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Background/objective: Dysnatremia is common in severe traumatic brain injury (TBI) patients and may contribute to mortality. However, serum sodium variability has not been studied in TBI patients. We hypothesized that such variability would be independently associated with mortality., Methods: We collected 6-hourly serum sodium levels for the first 7 days of ICU admission from 240 severe TBI patients in 14 neurotrauma ICUs in Europe and Australia. We evaluated the association between daily serum sodium standard deviation (dNa SD ), an index of variability, and 28-day mortality., Results: Patients were 46 ± 19 years of age with a median initial GCS of 6 [4-8]. Overall hospital mortality was 28%. Hypernatremia and hyponatremia occurred in 64% and 24% of patients, respectively. Over the first 7 days in ICU, serum sodium standard deviation was 2.8 [2.0-3.9] mmol/L. Maximum daily serum sodium standard deviation (dNa SD ) occurred at a median of 2 [1-4] days after admission. There was a significant progressive decrease in dNa SD over the first 7 days (coefficient - 0.15 95% CI [- 0.18 to - 0.12], p < 0.001). After adjusting for baseline TBI severity, diabetes insipidus, the use of osmotherapy, the occurrence of hypernatremia, and hyponatremia and center, dNa SD was significantly independently associated with 28-day mortality (HR 1.27 95% CI (1.01-1.61), p = 0.048)., Conclusions: Our study demonstrates that daily serum sodium variability is an independent predictor of 28-day mortality in severe TBI patients. Further prospective investigations are necessary to confirm the significance of sodium variability in larger cohorts of TBI patients and test whether attenuating such variability confers outcome benefits to such patients.

BACKGROUND: Barts Health National Health Service Trust (BHNHST) serves a diverse population of 2.5 million people in London, UK. We undertook a health services assessment of factors used to evaluate the risk of severe acute respiratory coronavirus 2 (SARS-CoV-2) infection. METHODS: Patients with confirmed polymerase chain reaction (PCR) test results admitted between 1 March and 1 August 2020 were included, alongwith clinician-diagnosed suspected cases. Prognostic factors from the 4C Mortality score and 4C Deterioration scores were extracted from electronic health records and logistic regression was used to quantify the strength of association with 28-day mortality and clinical deterioration using national death registry linkage. RESULTS: Of 2783 patients, 1621 had a confirmed diagnosis, of whom 61% were male and 54% were from Black and Minority Ethnic groups; 26% died within 28 days of admission. Mortality was strongly associated with older age. The 4C mortality score had good stratification of risk with a calibration slope of 1.14 (95% CI 1.01-1.27). It may have under-estimated mortality risk in those with a high respiratory rate or requiring oxygen. CONCLUSION: Patients in this diverse patient cohort had similar mortality associated with prognostic factors to the 4C score derivation sample, but survival might be poorer in those with respiratory failure.

Purpose: The trajectory of mechanically ventilated patients with coronavirus disease 2019 (COVID-19) is essential for clinical decisions, yet the focus so far has been on admission characteristics without consideration of the dynamic course of the disease in the context of applied therapeutic interventions., Methods: We included adult patients undergoing invasive mechanical ventilation (IMV) within 48 h of intensive care unit (ICU) admission with complete clinical data until ICU death or discharge. We examined the importance of factors associated with disease progression over the first week, implementation and responsiveness to interventions used in acute respiratory distress syndrome (ARDS), and ICU outcome. We used machine learning (ML) and Explainable Artificial Intelligence (XAI) methods to characterise the evolution of clinical parameters and our ICU data visualisation tool is available as a web-based widget ( https://www.CovidUK.ICU )., Results: Data for 633 adults with COVID-19 who underwent IMV between 01 March 2020 and 31 August 2020 were analysed. Overall mortality was 43.3% and highest with non-resolution of hypoxaemia [60.4% vs17.6%; P < 0.001; median PaO 2 /FiO 2 on the day of death was 12.3(8.9-18.4) kPa] and non-response to proning (69.5% vs.31.1%; P < 0.001). Two ML models using weeklong data demonstrated an increased predictive accuracy for mortality compared to admission data (74.5% and 76.3% vs 60%, respectively). XAI models highlighted the increasing importance, over the first week, of PaO 2 /FiO 2 in predicting mortality. Prone positioning improved oxygenation only in 45% of patients. A higher peak pressure (OR 1.42[1.06-1.91]; P < 0.05), raised respiratory component (OR 1.71[ 1.17-2.5]; P < 0.01) and cardiovascular component (OR 1.36 [1.04-1.75]; P < 0.05) of the sequential organ failure assessment (SOFA) score and raised lactate (OR 1.33 [0.99-1.79]; P = 0.057) immediately prior to application of prone positioning were associated with lack of oxygenation response. Prone positioning was not applied to 76% of patients with moderate hypoxemia and 45% of those with severe hypoxemia and patients who died without receiving proning interventions had more missed opportunities for prone intervention [7 (3-15.5) versus 2 (0-6); P < 0.001]. Despite the severity of gas exchange deficit, most patients received lung-protective ventilation with tidal volumes less than 8 mL/kg and plateau pressures less than 30cmH 2 O. This was despite systematic errors in measurement of height and derived ideal body weight., Conclusions: Refractory hypoxaemia remains a major association with mortality, yet evidence based ARDS interventions, in particular prone positioning, were not implemented and had delayed application with an associated reduced responsiveness. Real-time service evaluation techniques offer opportunities to assess the delivery of care and improve protocolised implementation of evidence-based ARDS interventions, which might be associated with improvements in survival.

Background: Acute kidney injury (AKI) is a common and important complication of coronavirus disease 2019 (COVID-19). Further characterization is required to reduce both short- and long-term adverse outcomes., Methods: We examined registry data including adults with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to five London Hospitals from 1 January to 14 May 2020. Prior end-stage kidney disease was excluded. Early AKI was defined by Kidney Disease: Improving Global Outcomes creatinine criteria within 7 days of admission. Independent associations of AKI and survival were examined in multivariable analysis. Results are given as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals., Results: Among 1855 admissions, 455 patients (24.5%) developed early AKI: 200 (44.0%) Stage 1, 90 (19.8%) Stage 2 and 165 (36.3%) Stage 3 (74 receiving renal replacement therapy). The strongest risk factor for AKI was high C-reactive protein [OR 3.35 (2.53-4.47), P < 0.001]. Death within 30 days occurred in 242 (53.2%) with AKI compared with 255 (18.2%) without. In multivariable analysis, increasing severity of AKI was incrementally associated with higher mortality: Stage 3 [HR 3.93 (3.04-5.08), P < 0.001]. In 333 patients with AKI surviving to Day 7, 134 (40.2%) recovered, 47 (14.1%) recovered then relapsed and 152 (45.6%) had persistent AKI at Day 7; an additional 105 (8.2%) patients developed AKI after Day 7. Persistent AKI was strongly associated with adjusted mortality at 90 days [OR 7.57 (4.50-12.89), P < 0.001]., Conclusions: AKI affected one in four hospital in-patients with COVID-19 and significantly increased mortality. Timing and recovery of COVID-19 AKI is a key determinant of outcome., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Non-communicable diseases (NCDs) are increasingly prevalent and were responsible for 40.5 million deaths (71%) globally in 2016. We examined the number of NCD-related emergency hospital admissions during the years 1998 to 2018 in the UK., Methods: Demographic features for those admitted as an emergency with NCDs as their primary diagnosis were collated for all admissions in England, Wales and Scotland. NCDs recorded as secondary diagnoses for all admissions in England from 2012 to 2018 were additionally recorded., Results: We identified 120,662,155 emergency episodes of care. From 1998 to 2018 there was an increase from 1,416,233 to 1,892,501 in annual emergency admissions due to NCDs. This, however, represented a fall in the proportion of NCD among all emergency admissions, from 33.4% to 26.9%. Mean age of all patients admitted increased from 46.3 to 53.8 years., Conclusion: Despite a fall in proportion of NCD admissions, the population acutely admitted to hospital was increasingly elderly and increasingly comorbid., (© Royal College of Physicians 2021. All rights reserved.)

Background: Socioeconomic deprivation is associated with health inequalities. We explored relationships between socioeconomic group and outcomes after elective surgery in the UK National Health Service (NHS)., Methods: We combined data from two observational studies in 115 NHS hospitals and determined socioeconomic group using the Index of Multiple Deprivation (IMD) quintiles based on place of residence. Postoperative complications and 3-yr survival were assessed using logistic and Cox regression. Univariate analyses were adjusted for age differences between IMD quintiles. Multivariable analyses were used to account for other baseline risk factors including sex and comorbid disease. Results are reported as n (%), hazard ratios (HR) or odds ratios (OR) with 95% confidence intervals., Results: Postoperative complications developed in 971/9051 patients (10.7%) and 1597/9043 patients (17.7%) died within 3 yr. Complication rates increased with deprivation (reference group least-deprived IMD5): IMD1 (OR=1.44 [1.17-1.78]; P<0.001), IMD2 (OR=1.38 [1.12-1.70]; P<0.01), IMD3 (OR=1.09 [0.88-1.35]: P=0.44), IMD4 (OR=0.89 [0.71-1.11]; P=0.30). More patients from the most deprived quintile died (IMD1) (n=349, 18.8%) compared with the least deprived (IMD5) (n=297, 15.9%) with a trend across the socioeconomic spectrum (P=0.01). After age adjustment, patients in the most deprived areas experienced reduced 3-yr survival: IMD1 (HR=1.43 [1.23-1.67]; P<0.0001), IMD2 (HR=1.35 [1.15-1.57]; P<0.001), IMD3 (HR=1.04 [0.89-1.23]; P=0.60), and IMD4 (HR=1.11 [0.95-1.30]; P=0.19). This finding persisted in risk-adjusted analyses. Increased complication rates only partially explained this reduced survival., Conclusions: Socioeconomic deprivation is associated with worse long-term outcomes after elective surgery. This risk factor should be considered when planning perioperative care for patients from deprived areas., (Copyright © 2020 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Purpose: To examine reported prognostic associations of routine blood measurements in the intensive care unit., Materials and Methods: We searched PubMed, EMBASE through 28 th May 2020 to identify all studies in adult critical care investigating associations between parameters measured routinely in whole blood, plasma or serum, and length of stay or mortality. Registration: PROSPERO; CRD42019122058., Results: A total of 128 studies, reporting 28 different putative prognostic biomarkers, met eligibility criteria. Those most frequently examined were red cell distribution width, neutrophil-to-lymphocyte ratio, C-reactive protein, and platelet count. A higher red cell distribution width, a lower platelet count, and a higher neutrophil-to-lymphocyte ratio were consistently associated with both increased mortality and length of stay. A lower level of albumin was consistently associated with greater mortality. C-reactive protein was inconsistent. Most studies (n = 110) used regression modelling with wide variation in variable selection and covariate-adjustment; none externally validated the proposed predictive models., Conclusions: Simple regression models have so far proved inadequate for the complexity of data available from routine blood sampling in critical care. Adoption of a direct causal framework may help better assess mechanistic processes, aid design of future studies, and guide clinical decision making using routine data.

Acute kidney injury (AKI) is a frequent complication of traumatic injury; however, long-term outcomes such as mortality and end-stage kidney disease (ESKD) have been rarely reported in this important patient population. We compared the long-term outcome of vehicle-traumatic and non-traumatic AKI requiring renal replacement therapy (AKI-RRT). This nationwide cohort study used data from the Taiwan National Health Insurance Research Database. Vehicle-trauma patients who were suffered from vehicle accidents developing AKI-RRT during hospitalization were identified, and matching non-traumatic AKI-RRT patients were identified between 2000 and 2010. The incidences of ESKD, 30-day, and long-term mortality were evaluated, and clinical and demographic associations with these outcomes were identified using Cox proportional hazards regression models. 546 vehicle-traumatic AKI-RRT patients, median age 47.6 years (interquartile range: 29.0-64.3) and 76.4% male, were identified. Compared to non-traumatic AKI-RRT, vehicle-traumatic AKI-RRT patients had longer length of stay in hospital [median (IQR):15 (5-34) days vs. 6 (3-11) days; p < 0.001). After propensity matching with non-traumatic AKI-RRT cases with similar demographic and clinical characteristics. Vehicle-traumatic AKI-RRT patients had lower rates of long-term mortality (adjusted hazard ratio (HR), 0.473; 95% CI, 0.392-0.571; p < 0.001), but similar rates of ESKD (HR, 1.166; 95% CI, 0.829-1.638; p = 0.377) and short-term risk of death (HR, 1.134; 95% CI, 0.894-1.438; p = 0.301) as non-traumatic AKI-RRT patients. In competing risk models that focused on ESKD, vehicle-traumatic AKI-RRT patients were associated with lower ESKD rates (HR, 0.552; 95% CI, 0.325-0.937; p = 0.028) than non-traumatic AKI-RRT patients. Despite severe injuries, vehicle-traumatic AKI-RRT patients had better long-term survival than non-traumatic AKI-RRT patients, but a similar risk of ESKD. Our results provide a better understanding of long-term outcomes after vehicle-traumatic AKI-RRT.

In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline on the classification and management of acute kidney injury (AKI). The guideline was derived from evidence available through February 2011. Since then, new evidence has emerged that has important implications for clinical practice in diagnosing and managing AKI. In April of 2019, KDIGO held a controversies conference entitled Acute Kidney Injury with the following goals: determine best practices and areas of uncertainty in treating AKI; review key relevant literature published since the 2012 KDIGO AKI guideline; address ongoing controversial issues; identify new topics or issues to be revisited for the next iteration of the KDIGO AKI guideline; and outline research needed to improve AKI management. Here, we present the findings of this conference and describe key areas that future guidelines may address., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of the RUBY study was to evaluate novel candidate biomarkers to enable prediction of persistence of renal dysfunction as well as further understand potential mechanisms of kidney tissue damage and repair in acute kidney injury (AKI)., Methods: The RUBY study was a multi-center international prospective observational study to identify biomarkers of the persistence of stage 3 AKI as defined by the KDIGO criteria. Patients in the intensive care unit (ICU) with moderate or severe AKI (KDIGO stage 2 or 3) were enrolled. Patients were to be enrolled within 36 h of meeting KDIGO stage 2 criteria. The primary study endpoint was the development of persistent severe AKI (KDIGO stage 3) lasting for 72 h or more (NCT01868724)., Results: 364 patients were enrolled of whom 331 (91%) were available for the primary analysis. One hundred ten (33%) of the analysis cohort met the primary endpoint of persistent stage 3 AKI. Of the biomarkers tested in this study, urinary C-C motif chemokine ligand 14 (CCL14) was the most predictive of persistent stage 3 AKI with an area under the receiver operating characteristic curve (AUC) (95% CI) of 0.83 (0.78-0.87). This AUC was significantly greater than values for other biomarkers associated with AKI including urinary KIM-1, plasma cystatin C, and urinary NGAL, none of which achieved an AUC > 0.75., Conclusion: Elevated urinary CCL14 predicts persistent AKI in a large heterogeneous cohort of critically ill patients with severe AKI. The discovery of CCL14 as a predictor of persistent AKI and thus, renal non-recovery, is novel and could help identify new therapeutic approaches to AKI.

The optimal osmotic agent to treat intracranial hypertension in patients with severe traumatic brain injury (TBI) remains uncertain. We aimed to test whether the choice of mannitol or hypertonic saline (HTS) as early (first 96 h) osmotherapy in these patients might be associated with a difference in mortality. We retrospectively analyzed data from 2015 from 14 tertiary intensive care units (ICUs) in Australia, UK, and Europe treating severe TBI patients with intracranial pressure (ICP) monitoring and compared mortality in those who received mannitol only versus HTS only. We performed multi-variable analysis adjusting for site and illness severity (Injury Severity Score, extended IMPACT score, and mean ICP over the first 96 h) using Cox proportional hazards regression. We collected data on 262 patients and compared patients who received early osmotherapy with mannitol alone ( n  = 46) with those who received HTS alone ( n  = 46). Mannitol patients were older (median age, 49.2 (19.2) vs. 40.5 (16.8) years; p  = 0.02), with higher Injury Severity Scores (42 (15.9) vs. 32.1 [11.3]; p  = 0.001), and IMPACT-TBI predicted 6-month mortality (34.5% [23-46] vs. 25% [13-38]; p  = 0.02), but had similar APACHE-II scores, and mean and maximum ICPs over the first 96 h. The unadjusted hazard ratio for in-hospital mortality in patients receiving only mannitol was 3.35 (95% confidence interval [CI], 1.60-7.03; p  = 0.001). After adjustment for key mortality predictors, the hazard ratio for in-hospital mortality in patients receiving only mannitol was 2.64 (95% CI, 0.96-7.30; p  = 0.06). The choice of early osmotherapy in severe TBI patients may affect survival, or simply reflect clinician beliefs about their different roles, and warrants controlled investigation.

Background: Acute kidney injury (AKI) is an important adverse outcome after major surgery. Peri-operative goal-directed haemodynamic therapy (GDT) may improve outcomes by reducing complications such as AKI., Objective: To determine if GDT was associated with a reduced incidence of postoperative AKI according to specific renal biomarkers., Design: Prospective substudy of the OPTIMISE trial, a multicentre randomised controlled trial comparing peri-operative GDT to usual patient care., Setting: Four UK National Health Service hospitals., Patients: A total of 287 high-risk patients aged at least 50 years undergoing major gastrointestinal surgery., Outcome Measures: The primary outcome measure was AKI defined as urinary neutrophil gelatinase-associated lipase (NGAL) at least 150 ng ml 24 and 72 h after surgery. Secondary outcomes were between-group differences in NGAL measurements and NGAL : creatinine ratios 24 and 72 h after surgery and AKI stage 2 or greater according to Kidney Disease Improving Global Outcomes (KDIGO) criteria within 30 days of surgery., Results: In total, 20 of 287 patients (7%) experienced postoperative AKI of KDIGO grade 2 or 3 within 30 days. The proportion of patients with urinary NGAL at least 150 ng ml 24 or 72 h after surgery was similar in the two groups [GDT 31/144 (21.5%) patients vs. usual patient care 28/143 (19.6%) patients; P = 0.88]. Absolute values of urinary NGAL were also similar at 24 h (GDT 53.5 vs. usual patient care 44.1 ng ml; P = 0.38) and 72 h (GDT 45.1 vs. usual patient care 41.1 ng ml; P = 0.50) as were urinary NGAL : creatinine ratios at 24 h (GDT 45 vs. usual patient care 43 ng mg; P = 0.63) and 72 h (GDT 66 vs. usual patient care 63 ng mg; P = 0.62). The incidence of KDIGO-defined AKI was also similar between the groups [GDT 9/144 (6%) patients vs. usual patient care 11/143 (8%) patients; P = 0.80]., Conclusion: In this trial, GDT did not reduce the incidence of AKI amongst high-risk patients undergoing major gastrointestinal surgery. This may reflect improving standards in usual patient care., Trial Registration: OPTIMISE Trial Registration ISRCTN04386758.

Purpose: Muscle wasting is common amongst patients with persistent critical illness and associated with increased urea production, but reduced creatinine production. We hypothesised that elevated urea:creatinine ratio would provide a biochemical signature of muscle catabolism and characterise prolonged intensive care (ICU) admissions after major trauma., Methods: Using pre-specified hypotheses, we analysed two existing data sets of adults surviving ≥ 10 days following admission to ICU after major trauma. We analysed trauma-ICU admissions to the major trauma centre serving the North East London and Essex Trauma Network, with a verification cohort of trauma-ICU cases from the MIMIC-III database. We compared serum urea, creatinine, and urea:creatinine ratio (ratio of concentrations in mmol/L) between patients with persistent critical illness (defined as ICU stay of ≥ 10 days) and those discharged from ICU before day 10. In a sub-group undergoing sequential abdominal computerised tomography (CT), we measured change in cross-sectional muscle area (psoas muscle at L4 vertebral level and total muscle at L3 level) and assessed for relationships with urea:creatinine ratio and ICU stay. Results are provided as median [interquartile range]., Results: We included 1173 patients between February 1st, 2012 and May 1st, 2016. In patients with ICU stay ≥ 10 days, day 10 urea:creatinine ratio had increased by 133% [72-215], from 62 [46-78] to 141 [114-178], p < 0.001; this rise was larger (p < 0.001) than in patients discharged from ICU before day 10, 59% [11-122%], 61 [45-75] to 97 [67-128], p < 0.001. A similar separation in trajectory of urea:creatinine ratio was observed in 2876 trauma-ICU admissions from MIMIC-III. In 107 patients undergoing serial CTs, decrease in L4 psoas and L3 muscle cross-sectional areas between CTs significantly correlated with time elapsed (R 2  = 0.64 and R 2  = 0.59, respectively). Rate of muscle decrease was significantly greater (p < 0.001 for interaction terms) in 53/107 patients with the second CT during evolving, current or recent persistent critical illness. In this group, at the second CT urea:creatinine ratio negatively correlated with L4 psoas and L3 muscle cross-sectional areas (R 2 0.39, p < 0.001 and 0.44, p < 0.001)., Conclusion: Elevated urea:creatinine ratio accompanies skeletal muscle wasting representing a biochemical signature of persistent critical illness after major trauma. If prospectively confirmed, urea:creatinine ratio is a potential surrogate of catabolism to examine in epidemiological and interventional studies.

Purpose of Review: A summary of recent research into the epidemiology, cause, management and outcomes of trauma-associated acute kidney injury (AKI). There is an increasing focus on subtypes of AKI to better target clinical management and future research., Recent Findings: AKI associated with trauma occurs in 20-24% of patients admitted to ICU. On the basis of creatinine and/or urine output, AKI occurs in the first few days of traumatic illness. Although various associations have been identified, shock and high-volume blood transfusion are the most consistent risks for development of trauma-associated AKI. Short-term outcomes appear worse for patients with AKI, but extent of longer term kidney function recovery remains unknown. Recent research in the general critical care population is beginning to better inform AKI management; however, currently, preventive and supportive strategies remain the mainstay of AKI management after trauma., Summary: Well-designed, prospective research is required to better understand the phenotype, pathophysiology and recovery trajectory of trauma-associated AKI. Only then can potentially unique therapeutic targets be developed for this common subtype of AKI.

Critically ill patients who develop acute kidney injury (AKI) are more than twice as likely to die in hospital. However, it is not clear to what extent AKI is the cause of excess mortality, or merely a correlate of illness severity. The Bradford Hill criteria for causality (plausibility, temporality, magnitude, specificity, analogy, experiment & coherence, biological gradient and consistency) were applied to assess the extent to which AKI may be causative in adverse short-term outcomes of critical illness. Plausible mechanisms exist to explain increased risk of death after AKI, both from direct pathophysiological effects of renal dysfunction and mechanisms of organ cross-talk in multiple-organ failure. The temporal relationship between increased mortality following AKI is consistent with its pathophysiology. AKI is associated with substantially increased mortality, an association that persists after accounting for known confounders. A biological gradient exists between increasing severity of AKI and increasing short-term mortality. This graded association shares similar features to the increased mortality observed in ARDS; an analogous condition with a multifactorial aetiology. Evidence for the outcomes of AKI from retrospective cohort studies and experimental animal models is coherent however both of these forms of evidence have intrinsic biases and shortcomings. The relationship between AKI and risk of death is maintained across a range of patient ages, comorbidities and underlying diagnoses. In conclusion many features of the relationship between AKI and short-term mortality suggest causality. Prevention and mitigation of AKI and its complications are valid targets for studies seeking to improve short-term survival in critical care., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: In traumatic brain injury (TBI) patients desmopressin administration may induce rapid decreases in serum sodium and increase intracranial pressure (ICP)., Aim: In an international multi-centre study, we aimed to report changes in serum sodium and ICP after desmopressin administration in TBI patients., Methods: We obtained data from 14 neurotrauma ICUs in Europe, Australia and UK for severe TBI patients (GCS ≤ 8) requiring ICP monitoring. We identified patients who received any desmopressin and recorded daily dose, 6-hourly serum sodium, and 6-hourly ICP., Results: We studied 262 severe TBI patients. Of these, 39 patients (14.9%) received desmopressin. Median length of treatment with desmopressin was 1 [1-3] day and daily intravenous dose varied between centres from 0.125 to 10 mcg. The median hourly rate of decrease in serum sodium was low (- 0.1 [- 0.2 to 0.0] mmol/L/h) with a median period of decrease of 36 h. The proportion of 6-h periods in which the rate of natremia correction exceeded 0.5 mmol/L/h or 1 mmol/L/h was low, at 8% and 3%, respectively, and ICPs remained stable. After adjusting for IMPACT score and injury severity score, desmopressin administration was independently associated with increased 60-day mortality [HR of 1.83 (1.05-3.24) (p = 0.03)]., Conclusions: In severe TBI, desmopressin administration, potentially representing instances of diabetes insipidus is common and is independently associated with increased mortality. Desmopressin doses vary markedly among ICUs; however, the associated decrease in natremia rarely exceeds recommended rates and median ICP values remain unchanged. These findings support the notion that desmopressin therapy is safe.

Intravenous crystalloid therapy is one of the most ubiquitous aspects of hospital and critical care medicine. In recent years, there has been increasing focus on the electrolyte composition, and particularly chloride content, of crystalloid solutions. This has led to increasing clinical adoption of balanced solutions, containing substrates for bicarbonate generation and consequently a lower chloride content, in place of 0.9% saline. In this article we review the physiochemical rationale for avoidance of 0.9% saline and the effects of hyperchloremic acidosis on renal physiology. Finally, we review the current evidence and rationale for use of balanced solutions greater than 0.9% saline in acutely ill patients in a variety of clinical settings, as well as considering the role for sodium bicarbonate in preventing or correcting metabolic acidosis. In conclusion, there is a strong physiological rationale for avoidance of iatrogenic hyperchloremic acidosis from 0.9% saline administration in acutely unwell patients and an association with adverse renal outcomes in several studies. However, evidence from large definitive multicenter randomized trials is not yet available to establish the dose-relationship between 0.9% saline administration and potential harm and inform us if some 0.9% saline use is acceptable or if any exposure confers harm., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Postoperative acute kidney injury (AKI) is associated with a high mortality rate. However, the relationship among AKI, its associations, and mortality is not well understood., Methods: Planned analysis of data was collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. AKI was defined using Kidney Disease Improving Global Outcomes criteria. Patients missing preoperative creatinine data were excluded. We used multivariable logistic regression to examine the relationships among preoperative creatinine-based estimated glomerular filtration rate (eGFR), postoperative AKI, and hospital mortality, accounting for the effects of age, major comorbid diseases, and nature and severity of surgical intervention on outcomes. We similarly modeled preoperative associations of AKI. Data are presented as n (%) or odds ratios (ORs) with 95% confidence intervals., Results: A total of 36,357 patients were included, 743 (2.0%) of whom developed AKI with 73 (9.8%) deaths in hospital. AKI affected 73 of 196 (37.2%) of all patients who died. Mortality was strongly associated with the severity of AKI (stage 1: OR, 2.57 [1.3-5.0]; stage 2: OR, 8.6 [5.0-15.1]; stage 3: OR, 30.1 [18.5-49.0]). Low preoperative eGFR was strongly associated with AKI. However, in our model, lower eGFR was not associated with increasing mortality in patients who did not develop AKI. Conversely, in older patients, high preoperative eGFR (>90 mL·minute·1.73 m) was associated with an increasing risk of death, potentially reflecting poor muscle mass., Conclusions: The occurrence and severity of AKI are strongly associated with risk of death after surgery. However, the relationship between preoperative renal function as assessed by serum creatinine-based eGFR and risk of death dependent on patient age and whether AKI develops postoperatively.

Background: As more patients are surviving the initial effects of traumatic injury clinicians are faced with managing the systemic complications of severe tissue injury. Of these, acute kidney injury (AKI) may be a sentinel complication contributing to adverse outcomes., Objective: To establish the incidence of AKI in patients admitted to critical care after major trauma, to explore any risk factors and to evaluate the association of AKI with outcomes., Data Sources: Systematic search of MEDLINE, Excerpta Medica database and Cochrane library from January 2004 to April 2018., Study Selection: Studies of adult major trauma patients admitted to critical care that applied consensus AKI criteria (risk injury failure loss end stage [RIFLE], AKI network, or kidney disease improving global outcomes) and reported clinical outcomes were assessed (PROSPERO Registration: CRD42017056781). Of the 35 full-text articles selected from the screening, 17 (48.6%) studies were included., Data Extraction and Synthesis: We followed the PRISMA guidelines and study quality was assessed using the Newcastle-Ottawa score. The pooled incidence of AKI and relative risk of death were estimated using random-effects models., Main Outcomes and Measures: Incidence of AKI was the primary outcome. The secondary outcome was study-defined mortality., Results: We included 17 articles describing AKI outcomes in 24,267 trauma patients. The pooled incidence of AKI was 20.4% (95% confidence interval [CI], 16.5-24.9). Twelve studies reported the breakdown of stages of AKI with 55.7% of patients classified as RIFLE-R or stage 1, 30.3% as RIFLE-I or stage 2, and 14.0% as RIFLE-F or stage 3. The pooled relative risk of death with AKI compared was 3.6 (95% CI, 2.4-5.3). In addition, there was a concordant increase in odds of death among six studies that adjusted for multiple variables (adjusted odds ratio, 2.7; 95% CI, 1.9-3.8; p = <0.01)., Conclusion: Acute kidney injury is common after major trauma and associated with increased mortality. Future research is warranted to reduce the potential for harm associated with this subtype of AKI., Level of Evidence: Systematic review and meta-analysis, level III.

Purpose of Review: Continuous renal replacement therapy (CRRT) is now the mainstay of renal organ support in the critically ill. As our understanding of CRRT delivery and its impact on patient outcomes improves there is a focus on researching the potential benefits of tailored, patient-specific treatments to meet dynamic needs., Recent Findings: The most up-to-date studies investigating aspects of CRRT prescription that can be individualized: CRRT dose, timing, fluid management, membrane selection, anticoagulation and vascular access are reviewed. The use of different doses of CRRT lack conventional high-quality evidence and importantly studies reveal variation in assessment of dose delivery. Research reveals conflicting evidence for clinicians in distinguishing which patients will benefit from 'watchful waiting' vs. early initiation of CRRT. Both dynamic CRRT dosing and precision fluid management using CRRT are difficult to investigate and currently only observational data supports individualization of prescriptions. Similarly, individualization of membrane choice is largely experimental., Summary: Clinicians have limited evidence to individualize the prescription of CRRT. To develop this, we need to understand the requirements for renal support for individual patients, such as electrolyte imbalance, fluid overload or clearance of systemic inflammatory mediators to allow us to target these abnormalities in appropriately designed randomized trials.

Background: Renal injury is a common perioperative complication. The adoption of renal endpoints, standardised and valid for use in perioperative clinical trials, would enhance the quality of perioperative clinical research. The Standardised Endpoints in Perioperative Medicine (StEP) initiative was established to derive standardised endpoints for use in perioperative clinical trials., Methods: A systematic review was conducted to identify renal endpoints currently reported in perioperative clinical trials. In parallel, an initial list of candidate endpoints was developed based on renal theme group expertise. A multi-round Delphi consensus process was used to refine this list and produce a suite of recommended perioperative renal outcome measures., Results: Based on our systematic review, 63 studies were included for analysis. Marked heterogeneity and imprecision of endpoint definitions were observed. Our initial list of candidate endpoints included 10 endpoints for consideration. The response rates for Delphi rounds 1, 2, and 3 were 89% (n=16), 90% (n=75), and 100% (n=6), respectively. A final list of four renal endpoints was identified: acute kidney injury defined by the Kidney Disease: Improving Global Outcomes (KDIGO) consensus criteria, acute kidney disease defined by ≥30% decline in estimated glomerular filtration rate from baseline at 30 days after operation in patients meeting the acute-kidney-injury criteria within 7 days of surgery, the composite of death or renal replacement therapy, and the Major Adverse Kidney Events (MAKE) composite., Conclusions: We identified four key renal outcome measures that should be considered for use in perioperative clinical trials. Using standardised definitions to capture and report these endpoints will facilitate improved benchmarking and meta-analysis of future trials., (Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Objective: Acute kidney injury requiring renal replacement therapy in severe vasodilatory shock is associated with an unfavorable prognosis. Angiotensin II treatment may help these patients by potentially restoring renal function without decreasing intrarenal oxygenation. We analyzed the impact of angiotensin II on the outcomes of acute kidney injury requiring renal replacement therapy., Design: Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial., Setting: ICUs., Patients: Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo (n = 45 and n = 60, respectively)., Interventions: IV angiotensin II or placebo., Measurements and Main Results: Primary end point: survival through day 28; secondary outcomes included renal recovery through day 7 and increase in mean arterial pressure from baseline of ≥ 10 mm Hg or increase to ≥ 75 mm Hg at hour 3. Survival rates through day 28 were 53% (95% CI, 38%-67%) and 30% (95% CI, 19%-41%) in patients treated with angiotensin II and placebo (p = 0.012), respectively. By day 7, 38% (95% CI, 25%-54%) of angiotensin II patients discontinued RRT versus 15% (95% CI, 8%-27%) placebo (p = 0.007). Mean arterial pressure response was achieved in 53% (95% CI, 38%-68%) and 22% (95% CI, 12%-34%) of patients treated with angiotensin II and placebo (p = 0.001), respectively., Conclusions: In patients with acute kidney injury requiring renal replacement therapy at study drug initiation, 28-day survival and mean arterial pressure response were higher, and rate of renal replacement therapy liberation was greater in the angiotensin II group versus the placebo group. These findings suggest that patients with vasodilatory shock and acute kidney injury requiring renal replacement therapy may preferentially benefit from angiotensin II.

Purpose: Acute kidney injury (AKI) has become a major medical and financial burden in China along with the rest of the world. There have been considerable advances in the understanding of the epidemiology and pathogenesis of AKI. However, there is no consensus regarding the optimal care for patients. The Acute Disease Quality Initiative (ADQI) 19 meeting focused on identifying and designing relevant and achievable AKI-related studies in China., Materials & Methods: The working group developed a list of preliminary questions and objectives and performed analysis of the existing literature. Relevant studies were identified through a literature search using the MEDLINE database and bibliographies of relevant research and review articles. We then used a two-step Delphi process to prioritize a research agenda and proposed specific study designs to address unmet needs., Results: Important gaps in existing knowledge were identified and pragmatic studies were proposed in three distinct areas: care bundles for AKI prevention, renal replacement therapy (RRT) for AKI, and fluid management. In addition, the use of biomarkers to guide clinical trials was discussed., Conclusions: Consensus was reached on a research agenda for AKI with a specific focus on pragmatic trials in China., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Acute kidney injury (AKI) is a heterogeneous clinical syndrome that has multiple aetiologies, variable pathogenesis and diverse outcomes. However, these heterogeneities are not reflected in current approaches to the diagnosis and, to some degree, treatment of AKI. For example, congestive heart failure and dehydration can produce identical changes in serum creatinine level and urine output (parameters that are used to define AKI); however, they differ vastly in their physiological contexts and demand completely opposite treatments. AKI is often still considered to be a homogeneous clinical entity, which implies a uniform pathogenesis and a well-defined prognosis. As a consequence, efforts to find effective AKI treatments have been hampered by a lack of clear clinical classifications for various types of AKI. In addition, subclassification of AKI into subclinical phenotypes - for example, on the basis of protein biomarkers and other in vitro diagnostics that take into account disease aetiology and underlying pathogenesis - might be necessary to develop therapeutic approaches that effectively target the widely differing pathomechanisms of AKI. In this Review, we discuss the major subtypes of AKI that are associated with sepsis, major surgery, renal hypoperfusion and nephrotoxin exposure -situations that are typically seen in the intensive care setting. We consider differences and similarities in their phenotype, pathogenesis and outcomes and how this information might be used to guide treatment.

Acute Kidney Injury (AKI) complicating major trauma is associated with increased mortality and morbidity. Traumatic AKI has specific risk factors and predictable time-course facilitating diagnostic modelling. In a single centre, retrospective observational study we developed risk prediction models for AKI after trauma based on data around intensive care admission. Models predicting AKI were developed using data from 830 patients, using data reduction followed by logistic regression, and were independently validated in a further 564 patients. AKI occurred in 163/830 (19.6%) with 42 (5.1%) receiving renal replacement therapy (RRT). First serum creatinine and phosphate, units of blood transfused in first 24 h, age and Charlson score discriminated need for RRT and AKI early after trauma. For RRT c-statistics were good to excellent: development: 0.92 (0.88-0.96), validation: 0.91 (0.86-0.97). Modelling AKI stage 2-3, c-statistics were also good, development: 0.81 (0.75-0.88) and validation: 0.83 (0.74-0.92). The model predicting AKI stage 1-3 performed moderately, development: c-statistic 0.77 (0.72-0.81), validation: 0.70 (0.64-0.77). Despite good discrimination of need for RRT, positive predictive values (PPV) at the optimal cut-off were only 23.0% (13.7-42.7) in development. However, PPV for the alternative endpoint of RRT and/or death improved to 41.2% (34.8-48.1) highlighting death as a clinically relevant endpoint to RRT.

Background: It is increasingly recognised that improved diagnosis, prognosis and treatment of acute kidney injury (AKI) requires an understanding of distinct underling cellular and molecular mechanisms (endotypes) that may distinguish overtly similar clinical AKI presentations. One important avenue of research is the post-transcriptional regulation of gene expression in response to kidney injury mediated by microRNAs., Summary: This mini-review summarises the use of microRNAs as diagnostic and prognostic biomarkers in AKI. The contribution of microRNAs to the pathophysiology of AKI will be highlighted along with the potential for therapeutic applications. Key Messages: While there is great potential for a better understanding of AKI, microRNAs form a complex regulatory network. Understanding the role and significance of microRNAs in the context of AKI and critical illness is a major endeavour in translational medicine, requiring the integration of clinical and experimental data., (© 2018 S. Karger AG, Basel.)

Background: Kidney transplant recipients often receive large volumes of intravenous fluid replacement in the peri-operative period. Administration of 0.9% saline has previously been associated with acidosis, hyperkalaemia and acute kidney injury. The perioperative use of physiologically balanced replacement fluids may reduce the incidence of post-operative renal replacement therapy and hyperkalaemia., Methods: A retrospective review of consecutive renal transplants before and after a change in perioperative fluid prescription from 0.9% saline to Plasma-Lyte 148., Results: A total of 97 patients were included in the study, 59 receiving exclusively 0.9% saline and 38 receiving exclusively Plasma-Lyte. Patients in the Plasma-Lyte group were less likely to require emergency postoperative dialysis than those receiving 0.9% saline [odds ratio (OR) 0.15 (95% confidence interval 0.03-0.48), P = 0.004], and these patients had more favourable biochemical parameters with less hyperkalaemia, less acidosis and better diuresis. Patients in the Plasma-Lyte group also had a shorter length of hospital stay (7 days versus 11 days; P < 0.0001) and better graft function at 3 months postoperatively (estimated glomerular filtration rate 51 versus 44 mL/min/1.73 m 2 ; P = 0.03); however, there was no difference in graft function at 1 year., Conclusions: Plasma-Lyte in the perioperative period is safe in renal transplantation and is associated with a favourable biochemical profile, including a reduced incidence of hyperkalaemia, better diuresis and less frequent use of renal replacement therapy early after surgery. In patients receiving Plasma-Lyte, graft function was better at 3 months, but this difference did not persist up to 1 year after transplantation.

Aims: Previous research suggests that patients undergoing upper gastrointestinal surgery are at high risk of poor postoperative outcomes. The aim of our study was to describe patient outcomes after elective upper gastrointestinal surgery at a global level., Methods: Prospective analysis of data collected during an international seven-day cohort study of 474 hospitals in 27 countries. Patients undergoing elective upper gastrointestinal surgery were recruited. Outcome measures were in-hospital complications and mortality at 30-days. Results are presented as n(%) and odds ratios with 95% confidence intervals., Results: 2139 patients were included, of whom 498 (23.2%) developed one or more postoperative complications, with 30 deaths (1.4%). Patients with complications had longer median hospital stay 11 (6-18) days vs. 5 (2-10) days. Infectious complications were most frequent, affecting 368 (17.2%) patients. 328 (15.3%) patients were admitted to critical care postoperatively, of whom 161 (49.1%) developed a complication with 14 deaths (4.3%). In a multivariable logistic regression model we identified age (OR 1.02 [1.01-1.03]), American Society of Anesthesiologists physical status III (OR 2.12 [1.44-3.16]) and IV (OR 3.23 [1.72-6.09]), surgery for cancer (OR 1.63 [1.27-2.11]), open procedure (OR 1.40 [1.10-1.78]), intermediate surgery (OR 1.75 [1.12-2.81]) and major surgery (OR 2.65 [1.72-4.23]) as independent risk factors for postoperative complications. Patients undergoing major surgery for upper gastrointestinal cancer experienced twice the rate of complications compared to those undergoing other procedures (224/578 patients [38.8%] versus 274/1561 patients [17.6%])., Conclusions: Complications and death are common after upper gastrointestinal surgery. Patients undergoing major surgery for cancer are at greatest risk., (Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Design and Objectives: To identify and compare how intensive care unit specialists in the United Kingdom and Australia and New Zealand self-reportedly define, assess and manage fluid overload in critically ill patients using a structured online questionnaire., Results: We assessed 219 responses. Australia and New Zealand and United Kingdom intensive care unit specialists reported using clinical examination findings, bedside tools and radiological features to assess fluid status, diagnose fluid overload and initiate fluid removal in the critically ill. An elevated central venous pressure is not regarded as helpful in diagnosing fluid overload and targeting a clinician-set fluid balance is the most popular management strategy. Renal replacement therapy is used ahead of more diuretic therapy in patients who are oligo/anuric, or when diuretic therapy has not generated an adequate response., Conclusions: This self-reported account of practice by United Kingdom and Australia and New Zealand intensivists demonstrates that fluid overload remains poorly defined with variability in both management and practice.

Objectives: Renal outcomes after critical illness are seldom assessed despite strong correlation between chronic kidney disease and survival. Outside hospital, renal dysfunction is more strongly associated with mortality when assessed by serum cystatin C than by creatinine. The relationship between creatinine and longer term mortality might be particularly weak in survivors of critical illness., Design: Retrospective observational cohort study., Patients: In 3,077 adult ICU survivors, we compared ICU discharge cystatin C and creatinine and their association with 1-year mortality. Exclusions were death within 72 hours of ICU discharge, ICU stay less than 24 hours, and end-stage renal disease., Interventions: None., Measurements and Main Results: During ICU admission, serum cystatin C and creatinine diverged, so that by ICU discharge, almost twice as many patients had glomerular filtration rate less than 60 mL/min/1.73 m when estimated from cystatin C compared with glomerular filtration rate estimated from creatinine, 44% versus 26%. In 743 patients without acute kidney injury, where ICU discharge renal function should reflect ongoing baseline, discharge glomerular filtration rate estimated from creatinine consistently overestimated follow-up glomerular filtration rate estimated from creatinine, whereas ICU discharge glomerular filtration rate estimated from cystatin C well matched follow-up chronic kidney disease status. By 1 year, 535 (17.4%) had died. In survival analysis adjusted for age, sex, and comorbidity, cystatin C was near-linearly associated with increased mortality, hazard ratio equals to 1.78 (95% CI, 1.46-2.18), 75th versus 25th centile. Conversely, creatinine demonstrated a J-shaped relationship with mortality, so that in the majority of patients, there was no significant association with survival, hazard ratio equals to 1.03 (0.87-1.2), 75th versus 25th centile. After adjustment for both creatinine and cystatin C levels, higher discharge creatinine was then associated with lower long-term mortality., Conclusions: In contrast to creatinine, cystatin C consistently associated with long-term mortality, identifying patients at both high and low risk, and better correlated with follow-up renal function. Conversely, lower creatinine relative to cystatin C appeared to confer adverse prognosis, confounding creatinine interpretation in isolation. Cystatin C warrants further investigation as a more meaningful measure of renal function after critical illness.

Background: Even mild and transient acute kidney injury (AKI), defined by increases in serum creatinine level, has been associated with adverse outcomes after major surgery. However, characteristic decreases in creatinine concentration during major illness could confound accurate assessment of postoperative AKI., Methods: In a single-hospital, retrospective cohort study of non-cardiac surgery, the association between postoperative AKI, defined using the Kidney Disease: Improving Global Outcomes criteria, and 1-year survival was modelled using a multivariable Cox proportional hazards analysis. Factors associated with development of AKI were examined by means of multivariable logistic regression. Temporal changes in serum creatinine during and after the surgical admission in patients with and without AKI were compared., Results: Some 1869 patients were included in the study, of whom 128 (6·8 per cent) sustained AKI (101 stage 1, 27 stage 2-3). Seventeen of the 128 patients with AKI (13·3 per cent) died in hospital compared with 16 of 1741 (0·9 per cent) without AKI (P < 0·001). By 1 year, 34 patients with AKI (26·6 per cent) had died compared with 106 (6·1 per cent) without AKI (P < 0·001). Over the 8-365 days after surgery, AKI was associated with an adjusted hazard ratio for death of 2·96 (95 per cent c.i. 1·86 to 4·71; P < 0·001). Among hospital survivors without AKI, the creatinine level fell consistently (median difference at discharge versus baseline -7 (i.q.r. -15 to 0) µmol/l), but not in those with AKI (0 (-16 to 26) µmol/l) (P < 0·001)., Conclusion: Although the majority of postoperative AKI was mild, there was a strong association with risk of death in the year after surgery. Underlying decreases in serum creatinine concentration after major surgery could lead to underestimation of AKI severity and overestimation of recovery., (© 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Acute kidney injury (AKI) is a frequent complication of critical illness and carries a significant risk of short- and long-term mortality, chronic kidney disease (CKD) and cardiovascular events. The degree of renal recovery from AKI may substantially affect these long-term endpoints. Therefore maximising recovery of renal function should be the goal of any AKI prevention and treatment strategy. Defining renal recovery is far from straightforward due in part to the limitations of the tests available to assess renal function. Here, we discuss common pitfalls in the evaluation of renal recovery and provide suggestions for improved assessment in the future. We review the epidemiology of renal recovery and of the association between AKI and the development of CKD. Finally, we stress the importance of post-discharge follow-up of AKI patients and make suggestions for its incorporation into clinical practice. Summary key points are that risk factors for non-recovery of AKI are age, CKD, comorbidity, higher severity of AKI and acute disease scores. Second, AKI and CKD are mutually related and seem to have a common denominator. Third, despite its limitations full recovery of AKI may best be defined as the absence of AKI criteria, and partial recovery as a fall in AKI stage. Fourth, after an episode of AKI, serial follow-up measurements of serum creatinine and proteinuria are warranted to diagnose renal impairment and prevent further progression. Measures to promote recovery are similar to those preventing renal harm. Specific interventions promoting repair are still experimental.

Background: The role of goal-directed therapy (GDT) in preventing creatinine rise following noncardiac surgery is unclear. We performed a post-hoc analysis of a randomized controlled trial to assess the relationship between postoperative optimization of oxygen delivery and development of acute kidney injury (AKI)/creatinine rise following noncardiac surgery. Methods: Patients were randomly assigned immediately postoperatively to receive either fluid and/or dobutamine therapy to maintain/restore their preoperative oxygen delivery, or protocolized standard care (oxygen delivery only recorded). Primary end point was serial changes in postoperative creatinine within 48 h postoperatively. Secondary outcomes were development of AKI (KDIGO criteria) and minimal creatinine rise (MCR; no decline from preoperative creatinine), related to all-cause morbidity and length of stay. Results: Postoperative reductions in serum creatinine were similar (P = 0.76) in patients randomized to GDT [10 µmol/L (95% confidence interval, CI: 17 to -1); n  = 95] or protocolized care [8 µmol/L (95% CI: 17 to -6); n  = 92]. Postoperative haemodynamic management was not associated with the development of MCR [78/187 (41.7%)] or AKI [13/187; (7.0%)]. Intraoperative requirement for norepinephrine was more likely in patients who developed postoperative rises in creatinine [relative risk (RR): 1.66 (95% CI: 1.04-2.67); P = 0.04], despite similar volumes of intraoperative fluid being administered. Persistently higher lactate during the intervention period was associated with AKI (mean difference: 1.15 mmol/L (95% CI: 0.48-1.81); P = 0.01]. Prolonged hospital stay was associated with AKI but not MCR [RR: 2.71 (95% CI: 1.51-4.87); P = 0.0008]. Conclusion: These data provide further insights into how perioperative haemodynamic alterations relate to postoperative increases in creatinine once systemic inflammation is established.

Background: Chronic kidney disease is an important preoperative risk factor. However, the association between renal dysfunction and risk of death has not been well explored in non-cardiac surgery., Methods: Two prospective observational studies in non-cardiac surgery were analysed: the European Surgical Outcomes Study (EuSOS) and the UK National Confidential Enquiry into Patient Outcome and Death (NCEPOD). The relationship between preoperative estimated glomerular filtration rate (eGFR) and postoperative mortality was examined using multivariable Cox proportional hazards models., Results: In EuSOS, 1580 (4·3 per cent) of 36 779 patients died in hospital; in NCEPOD, 298 (2·8 per cent) of 10 466 patients had died by 60 days after surgery. Chronic kidney disease (eGFR below 60·0 ml per min per 1·73 m(2) ) was present in 6415 patients (17·4 per cent) in EuSOS and 2262 (21·6 per cent) in NCEPOD. Preoperative chronic kidney disease was associated with older age, men, diagnosis of diabetes, cardiovascular or respiratory disease, and non-elective surgery. Preoperative eGFR categories below 60·0 ml per min per 1·73 m(2) were associated with increasing adjusted hazard ratios (HRs) for death compared with a value of 90·0 ml per min per 1·73 m(2) and above. In EuSOS, the risk of death increased with lower eGFR category, to a maximum with eGFR 15·0-29·9 ml per min per 1·73 m(2) (HR 3·37, 95 per cent c.i. 2·70 to 4·22). In NCEPOD, the risk of death also increased with declining eGFR and was maximal for eGFR below 15·0 ml per min per 1·73 m(2) (HR 3·40, 1·78 to 6·50)., Conclusion: Renal dysfunction is an important risk factor for death after non-cardiac surgery and the risk increases steeply for patients with moderate to severe kidney dysfunction., (© 2016 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Purpose: Acute kidney injury (AKI) is a recognised risk factor for adverse outcomes in critical illness and hospitalised patients in general. To understand the incidence and associations of AKI as a peri-operative complication of major abdominal surgery, we conducted a systematic literature review and meta-analysis., Methods: Using a systematic strategy, we searched the electronic reference databases for articles describing post-operative renal outcomes using consensus criteria for AKI diagnosis (RIFLE, AKIN or KDIGO) in the setting of major abdominal surgery. Pooled incidence of AKI and, where reported, pooled relative risk of death after post-operative AKI were estimated using random effects models., Results: From 4287 screened titles, 19 articles met our inclusion criteria describing AKI outcomes in 82,514 patients undergoing abdominal surgery. Pooled incidence of AKI was 13.4% (95% CI 10.9-16.4%). In eight studies that reported the short-term mortality, relative risk of death in the presence of post-operative AKI was 12.6 fold (95% CI, 6.8-23.4). Where reported, length of stay was greater and non-renal post-operative complications were also more frequent in patients experiencing AKI., Conclusions: Using modern consensus definitions, AKI is a common complication of major abdominal surgery that is associated with adverse patient outcomes including death. While a causative role for AKI cannot be concluded from this analysis, as an important signal of peri-operative harm, AKI should be regarded as an important surgical outcome measure and potential target for clinical interventions.

Objective: Reduced exercise capacity is well documented in end-stage chronic kidney disease (CKD), preceded by changes in cardiac morphology in CKD stage 3. However, it is unknown whether subclinical cardiopulmonary dysfunction occurs in CKD stage 3 independently of heart failure., Methods: Prospective observational cross-sectional study of exercise capacity assessed by cardiopulmonary exercise testing in 993 preoperative patients. Primary outcome was peak oxygen consumption (VO2peak). Anaerobic threshold (AT), oxygen pulse and exercise-evoked measures of autonomic function were analysed, controlling for CKD stage 3, age, gender, diabetes mellitus and hypertension., Results: CKD stage 3 was present in 93/993 (9.97%) patients. Diabetes mellitus (RR 2.49 (95% CI 1.59 to 3.89); p<0.001), and hypertension (RR 3.20 (95% CI 2.04 to 5.03); p<0.001)) were more common in CKD stage 3. Cardiac failure (RR 0.83 (95% CI 0.30 to 2.24); p=0.70) and ischaemic heart disease (RR 1.40 (95% CI 0.97 to 2.02); p=0.09) were not more common in CKD stage 3. Patients with CKD stage 3 had lower predicted VO2peak (mean difference: 6% (95% CI 1% to 11%); p=0.02), lower peak heart rate (mean difference:9 bpm (95% CI 3 to 14); p=0.03)), lower AT (mean difference: 1.1 mL/min/kg (95% CI 0.4 to 1.7); p<0.001) and impaired heart rate recovery (mean difference: 4 bpm (95% CI 1 to 7); p<0.001))., Conclusions: Subclinical cardiopulmonary dysfunction in CKD stage 3 is common. This study suggests that maladaptive cardiovascular/autonomic dysfunction may be established in CKD stage 3, preceding pathophysiology reported in end-stage CKD.

Background/aims: Recent updates to the Nikkiso Aquarius continuous renal replacement therapy (CRRT) platform allowed us to develop a post-dilution protocol for regional citrate anticoagulation (RCA) using standard bicarbonate buffered, calcium containing replacement solution with acid citrate dextrose formula-A as a citrate source. Our objective was to demonstrate that the protocol was safe and effective., Methods: Prospective audit of consecutive patients receiving RCA for CRRT within intensive care unit, who were either contraindicated to heparin or had poor filter lifespan (<12 h for 2 consecutive filters) on heparin., Results: We present the first 29 patients who used 98 filters. After excluding 'non-clot' filter loss, 50% had a duration of >27 h. Calcium supplementation was required for 30 (30%) filter circuits, in 17 of 29 (58%) patients. One patient discontinued the treatment due to metabolic alkalosis, but there were no adverse bleeding events., Conclusion: Post-dilution RCA system is effective and simple to use on the Aquarius platform and results in comparable filter life for patients relatively contraindicated to heparin., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Purpose . Fluid therapy aimed at increasing urine output is a commonly employed strategy to prevent acute kidney injury (AKI) in critically ill patients with rhabdomyolysis. Automated fluid management has the potential to optimise urine output while avoiding fluid accumulation in rhabdomyolysis patients. Methods . In a single centre clinical service evaluation we compared a convenience sample of critically ill adults with rhabdomyolysis treated with automated fluid management using the RenalGuard® device to patients managed with manual fluid adjustment following our standard rhabdomyolysis protocol. Primary outcome was number of hours with urine output >2 mL/kg during first 48 h of therapy. Results . Eight patients treated with RenalGuard were compared to 28 patients treated with manual fluid management. Number of hours of target urine output was greater in the RenalGuard versus the Standard group (176/312 (56.4%) versus 534/1305 (40.9%); p < 0.01). Urine output was significantly higher in the first 24 h in the RenalGuard group (median (IQR) 4033 mL (3682-7363) versus 2913 mL (2263-4188 mL); p < 0.01). Fluid balance, electrolyte, diuretics, and bicarbonate use were comparable between groups. Conclusions . Automated fluid management resulted in a higher urine output more quickly in the treatment of rhabdomyolysis. Further research is needed to analyse the effect of diuresis-matched hydration for the prevention of AKI in rhabdomyolysis., Competing Interests: The authors have no competing interests in regard to this paper.

There is a paucity of high-quality evidence to guide clinicians on thresholds for commencement of renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI), and wide international practice variation. Wald et al. report a pilot randomized trial examining accelerated use of RRT for moderate AKI in the intensive care unit, providing a workable design for a definitive trial examining the timing of RRT in critical illness.