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

Improving risk prediction model quality in the critically ill:data linkage study

Background: 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. Objectives: 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. Design: Risk modelling study linking existing data. Setting: NHS adult critical care units and acute hospitals in England. Participants: Patients admitted to an adult critical care unit or experiencing an in-hospital cardiac arrest. Interventions: None. Main outcome measures: 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. Data sources: 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. Results: 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. Limitations: Delays in obtaining linked data resulted in the data used being 5 years old at the point of publication: models will already require recalibration. Conclusions: 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. Future work: (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

Selective digestive tract decontamination to prevent healthcare associated infections in critically ill children: the PICNIC multicentre randomised pilot clinical trial.

Healthcare-associated infections (HCAIs) are a major cause of morbidity and mortality in critically ill children. Data from adult studies suggest Selective Decontamination of the Digestive tract (SDD) may reduce the incidence of HCAIs and improve survival. There are no data from randomised clinical trials in the paediatric setting. An open label, parallel group pilot cRCT and mixed-methods perspectives study was conducted in six paediatric intensive care units (PICUs) in England. Participants were children (> 37 weeks corrected gestational age, up to 16 years) requiring mechanical ventilation expected to last for at least 48 h. Sites undertook standard care for a period of 9 weeks and were randomised into 3 sites which continued standard care and 3 where SDD was incorporated into infection control practice for eligible children. Interviews and focus groups were conducted for parents and staff working in PICU. 434 children fulfilled eligibility criteria, of whom 368 (85%) were enrolled. This included 207 in the baseline phase (Period One) and 161 in the intervention period (Period Two). In sites delivering SDD, the majority (98%) of children received at least one dose of SDD and of these, 68% commenced within the first 6 h. Whilst admission swabs were collected in 91% of enrolled children, consent for the collection of additional swabs was low (44%). Recruited children were representative of the wider PICU population. Overall, 3.6 children/site/week were recruited compared with the potential recruitment rate for a definitive cRCT of 3 children/site/week, based on data from all UK PICUs. Parents (n = 65) and staff (n = 44) were supportive of the aims of the study, suggesting adaptations for a larger definitive trial including formulation and administration of SDD paste, approaches to consent and ecology monitoring. Stakeholders identified preferred clinical outcomes, focusing on complications of critical illness and quality-of-life. A definitive cRCT in SDD to prevent HCAIs in critically ill children is feasible but should include adaptations to ecology monitoring along with the dosing schedule and packaging into a paediatric specific format. A definitive study is supported by the findings with adaptations to ecology monitoring and SDD administration.Trial Registration: ISRCTN40310490 Registered 30/10/2020

Ensuring comparisons of health-care providers are fair: development and validation of risk prediction models for critically ill patients

Background: National clinical audit has a key role in ensuring quality in health care. When comparing outcomes between providers, it is essential to take the differing case mix of patients into account to make fair comparisons. Accurate risk prediction models are therefore required. Objectives: To improve risk prediction models to underpin quality improvement programmes for the critically ill (i.e. patients receiving general or specialist adult critical care or experiencing an in-hospital cardiac arrest). Design: Risk modelling study nested within prospective data collection. Setting: Adult (general/specialist) critical care units and acute hospitals in the UK. Participants: Patients admitted to an adult critical care unit and patients experiencing an in-hospital cardiac arrest attended by the hospital-based resuscitation team. Interventions: None. Main outcome measures: Acute hospital mortality (adult critical care); return of spontaneous circulation (ROSC) greater than 20 minutes and survival to hospital discharge (in-hospital cardiac arrest). Data sources: The Case Mix Programme (adult critical care) and National Cardiac Arrest Audit (in-hospital cardiac arrest). Results: The current Intensive Care National Audit & Research Centre (ICNARC) model was externally validated using data for 29,626 admissions to critical care units in Scotland (2007–9) and outperformed the Acute Physiology And Chronic Health Evaluation (APACHE) II model in terms of discrimination (c-index 0.848 vs. 0.806) and accuracy (Brier score 0.140 vs. 0.157). A risk prediction model for cardiothoracic critical care was developed using data from 17,002 admissions to five units (2010–12) and validated using data from 10,238 admissions to six units (2013–14). The model included prior location/urgency, blood lactate concentration, Glasgow Coma Scale (GCS) score, age, pH, platelet count, dependency, mean arterial pressure, white blood cell (WBC) count, creatinine level, admission following cardiac surgery and interaction terms, and it had excellent discrimination (c-index 0.904) and accuracy (Brier score 0.055). A risk prediction model for admissions to all (general/specialist) adult critical care units was developed using data from 155,239 admissions to 232 units (2012) and validated using data from 90,017 admissions to 216 units (2013). The model included systolic blood pressure, temperature, heart rate, respiratory rate, partial pressure of oxygen in arterial blood/fraction of inspired oxygen, pH, partial pressure of carbon dioxide in arterial blood, blood lactate concentration, urine output, creatinine level, urea level, sodium level, WBC count, platelet count, GCS score, age, dependency, past medical history, cardiopulmonary resuscitation, prior location/urgency, reason for admission and interaction terms, and it outperformed the current ICNARC model for discrimination and accuracy overall (c-index 0.885 vs. 0.869; Brier score 0.108 vs. 0.115) and across unit types. Risk prediction models for in-hospital cardiac arrest were developed using data from 14,688 arrests in 122 hospitals (2011–12) and validated using data from 7791 arrests in 143 hospitals (2012–13). The models included age, sex (for ROSC > 20 minutes), prior length of stay in hospital, reason for attendance, location of arrest, presenting rhythm, and interactions between rhythm and location. Discrimination for hospital survival exceeded that for ROSC > 20 minutes (c-index 0.811 vs. 0.720). Limitations: The risk prediction models developed were limited by the data available within the current national clinical audit data sets. Conclusions: We have developed and validated risk prediction models for cardiothoracic and adult (general and specialist) critical care units and for in-hospital cardiac arrest. Future work: Future development should include linkage with other routinely collected data to enhance available predictors and outcomes. Funding details: The National Institute for Health Research Health Services and Delivery Research programme

Relationship between peak lactate and patient outcome following high-risk gastrointestinal surgery: Influence of the nature of their surgery: Elective versus emergency

Objectives: The association between hyperlactatemia and adverse outcome in patients admitted to ICUs following gastrointestinal surgery has not been reported. To explore the hypothesis that in a large cohort of gastrointestinal surgical patients, the peak serum lactate (in the first 24 hr) observed in patients admitted to ICU following surgery is associated with unadjusted and severity-adjusted acute hospital mortality and that the strength of association is greater in patients admitted following “emergency” surgery than in patients admitted following “elective” surgery. Design: A retrospective cohort study of all patients who had gastrointestinal surgery and were admitted directly to the ICU between 2008 and 2012. Setting: Two hundred forty-nine hospitals in the United Kingdom. Patients: One hundred twenty-one thousand nine hundred ninety patients. Interventions: None. Measurements and Main Results: Peak blood lactate in the first 24 hours of admission to critical care, acute hospital mortality, length of stay, and other variables routinely collected within the U.K. Intensive Care National Audit and Research Centre Case Mix Programme database. Elevated blood lactate was associated with increased risk of death and prolonged duration of stay, and the relationship was maintained once adjusted for confounding variables. The positive association between mortality and levels of blood lactate continued down into the “normal range,” without evidence of a plateau. There was no difference in the extent to which hyperlactatemia was related to mortality between patients admitted following elective and emergency surgery. Conclusions: These findings have implications for our understanding of the role of lactate in critically ill patients.</p

Use of Mechanical Ventilation Across 3 Countries

The ability to provide invasive mechanical ventilation (IMV) is a mainstay of modern intensive care; however, whether rates of IMV vary among countries is unclear. To estimate the per capita rates of IMV in adults across 3 high-income countries with large variation in per capita intensive care unit (ICU) bed availability. This cohort study examined 2018 data of patients aged 20 years or older who received IMV in England, Canada, and the US. The country in which IMV was received. The main outcome was the age-standardized rate of IMV and ICU admissions in each country. Rates were stratified by age, specific diagnoses (acute myocardial infarction, pulmonary embolus, upper gastrointestinal bleed), and comorbidities (dementia, dialysis dependence). Data analyses were conducted between January 1, 2021, and December 1, 2022. The study included 59 873 hospital admissions with IMV in England (median [IQR] patient age, 61 [47-72] years; 59% men, 41% women), 70 250 in Canada (median [IQR] patient age, 65 [54-74] years; 64% men, 36% women), and 1 614 768 in the US (median [IQR] patient age, 65 [54-74] years; 57% men, 43% women). The age-standardized rate per 100 000 population of IMV was the lowest in England (131; 95% CI, 130-132) compared with Canada (290; 95% CI, 288-292) and the US (614; 95% CI, 614-615). Stratified by age, per capita rates of IMV were more similar across countries among younger patients and diverged markedly in older patients. Among patients aged 80 years or older, the crude rate of IMV per 100 000 population was highest in the US (1788; 95% CI, 1781-1796) compared with Canada (694; 95% CI, 679-709) and England (209; 95% CI, 203-214). Concerning measured comorbidities, 6.3% of admitted patients who received IMV in the US had a diagnosis of dementia (vs 1.4% in England and 1.3% in Canada). Similarly, 5.6% of admitted patients in the US were dependent on dialysis prior to receiving IMV (vs 1.3% in England and 0.3% in Canada). This cohort study found that patients in the US received IMV at a rate 4 times higher than in England and twice that in Canada in 2018. The greatest divergence was in the use of IMV among older adults, and patient characteristics among those who received IMV varied markedly. The differences in overall use of IMV among these countries highlight the need to better understand patient-, clinician-, and systems-level choices associated with the varied use of a limited and expensive resource