ICU) by comparing the standard SCr criteria to consistent, real-time, consecutive, electronic urine output measurements. METHODS: Ninety five catheterized patients in the General ICU (GICU) of Hadassah Medical Center, Israel, were connected to the RenalSense™ Clarity RMS™ device to automatically monitor UO electronically (UOelec). UOelec and SCr were recorded for 24-48 h and up to 1 week, respectively, after ICU admission. RESULTS: Real-time consecutive UO measurements identified significantly more AKI patients than SCr in the patient population, 57.9% (N = 55) versus 26.4% (N = 25), respectively (P < 0.0001). In 20 patients that had AKI according to both criteria, time to AKI identification was significantly earlier using the UOelec criteria as compared to the SCr criteria (P < 0.0001). Among this population, the median (interquartile range (IQR)) identification time of AKI UOelec was 12.75 (8.75, 26.25) hours from ICU admission versus 39.06 (25.8, 108.64) hours for AKI SCr. CONCLUSION: Application of KDIGO criteria for AKI using continuous electronic monitoring of UO identifies more AKI patients, and identifies them earlier, than using the SCr criteria alone. This can enable the clinician to set protocol goals for earlier intervention for the prevention or treatment of AKI.

Lipopolysaccharide induces filtrate leakage from renal tubular lumina into the interstitial space via a proximal tubular Toll-like receptor 4-dependent pathway and limits sensitivity to fluid therapy in mice.

Sustained oliguria during fluid resuscitation represents a perplexing problem in patients undergoing therapy for septic acute kidney injury. Here, we tested whether lipopolysaccharide induces filtrate leakage from the proximal tubular lumen into the interstitium, thus disturbing the recovery of urine output during therapy, such as fluid resuscitation, aiming to restore the glomerular filtration rate. Intravital imaging of the tubular flow rate in the proximal tubules in mice showed that lipopolysaccharide did not change the inflow rate of proximal tubule filtrate, reflecting an unchanged glomerular filtration rate, but significantly reduced the outflow rate, resulting in oliguria. Lipopolysaccharide disrupted tight junctions in proximal tubules and induced both paracellular leakage of filtered molecules and interstitial accumulation of extracellular fluid. These changes were diminished by conditional knockout of Toll-like receptor 4 in the proximal tubules. Importantly, these conditional knockout mice showed increased sensitivity to fluid resuscitation and attenuated acute kidney injury. Thus, lipopolysaccharide induced paracellular leakage of filtrate into the interstitium via a Toll-like receptor 4-dependent mechanism in the proximal tubules of endotoxemic mice. Hence, this leakage might diminish the efficacy of fluid resuscitation aiming to maintain renal hemodynamics and glomerular filtration rate.

Noninterventional follow-up vs fluid bolus in RESPONSE to oliguria-The RESPONSE trial protocol and statistical analysis plan.

BACKGROUND: Oliguria is a frequent trigger for administering a fluid bolus, but the effect of fluid bolus in improving urine output is inadequately demonstrated. Here, we summarize the protocol and detailed statistical analysis plan of the randomized, controlled RESPONSE trial comparing follow-up as the experimental group and a 500 mL crystalloid fluid bolus as the control group for oliguria in critically ill oliguric patients. METHODS: Our trial is an investigator-initiated, randomized, controlled, pilot trial conducted in three ICUs in two centers. We aim to randomize 1:1 altogether 130 hemodynamically stable oliguric patients either to a 2-hour follow-up without interventions or to receive a crystalloid bolus of 500 mL over 30 minutes. The primary outcome is the change in individual urine output during the 2-hour period compared to 2 hours preceding randomization. Doubling of the urine output is considered clinically significant. Additionally, we record the duration of oliguria, physiological and biochemical variables, adverse events, and the incidences of acute kidney injury and renal replacement therapy. CONCLUSIONS: Oliguria is a frequent trigger for potentially harmful fluid loading. Therefore, the RESPONSE trial will give information of the potential effect of fluid bolus on oliguria in critically ill patients. TRIAL REGISTRATION: clinical.trials.gov, NCT02860572.

[Impact of oliguria during lung surgery on postoperative acute kidney injury].

OBJECTIVE: To explore the influence of intraoperative urine volume on postoperative acute kidney injury (AKI) and the independent risk factors of AKI. METHODS: This was a retrospective cohort study recruiting patients who received selective pulmonary resection under general anesthesia in Peking University First Hospital from July, 2017 to June, 2019. The patients were divided into the AKI group and the control group according to whether they developed postoperative AKI or not. Firstly, univariate analysis was used to analyze the relationship between perioperative variables and postoperative AKI. Secondly, receiver operating characteristic (ROC) curve was used to explore the predictive value of intraoperative urine output for postoperative AKI. The nearest four cutoff values [with the interval of 0.1 mL/(kg·h)] at maximum Youden index were used as cutoff values of oliguria. Then univariate analysis was used to explore the relationship between oliguria defined by these four cutoff values and the risk of AKI. And the cutoff value with maximum OR was chosen as the threshold of oliguria in this study. Lastly, the variables with P < 0.10 in the univariate analysis were selected for inclusion in a multivariate Logistic model to analyze the independent predictors of postoperative AKI. RESULTS: A total of 1 393 patients were enrolled in the study. The incidence of postoperative AKI was 2.2%. ROC curve analysis showed that the area under curve (AUC) of intraoperative urine volume used for predicting postoperative AKI was 0.636 (P=0.009), and the cutoff value of oliguria was 0.785 mL/(kg·h) when Youden index was maximum (Youden index =0.234, sensitivity =48.4%, specificity =75.0%). Furthermore, 0.7, 0.8, 0.9, 1.0 mL/(kg·h) and the traditional cutoff value of 0.5 mL/(kg·h) were used to analyze the influence of oliguria on postoperative AKI. Univariate analysis showed that, when 0.8 mL/(kg·h) was selected as the threshold of oliguria, the patients with oliguria had the most significantly increased risk of AKI (AKI group 48.4% vs. control group 25.3%, OR=2.774, 95%CI 1.357－5.671, P=0.004). Multivariate regression analysis showed that intraoperative urine output < 0.8 mL/(kg·h) was one of the independent risk factors of postoperative AKI (OR=2.698, 95%CI 1.260－5.778, P=0.011). The other two were preoperative hemoglobin ≤120.0 g/L (OR=3.605, 95%CI 1.545－8.412, P=0.003) and preoperative estimated glomerular filtration rate < 30 mL/(min·1.73 m2) (OR=11.009, 95%CI 1.813－66.843, P=0.009). CONCLUSION: Oliguria is an independent risk fact or of postoperative AKI after pulmonary resection, and urine volume < 0.8 mL/(kg·h) is a possible screening criterium.

Community Acquired Urosepsis: A surgical intensive care Experience.

Urosepsis contributes significantly to the epidemiology of sepsis. Urosepsis can be classified as community acquired or hospital acquired, depending upon the origin of infection acquisition: either from the community or from a healthcare facility. A great deal of literature is available about nosocomial urosepsis, but the literature regarding community-acquired urosepsis (CAUs) is limited, and studies are underpowered. The aim of our study was to determine the epidemiology, bacteriology, severity, and outcome of CAUs. Methods and Patients: All patients admitted from the emergency department to the surgical intensive care unit (SICU) with urosepsis over a period of 10 years were identified and included retrospectively from the SICU registry. The study was retrospective. Data were entered into the SPSS program version 23, and groups were compared by using chi-square and t-tests. Results were considered statistically significant at p ≤ 0.05. Results: During the study period, 302 patients with CAUs were admitted to the SICU. The common etiology was obstructive uropathy (60%). The Local Arab population outnumbered the non-Arab population (164/54.3%), and there were equal numbers of patients of both genders. Diabetes mellitus and hypertension together were the common comorbidities. Seventy-five percent of patients had acute kidney injury (AKI). Thirty-eight percent of patients had percutaneous nephrostomy, and 24.8% of patients underwent endoscopic stent insertion to relieve the obstruction. Ninety-three percent of patients were admitted with septic shock, and 71.5% had bacteremia. The common bacteria (36.1%) was extended-spectrum beta-lactamase-(ESBL)-producing bacteria, with a predominance of Escherichia coli (31.5%). Fifty-four percent of patients required a change of antibiotics to carbapenem. Eighty-two percent of patients had acute respiratory distress syndrome (ARDS). Patients with bacteremia had a statistically significant AKI, ARDS, and septic shock (p < 0.001). Male patients had a significantly higher incidence of oliguria, intubation, and ARDS (p < 0.05). Eight patients died of urosepsis during the study period, giving a mortality rate of 2.6%. Conclusion: In our patients, obstruction of urine flow was the most common cause of CAUs. Our urosepsis patients had a higher bacteremia rate, which led to higher incidences of organ dysfunction and septic shock. ESBL bacteria were a frequent cause of urosepsis, requiring a change of the initial antibiotic to carbapenem. Male patients had a significantly higher rate of organ dysfunction. Mortality in our urosepsis patients was lower than mentioned in the literature.

Efficacy and safety of pharmacological treatments for patent ductus arteriosus closure: A systematic review and network meta-analysis of clinical trials and observational studies.

Efficacy and safety profiles of different pharmacological interventions used to treat patent ductus arteriosus (PDA) are relatively unexplored. Integrating the findings of randomized clinical trials (RCTs) with those from observational studies may provide key evidence on this important issue. We aimed at estimating the relative likelihood of failure to close the PDA, need for surgical closure, and occurrence of adverse events among preterm and full-term infants treated with indomethacin, ibuprofen, or acetaminophen, placebo, or no treatment including both RCTs and observational studies. We searched PubMed, Embase, and the Register of Controlled Trials from inception to October 30, 2018. We first estimated proportions of subjects with failure to close the PDA, subjects in whom surgical closure was performed after pharmacological treatment, death, and subjects with selected adverse events (AEs). These estimates were obtained using frequentist random-effect meta-analysis of arm-specific proportions. We then compared active drugs with each other and with control (either placebo or no treatment) by summarizing results at the end of treatment reported in the papers, regardless of number of administration(s), dose, route and type of administration, and study design and quality. We also summarized primary outcome results separately at first, second and third cycles of treatment. These estimates were obtained using Bayesian random-effects network meta-analysis for mixed comparisons, and frequentist random-effect pairwise meta-analysis for direct comparisons. We included 64 RCTs and 24 observational studies including 14,568 subjects (5339 in RCTs and 9229 in observational studies, 8292 subjects received indomethacin, 4761 ibuprofen, 574 acetaminophen, and 941 control (including placebo or no intervention).The proportion of subjects with failure to close the PDA was 0.24 (95% Confidence Interval, CI: 0.20, 0.29) for indomethacin, 0.18 (0.14, 0.22) for ibuprofen, 0.19 (0.09, 0.30) for acetaminophen, and 0.59 (0.48, 0.69) for control. At end of treatment, compared to control, we found inverse associations between all active drugs and failure to close PDA (for indomethacin Odds Ratio, OR, was 0.17 [95% Credible Interval, CrI: 0.11-0.24], ibuprofen 0.19 [0.12-0.28], and acetaminophen 0.15 [0.09-0.26]), without differences among active drugs. We showed inverse associations between effective drugs and need for surgical closure, as compared to control (for indomethacin OR was 0.28 [0.15-0.50], ibuprofen 0.30 [0.16-0.54], and acetaminophen 0.19 [0.07-0.46]), without differences among drugs. Indomethacin was directly associated with intraventricular hemorrhage (IVH) (1.27; 1.00, 1.62) compared to ibuprofen, and to oliguria as compared to ibuprofen (3.92; 1.69, 9.82) or acetaminophen (10.8; 1.86, 93.1). In conclusion, active pharmacological treatment, with indomethacin, ibuprofen, or acetaminophen, is inversely associated with failure to close the PDA compared to non-treatment. Ibuprofen should be preferred to indomethacin to avoid occurrence of IVH or oliguria, acetaminophen should be preferred to indomethacin to avoid oliguria.