Fluid balance, intradialytic hypotension, and outcomes in critically ill patients undergoing renal replacement therapy: a cohort study

Introduction: In this cohort study, we explored the relationship between fluid balance, intradialytic hypotension and outcomes in critically ill patients with acute kidney injury (AKI) who received renal replacement therapy (RRT).

Methods: We analysed prospectively collected registry data on patients older than 16 years who received RRT for at least two days in an intensive care unit at two university-affiliated hospitals. We used multivariable logistic regression to determine the relationship between mean daily fluid balance and intradialytic hypotension, both over seven days following RRT initiation, and the outcomes of hospital mortality and RRT dependence in survivors.

Results: In total, 492 patients were included (299 male (60.8%), mean (standard deviation (SD)) age 62.9 (16.3) years); 251 (51.0%) died in hospital. Independent risk factors for mortality were mean daily fluid balance (odds ratio (OR) 1.36 per 1000 mL positive (95% confidence interval (CI) 1.18 to 1.57), intradialytic hypotension (OR 1.14 per 10% increase in days with intradialytic hypotension (95% CI 1.06 to 1.23)), age (OR 1.15 per five-year increase (95% CI 1.07 to 1.25)), maximum sequential organ failure assessment score on days 1 to 7 (OR 1.21 (95% CI 1.13 to 1.29)), and Charlson comorbidity index (OR 1.28 (95% CI 1.14 to 1.44)); higher baseline creatinine (OR 0.98 per 10 mu mol/L (95% CI 0.97 to 0.996)) was associated with lower risk of death. Of 241 hospital survivors, 61 (25.3%) were RRT dependent at discharge. The only independent risk factor for RRT dependence was pre-existing heart failure (OR 3.13 (95% CI 1.46 to 6.74)). Neither mean daily fluid balance nor intradialytic hypotension was associated with RRT dependence in survivors. Associations between these exposures and mortality were similar in sensitivity analyses accounting for immortal time bias and dichotomising mean daily fluid balance as positive or negative. In the subgroup of patients with data on pre-RRT fluid balance, fluid overload at RRT initiation did not modify the association of mean daily fluid balance with mortality.

Conclusions: In this cohort of patients with AKI requiring RRT, a more positive mean daily fluid balance and intradialytic hypotension were associated with hospital mortality but not with RRT dependence at hospital discharge in survivors.

Parents’ and young people’s involvement in designing a trial of ventilator weaning

Consulting with users is considered best practice and is highly recommended in designing new trials. As part of our feasibility work, we undertook a consultation exercise with parents, ex-patients and young people prior to designing a trial of protocol-based ventilator weaning. Our aims were to (1) ascertain views on the relevance and importance of the trial; (2) determine the important parent/patient outcome measures; and (3) ascertain views on informed consent in a cluster randomized controlled trial. We conducted audio-recorded face-to-face, telephone and focus group interviews with parents and young people. Data were content analysed to generate information to address our specific consultation objectives. The setting was the north-western region of England. A total of 16 participants were interviewed: 2 parents of paediatric intensive care unit (PICU) survivors; 1 PICU survivor; and 13 young people from the former Medicines for Children Research Network. The trial objectives were deemed important and relevant, and participants considered the most important outcome measure to be the length of time on ventilation. Parents and young people did not consider written informed consent to be a necessary requirement in the context of this trial, rather awareness of unit participation in the trial was important with the opportunity of opting out of data collection. This consultation provided useful, pragmatic insights to inform trial design. We encountered significant challenges in recruiting parents and young people for this consultation exercise, and novel recruitment methods need to be considered for future work in this field. Patient and public involvement is essential to ensure that future trials answer parent-relevant questions and have meaningful outcome measures, as well as involving parents and young people in the general development of health care services.

Core Outcomes in Ventilation Trials (COVenT): protocol for a core outcome set using a Delphi survey with a nested randomised trial and observational cohort study

Background
Among clinical trials of interventions that aim to modify time spent on mechanical ventilation for critically ill patients there is considerable inconsistency in chosen outcomes and how they are measured. The Core Outcomes in Ventilation Trials (COVenT) study aims to develop a set of core outcomes for use in future ventilation trials in mechanically ventilated adults and children.

Methods/design
We will use a mixed methods approach that incorporates a randomised trial nested within a Delphi study and a consensus meeting. Additionally, we will conduct an observational cohort study to evaluate uptake of the core outcome set in published studies at 5 and 10 years following core outcome set publication. The three-round online Delphi study will use a list of outcomes that have been reported previously in a review of ventilation trials. The Delphi panel will include a range of stakeholder groups including patient support groups. The panel will be randomised to one of three feedback methods to assess the impact of the feedback mechanism on subsequent ranking of outcomes. A final consensus meeting will be held with stakeholder representatives to review outcomes.

Discussion
The COVenT study aims to develop a core outcome set for ventilation trials in critical care, explore the best Delphi feedback mechanism for achieving consensus and determine if participation increases use of the core outcome set in the long term.

A randomized clinical trial of ascorbic acid in open abdominal aortic aneurysm repair

BACKGROUND: Open AAA repair is associated with ischaemia-reperfusion injury where systemic inflammation and endothelial dysfunction can lead to multiple organ injury including acute lung injury. Oxidative stress plays a role that may be inhibited by ascorbic acid.

METHODS: A double blind, allocation concealed, randomized placebo-controlled trial was performed to test the hypothesis that a single bolus dose (2g) of intra-operative parenteral ascorbic acid would attenuate biomarkers of ischaemia-reperfusion injury in patients undergoing elective open AAA repair.

RESULTS: Thirty one patients completed the study; 18 received placebo and 13 ascorbic acid. Groups were comparable demographically. Open AAA repair caused an increase in urinary Albumin:Creatinine Ratio (ACR) as well as plasma IL-6 and IL-8. There was a decrease in exhaled breath pH and oxygenation. Lipid hydroperoxides were significantly higher in the ascorbic acid group following open AAA repair. There were no other differences between the ascorbic acid or placebo groups up to 4 hours after removal of the aortic clamping.

CONCLUSIONS: Open AAA repair caused an increase in markers of systemic endothelial damage and systemic inflammation. Administration of 2g parenteral ascorbic acid did not attenuate this response and with higher levels of lipid hydroperoxides post-operatively a pro-oxidant effect could not be excluded.

TRIAL REGISTRATION: ISRCTN27369400.

Managing patient deterioration: evaluation of what works.

Background: Rapid Response Systems (RRS) have been implemented nationally and internationally to improve patient safety in hospital. However, to date the majority of the RRS research evidence has focused on measuring the effectiveness of the intervention on patient outcomes. To evaluate RRS it has been recommended that a multimodal approach is required to address the broad range of process and outcome measures required to determine the effectiveness of the RRS concept. Aim: The aim of this paper is to evaluate the official RRS programme theoretical assumptions regarding how the programme is meant to work against actual practice in order to determine what works. Methods: The research design was a multiple case study approach of four wards in two hospitals in Northern Ireland. It followed the principles of realist evaluation research which allowed empirical data to be gathered to test and refine RRS programme theory [1]. This approach used a variety of mixed methods to test the programme theories including individual and focus group interviews with a purposive sample of 75 nurses and doctors, observation of ward practices and documentary analysis. The findings from the case studies were analysed and compared within and across cases to identify what works for whom and in what circumstances. Results: The RRS programme theories were critically evaluated and compared with study findings to develop a mid-range theory to explain what works, for whom in what circumstances. The findings of what works suggests that clinical experience, established working relationships, flexible implementation of protocols, ongoing experiential learning, empowerment and pre-emptive management are key to the success of RRS implementation.  Conclusion:These findings highlight the combination of factors that can improve the implementation of RRS and in light of this evidence several recommendations are made to provide policymakers with guidance and direction for their success and sustainability.References: 1.Pawson R and Tilley N. (1997) Realistic Evaluation. Sage Publications; LondonType of submission: Concurrent session Source of funding: Sandra Ryan Fellowship funded by the School of Nursing & Midwifery, Queen’s University of Belfast

Realistic evaluation of EWS and ALERT: factors enabling and constraining implementation.

Realistic Evaluation of EWS and ALERT: factors enabling and constraining implementation Background The implementation of EWS and ALERT in practice is essential to the success of Rapid Response Systems but is dependent upon nurses utilising EWS protocols and applying ALERT best practice guidelines. To date there is limited evidence on the effectiveness of EWS or ALERT as research has primarily focused on measuring patient outcomes (cardiac arrests, ICU admissions) following the implementation of a Rapid Response Team. Complex interventions in healthcare aimed at changing service delivery and related behaviour of health professionals require a different research approach to evaluate the evidence. To understand how and why EWS and ALERT work, or might not work, research needs to consider the social, cultural and organisational influences that will impact on successful implementation in practice. This requires a research approach that considers both the processes and outcomes of complex interventions, such as EWS and ALERT, implemented in practice. Realistic Evaluation is such an approach and was used to explain the factors that enable and constrain the implementation of EWS and ALERT in practice [1]. Aim The aim of this study was to evaluate factors that enabled and constrained the implementation and service delivery of early warnings systems (EWS) and ALERT in practice in order to provide direction for enabling their success and sustainability. Methods The research design was a multiple case study approach of four wards in two hospitals in Northern Ireland. It followed the principles of realist evaluation research which allowed empirical data to be gathered to test and refine RRS programme theory. This approach used a variety of mixed methods to test the programme theories including individual and focus group interviews, observation and documentary analysis in a two stage process. A purposive sample of 75 key informants participated in individual and focus group interviews. Observation and documentary analysis of EWS compliance data and ALERT training records provided further evidence to support or refute the interview findings. Data was analysed using NVIVO8 to categorise interview findings and SPSS for ALERT documentary data. These findings were further synthesised by undertaking a within and cross case comparison to explain the factors enabling and constraining EWS and ALERT. Results A cross case analysis highlighted similarities, differences and factors enabling or constraining successful implementation across the case study sites. Findings showed that personal (confidence; clinical judgement; personality), social (ward leadership; communication), organisational (workload and staffing issues; pressure from managers to complete EWS audit and targets), educational (constraints on training; no clinical educator on ward) and cultural (routine task delegated) influences impact on EWS and acute care training outcomes. There were also differences noted between medical and surgical wards across both case sites. Conclusions Realist Evaluation allows refinement and development of the RRS programme theory to explain the realities of practice. These refined RRS programme theories are capable of informing the planning of future service provision and provide direction for enabling their success and sustainability. References: 1. McGaughey J, Blackwood B, O’Halloran P, Trinder T. J. & Porter S. (2010) A realistic evaluation of Track and Trigger systems and acute care training for early recognition and management of deteriorating ward–based patients. Journal of Advanced Nursing 66 (4), 923-932. Type of submission: Concurrent session Source of funding: Sandra Ryan Fellowship funded by the School of Nursing & Midwifery, Queen’s University of Belfast

Evidence-based practice: the relevance of systematic reviews.

Aim:
To demonstrate how systematic reviews provide robust evidence to inform clinical decision making in practice.

Background
Systematic reviews collate findings from a number of research studies in order to provide a comprehensive and reliable summary of the best available evidence. The use of systematic reviews to inform practice based decisions has increased as a result of the overwhelming amount of research literature available, poor quality of research evidence and the need to ensure practice is based upon the best available evidence. Systematic reviews are an efficient way of coping with large volumes of data to answer focused research questions. They differ from traditional literature reviews as they adhere to an explicit scientific process. The use of explicit and rigorous methods to identify, appraise and synthesise relevant studies minimises bias and provides a reliable basis for decision making. As a result systematic reviews provide clear evidence on the effectiveness of a healthcare intervention to inform policy and decision making across healthcare systems. An example of how the findings from systematic reviews can provide reliable evidence to inform healthcare decisions will be provided in this presentation1. This will demonstrate how focused clinical questions can be answered by systematic reviews and translated into practice.

Reference:
1. McGaughey J, Alderdice F, Fowler R, Kapila A, Moutray M. (2007) Outreach and Early Warning Systems (EWS) for the prevention of Intensive Care admission admission and death of critically ill adult patients on general hospital wards (REVIEW). The Cochrane Database of Systematic Reviews 3. art no CD005529

Early warning systems: problems, pragmatics and potential

Symposium Chair: Dr Jennifer McGaughey

Title: Early Warning Systems: problems, pragmatics and potential

Early Warning Systems (EWS) provide a mechanism for staff to recognise, refer and manage deteriorating patients on general hospital wards. Implementation of EWS in practice has required considerable change in the delivery of critical care across hospitals. Drawing their experience of these changes the authors will demonstrate the problems and potential of using EWS to improve patient outcomes.

The first paper (Dr Jennifer McGaughey: Early Warning Systems: what works?) reviews the research evidence regarding the factors that support or constrain the implementation of Early Warning System (EWS) in practice. These findings explain those processes which impact on the successful achievement of patient outcomes. In order to improve detection and standardise practice National EWS have been implemented in the United Kingdom. The second paper (Catherine Plowright: The implementation of the National EWS in a District General Hospital) focuses on the process of implementing and auditing a National EWS. This process improvement is essential to contribute to future collaborative research and collection of robust datasets to improve patient safety as recommended by the Royal College of Physicians (RCP 2012). To successfully implement NEWS in practice requires strategic planning and staff education. The practical issues of training staff is discussed in the third paper. This paper (Collette Laws-Chapman: Simulation as a modality to embed the use of Early Warning Systems) focuses on using simulation and structured debrief to enhance learning in the early recognition and management of deteriorating patients. This session emphasises the importance of cognitive and social skills developed alongside practical skills in the simulated setting.

Effectiveness of a biomarker-based exclusion of ventilator-acquired pneumonia to reduce antibiotic use: protocol for a randomised controlled trial (VAPrapid-2):Study protocol for a randomised controlled trial

Background Ventilator-acquired pneumonia (VAP) is a common reason for antimicrobial therapy in the intensive care unit (ICU). Biomarker-based diagnostics could improve antimicrobial stewardship through rapid exclusion of VAP. Bronchoalveloar lavage (BAL) fluid biomarkers have previously been shown to allow the exclusion of VAP with high confidence. Methods/Design This is a prospective, multi-centre, randomised, controlled trial to determine whether a rapid biomarker-based exclusion of VAP results in fewer antibiotics and improved antimicrobial management. Patients with clinically suspected VAP undergo BAL, and VAP is confirmed by growth of a potential pathogen at > 104 colony-forming units per millilitre (CFU/ml). Patients are randomised 1:1, to either a ‘biomarker-guided recommendation on antibiotics’ in which BAL fluid is tested for IL-1β and IL-8 in addition to routine microbiology testing, or to ‘routine use of antibiotics’ in which BAL undergoes routine microbiology testing only. Clinical teams are blinded to intervention until 6 hours after randomisation, when biomarker results are reported to the clinician. The primary outcome is a change in the frequency distribution of antibiotic-free days (AFD) in the 7 days following BAL. Secondary outcome measures include antibiotic use at 14 and 28 days; ventilator-free days; 28-day mortality and ICU mortality; sequential organ failure assessment (SOFA) at days 3, 7 and 14; duration of stay in critical care and the hospital; antibiotic-associated infections; and antibiotic-resistant pathogen cultures up to hospital discharge, death or 56 days. A healthcare-resource-utilisation analysis will be calculated from the duration of critical care and hospital stay. In addition, safety data will be collected with respect to performing BAL. A sample size of 210 will be required to detect a clinically significant shift in the distribution of AFD towards more patients having fewer antibiotics and therefore more AFD. Discussion This trial will test whether a rapid biomarker-based exclusion of VAP results in rapid discontinuation of antibiotics and therefore improves antibiotic management in patients with suspected VAP.