Use of selective gut decontamination in critically ill children: PICnIC a pilot RCT and mixed-methods study.

Background: Healthcare-associated infections are a major cause of morbidity and mortality in critically ill children. In adults, data suggest the use of selective decontamination of the digestive tract may reduce the incidence of healthcare-associated infections. Selective decontamination of the digestive tract has not been evaluated in the paediatric intensive care unit population. Objectives: To determine the feasibility of conducting a multicentre, cluster-randomised controlled trial in critically ill children comparing selective decontamination of the digestive tract with standard infection control. Design: Parallel-group pilot cluster-randomised controlled trial with an integrated mixed-methods study. Setting: Six paediatric intensive care units in England. Participants: Children (> 37 weeks corrected gestational age, up to 16 years) requiring mechanical ventilation expected to last for at least 48 hours were eligible for the PICnIC pilot cluster-randomised controlled trial. During the ecology periods, all children admitted to the paediatric intensive care units were eligible. Parents/legal guardians of recruited patients and healthcare professionals working in paediatric intensive care units were eligible for inclusion in the mixed-methods study. Interventions: The interventions in the PICnIC pilot cluster-randomised controlled trial included administration of selective decontamination of the digestive tract as oro-pharyngeal paste and as a suspension given by enteric tube during the period of mechanical ventilation. Main outcome measures: The decision as to whether a definitive cluster-randomised controlled trial is feasible is based on multiple outcomes, including (but not limited to): (1) willingness and ability to recruit eligible patients; (2) adherence to the selective decontamination of the digestive tract intervention; (3) acceptability of the definitive cluster-randomised controlled trial; (4) estimation of recruitment rate; and (5) understanding of potential clinical and ecological outcome measures. Results: A total of 368 children (85% of all those who were eligible) were enrolled in the PICnIC pilot cluster-randomised controlled trial across six paediatric intensive care units: 207 in the baseline phase (Period One) and 161 in the intervention period (Period Two). In sites delivering selective decontamination of the digestive tract, the majority (98%) of children received at least one dose of selective decontamination of the digestive tract, and of these, 68% commenced within the first 6 hours. Consent for the collection of additional swabs was low (44%), though data completeness for potential outcomes, including microbiology data from routine clinical swab testing, was excellent. Recruited children were representative of the wider paediatric intensive care unit population. Overall, 3.6 children/site/week were recruited compared with the potential recruitment rate for a definitive cluster-randomised controlled trial of 3 children/site/week, based on data from all UK paediatric intensive care units. The proposed trial, including consent and selective decontamination of the digestive tract, was acceptable to parents and staff with adaptations, including training to improve consent and communication, and adaptations to the administration protocol for the paste and ecology monitoring. Clinical outcomes that were considered important included duration of organ failure and hospital stay, healthcare-acquired infections and survival. Limitations: The delivery of the pilot cluster-randomised controlled trial was disrupted by the COVID-19 pandemic, which led to slow set-up of sites, and a lack of face-to face training. Conclusions: PICnIC's findings indicate that a definitive cluster-randomised controlled trial in selective decontamination of the digestive tract in paediatric intensive care units is feasible with the inclusion modifications, which would need to be included in a definitive cluster-randomised controlled trial to ensure that the efficiency of trial processes is maximised. Future work: A definitive trial that incorporates the protocol adaptations and outcomes arising from this study is feasible and should be conducted. Trial registration: This trial is registered as ISRCTN40310490. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/152/01) and is published in full in Health Technology Assessment; Vol. 28, No. 8. See the NIHR Funding and Awards website for further award information.

Each year, around 20,000 critically ill children are admitted to paediatric intensive care units in the UK. These children are at a higher risk of healthcare-associated infections, one of the main sources of which is the large number of bacteria in the digestive tract. Spread of bacteria from the digestive tract into other organs, such as the lung (causing ventilator-associated pneumonia) or bloodstream (causing sepsis), can be life-threatening. The risk is highest in those children whose illness is so severe that they require prolonged mechanical ventilation. Stopping the growth of bacteria in the digestive tract (called selective decontamination of the digestive tract) has been shown in adults to reduce the number of hospital-acquired infections. However, there have been no trials in children. We wanted to assess how practical and acceptable such a trial would be comparing standard infection control to selective decontamination of the digestive tract-enhanced infection control and monitoring how each intervention affected antimicrobial resistance. We undertook a pilot study to examine whether clinicians could identify eligible children, enrol them in the study and follow study procedures during the course of paediatric intensive care unit admission. Alongside this, we interviewed parents and clinicians to get their views on the proposed trial. Six hospitals recruited 559 patients over a period of roughly 7 months. Hospitals were randomly allocated to continue with the standard infection control procedure or to give selective decontamination of the digestive tract. Overall, recruitment was higher than expected. Alongside this, we examined the views of patients, caregivers and healthcare professionals to assess their views on whether a trial should be carried out to see if selective decontamination of the digestive tract should become part of the infection control regime for children most at risk of hospital-acquired infection in the paediatric intensive care unit. Overall results suggest that a larger PICnIC trial incorporating patient stakeholder and clinical staff feedback on design and outcomes is feasible and that it is appropriate to conduct a trial into the effectiveness of selective decontamination of the digestive tract administration to minimise hospital-acquired infections.

Pharmacological and non-pharmacological treatments and outcomes for new-onset atrial fibrillation in ICU patients: the CAFE scoping review and database analyses.

BACKGROUND: New-onset atrial fibrillation occurs in around 10% of adults treated in an intensive care unit. New-onset atrial fibrillation may lead to cardiovascular instability and thromboembolism, and has been independently associated with increased length of hospital stay and mortality. The long-term consequences are unclear. Current practice guidance is based on patients outside the intensive care unit; however, new-onset atrial fibrillation that develops while in an intensive care unit differs in its causes and the risks and clinical effectiveness of treatments. The lack of evidence on new-onset atrial fibrillation treatment or long-term outcomes in intensive care units means that practice varies. Identifying optimal treatment strategies and defining long-term outcomes are critical to improving care. OBJECTIVES: In patients treated in an intensive care unit, the objectives were to (1) evaluate existing evidence for the clinical effectiveness and safety of pharmacological and non-pharmacological new-onset atrial fibrillation treatments, (2) compare the use and clinical effectiveness of pharmacological and non-pharmacological new-onset atrial fibrillation treatments, and (3) determine outcomes associated with new-onset atrial fibrillation. METHODS: We undertook a scoping review that included studies of interventions for treatment or prevention of new-onset atrial fibrillation involving adults in general intensive care units. To investigate the long-term outcomes associated with new-onset atrial fibrillation, we carried out a retrospective cohort study using English national intensive care audit data linked to national hospital episode and outcome data. To analyse the clinical effectiveness of different new-onset atrial fibrillation treatments, we undertook a retrospective cohort study of two large intensive care unit databases in the USA and the UK. RESULTS: Existing evidence was generally of low quality, with limited data suggesting that beta-blockers might be more effective than amiodarone for converting new-onset atrial fibrillation to sinus rhythm and for reducing mortality. Using linked audit data, we showed that patients developing new-onset atrial fibrillation have more comorbidities than those who do not. After controlling for these differences, patients with new-onset atrial fibrillation had substantially higher mortality in hospital and during the first 90 days after discharge (adjusted odds ratio 2.32, 95% confidence interval 2.16 to 2.48; adjusted hazard ratio 1.46, 95% confidence interval 1.26 to 1.70, respectively), and higher rates of subsequent hospitalisation with atrial fibrillation, stroke and heart failure (adjusted cause-specific hazard ratio 5.86, 95% confidence interval 5.33 to 6.44; adjusted cause-specific hazard ratio 1.47, 95% confidence interval 1.12 to 1.93; and adjusted cause-specific hazard ratio 1.28, 95% confidence interval 1.14 to 1.44, respectively), than patients who did not have new-onset atrial fibrillation. From intensive care unit data, we found that new-onset atrial fibrillation occurred in 952 out of 8367 (11.4%) UK and 1065 out of 18,559 (5.7%) US intensive care unit patients in our study. The median time to onset of new-onset atrial fibrillation in patients who received treatment was 40 hours, with a median duration of 14.4 hours. The clinical characteristics of patients developing new-onset atrial fibrillation were similar in both databases. New-onset atrial fibrillation was associated with significant average reductions in systolic blood pressure of 5 mmHg, despite significant increases in vasoactive medication (vasoactive-inotropic score increase of 2.3; p < 0.001). After adjustment, intravenous beta-blockers were not more effective than amiodarone in achieving rate control (adjusted hazard ratio 1.14, 95% confidence interval 0.91 to 1.44) or rhythm control (adjusted hazard ratio 0.86, 95% confidence interval 0.67 to 1.11). Digoxin therapy was associated with a lower probability of achieving rate control (adjusted hazard ratio 0.52, 95% confidence interval 0.32 to 0.86) and calcium channel blocker therapy was associated with a lower probability of achieving rhythm control (adjusted hazard ratio 0.56, 95% confidence interval 0.39 to 0.79) than amiodarone. Findings were consistent across both the combined and the individual database analyses. CONCLUSIONS: Existing evidence for new-onset atrial fibrillation management in intensive care unit patients is limited. New-onset atrial fibrillation in these patients is common and is associated with significant short- and long-term complications. Beta-blockers and amiodarone appear to be similarly effective in achieving cardiovascular control, but digoxin and calcium channel blockers appear to be inferior. FUTURE WORK: Our findings suggest that a randomised controlled trial of amiodarone and beta-blockers for management of new-onset atrial fibrillation in critically ill patients should be undertaken. Studies should also be undertaken to provide evidence for or against anticoagulation for patients who develop new-onset atrial fibrillation in intensive care units. Finally, given that readmission with heart failure and thromboembolism increases following an episode of new-onset atrial fibrillation while in an intensive care unit, a prospective cohort study to demonstrate the incidence of atrial fibrillation and/or left ventricular dysfunction at hospital discharge and at 3 months following the development of new-onset atrial fibrillation should be undertaken. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13252515. FUNDING: 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. 71. See the NIHR Journals Library website for further project information.

BACKGROUND: Atrial fibrillation can cause heart failure and stroke. It can also affect heart rate in different ways. It is common for patients admitted to intensive care units to develop atrial fibrillation. When patients have never had atrial fibrillation before, this is called 'new-onset atrial fibrillation'. We do not know how new-onset atrial fibrillation in patients treated in an intensive care unit affects heart rate and blood pressure, what the best treatments are or how treatments affect how people recover. METHODS: We looked at studies of new-onset atrial fibrillation treatments in intensive care units to see if some treatments have been shown to work better. We used a national database to see what happens to intensive care unit patients in the UK who develop new-onset atrial fibrillation. We also used two databases from intensive care units in the UK and the USA to see how many patients in the intensive care units have new-onset atrial fibrillation, how atrial fibrillation affects heart rate and blood pressure, and whether or not some treatments work better than others. RESULTS: Between 6% and 11% of intensive care unit patients develop new-onset atrial fibrillation. These patients are more likely to die in hospital and in the first 90 days after discharge than those who do not. They are also more likely to be readmitted to hospital with atrial fibrillation, stroke and heart failure. The evidence for new-onset atrial fibrillation treatments is limited, but suggests that beta-blockers or amiodarone may work better than calcium channel blockers or digoxin. CONCLUSIONS: New-onset atrial fibrillation in intensive care units is common, and outcomes are worse in patients who develop new-onset atrial fibrillation than in those who do not. Our research shows that some new-onset atrial fibrillation treatments work better than others. This information will help us to plan a study to improve health after new-onset atrial fibrillation.

Development, Validation, and Clinical Utility Assessment of a Prognostic Score for 1-Year Unplanned Rehospitalization or Death of Adult Sepsis Survivors.

Importance: The longer-term risk of rehospitalizations and death of adult sepsis survivors is associated with index sepsis illness characteristics. Objective: To derive and validate a parsimonious prognostic score for unplanned rehospitalizations or death in the first year after hospital discharge of adult sepsis survivors. Design, Setting, and Participants: This cohort study used data from the Intensive Care National Audit & Research Centre Case Mix Programme database on adult sepsis survivors identified from consecutive critical care admissions to 192 adult general critical care units in England, United Kingdom, between April 1, 2009, and March 31, 2014 (94 748 patients in the derivation cohort), and between April 1, 2014, and March 31, 2015 (24 669 patients in the validation cohort). Statistical analysis was performed from July 5 to October 31, 2019. Generic characteristics (age, sex, race/ethnicity, 2015 Index of Multiple Deprivation [IMD2015] in England quintiles, preadmission dependence, previous hospitalizations in the year preceding index sepsis admission, comorbidity, admission type, Acute Physiology and Chronic Health Evaluation II physiology score, hospital length of stay, worst blood lactate and blood hemoglobin concentrations, and type of hospital) and sepsis-specific characteristics (site of infection, numbers of organ dysfunctions, and organ support) at the index sepsis admission were used as predictors. Main Outcomes and Measures: Prognostic score derived and validated using multivariable logistic regression for the outcome of unplanned rehospitalization or death in the first year after hospital discharge of adult sepsis survivors, as well as clinical usefulness assessed using decision curve analysis. Prognostic score validation was performed for internal validation with bootstrapping and temporal cohort external validation. Results: This cohort study included 94 748 patients (51 164 men [54.0%]; mean [SD] age, 61.3 [17.0] years) in the derivation cohort and 24 669 patients (13 255 men [53.7%]; mean [SD] age, 62.1 [16.8%]) in the validation cohort. Unplanned rehospitalization or death in the first year after hospital discharge occurred for 48 594 patients (51.3%) in the derivation cohort and 13 129 patients (53.2%) in the validation cohort. Eight independent predictors were identified and weighted to generate a prognostic score for every patient: previous hospitalizations, age in 10-year increments, IMD2015 in England quintiles, preadmission dependence, comorbidities, admission type, blood hemoglobin level, and site of infection. The total prognostic score ranged from 0 to 22 points, with lower scores indicating a lower risk of the outcome. The derivation and validation cohorts had similar rates of prognostic scores of 0 to 4 points (5088 of 16 684 patients [30.5%] and 471 of 1725 patients [27.3%]) and prognostic scores of 11 points or more (15 732 of 21 641 patients [72.7%] and 5753 of 7952 patients [72.3%]). The area under the receiver operating characteristic curve for the prognostic score was 0.675 (95% CI, 0.672-0.679). The decision curve analysis highlighted an optimal score cutoff of 7 points or more. Conclusions and Relevance: The prognostic score reported in this study uses 8 internationally feasible predictors measured during the index sepsis admission and provides clinically useful information on sepsis survivors' risk of unplanned rehospitalization or death in the first year after hospital discharge.

Psychometric assessment of the Family Satisfaction in the Intensive Care Unit questionnaire in the United Kingdom.

PURPOSE: To establish the psychometric properties of the Family Satisfaction in the Intensive Care Unit 24-item (FS-ICU-24) questionnaire in the United Kingdom. MATERIALS AND METHODS: The Family-Reported Experiences Evaluation study recruited family members of patients staying at least 24 hours in 20 participating intensive care units. Questionnaires were evaluated for nonresponse, floor/ceiling effects, redundancy, and construct validity. Internal consistency was evaluated with item-to-own scale correlations and Cronbach α. Confirmatory and exploratory factor analyses were used to explore the underlying structure. RESULTS: Twelve thousand three hundred forty-six family members of 6380 patients were recruited and 7173 (58%) family members of 4615 patients returned a completed questionnaire. One family member per patient was included in the psychometric assessment. Six items had greater than 10% nonresponse; 1 item had a ceiling effect; and 11 items had potential redundancy. Internal consistency was high (Cronbach α, overall .96; satisfaction with care, .94; satisfaction with decision making, .93). The 2-factor solution was not a good fit. Exploratory factor analysis indicated that satisfaction with decision making encompassed 2 constructs-satisfaction with information and satisfaction with the decision-making process. CONCLUSIONS: The Family Satisfaction in the Intensive Care Unit 24-item questionnaire demonstrated good psychometric properties in the United Kingdom setting. Construct validity could be improved by use of 3 domains and some scope for further improvement was identified.