ORCID Profile
0000-0001-9500-9080
Current Organisations
Institute for Computational and Data Sciences, Pennsylvania State University
,
Guy's and St Thomas' NHS Foundation Trust
,
Georg-August-Universität Göttingen
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Publications
A Novel Empirical and Deep Ensemble Super Learning Approach in Predicting Reservoir Wettability via Well Logs
Publisher: MDPI AG
Date: 14-03-2022
DOI: 10.3390/APP12062942
Abstract: Accurately measuring wettability is of the utmost importance because it influences several reservoir parameters while also impacting reservoir potential, recovery, development, and management plan. As such, this study proposes a new formulated mathematical model based on the correlation between the Amott-USBM wettability measurement and field NMR T2LM log. The exponential relationship based on the existence of immiscible fluids in the pore space had a correlation coefficient of 0.95. Earlier studies on laboratory core wettability measurements using T2 distribution as a function of increasing water saturation were modified to include T2LM field data. Based on the trends observed, water-wet and oil-wet conditions were qualitatively identified. Using the mean T2LM for the intervals of interest and the formulated mathematical formula, the various wetting conditions in existence were quantitatively measured. Results of this agreed with the various core wettability measurements used to develop the mathematical equation. The results expressed the validity of the mathematical equation to characterise wettability at the field scale. With the cost of running NMR logs not favourable, and hence not always run, a deep ensemble super learner was employed to establish a relationship between NMR T2LM and wireline logs. This model is based on the architecture of a deep learning model and the theoretical background of ensemble models due to their reported superiority. The super learner was developed using nine ensemble models as base learners. The performance of nine ensemble models was compared to the deep ensemble super learner. Based on the RMSE, R2, MAE, MAPD and MPD the deep ensemble super learner greatly outperformed the base learners. This indicates that the deep ensemble super learner can be used to predict NMR T2LM in the field. By applying the methodology and mathematical formula proposed in this study, the wettability of reservoirs can be accurately characterised as illustrated in the field deployment.
Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis
Publisher: Springer Science and Business Media LLC
Date: 14-08-2013
DOI: 10.1007/S00134-013-3044-3
Abstract: Bleeding frequently complicates critical illness and may have serious consequences. Our objectives are to describe the predictors of major bleeding and the association between bleeding and mortality in medical-surgical critically ill patients receiving heparin thromboprophylaxis. We prospectively studied patients from 67 intensive care units and six countries enrolled in a thromboprophylaxis trial (NCT00182143) comparing dalteparin with unfractionated heparin. Patients with trauma, orthopedic surgery or neurosurgery were excluded. Trained research coordinators used a validated tool to document bleeding, which underwent duplicate independent blinded adjudication. Major bleeding was defined as hypovolemic shock, bleeding into critical sites, requiring an invasive intervention or transfusion of at least two units of red blood cells, or associated with hypotension or tachycardia in the absence of other causes. Adjusted Cox proportional hazard regression analysis was used to identify major bleeding predictors and the association between bleeding and mortality. Among 3,746 patients, bleeding occurred in 208 [5.6 %, 95 % confidence interval (CI) 4.9-6.3 %]. Time-dependent predictors were prolonged activated partial thromboplastin time [hazard ratio (HR) 1.10, 1.05-1.14 per 10 s increase], lower platelet count (HR 1.16, 1.09-1.24 per 50 × 10(9)/L decrease), therapeutic heparin (HR 3.26, 1.72-6.17), antiplatelet agents (HR 1.38, 1.02-1.88), renal replacement therapy (HR 1.75, 1.20-2.56), and recent surgery (HR 1.64, 1.01-2.65). Type of pharmacologic thromboprophylaxis was not associated with bleeding. Patients with bleeding had a higher risk of in-hospital death (HR 2.09, 1.69-2.57). As major bleeding has modifiable risk factors and is associated with in-hospital mortality, strategies to mitigate these factors should be evaluated in critically ill patients.
Effect of Human Recombinant Alkaline Phosphatase on 7-Day Creatinine Clearance in Patients With Sepsis-Associated Acute Kidney Injury
Publisher: American Medical Association (AMA)
Date: 20-11-2018
Extracorporeal Treatment for Chloroquine, Hydroxychloroquine, and Quinine Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 22-09-2020
Abstract: Although poisoning by chloroquine, hydroxychloroquine, or quinine is relatively uncommon, recent use of chloroquine and hydroxychloroquine for COVID-19 has elevated concerns regarding management of such poisonings. To investigate the effect of and indications for extracorporeal treatments in cases of poisoning with these drugs, the Extracorporeal Treatments in Poisoning workgroup conducted systematic reviews of the relevant literature, screened studies, extracted data, and summarized findings. The group concluded that chloroquine, hydroxychloroquine, and quinine are not dialyzable (not amenable to clinically significant removal by extracorporeal treatments) and the current clinical evidence does not support the use of such treatments for chloroquine and quinine poisonings. Considering that data on extracorporeal treatments for hydroxychloroquine toxicity are sparse, the group proposed pharmacokinetic studies to confirm or refute the current impression that the drug is non-dialyzable. Although chloroquine, hydroxychloroquine, and quinine are used for a range of medical conditions, recent research suggested a potential role in treating COVID-19. The resultant increase in prescribing was accompanied by an increase in adverse events, including severe toxicity and death. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup sought to determine the effect of and indications for extracorporeal treatments in cases of poisoning with these drugs. We conducted systematic reviews of the literature, screened studies, extracted data, and summarized findings following published EXTRIP methods. A total of 44 studies (three in vitro studies, two animal studies, 28 patient reports or patient series, and 11 pharmacokinetic studies) met inclusion criteria regarding the effect of extracorporeal treatments. Toxicokinetic or pharmacokinetic analysis was available for 61 patients (13 chloroquine, three hydroxychloroquine, and 45 quinine). Clinical data were available for analysis from 38 patients, including 12 with chloroquine toxicity, one with hydroxychloroquine toxicity, and 25 with quinine toxicity. All three drugs were classified as non-dialyzable (not amenable to clinically significant removal by extracorporeal treatments). The available data do not support using extracorporeal treatments in addition to standard care for patients severely poisoned with either chloroquine or quinine (strong recommendation, very low quality of evidence). Although hydroxychloroquine was assessed as being non-dialyzable, the clinical evidence was not sufficient to support a formal recommendation regarding the use of extracorporeal treatments for this drug. On the basis of our systematic review and analysis, the EXTRIP workgroup recommends against using extracorporeal methods to enhance elimination of these drugs in patients with severe chloroquine or quinine poisoning.
Extracorporeal Blood Purification and Organ Support in the Critically Ill Patient during COVID-19 Pandemic: Expert Review and Recommendation
Publisher: S. Karger AG
Date: 26-05-2020
DOI: 10.1159/000508125
Abstract: Critically ill COVID-19 patients are generally admitted to the ICU for respiratory insufficiency which can evolve into a multiple-organ dysfunction syndrome requiring extracorporeal organ support. Ongoing advances in technology and science and progress in information technology support the development of integrated multi-organ support platforms for personalized treatment according to the changing needs of the patient. Based on pathophysiological derangements observed in COVID-19 patients, a rationale emerges for sequential extracorporeal therapies designed to remove inflammatory mediators and support different organ systems. In the absence of vaccines or direct therapy for COVID-19, extracorporeal therapies could represent an option to prevent organ failure and improve survival. The enormous demand in care for COVID-19 patients requires an immediate response from the scientific community. Thus, a detailed review of the available technology is provided by experts followed by a series of recommendation based on current experience and opinions, while waiting for generation of robust evidence from trials.
The impact of viral mutations on recognition by SARS-CoV-2 specific T cells
Publisher: Elsevier BV
Date: 11-2021
Restrictive versus standard IV fluid therapy in adult ICU patients with septic shock—Bayesian analyses of the CLASSIC trial
Publisher: Wiley
Date: 23-10-2023
DOI: 10.1111/AAS.14345
Angiotensin I and angiotensin II concentrations and their ratio in catecholamine-resistant vasodilatory shock
Publisher: Springer Science and Business Media LLC
Date: 06-02-2020
DOI: 10.1186/S13054-020-2733-X
Abstract: In patients with vasodilatory shock, plasma concentrations of angiotensin I (ANG I) and II (ANG II) and their ratio may reflect differences in the response to severe vasodilation, provide novel insights into its biology, and predict clinical outcomes. The objective of these protocol prespecified and subsequent post hoc analyses was to assess the epidemiology and outcome associations of plasma ANG I and ANG II levels and their ratio in patients with catecholamine-resistant vasodilatory shock (CRVS) enrolled in the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) study. We measured ANG I and ANG II levels at baseline, calculated their ratio, and compared these results to values from healthy volunteers (controls). We dichotomized patients according to the median ANG I/II ratio (1.63) and compared demographics, clinical characteristics, and clinical outcomes. We constructed a Cox proportional hazards model to test the independent association of ANG I, ANG II, and their ratio with clinical outcomes. Median baseline ANG I level (253 pg/mL [interquartile range (IQR) 72.30–676.00 pg/mL] vs 42 pg/mL [IQR 30.46–87.34 pg/mL] in controls P 0.0001) and median ANG I/II ratio (1.63 [IQR 0.98–5.25] vs 0.4 [IQR 0.28–0.64] in controls P 0.0001) were elevated, whereas median ANG II levels were similar (84 pg/mL [IQR 23.85–299.50 pg/mL] vs 97 pg/mL [IQR 35.27–181.01 pg/mL] in controls P = 0.9895). At baseline, patients with a ratio above the median (≥1.63) had higher ANG I levels ( P 0.0001), lower ANG II levels ( P 0.0001), higher albumin concentrations ( P = 0.007), and greater incidence of recent (within 1 week) exposure to angiotensin-converting enzyme inhibitors ( P 0.00001), and they received a higher norepinephrine-equivalent dose ( P = 0.003). In the placebo group, a baseline ANG I/II ratio .63 was associated with improved survival (hazard ratio 0.56 95% confidence interval 0.36–0.88 P = 0.01) on unadjusted analyses. Patients with CRVS have elevated ANG I levels and ANG I/II ratios compared with healthy controls. In such patients, a high ANG I/II ratio is associated with greater norepinephrine requirements and is an independent predictor of mortality, thus providing a biological rationale for interventions aimed at its correction. ClinicalTrials.gov identifier NCT02338843 . Registered 14 January 2015.
Rates and determinants of informed consent: A case study of an international thromboprophylaxis trial
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.JCRC.2012.08.005
Abstract: Successful completion of randomized trials depends upon efficiently and ethically screening patients and obtaining informed consent. Awareness of modifiable barriers to obtaining consent may inform ongoing and future trials. The objective of this study is to describe and examine determinants of consent rates in an international heparin thromboprophylaxis trial (Prophylaxis for ThromboEmbolism in Critical Care Trial, clinicaltrials.gov NCT00182143). Throughout the 4-year trial, research personnel approached eligible critically ill patients or their substitute decision makers for informed consent. Whether consent was obtained or declined was documented daily. The trial was conducted in 67 centers in 6 countries. A total of 3764 patients were randomized. The overall consent rate was 82.2% (range, 50%-100%) across participating centers. Consent was obtained from substitute decision makers and patients in 90.1% and 9.9% of cases, respectively. Five factors were independently associated with consent rates. Research coordinators with more experience achieved higher consent rates (odds ratio [OR], 3.43 95% confidence interval, 2.42-4.86 P 10 years of experience). Consent rates were higher in smaller intensive care units with less than 15 beds compared with intensive care units with 15 to 20 beds, 21 to 25 beds, and greater than 25 beds (all ORs, <0.5 P < .001) and were higher in centers with more than 1 full-time research staff (OR, 1.95 95% confidence interval, 1.28-2.99 P < .001). Consent rates were lower in centers affiliated with the Canadian Critical Care Trials Group or the Australian and New Zealand Intensive Care Society Clinical Trials Group compared with other centers (OR, 0.57 95% confidence interval, 0.42-0.77 P < .001). Finally, consent rates were highest during the pilot trial, lowest during the initiation of the full trial, and increased over years of recruitment (P < .001). Characteristics of study centers, research infrastructure, and experience were important factors associated with successfully procuring informed consent to participate in this thromboprophylaxis trial.
Designing acute kidney injury clinical trials
Publisher: Springer Science and Business Media LLC
Date: 31-08-2023
Preferences for the measurement and supplementation of magnesium, phosphate and zinc in ICUs: The international WhyTrace survey
Publisher: Wiley
Date: 25-11-2020
DOI: 10.1111/AAS.13738
Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Definin
Publisher: Oxford University Press (OUP)
Date: 03-10-2015
DOI: 10.1093/JAC/DKV288
Abstract: We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic harmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies. This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries. Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT>MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic harmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving β-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30) P = 0.012]. Additionally, in patients with a SOFA score of ≥9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20) P = 0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20) P = 0.025]. Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections.
Erratum: Heparin versus citrate anticoagulation for continuous renal replacement therapy in intensive care: the RRAM observational study
Publisher: National Institute for Health and Care Research
Date: 04-2022
Abstract: Data corrected and figures revised.
Angiotensin II infusion in COVID‐19: An international, multicenter, registry‐based study
Publisher: Wiley
Date: 21-01-2022
DOI: 10.1002/JMV.27592
Abstract: To expand our understanding of the role of angiotensin II (ANGII) in coronavirus infectious disease 2019 (COVID‐19), we conducted an international, multicenter registry study to assess the use of ANGII in patients with COVID‐19 compared to patients not receiving ANGII. Critically ill adult patients who were diagnosed with COVID‐19 and received ANGII were matched with COVID‐19 patients not receiving ANGII according to age, respiratory support, history of hypertension, use of angiotensin‐converting enzyme inhibitors and/or ANGII receptor blocker, and date of admission. All outcomes were exploratory in nature and included improvement in oxygenation, duration of organ support, and mortality. In one year, 132 patients were included (65 in the ANGII group and 67 in the control group), and patients were comparable in baseline characteristics. During the first 12 h of infusion, patients in the ANGII had a faster decrease in FiO 2 and maintained similar mean arterial pressure levels. Hospital mortality was not statistically significantly different between the groups (53.8% vs. 40.3% p = 0.226). Within the limitations of such a study design, our findings confirm previous observations of a potentially positive effect of ANGII on blood pressure and FiO 2 but no effect on patient‐centered outcomes.
Improving risk prediction model quality in the critically ill: data linkage study
Publisher: National Institute for Health and Care Research
Date: 12-2022
DOI: 10.3310/EQAB4594
Abstract: A previous National Institute for Health and Care Research study [Harrison DA, Ferrando-Vivas P, Shahin J, Rowan KM. Ensuring comparisons of health-care providers are fair: development and validation of risk prediction models for critically ill patients. Health Serv Deliv Res 2015 3 (41)] identified the need for more research to understand risk factors and consequences of critical care and subsequent outcomes. First, to improve risk models for adult general critical care by developing models for mortality at fixed time points and time-to-event outcomes, end-stage renal disease, type 2 diabetes, health-care utilisation and costs. Second, to improve risk models for cardiothoracic critical care by enhancing risk factor data and developing models for longer-term mortality. Third, to improve risk models for in-hospital cardiac arrest by enhancing risk factor data and developing models for longer-term mortality and critical care utilisation. Risk modelling study linking existing data. NHS adult critical care units and acute hospitals in England. Patients admitted to an adult critical care unit or experiencing an in-hospital cardiac arrest. None. Mortality at hospital discharge, 30 days, 90 days and 1 year following critical care unit admission mortality at 1 year following discharge from acute hospital new diagnosis of end-stage renal disease or type 2 diabetes hospital resource use and costs return of spontaneous circulation sustained for 20 minutes survival to hospital discharge and 1 year and length of stay in critical care following in-hospital cardiac arrest. Case Mix Programme, National Cardiac Arrest Audit, UK Renal Registry, National Diabetes Audit, National Adult Cardiac Surgery Audit, Hospital Episode Statistics and Office for National Statistics. Data were linked for 965,576 critical care admissions between 1 April 2009 and 31 March 2016, and 83,939 in-hospital cardiac arrests between 1 April 2011 and 31 March 2016. For admissions to adult critical care units, models for 30-day mortality had similar predictors and performance to those for hospital mortality and did not reduce heterogeneity. Models for longer-term outcomes reflected increasing importance of chronic over acute predictors. New models for end-stage renal disease and diabetes will allow benchmarking of critical care units against these important outcomes and identification of patients requiring enhanced follow-up. The strongest predictors of health-care costs were prior hospitalisation, prior dependency and chronic conditions. Adding pre- and intra-operative risk factors to models for cardiothoracic critical care gave little improvement in performance. Adding comorbidities to models for in-hospital cardiac arrest provided modest improvements but were of greater importance for longer-term outcomes. Delays in obtaining linked data resulted in the data used being 5 years old at the point of publication: models will already require recalibration. Data linkage provided enhancements to the risk models underpinning national clinical audits in the form of additional predictors and novel outcomes measures. The new models developed in this report may assist in providing objective estimates of potential outcomes to patients and their families. (1) Develop and test care pathways for recovery following critical illness targeted at those with the greatest need (2) explore other relevant data sources for longer-term outcomes (3) widen data linkage for resource use and costs to primary care, outpatient and emergency department data. This study is registered as NCT02454257. This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research Vol. 10, No. 39. See the NIHR Journals Library website for further project information.
Report of the first AKI Round Table meeting: an initiative of the ESICM AKI Section
Publisher: Springer Science and Business Media LLC
Date: 12-2019
DOI: 10.1186/S40635-019-0280-Z
Abstract: Critical Care Nephrology is an emerging sub-specialty of Critical Care. Despite increasing awareness about the serious impact of acute kidney injury (AKI) and renal replacement therapy (RRT), important knowledge gaps persist. This report represents a summary of a 1-day meeting of the AKI section of the European Society of Intensive Care Medicine (ESICM) identifying priorities for future AKI research. International Members of the AKI section of the ESICM were selected and allocated to one of three subgroups: “AKI diagnosis and evaluation”, “Medical management of AKI” and “Renal Replacement Therapy for AKI.” Using a modified Delphi methodology, each group identified knowledge gaps and developed potential proposals for future collaborative research. The following key research projects were developed: Systematic reviews: (a) epidemiology of AKI with stratification by patient cohorts and diagnostic criteria (b) role of higher blood pressure targets in patients with hypertension admitted to the Intensive Care Unit, and (c) specific clearance characteristics of different modalities of continuous renal replacement therapy (CRRT). Observational studies: (a) epidemiology of critically ill patients according to AKI duration, and (b) current clinical practice of CRRT. Intervention studies:( a) Comparison of different blood pressure targets in critically ill patients with hypertension, and (b) comparison of clearance of solutes with various molecular weights between different CRRT modalities. Consensus was reached on a future research agenda for the AKI section of the ESICM.
Reduced exposure to vasopressors through permissive hypotension to reduce mortality in critically ill people aged 65 and over: the 65 RCT
Publisher: National Institute for Health and Care Research
Date: 02-2021
DOI: 10.3310/HTA25140
Abstract: Vasopressors are administered to critical care patients to avoid hypotension, which is associated with myocardial injury, kidney injury and death. However, they work by causing vasoconstriction, which may reduce blood flow and cause other adverse effects. A mean arterial pressure target typically guides administration. An in idual patient data meta-analysis (Lamontagne F, Day AG, Meade MO, Cook DJ, Guyatt GH, Hylands M, et al. Pooled analysis of higher versus lower blood pressure targets for vasopressor therapy septic and vasodilatory shock. Intensive Care Med 2018 44 :12–21) suggested that greater exposure, through higher mean arterial pressure targets, may increase risk of death in older patients. To estimate the clinical effectiveness and cost-effectiveness of reduced vasopressor exposure through permissive hypotension (i.e. a lower mean arterial pressure target of 60–65 mmHg) in older critically ill patients. A pragmatic, randomised clinical trial with integrated economic evaluation. Sixty-five NHS adult general critical care units. Critically ill patients aged ≥ 65 years receiving vasopressors for vasodilatory hypotension. Intervention – permissive hypotension (i.e. a mean arterial pressure target of 60–65 mmHg). Control (usual care) – a mean arterial pressure target at the treating clinician’s discretion. The primary clinical outcome was 90-day all-cause mortality. The primary cost-effectiveness outcome was 90-day incremental net monetary benefit. Secondary outcomes included receipt and duration of advanced respiratory and renal support, mortality at critical care and acute hospital discharge, and questionnaire assessment of cognitive decline and health-related quality of life at 90 days and 1 year. Of 2600 patients randomised, 2463 (permissive hypotension, n = 1221 usual care, n = 1242) were analysed for the primary clinical outcome. Permissive hypotension resulted in lower exposure to vasopressors than usual care [mean duration 46.0 vs. 55.9 hours, difference –9.9 hours (95% confidence interval –14.3 to –5.5 hours) total noradrenaline-equivalent dose 31.5 mg vs. 44.3 mg, difference –12.8 mg (95% CI –18.0 mg to –17.6 mg)]. By 90 days, 500 (41.0%) patients in the permissive hypotension group and 544 (43.8%) patients in the usual-care group had died (absolute risk difference –2.85%, 95% confidence interval –6.75% to 1.05% p = 0.154). Adjustment for prespecified baseline variables resulted in an odds ratio for 90-day mortality of 0.82 (95% confidence interval 0.68 to 0.98) favouring permissive hypotension. There were no significant differences in prespecified secondary outcomes or subgroups however, patients with chronic hypertension showed a mortality difference favourable to permissive hypotension. At 90 days, permissive hypotension showed similar costs to usual care. However, with higher incremental life-years and quality-adjusted life-years in the permissive hypotension group, the incremental net monetary benefit was positive, but with high statistical uncertainty (£378, 95% confidence interval −£1347 to £2103). The intervention was unblinded, with risk of bias minimised through central allocation concealment and a primary outcome not subject to observer bias. The control group event rate was higher than anticipated. In critically ill patients aged ≥ 65 years receiving vasopressors for vasodilatory hypotension, permissive hypotension did not significantly reduce 90-day mortality compared with usual care. The absolute treatment effect on 90-day mortality, based on 95% confidence intervals, was between a 6.8-percentage reduction and a 1.1-percentage increase in mortality. Future work should (1) update the in idual patient data meta-analysis, (2) explore approaches for evaluating heterogeneity of treatment effect and (3) explore 65 trial conduct, including use of deferred consent, to inform future trials. Current Controlled Trials ISRCTN10580502. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 25, No. 14. See the NIHR Journals Library website for further project information.
Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure: the DIANA study
Publisher: Springer Science and Business Media LLC
Date: 09-06-2020
Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup
Publisher: Springer Science and Business Media LLC
Date: 23-02-2023
Outcomes in Patients with Vasodilatory Shock and Renal Replacement Therapy Treated with Intravenous Angiotensin II
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2018
DOI: 10.1097/CCM.0000000000003092
Abstract: 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. Post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock 3 trial. ICUs. Patients with acute kidney injury treated with renal replacement therapy at initiation of angiotensin II or placebo ( n = 45 and n = 60, respectively). IV angiotensin II or placebo. 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. 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.
Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial
Publisher: Springer Science and Business Media LLC
Date: 12-07-2021
Surviving Sepsis Campaign Guidelines on the Management of Adults With Coronavirus Disease 2019 (COVID-19) in the ICU: First Update
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-01-2021
DOI: 10.1097/CCM.0000000000004899
Abstract: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU. The Surviving Sepsis C aign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization’s definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. The Surviving Sepsis C aign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis C aign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning. The Surviving Sepsis C aign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.
Thrombocytopenia in Critically Ill Patients Receiving Thromboprophylaxis
Publisher: Elsevier BV
Date: 10-2013
Abstract: Thrombocytopenia is the most common hemostatic disorder in critically ill patients. The objective of this study was to describe the incidence, risk factors, and outcomes of thrombocytopenia in patients admitted to medical-surgical ICUs. Three thousand seven hundred forty-six patients in 67 centers were enrolled in a randomized trial in which unfractionated heparin was compared with low-molecular-weight heparin (LMWH) for thromboprophylaxis. Patients who had baseline platelet counts < 75 × 10(9)/L or severe coagulopathy at screening were excluded. We analyzed the risk of developing mild (100-149 × 10(9)/L), moderate (50-99 × 10(9)/L), and severe (< 50 × 109/L) thrombocytopenia during an ICU stay. We also assessed independent and time-varying predictors of thrombocytopenia and the effect of thrombocytopenia on major bleeding, transfusions, and death. The incidences of mild, moderate, and severe thrombocytopenia were 15.3%, 5.1%, and 1.6%, respectively. The predictors of each category of thrombocytopenia were APACHE (Acute Physiology and Chronic Health Evaluation) II score, use of inotropes or vasopressors, and renal replacement therapy. The risk of moderate thrombocytopenia was lower in patients who received LMWH thromboprophylaxis but higher in surgical patients and in patients who had liver disease. Each category of thrombocytopenia was associated with subsequent bleeding and transfusions. Moderate and severe thrombocytopenia were associated with increased ICU and hospital mortality. A high severity of illness, prior surgery, use of inotropes or vasopressors, renal replacement therapy, and liver dysfunction are associated with a higher risk of thrombocytopenia developing in the ICU, whereas LMWH thromboprophylaxis is associated with a lower risk. Patients who develop thrombocytopenia in the ICU are more likely to bleed, receive transfusions, and die.
Infrared thermography reveals effect of working posture on skin temperature in office workers.
Publisher: Informa UK Limited
Date: 09-08-2018
DOI: 10.1080/10803548.2017.1336299
Abstract: Musculoskeletal symptoms related to using traditional computer workstations are common. Quantitative methods for measuring muscle stress and strain are needed to improve ergonomics of workstations. We hypothesize that infrared thermography (IRT) is suited for this purpose. This hypothesis was evaluated by estimating muscle activity in upright and traditional working postures with IRT and surface electromyography (sEMG). IRT and sEMG measurements were conducted in 14 female participants with both working postures. First, measurements with the traditional posture were performed. Later, participants had 1 month to adjust to the upright working posture before repeating the measurements. IRT images were acquired before and after a full working day, with sEMG recordings being conducted throughout the measurement days. Participants evaluated their neck pain severity using neck disability index (NDI) questionnaires before the first and after the second measurement day. Spatial variation in upper back temperature was higher (p = 0.008) when working in traditional posture and the upright working posture reduced (p < 0.05) upper back muscle activity. The NDI was significantly lower (p = 0.003) after working in the upright posture. IRT was found suitable for evaluating muscle activity and upright working posture to reduce the NDI and muscle activity in the upper back.
Heparin versus citrate anticoagulation for continuous renal replacement therapy in intensive care: the RRAM observational study
Publisher: National Institute for Health and Care Research
Date: 02-2022
DOI: 10.3310/ZXHI9396
Abstract: In the UK, 10% of admissions to intensive care units receive continuous renal replacement therapy with regional citrate anticoagulation replacing systemic heparin anticoagulation over the last decade. Regional citrate anticoagulation is now used in 50% of intensive care units, despite little evidence of safety or effectiveness. The aim of the Renal Replacement Anticoagulant Management study was to evaluate the clinical and health economic impacts of intensive care units moving from systemic heparin anticoagulation to regional citrate anticoagulation for continuous renal replacement therapy. This was an observational comparative effectiveness study. The setting was NHS adult general intensive care units in England and Wales. Participants were adults receiving continuous renal replacement therapy in an intensive care unit participating in the Intensive Care National Audit & Research Centre Case Mix Programme national clinical audit between 1 April 2009 and 31 March 2017. Exposure – continuous renal replacement therapy in an intensive care unit after completion of transition to regional citrate anticoagulation. Comparator – continuous renal replacement therapy in an intensive care unit before starting transition to regional citrate anticoagulation or had not transitioned. Primary effectiveness – all-cause mortality at 90 days. Primary economic – incremental net monetary benefit at 1 year. Secondary outcomes – mortality at hospital discharge, 30 days and 1 year days of renal, cardiovascular and advanced respiratory support in intensive care unit length of stay in intensive care unit and hospital bleeding and thromboembolic events prevalence of end-stage renal disease at 1 year and estimated lifetime incremental net monetary benefit. In idual patient data from the Intensive Care National Audit & Research Centre Case Mix Programme were linked with the UK Renal Registry, Hospital Episode Statistics (for England), Patient Episodes Data for Wales and Civil Registrations (Deaths) data sets, and combined with identified periods of systemic heparin anticoagulation and regional citrate anticoagulation (survey of intensive care units). Staff time and consumables were obtained from micro-costing. Continuous renal replacement therapy system failures were estimated from the Post-Intensive Care Risk-adjusted Alerting and Monitoring data set. EuroQol-3 Dimensions, three-level version, health-related quality of life was obtained from the Intensive Care Outcomes Network study. Out of the 188 (94.9%) units that responded to the survey, 182 (96.8%) use continuous renal replacement therapy. After linkage, data were available from 69,001 patients across 181 intensive care units (60,416 during periods of systemic heparin anticoagulation use and 8585 during regional citrate anticoagulation use). The change to regional citrate anticoagulation was not associated with a step change in 90-day mortality (odds ratio 0.98, 95% confidence interval 0.89 to 1.08). Secondary outcomes showed step increases in days of renal support (difference in means 0.53 days, 95% confidence interval 0.28 to 0.79 days), advanced cardiovascular support (difference in means 0.23 days, 95% confidence interval 0.09 to 0.38 days) and advanced respiratory support (difference in means, 0.53 days, 95% CI 0.03 to 1.03 days) with a trend toward fewer bleeding episodes (odds ratio 0.90, 95% confidence interval 0.76 to 1.06) with transition to regional citrate anticoagulation. The micro-costing study indicated that regional citrate anticoagulation was more expensive and was associated with an estimated incremental net monetary loss (step change) of –£2376 (95% confidence interval –£3841 to –£911). The estimated likelihood of cost-effectiveness at 1 year was less than 0.1%. Lack of patient-level treatment data means that the results represent average effects of changing to regional citrate anticoagulation in intensive care units. Administrative data are subject to variation in data quality over time, which may contribute to observed trends. The introduction of regional citrate anticoagulation has not improved outcomes for patients and is likely to have substantially increased costs. This study demonstrates the feasibility of evaluating effects of changes in practice using routinely collected data. (1) Prioritise other changes in clinical practice for evaluation and (2) methodological research to understand potential implications of trends in data quality. This trial is registered as ClinicalTrials.gov NCT03545750. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 26, No. 13. See the NIHR Journals Library website for further project information.
Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
Publisher: Elsevier BV
Date: 2022
Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19
Publisher: Massachusetts Medical Society
Date: 26-08-2021
Health-related quality of life in survivors of septic shock: 6-month follow-up from the ADRENAL trial
Publisher: Springer Science and Business Media LLC
Date: 16-07-2020
Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference
Publisher: Elsevier BV
Date: 08-2020
Neuromuscular blockade in patients with ARDS: a rapid practice guideline
Publisher: Springer Science and Business Media LLC
Date: 26-10-2020
The AKI glossary
Publisher: Springer Science and Business Media LLC
Date: 04-2017
Early sedation with dexmedetomidine in ventilated critically ill patients and heterogeneity of treatment effect in the SPICE III randomised controlled trial
Publisher: Springer Science and Business Media LLC
Date: 08-03-2021
Long-term effects of restriction of intravenous fluid in adult ICU patients with septic shock
Publisher: Springer Science and Business Media LLC
Date: 18-06-2023
Risk prediction for acute kidney injury in acute medical admissions in the UK
Publisher: Oxford University Press (OUP)
Date: 28-11-2018
DOI: 10.1093/QJMED/HCY277
Abstract: Acute Kidney Injury (AKI) is associated with adverse outcomes therefore identifying patients who are at risk of developing AKI in hospital may lead to targeted prevention. We undertook a UK-wide study in acute medical units (AMUs) to define those who develop hospital-acquired AKI (hAKI) to determine risk factors associated with hAKI and to assess the feasibility of developing a risk prediction score. Prospective multi-centre cohort study across 72 AMUs in the UK. Data collected from all patients who presented over a 24-h period. Chronic dialysis, community-acquired AKI (cAKI) and those with fewer than two creatinine measurements were excluded. Primary outcome was the development of h-AKI. Two thousand four hundred and fourty-six in iduals were admitted to the seventy-two participating centres. Three hundred and eighty-four patients (16%) sustained AKI of whom two hundred and eighty-seven (75%) were cAKI and ninety-seven (25%) were hAKI. After exclusions, chronic kidney disease [Odds Ratio (OR) 3.08, 95% Confidence Interval (CI) 1.96-4.83], diuretic prescription (OR 2.33, 95% CI 1.5-3.65), a lower haemoglobin concentration and elevated serum bilirubin were independently associated with development of hAKI. Multi-variable model discrimination was only moderate (c-statistic 0.75). AKI in AMUs is common and associated with worse outcomes, with the majority of cases community acquired. Only a small proportion of patients develop hAKI. Prognostic risk factor modelling demonstrated only moderate discrimination implying that widespread adoption of such an AKI clinical risk score across all AMU admissions is not currently justified. More targeted risk assessment or automated methods of calculating in idual risk may be more appropriate alternatives.
Acute kidney injury in the critically ill: an updated review on pathophysiology and management
Publisher: Springer Science and Business Media LLC
Date: 02-07-2021
Renal replacement therapy in extra-corporeal membrane oxygenation patients: A survey of practices and new insights for future studies
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.ACCPM.2021.100971
Abstract: Patients under extra-corporeal membrane oxygenation (ECMO) are at high risk of developing acute kidney injury and renal replacement therapy (RRT) is frequently needed. The aim of this study was to explore RRT use in ECMO patients, as no recommendations exist in this setting. An online questionnaire about RRT management in ECMO patients was sent to the members of the ARCOTHOVA (Anesthésie-Réanimation Coeur-Thorax-Vaisseaux) association and to the GFRUP (Groupe Francophone de Réanimation et Urgences Pédiatriques). Ninety intensivists from adult ICU and twenty from paediatric ICU responded to the questionnaire. RRT use was common as 67% respondents reported that more than 25% of their ECMO patients needed RRT. RRT indications were similar between centres, with persistent anuria (83%), metabolic acidosis (80%), fluid overload (78%) and hyperkalaemia (80%) being the more prevalent. Continuous renal replacement therapy was the preferred technique (97%). Continuous veno-venous haemofiltration was predominant (64%) over continuous veno-venous haemodiafiltration (21%). Unfractionated heparin was employed as first line choice anticoagulation in 61% and regional citrate anticoagulation in 16%. Integration of RRT device directly into the ECMO circuit was the preferred configuration (40%) while parallel systems with separate catheter were used in 30%. When the integrated approach was chosen, RRT device was most frequently connected with inlet and outlet lines after the ECMO pump (58%) and pressure alarms were encountered for 60% of participants. Our results highlight the high variability of practice between centres. They suggest the need to compare the integrated and parallel configurations of combining RRT and ECMO.
The intensive care medicine agenda on acute kidney injury
Publisher: Springer Science and Business Media LLC
Date: 30-01-2017
Clinical and organizational factors associated with mortality during the peak of first COVID-19 wave: the global UNITE-COVID study
Publisher: Springer Science and Business Media LLC
Date: 21-05-2022
Angiotensin II for the Treatment of Vasodilatory Shock
Publisher: Massachusetts Medical Society
Date: 03-08-2017
Protocol and statistical analysis plan for the REstricted fluid therapy VERsus Standard trEatment in Acute Kidney Injury—REVERSE‐AKI randomized controlled pilot trial
Publisher: Wiley
Date: 26-02-2020
DOI: 10.1111/AAS.13557
Heparin-Induced Thrombocytopenia in Medical Surgical Critical Illness
Publisher: Elsevier BV
Date: 09-2013
Abstract: In a recent multicenter randomized trial comparing unfractionated heparin (UFH) with low-molecular-weight heparin (dalteparin) for thromboprophylaxis in 3,746 critically ill patients, 17 patients (0.5%) developed heparin-induced thrombocytopenia (HIT) based on serotonin-release assay-positive (SRA+) status. A trend to a lower frequency of HIT with dalteparin vs UFH was observed in the intention-to-treat analysis (five vs 12 patients, P = .14), which was statistically significant (three vs 12 patients, P = .046) in a prespecified per-protocol analysis that excluded patients with DVT at study entry. We sought to characterize HIT outcomes and to determine how dalteparin thromboprophylaxis may reduce HIT frequency in patients in the ICU. In 17 patients with HIT, we analyzed platelet counts and thrombotic events in relation to the study drug and other open-label heparin, to determine whether the study drug plausibly explained seroconversion to SRA+ status and/or breakthrough of thrombocytopenia/thrombosis. We also compared antibody frequencies (dalteparin vs UFH) in 409 patients serologically investigated for HIT. HIT-associated thrombosis occurred in 10 of 17 patients (58.8%) (8:1:1 venous:arterial:both). Dalteparin was associated with fewer study drug-attributable HIT-related events (P = .020), including less seroconversion (P = .058) and less breakthrough of thrombocytopenia/thrombosis (P = .032). Antiplatelet factor 4/heparin IgG antibodies by enzyme-linked immunosorbent assay were less frequent among patients receiving dalteparin vs UFH (13.5% vs 27.3%, P .001). One patient with HIT-associated DVT died after UFH bolus (anaphylactoid reaction), whereas platelet counts recovered in two others with HIT-associated VTE despite continuation of therapeutic-dose UFH. The lower risk of HIT in patients in the ICU receiving dalteparin appears related to both decreased antibody formation and decreased clinical breakthrough of HIT among patients forming antibodies.
Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury
Publisher: Massachusetts Medical Society
Date: 16-07-2020
Conservative vs liberal fluid therapy in septic shock (CLASSIC) trial-Protocol and statistical analysis plan.
Publisher: Wiley
Date: 24-07-2019
DOI: 10.1111/AAS.13434
Abstract: Intravenous (IV) fluid is a key intervention in the management of septic shock. The benefits and harms of lower versus higher fluid volumes are unknown and thus clinical equipoise exists. We describe the protocol and detailed statistical analysis plan for the conservative versus liberal approach to fluid therapy of septic shock in the Intensive Care (CLASSIC) trial. The aim of the CLASSIC trial is to assess benefits and harms of IV fluid restriction versus standard care in adult intensive care unit (ICU) patients with septic shock. CLASSIC trial is an investigator-initiated, international, randomised, stratified, and analyst-blinded trial. We will allocate 1554 adult patients with septic shock, who are planned to be or are admitted to an ICU, to IV fluid restriction versus standard care. The primary outcome is mortality at day 90. Secondary outcomes are serious adverse events (SAEs), serious adverse reactions (SARs), days alive at day 90 without life support, days alive and out of the hospital at day 90 and mortality, health-related quality of life (HRQoL), and cognitive function at 1 year. We will conduct the statistical analyses according to a pre-defined statistical analysis plan, including three interim analyses. For the primary analysis, we will use logistic regression adjusted for the stratification variables comparing the two interventions in the intention-to-treat (ITT) population. The CLASSIC trial results will provide important evidence to guide clinicians' choice regarding the IV fluid therapy in adults with septic shock.
Renal replacement anticoagulant management: Protocol and analysis plan for an observational comparative effectiveness study of linked data sources
Publisher: SAGE Publications
Date: 02-04-2022
Abstract: Acute kidney injury is common in critical illness. In patients with severe acute kidney injury, renal replacement therapy is needed to prevent harm from metabolic and electrolyte disturbances and fluid overload. In the UK, continuous renal replacement therapy (CRRT) is the preferred modality, which requires anticoagulation. Over the last decade, conventional systemic heparin anticoagulation has started being replaced by regional citrate anticoagulation for CRRT, which is now used in approximately 50% of ICUs. This shift towards regional citrate anticoagulation for CRRT is occurring with little evidence of safety or longer term effectiveness. Renal replacement anticoagulant management (RRAM) is an observational comparative effectiveness study, utilising existing data sources to address the clinical and cost-effectiveness of the change to regional citrate anticoagulation for CRRT in UK ICUs. The study will use data from approximately 85,000 patients who were treated in adult, general ICUs participating in the case mix programme national clinical audit between 1 April 2009 and 31 March 2017. A survey of health service providers’ anticoagulation practices will be combined with treatment and hospital outcome data from the case mix programme and linked with long-term outcomes from the Civil Registrations (deaths), Hospital Episodes Statistics for England, Patient Episodes Data for Wales, and the UK Renal Registry datasets. The primary clinical effectiveness outcome is all-cause mortality at 90-days. The study will incorporate an economic evaluation with micro-costing of both regional citrate anticoagulation and systemic heparin anticoagulation. Study registration: NCT03545750
Acute kidney disease and renal recovery: consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup
Publisher: Springer Science and Business Media LLC
Date: 27-02-2017
Abstract: Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney disease for a period of >90 days. AKI and CKD are increasingly recognized as related entities and in some instances probably represent a continuum of the disease process. For patients in whom pathophysiologic processes are ongoing, the term acute kidney disease (AKD) has been proposed to define the course of disease after AKI however, definitions of AKD and strategies for the management of patients with AKD are not currently available. In this consensus statement, the Acute Disease Quality Initiative (ADQI) proposes definitions, staging criteria for AKD, and strategies for the management of affected patients. We also make recommendations for areas of future research, which aim to improve understanding of the underlying processes and improve outcomes for patients with AKD.
Renal replacement therapy in critically ill patients with acute kidney injury--when to start
Publisher: Oxford University Press (OUP)
Date: 09-01-2012
DOI: 10.1093/NDT/GFR707
Abstract: Despite the frequent use of renal replacement therapy (RRT) for patients with acute kidney injury (AKI) in the intensive care unit (ICU), there is no accepted consensus on the optimal indications and timing. The aim of this paper is to identify optimal triggers for RRT in critically ill patients with AKI. We examined data from 2 randomized controlled trials, 2 prospective studies and 13 retrospective trials and found large variation in the different parameters and cut-offs for initiation of RRT. No single biochemical parameter was adequate to define the optimal indication and time to commence RRT. Degree of fluid overload, oliguria and associated non-renal organ failure appeared to be more appropriate parameters for initiation of RRT. We propose a clinical algorithm based on regular assessment of the patient's condition and trends in these parameters. It is intended to aid the process of deciding when to start RRT in critically ill adult patients with AKI. Available evidence suggests that the decision when to start RRT in critically ill patients with AKI should be based on trends in the patient's severity of illness, presence of oliguria and fluid overload and associated non-renal organ failure rather than specific serum creatinine or urea values.
Restrictive fluid management versus usual care in acute kidney injury (REVERSE-AKI): a pilot randomized controlled feasibility trial
Publisher: Springer Science and Business Media LLC
Date: 07-05-2021
STandard versus Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury: Study Protocol for a Multi-National, Multi-Center, Randomized Controlled Trial
Publisher: SAGE Publications
Date: 2019
The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study
Publisher: Oxford University Press (OUP)
Date: 09-03-2020
DOI: 10.1093/CID/CIAA224
Abstract: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4–8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35–65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P & .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9–18.8), piperacillin was 78.6 mg/L (49.5–127.3), tazobactam was 9.5 mg/L (6.3–14.2), and vancomycin was 14.3 mg/L (11.6–21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.
Diagnostic work-up and specific causes of acute kidney injury
Publisher: Springer Science and Business Media LLC
Date: 25-04-2017
DOI: 10.1007/S00134-017-4799-8
Abstract: Acute kidney injury (AKI) is common in critically ill patients and associated with grim short- and long-term outcome. Although in the vast majority of cases AKI is multifactorial, with sepsis, shock and nephrotoxicity accounting for most episodes, specific causes of AKI are not uncommon. Despite remaining uncertainties regarding their prevalence in the ICU, prompt recognition of specific aetiologies of AKI is likely to ensure timely management, limit worsening of renal dysfunction, and ultimately limit renal and systemic consequences of AKI. The ability to recognize conditions that may be associated with specific aetiologies and the appropriate use of clinical imaging, biological and immunological tests, along with optimal assessment of the need for renal biopsies, should be part of routine ICU care. In this review, we summarize uncertainties, current knowledge and recent advances regarding specific types of AKI. We describe the most common specific causes as well as rare aetiologies requiring urgent management, and outline available tools that may be used during the diagnostic work-up along with their limitations.
Long-term patient-important outcomes after septic shock: A protocol for 1-year follow-up of the CLASSIC trial.
Publisher: Wiley
Date: 26-12-2020
DOI: 10.1111/AAS.13519
Abstract: In patients with septic shock, mortality is high, and survivors experience long-term physical, mental and social impairments. The ongoing Conservative vs Liberal Approach to fluid therapy of Septic Shock in Intensive Care (CLASSIC) trial assesses the benefits and harms of a restrictive vs standard-care intravenous (IV) fluid therapy. The hypothesis is that IV fluid restriction improves patient-important long-term outcomes. To assess the predefined patient-important long-term outcomes in patients randomised into the CLASSIC trial. In this pre-planned follow-up study of the CLASSIC trial, we will assess all-cause mortality, health-related quality of life (HRQoL) and cognitive function 1 year after randomisation in the two intervention groups. The 1-year mortality will be collected from electronic patient records or central national registries in most participating countries. We will contact survivors and assess EuroQol 5-Dimension, -5-Level (EQ-5D-5L) and EuroQol-Visual Analogue Scale and Montreal Cognitive Assessment 5-minute protocol score. We will analyse mortality by logistic regression and use general linear models to assess HRQoL and cognitive function. With this pre-planned follow-up study of the CLASSIC trial, we will provide patient-important data on long-term survival, HRQoL and cognitive function of restrictive vs standard-care IV fluid therapy in patients with septic shock.
Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest
Publisher: Massachusetts Medical Society
Date: 05-12-2013
Renin and Survival in Patients Given Angiotensin II for Catecholamine-Resistant Vasodilatory Shock. A Clinical Trial
Publisher: American Thoracic Society
Date: 11-2020
Competing Risk Analysis for Evaluation of Dalteparin Versus Unfractionated Heparin for Venous Thromboembolism in Medical-Surgical Critically Ill Patients
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2015
Indications and management of mechanical fluid removal in critical illness
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1093/BJA/AEU297
Abstract: The Acute Dialysis Quality Initiative (ADQI) dedicated its Twelfth Consensus Conference (2013) to all aspects of fluid therapy, including the management of fluid overload (FO). The aim of the working subgroup 'Mechanical fluid removal' was to review the indications, prescription, and management of mechanical fluid removal within the broad context of fluid management of critically ill patients. The working group developed a list of preliminary questions and objectives and performed a modified Delphi 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. After review of the existing literature, the group agreed the following consensus statements: (i) in critically ill patients with FO and with failure of or inadequate response to pharmacological therapy, mechanical fluid removal should be considered as a therapy to optimize fluid balance. (ii) When using mechanical fluid removal or management, targets for rate of fluid removal and net fluid removal should be based upon the overall fluid balance of the patient and also physiological variables, in idualized, and reassessed frequently. (iii) More research on the role and practice of mechanical fluid removal in critically ill patients not meeting fluid balance goals (including in children) is necessary. Mechanical fluid removal should be considered as a therapy for FO, but more research is necessary to determine its exact role and clinical application.
Failure of Anticoagulant Thromboprophylaxis
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2015
Elevated preoperative heart rate is associated with cardiopulmonary and autonomic impairment in high-risk surgical patients
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1093/BJA/AEX164
Abstract: Elevated preoperative heart rate (HR) is associated with perioperative myocardial injury and death. In apparently healthy in iduals, high resting HR is associated with development of cardiac failure. Given that patients with overt cardiac failure have poor perioperative outcomes, we hypothesized that subclinical cardiac failure, identified by cardiopulmonary exercise testing, was associated with elevated preoperative HR > 87 beats min -1 (HR > 87). This was a secondary analysis of an observational cohort study of surgical patients aged ≥45 yr. The exposure of interest was HR > 87, recorded at rest before preoperative cardiopulmonary exercise testing. The predefined outcome measures were the following established predictors of mortality in patients with overt cardiac failure in the general population: ventilatory equivalent for carbon dioxide ( V˙E/V˙co2 ) ratio ≥34, heart rate recovery ≤6 and peak oxygen uptake ( V˙o2 ) ≤14 ml kg -1 min -1 . We used logistic regression analysis to test for association between HR > 87 and markers of cardiac failure. We also examined the relationship between HR > 87 and preoperative left ventricular stroke volume in a separate cohort of patients. HR > 87 was present in 399/1250 (32%) patients, of whom 438/1250 (35%) had V˙E/V˙co2 ratio ≥34, 200/1250 (16%) had heart rate recovery ≤6, and 396/1250 (32%) had peak V˙o2 ≤14 ml kg -1 min -1 . HR > 87 was independently associated with peak V˙o2 ≤14 ml kg -1 min -1 {odds ratio (OR) 1.69 [1.12-3.55] P =0.01} and heart rate recovery ≤6 (OR 2.02 [1.30-3.14] P 87 was not associated with V˙E/V˙co2 ratio ≥34 (OR 1.31 [0.92-1.87] P =0.14). In a separate cohort, HR > 87 (33/181 18.5%) was associated with impaired preoperative stroke volume (OR 3.21 [1.26-8.20] P =0.01). Elevated preoperative heart rate is associated with impaired cardiopulmonary performance consistent with clinically unsuspected, subclinical cardiac failure. ISRCTN88456378.
Related Organisations
University Of Manchester
Location: United Kingdom of Great Britain and Northern Ireland
Institute For Computational And Data Sciences, Pennsylvania State University
Location: United States of America
Guy's And St Thomas' NHS Foundation Trust
Location: United Kingdom of Great Britain and Northern Ireland
Guy's And St Thomas' NHS Foundation Trust
Location: No location found
Related Funding Activities
No related grants have been discovered for Marlies Ostermann.