Hemoadsorption: Consensus report of the 30th Acute Disease Quality Initiative workgroup.

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex-vivo, experimental, and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative (ADQI) consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility, and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials (RCTs). Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

Association between urea trajectory and protein dose in critically ill adults: a secondary exploratory analysis of the effort protein trial (RE-EFFORT).

BACKGROUND: Delivering higher doses of protein to mechanically ventilated critically ill patients did not improve patient outcomes and may have caused harm. Longitudinal urea measurements could provide additional information about the treatment effect of higher protein doses. We hypothesised that higher urea values over time could explain the potential harmful treatment effects of higher doses of protein. METHODS: We conducted a reanalysis of a randomised controlled trial of higher protein doses in critical illness (EFFORT Protein). We applied Bayesian joint models to estimate the strength of association of urea with 30-day survival and understand the treatment effect of higher protein doses. RESULTS: Of the 1301 patients included in EFFORT Protein, 1277 were included in this analysis. There were 344 deaths at 30 days post-randomisation. By day 6, median urea was 2.1 mmol/L higher in the high protein group (95% CI 1.1-3.2), increasing to 3.0 mmol/L (95% CI 1.3-4.7) by day 12. A twofold rise in urea was associated with an increased risk of death at 30 days (hazard ratio 1.34, 95% credible interval 1.21-1.48), following adjustment of baseline characteristics including age, illness severity, renal replacement therapy, and presence of AKI. This association persisted over the duration of 30-day follow-up and in models adjusting for evolution of organ failure over time. CONCLUSIONS: The increased risk of death in patients randomised to a higher protein dose in the EFFORT Protein trial was estimated to be mediated by increased urea cycle activity, of which serum urea is a biological signature. Serum urea should be taken into consideration when initiating and continuing protein delivery in critically ill patients. CLINICALTRIALS: gov Identifier: NCT03160547 (2017-05-17).

Supporting effective shared decision-making in surgical context: Why framing of choices matters for high-risk patients and clinicians.

AIM: In the context of high-risk surgery, shared decision-making (SDM) is important. However, the effectiveness of SDM can be hindered by misalignment between patients and clinicians in their expectations of postoperative outcomes. This study investigated the extent and the effects of this misalignment, as well as its amenability to interventions that encourage perspective-taking. METHOD: Lay participants with a Charlson Comorbidity Index of ≥4 (representing patients) and surgeons and anaesthetists (representing doctors) were recruited. During an online experiment, subjects in both groups forecast their expectations regarding short-term (0, 1 and 3 months after treatment) and long-term (6, 9 and 12 months after treatment) outcomes of different treatment options for one of three hypothetical clinical scenarios - ischaemic heart disease, colorectal cancer or osteoarthritis of the hip - and then chose between surgical or non-surgical treatment. Subjects in both groups were asked to consider the scenarios from their own perspective (Estimation task), and then to adopt the perspective of subjects in the other study group (Perspective task). The decisions of all participants (surgery vs. non-surgical alternative) were analysed using binomial generalized linear mixed models. RESULTS: In total, 55 lay participants and 54 doctors completed the online experiment. Systematic misalignment in expectations between high-risk patients and doctors was observed, with patients expecting better surgical outcomes than clinicians. Patients forecast a significantly higher likelihood of engaging in normal activities in the long term (ß = -1.09, standard error [SE] = 0.20, t = -5.38, p < 0.001), a lower likelihood of experiencing complications in the long term (ß = 0.92, SE = 0.21, t = 4.45, p < 0.001) and a lower likelihood of experiencing depression in both the short term and the long term (ß = 1.01, SE = 0.19, t = 5.38, p < 0.001), than did doctors. Compared with doctors, patients forecast higher estimates of experiencing complications in the short term when a non-surgical alternative was selected (ß = -0.91, SE = 0.26, t = -3.50, p = 0.003). Despite this misalignment, in both groups surgical treatment was strongly preferred (estimation task: 88.7% of doctors and 80% of patients; perspective task: 82.2% of doctors and 90.1% of patients). CONCLUSION: When high-risk surgery is discussed, a non-surgical option may be viewed as 'doing nothing', hence reducing the sense of agency and control. This biases the decision-making process, regardless of the expectations that doctors and patients might have about the outcomes of surgery. Therefore, to improve SDM and to increase the agency and control of patients regarding decisions about their care, we advocate framing the non-surgical treatment options in a way that emphasizes action, agency and change.

Assessing the role of Chemokine (C-C motif) ligand 14 in AKI: a European consensus meeting.

BACKGROUND: Urinary Chemokine (C-C motif) ligand 14 (CCL14) is a biomarker associated with persistent severe acute kidney injury (AKI). There is limited data to support the implementation of this AKI biomarker to guide therapeutic actions. METHODS: Sixteen AKI experts with clinical CCL14 experience participated in a Delphi-based method to reach consensus on when and how to potentially use CCL14. Consensus was defined as ≥ 80% agreement (participants answered with 'Yes', or three to four points on a five-point Likert Scale). RESULTS: Key consensus areas for CCL14 test implementation were: identifying challenges and mitigations, developing a comprehensive protocol and pairing it with a treatment plan, and defining the target population. The majority agreed that CCL14 results can help to prioritize AKI management decisions. CCL14 levels above the high cutoff (> 13 ng/mL) significantly changed the level of concern for modifying the AKI treatment plan (p < 0.001). The highest level of concern to modify the treatment plan was for discussions on renal replacement therapy (RRT) initiation for CCL14 levels > 13 ng/mL. The level of concern for discussion on RRT initiation between High and Low, and between Medium and Low CCL14 levels, showed significant differences. CONCLUSION: Real world urinary CCL14 use appears to provide improved care options to patients at risk for persistent severe AKI. Experts believe there is a role for CCL14 in AKI management and it may potentially reduce AKI-disease burden. There is, however, an urgent need for evidence on treatment decisions and adjustments based on CCL14 results.

The rate and assessment of muscle wasting during critical illness: a systematic review and meta-analysis.

BACKGROUND: Patients with critical illness can lose more than 15% of muscle mass in one week, and this can have long-term detrimental effects. However, there is currently no synthesis of the data of intensive care unit (ICU) muscle wasting studies, so the true mean rate of muscle loss across all studies is unknown. The aim of this project was therefore to systematically synthetise data on the rate of muscle loss and to identify the methods used to measure muscle size and to synthetise data on the prevalence of ICU-acquired weakness in critically ill patients. METHODS: We conducted a systematic literature search of MEDLINE, PubMed, AMED, BNI, CINAHL, and EMCARE until January 2022 (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD420222989540. We included studies with at least 20 adult critically ill patients where the investigators measured a muscle mass-related variable at two time points during the ICU stay. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and assessed the study quality using the Newcastle-Ottawa Scale. RESULTS: Fifty-two studies that included 3251 patients fulfilled the selection criteria. These studies investigated the rate of muscle wasting in 1773 (55%) patients and assessed ICU-acquired muscle weakness in 1478 (45%) patients. The methods used to assess muscle mass were ultrasound in 85% (n = 28/33) of the studies and computed tomography in the rest 15% (n = 5/33). During the first week of critical illness, patients lost every day -1.75% (95% CI -2.05, -1.45) of their rectus femoris thickness or -2.10% (95% CI -3.17, -1.02) of rectus femoris cross-sectional area. The overall prevalence of ICU-acquired weakness was 48% (95% CI 39%, 56%). CONCLUSION: On average, critically ill patients lose nearly 2% of skeletal muscle per day during the first week of ICU admission.

Characterising biological mechanisms underlying ethnicity-associated outcomes in COVID-19 through biomarker trajectories: a multicentre registry analysis.

BACKGROUND: Differences in routinely collected biomarkers between ethnic groups could reflect dysregulated host responses to disease and to treatments, and be associated with excess morbidity and mortality in COVID-19. METHODS: A multicentre registry analysis from patients aged ≥16 yr with SARS-CoV-2 infection and emergency admission to Barts Health NHS Trust hospitals during January 1, 2020 to May 13, 2020 (wave 1) and September 1, 2020 to February 17, 2021 (wave 2) was subjected to unsupervised longitudinal clustering techniques to identify distinct phenotypic patient clusters based on trajectories of routine blood results over the first 15 days of hospital admission. Distribution of trajectory clusters across ethnic categories was determined, and associations between ethnicity, trajectory clusters, and 30-day survival were assessed using multivariable Cox proportional hazards modelling. Secondary outcomes were ICU admission, survival to hospital discharge, and long-term survival to 640 days. RESULTS: We included 3237 patients with hospital length of stay ≥7 days. In patients who died, there was greater representation of Black and Asian ethnicity in trajectory clusters for C-reactive protein and urea-to-creatinine ratio associated with increased risk of death. Inclusion of trajectory clusters in survival analyses attenuated or abrogated the higher risk of death in Asian and Black patients. Inclusion of C-reactive protein went from hazard ratio (HR) 1.36 [0.95-1.94] to HR 0.97 [0.59-1.59] (wave 1), and from HR 1.42 [1.15-1.75]) to HR 1.04 [0.78-1.39] (wave 2) in Asian patients. Trajectory clusters associated with reduced 30-day survival were similarly associated with worse secondary outcomes. CONCLUSIONS: Clinical biochemical monitoring of COVID-19 and progression and treatment response in SARS-CoV-2 infection should be interpreted in the context of ethnic background.

Long-term disease interactions amongst surgical patients: a population cohort study.

BACKGROUND: The average age of the surgical population continues to increase, as does prevalence of long-term diseases. However, outcomes amongst multi-morbid surgical patients are not well described. METHODS: We included adults undergoing non-obstetric surgical procedures in the English National Health Service between January 2010 and December 2015. Patients could be included multiple times in sequential 90-day procedure spells. Multi-morbidity was defined as presence of two or more long-term diseases identified using a modified Charlson comorbidity index. The primary outcome was 90-day postoperative death. Secondary outcomes included emergency hospital readmission within 90 days. We calculated age- and sex-adjusted odds ratios (OR) with 95% confidence intervals (CI) using logistic regression. We compared the outcomes associated with different disease combinations. RESULTS: We identified 20 193 659 procedure spells among 13 062 715 individuals aged 57 (standard deviation 19) yr. Multi-morbidity was present among 2 577 049 (12.8%) spells with 195 965 deaths (7.6%), compared with 17 616 610 (88.2%) spells without multi-morbidity with 163 529 deaths (0.9%). Multi-morbidity was present in 1 902 859/16 946 808 (11.2%) elective spells, with 57 663 deaths (2.7%, OR 4.9 [95% CI: 4.9-4.9]), and 674 190/3 246 851 (20.7%) non-elective spells, with 138 302 deaths (20.5%, OR 3.0 [95% CI: 3.0-3.1]). Emergency readmission followed 547 399 (22.0%) spells with multi-morbidity compared with 1 255 526 (7.2%) without. Multi-morbid patients accounted for 57 663/114 783 (50.2%) deaths after elective spells, and 138 302/244 711 (56.5%) after non-elective spells. The rate of death varied five-fold from lowest to highest risk disease pairs. CONCLUSION: One in eight patients undergoing surgery have multi-morbidity, accounting for more than half of all postoperative deaths. Disease interactions amongst multi-morbid patients is an important determinant of patient outcome.

Nomenclature of Extracorporeal Blood Purification Therapies for Acute Indications: The Nomenclature Standardization Conference.

The development of new extracorporeal blood purification (EBP) techniques has led to increased application in clinical practice but also inconsistencies in nomenclature and misunderstanding. In November 2022, an international consensus conference was held to establish consensus on the terminology of EBP therapies. It was agreed to define EBP therapies as techniques that use an extracorporeal circuit to remove and/or modulate circulating substances to achieve physiological homeostasis, including support of the function of specific organs and/or detoxification. Specific acute EBP techniques include renal replacement therapy, isolated ultrafiltration, hemoadsorption, and plasma therapies, all of which can be applied in isolation and combination. This paper summarizes the proposed nomenclature of EBP therapies and serves as a framework for clinical practice and future research.

Catabolism in Critical Illness: A Reanalysis of the REducing Deaths due to OXidative Stress (REDOXS) Trial.

OBJECTIVES: Ongoing risk of death and poor functional outcomes are important consequences of prolonged critical illness. Characterizing the catabolic phenotype of prolonged critical illness could illuminate biological processes and inform strategies to attenuate catabolism. We aimed to examine if urea-to-creatinine ratio, a catabolic signature of prolonged critical illness, was associated with mortality after the first week of ICU stay. DESIGN: Reanalysis of multicenter randomized trial of glutamine supplementation in critical illness (REducing Deaths due to OXidative Stress [REDOXS]). SETTING: Multiple adult ICUs. PATIENTS: Adult patients admitted to ICU with two or more organ failures related to their acute illness and surviving to day 7. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The association between time-varying urea-to-creatinine ratio and 30-day mortality was tested using Bayesian joint models adjusted for prespecified-covariates (age, kidney replacement therapy, baseline Sequential Organ Failure Assessment, dietary protein [g/kg/d], kidney dysfunction, and glutamine-randomization). From 1,021 patients surviving to day 7, 166 (16.3%) died by day 30. After adjustment in a joint model, a higher time-varying urea-to-creatinine ratio was associated with increased mortality (hazard ratio [HR], 2.15; 95% credible interval, 1.66-2.82, for a two-fold greater urea-to-creatinine ratio). This association persisted throughout the 30-day follow-up. Mediation analysis was performed to explore urea-to-creatinine ratio as a mediator-variable for the increased risk of death reported in REDOXS when randomized to glutamine, an exogenous nitrogen load. Urea-to-creatinine ratio closest to day 7 was estimated to mediate the risk of death associated with randomization to glutamine supplementation (HR, 1.20; 95% CI, 1.04-1.38; p = 0.014), with no evidence of a direct effect of glutamine (HR, 0.90; 95% CI, 0.62-1.30; p = 0.566). CONCLUSIONS: The catabolic phenotype measured by increased urea-to-creatinine ratio is associated with increased risk of death during prolonged ICU stay and signals the deleterious effects of glutamine administration in the REDOXS study. Urea-to-creatinine ratio is a promising catabolic signature and potential interventional target.

COVID-19-associated AKI.

PURPOSE OF REVIEW: While it is now widely established acute kidney injury (AKI) is a common and important complication of coronavirus disease (COVID-19) disease, there is marked variability in its reported incidence and outcomes. This narrative review provides a mid-2022 summary of the latest epidemiological evidence on AKI in COVID-19. RECENT FINDINGS: Large observational studies and meta-analyses report an AKI incidence of 28-34% in all inpatients and 46-77% in intensive care unit (ICU). The incidence of more severe AKI requiring renal replacement therapy (RRT) in ICU appears to have declined over time, in data from England and Wales RRT use declined from 26% at the start of the pandemic to 14% in 2022. The majority of survivors apparently recover their kidney function by hospital discharge; however, these individuals appear to remain at increased risk of future AKI, estimated glomerular filtration rate (eGFR) decline and chronic kidney disease. Importantly even in the absence of overt AKI a significant proportion of survivors of COVID-19 hospitalisation had reduced eGFR on follow-up. SUMMARY: This review summarises the epidemiology, risk factors, outcomes and treatment of COVID-19-associated AKI across the global pandemic. In particular the long-term impact of COVID-19 disease on kidney health is uncertain and requires further characterisation.

Change in healthcare utilisation after surgical treatment: observational study of routinely collected patient data from primary and secondary care.

BACKGROUND: Most patients fully recover after surgery. However, high-risk patients may experience an increased burden of medical disease. METHODS: We performed a prospectively planned analysis of linked routine primary and secondary care data describing adult patients undergoing non-obstetric surgery at four hospitals in East London between January 2012 and January 2017. We categorised patients by 90-day mortality risk using logistic regression modelling. We calculated healthcare contact days per patient year during the 2 yr before and after surgery, and express change using rate ratios (RaR) with 95% confidence intervals. RESULTS: We included 70 021 patients, aged (mean [standard deviation, sd]) 49.8 (19) yr, with 1238 deaths within 2 yr after surgery (1.8%). Most procedures were elective (51 693, 74.0%), and 20 441 patients (29.1%) were in the most deprived national quintile for social deprivation. Elective patients had 12.7 healthcare contact days per patient year before surgery, increasing to 15.5 days in the 2 yr after surgery (RaR, 1.22 [1.21-1.22]), and those at high-risk of 90-day mortality (11% of population accounting for 80% of all deaths) had the largest increase (37.0 days per patient year before vs 60.8 days after surgery; RaR, 1.64 [1.63-1.65]). Emergency patients had greater increases in healthcare burden (13.8 days per patient year before vs 24.8 days after surgery; RaR, 1.8 [1.8-1.8]), particularly in high-risk patients (28% of patients accounting for 80% of all deaths by day 90), with 21.6 days per patient year before vs 49.2 days after surgery; RaR, 2.28 [2.26-2.29]. DISCUSSION: High-risk patients who survive the immediate perioperative period experience large and persistent increases in healthcare utilisation in the years after surgery. The full implications of this require further study.

Death after surgery among patients with chronic disease: prospective study of routinely collected data in the English NHS.

BACKGROUND: Five million surgeries take place in the NHS each year. Little is known about the prevalence of chronic diseases among these patients, and the association with postoperative outcomes. METHODS: Analysis of routine data from all NHS hospitals in England including patients aged ≥18 yr undergoing non-obstetric surgery between January 1, 2010 and December 31, 2015. The primary outcome was death within 90 days after surgery. For each chronic disease, we adjusted for age, sex, presence of other diseases, emergency surgery, and year using logistic regression models. We defined high-risk diseases as those with an adjusted odds ratio (OR) for death ≥2 and report associated 2-yr survival. RESULTS: We included 8 624 611 patients (median age, 53 [36-68] yr), of whom 6 913 451 (80.2%) underwent elective surgery and 1 711 160 (19.8%) emergency surgery. Overall, 2 311 600 (26.8%) patients had a chronic disease, of whom 109 686 (4.7%) died within 90 days compared with 24 136 (0.4%) of 6 313 011 without chronic disease. Respiratory disease (1 002 281 [11.6%]), diabetes mellitus (662 706 [7.7%]), and cancer (310 363; 3.6%) were the most common. Four chronic diseases accounted for 7.7% of patients but 59.0% of deaths: cancer (37 693 deaths [12.1%]; OR=8.3 [8.2-8.5]), liver disease (8638 deaths [10.3%]; OR=4.5 [4.4-4.7]), cardiac failure (26 604 deaths [12.6%]; OR=2.4 [2.4-2.5]), and dementia (19 912 deaths [17.9%]; OR=2.0 [1.9-2.0]). Two-year survival was 67.7% among patients with high-risk chronic disease, compared with 97.1% without. CONCLUSION: One in four surgical patients has a chronic disease with an associated 10-fold increase in risk of postoperative death. Two-thirds of all deaths after surgery occur among patients with high-risk diseases (cancer, cardiac failure, liver disease, dementia).

Long-term mortality following complications after elective surgery: a secondary analysis of pooled data from two prospective cohort studies.

BACKGROUND: Complications after surgery affect survival and quality of life. We aimed to confirm the relationship between postoperative complications and death within 1 yr after surgery. METHODS: We conducted a secondary analysis of pooled data from two prospective cohort studies of patients undergoing surgery in five high-income countries between 2012 and 2014. Exposure was any complication within 30 days after surgery. Primary outcome was death within 1 yr after surgery, ascertained by direct follow-up or linkage to national registers. We adjusted for clinically important covariates using a mixed-effect multivariable Cox proportional hazards regression model. We conducted a planned subgroup analysis by type of complication. Data are presented as mean with standard deviation (sd), n (%), and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). RESULTS: The pooled cohort included 10 132 patients. After excluding 399 (3.9%) patients with missing data or incomplete follow-up, 9733 patients were analysed. The mean age was 59 [sd 16.8] yr, and 5362 (55.1%) were female. Of 9733 patients, 1841 (18.9%) had complications within 30 days after surgery, and 319 (3.3%) died within 1 yr after surgery. Of 1841 patients with complications, 138 (7.5%) died within 1 yr after surgery compared with 181 (2.3%) of 7892 patients without complications (aHR 1.94 [95% CI: 1.53-2.46]). Respiratory failure was associated with the highest risk of death, resulting in six deaths amongst 28 patients (21.4%). CONCLUSIONS: Postoperative complications are associated with increased mortality at 1 yr. Further research is needed to identify patients at risk of complications and to reduce mortality.

Novel methods to identify and measure catabolism.

PURPOSE OF REVIEW: Assess current potential catabolism-biomarkers to characterize patients developing prolonged critical illness. RECENT FINDINGS: A raised urea-to-creatinine ratio (UCR) during critical illness is negatively associated with muscle mass with greater increases in UCR seen patients developing persistent critical illness. Similarly, sarcopenia index (a ratio of creatinine to cystatin-c concentrations) correlates well to muscle mass in intensive care populations. Elevated growth/differentiation factor-15 (GDF-15) has been inconsistently associated with muscle loss. Although GDF-15 was a poor marker of feeding tolerance, it has been associated with worse prognosis in intensive care. SUMMARY: UCR is an available and clinically applicable biomarker of catabolism. Similarly, sarcopenia index can be used to assess muscle mass and indirectly measure catabolism based on readily available biochemical measurements. The utility of novel biomarkers, such as GDF-15 is less established.

Prognostic association of routinely measured biomarkers in patients admitted to critical care: a systematic review.

PURPOSE: To examine reported prognostic associations of routine blood measurements in the intensive care unit. MATERIALS AND METHODS: We searched PubMed, EMBASE through 28th 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.

Fluid balance management during continuous renal replacement therapy.

In critically ill patients, particularly in the setting of shock and sepsis volume management frequently results in a fluid overloaded state, requiring diuresis or intervention with renal replacement therapy. Achieving appropriate volume management requires knowledge of the underlying cardiovascular pathophysiology and careful evaluation of intravascular and extravascular volume status. In the presence of a failing kidney, fluid removal is often a challenge. Continuous renal replacement therapy (CRRT) techniques offer a significant advantage over intermittent dialysis for fluid control, however, any form of RRT in the critically ill patient requires careful attention to prescription and monitoring to avoid complications. In order to utilize these therapies for their maximum potential it is necessary to understand which factors influence fluid balance and have an understanding of the principles and kinetics of fluid removal with extra-corporeal techniques.

Socioeconomic deprivation and long-term outcomes after elective surgery: analysis of prospective data from two observational studies.

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.

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

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

Variability in Serum Sodium Concentration and Prognostic Significance in Severe Traumatic Brain Injury: A Multicenter Observational Study.

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 (dNaSD), 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 (dNaSD) occurred at a median of 2 [1-4] days after admission. There was a significant progressive decrease in dNaSD 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, dNaSD 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.

Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference.

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.