Association Between Early Hyperoxemia Exposure and Intensive Care Unit Mortality in Intracerebral Hemorrhage: An Observational Cohort Analysis.

BACKGROUND: Supraphysiologic levels of oxygen could have potential adverse effects on the brain that may be dose and time dependent in patients with brain injury. We therefore aimed to assess whether exposure to excess supplemental oxygen, measured as time-weighted mean exposure to hyperoxemia, was associated with intensive care unit (ICU) mortality in patients with intracerebral hemorrhage (ICH). METHODS: In this single-center retrospective cohort study, we included all patients admitted to our ICU with a diagnosis of primary spontaneous ICH. To provide a longitudinal measure of hyperoxemia exposure, we calculated the hyperoxemia dose, defined as the area under the partial pressure of oxygen in arterial blood (PaO2) time curve above the threshold PaO2 value of 100 mm Hg (13.3 kPa) divided by the number of hours of potential exposure. To provide consistent potential exposure windows and limit bias from informative censoring, nested subsets were created with progressively longer exposure periods (0-1 day, 0-2 days, 0-3 days, 0-4 days, 0-5 days, 0-6 days, 0-7 days). We used multivariable Cox regression, with hyperoxemia dose as a time-dependent covariate, to model ICU mortality. Admission ICH and Acute Physiology and Chronic Health Evaluation II scores were included as predictor covariables. A step-function extended Cox model was also fitted. RESULTS: Between September 2019 and July 2022, 275 patients met the inclusion criteria, with 24,588 arterial blood gas results available for analysis. The mean age was 57.19 years (± 13.99), 59.64% were male, 23.64% had an infratentorial origin of hemorrhage, and ICU mortality was 35.64%. Almost all patients (97.45%) were exposed to hyperoxemia during their ICU admission. Cox regression modeling showed an association between hyperoxemia dose and ICU mortality (hazard ratio 1.15, confidence interval 1.05-1.25, p = 0.003). This association was observed in the 0-1 day subset in the step-function extended Cox model (hazard ratio 1.19, confidence interval 1.06-1.35, p = 0.005) but not in any of the subsequent exposure periods. CONCLUSIONS: In patients with ICH admitted to the ICU, we observed an association between hyperoxemia dose and ICU mortality. Further prospective study is required to inform guidance on early systemic oxygen targets in ICH.

Early and late withdrawal of life-sustaining treatment after out-of-hospital cardiac arrest in the United Kingdom: Institutional variation and association with hospital mortality.

AIM: Frequency and timing of Withdrawal of Life-Sustaining Treatment (WLST) after Out-of-Hospital Cardiac Arrest (OHCA) vary across Intensive Care Units (ICUs) in the United Kingdom (UK) and may be a marker of lower healthcare quality if instituted too frequently or too early. We aimed to describe WLST practice, quantify its variability across UK ICUs, and assess the effect of institutional deviation from average practice on patients' risk-adjusted hospital mortality. METHODS: We conducted a retrospective multi-centre cohort study including all adult patients admitted after OHCA to UK ICUs between 2010 and 2017. We identified patient and ICU characteristics associated with early (within 72 h) and late (>72 h) WLST and quantified the between-ICU variation. We used the ICU-level observed-to-expected (O/E) ratios of early and late-WLST frequency as separate metrics of institutional deviation from average practice and calculated their association with patients' hospital mortality. RESULTS: We included 28,438 patients across 204 ICUs. 10,775 (37.9%) had WLST and 6397 (59.4%) of them had early-WLST. Both WLST types were strongly associated with patient-level demographics and pre-existing conditions but weakly with ICU-level characteristics. After adjustment, we found unexplained between-ICU variation for both early-WLST (Median Odds Ratio 1.59, 95%CrI 1.49-1.71) and late-WLST (MOR 1.39, 95%CrI 1.31-1.50). Importantly, patients' hospital mortality was higher in ICUs with higher O/E ratio of early-WLST (OR 1.29, 95%CI 1.21-1.38, p < 0.001) or late-WLST (OR 1.39, 95%CI 1.31-1.48, p < 0.001). CONCLUSIONS: Significant variability exists between UK ICUs in WLST frequency and timing. This matters because unexplained higher-than-expected WLST frequency is associated with higher hospital mortality independently of timing, potentially signalling prognostic pessimism and lower healthcare quality.

The association of a critical care electronic prescribing system with the quality of patient care provided by clinical pharmacists - a prospective, observational cohort study.

BACKGROUND: Despite the strong face validity of electronic prescribing (EP), the empiric data in support of improved patient safety is sparse. The objective of this study was to compare the clinical significance of pharmacist contributions between an established EP and paper-based prescribing (PBP) system in the intensive care unit (ICU) to understand the EP impact on the quality of patient care. MATERIALS AND METHODS: We conducted a prospective longitudinal study in two 18-bed ICUs; one with EP and the other, PBP. Pharmacist contributions were analysed over three months. Demographic, clinical and adjunctive intervention data were also collected. A multilevel ordinal logistic regression model was used and patients were followed up for 28 days. The primary outcome was the distribution of clinical significance levels of pharmacist contributions. RESULTS: There were 303 patients admitted to the ICU between April 1st and June 30th 2018. EP was used in 171 patients and PBP in 132 patients. 1658 contributions were analysed. There were 14.9% highly clinically significant contributions with EP compared to 44.6% with PBP. The EP group had lower odds (OR 0.05, 95% CI 0.02-0.12) for a higher clinical significance contribution compared to the PBP group, but this changed over the admission and differed between groups, with decreasing odds of a higher-level clinical contribution for each additional admission day with PBP (OR 0.57, 95%CI 0.42-0.78). CONCLUSION: This study showed a significant difference in the distribution of pharmacist contributions made over time, with clinical significance levels remaining stable in the EP group at low severity, as opposed to PBP which were initially high and then gradually decreased in severity over time. This contemporaneous controlled study found that the EP system required less significant input both in the severity and frequency of pharmacist contributions to maintain patient safety.

The Association Between the Decision to Withdraw Life-Sustaining Therapy and Patient Mortality in U.K. ICUs.

OBJECTIVES: Differences in decisions to limit life-sustaining therapy are often supported by perceptions that patients receive unnecessary and expensive treatment which provide negligible survival benefit. However, the assumption behind those beliefs-that is, that life-sustaining therapy provides no significant marginal survival benefit-remains unproven. Our objective was to quantify the effects of variations in decisions to withdraw or withhold life-sustaining treatment on 180-day mortality in critically ill patients. DESIGN: Retrospective observational cohort study of a national clinical database. SETTING: Adult ICUs participating in the Intensive Care National Audit and Research Center Case Mix Program in the United Kingdom. PATIENTS: Adult patients admitted to general ICUs between April 1, 2009, and March 31, 2016. MEASUREMENTS AND MAIN RESULTS: During the study period, 795,721 patients were admitted to 247 ICUs across the United Kingdom. A decision to withdraw or withhold life-sustaining treatment was made for 92,327 patients (11.6%). A multilevel model approach was used to estimate ICU-level practice variation. The ICU-level practice variation was then used as an instrument to measure the effects of decision to withdraw or withhold life-sustaining treatment on 180-day mortality. The marginal population was estimated to be 5.9% of the total cohort. A decision to withdraw or withhold life-sustaining treatment was associated with a marginal increase in 180-day mortality of 25.6% (95% CI, 23.2-27.9%). CONCLUSIONS: Decision to withdraw or withhold life-sustaining treatment in critically ill adults in the United Kingdom was associated with increased 180-day mortality in the marginal patients. The increased mortality from a decision to withdraw or withhold life-sustaining treatment in the marginal patient may be informative when establishing patients' preferences and evaluating the cost-effectiveness of intensive treatments.

Association of Annual Intensive Care Unit Sepsis Caseload With Hospital Mortality From Sepsis in the United Kingdom, 2010-2016.

Importance: Sepsis is associated with a high burden of inpatient mortality. Treatment in intensive care units (ICUs) that have more experience treating patients with sepsis may be associated with lower mortality. Objective: To assess the association between the volume of patients with sepsis receiving care in an ICU and hospital mortality from sepsis in the UK. Design, Setting, and Participants: This retrospective cohort study used data from adult patients with sepsis from 231 UK ICUs between 2010 and 2016. Demographic and clinical data were extracted from the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme database. Data were analyzed from January 1, 2010, to December 31, 2016. Exposures: Annual sepsis case volume in an ICU in the year of a patient's admission. Main Outcomes and Measures: Hospital mortality after ICU admission for sepsis assessed using a mixed-effects logistic model in a 3-level hierarchical structure based on the number of individual patients nested in years nested within ICUs. Results: Among 273 001 patients included in the analysis, the median age was 66 years (interquartile range, 53-76 years), 148 149 (54.3%) were male, and 248 275 (91.0%) were White. The mean ICNARC-2018 illness severity score was 21.0 (95% CI, 20.9-21.0). Septic shock accounted for 19.3% of patient admissions, and 54.3% of patients required mechanical ventilation. The median annual sepsis volume per ICU was 242 cases (interquartile range, 177-334 cases). The study identified a significant association between the volume of sepsis cases in the ICU and mortality from sepsis; in the logistic regression model, hospital mortality was significantly lower among patients admitted to ICUs in the highest quartile of sepsis volume compared with the lowest quartile (odds ratio [OR], 0.89; 95% CI, 0.82-0.96; P = .002). With volume modeled as a restricted cubic spline, treatment in a larger ICU was associated with lower hospital mortality. A lower annual volume threshold of 215 patients above which hospital mortality decreased significantly was found; 38.8% of patients were treated in ICUs below this threshold volume. There was no significant interaction between ICU volume and severity of illness as described by the ICNARC-2018 score (ß [SE], -0.00014 [0.00024]; P = .57). Conclusions and Relevance: The findings suggest that patients with sepsis in the UK have higher odds of survival if they are treated in an ICU with a larger sepsis case volume. The benefit of a high sepsis case volume was not associated with the severity of the sepsis episode.

Hospital Mortality and Resource Implications of Hospitalisation with COVID-19 in London, UK: A Prospective Cohort Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) had a significant impact on the National Health Service in the United Kingdom (UK), with over 35 000 cases reported in London by July 30, 2020. Detailed hospital-level information on patient characteristics, outcomes, and capacity strain is currently scarce but would guide clinical decision-making and inform prioritisation and planning. METHODS: We aimed to determine factors associated with hospital mortality and describe hospital and ICU strain by conducting a prospective cohort study at a tertiary academic centre in London, UK. We included adult patients admitted to the hospital with laboratory-confirmed COVID-19 and followed them up until hospital discharge or 30 days. Baseline factors that are associated with hospital mortality were identified via semiparametric and parametric survival analyses. RESULTS: Our study included 429 patients: 18% of them were admitted to the ICU, 52% met criteria for ICU outreach team activation, and 61% had treatment limitations placed during their admission. Hospital mortality was 26% and ICU mortality was 34%. Hospital mortality was independently associated with increasing age, male sex, history of chronic kidney disease, increasing baseline C-reactive protein level, and dyspnoea at presentation. COVID-19 resulted in substantial ICU and hospital strain, with up to 9 daily ICU admissions and 41 daily hospital admissions, to a peak census of 80 infected patients admitted in the ICU and 250 in the hospital. Management of such a surge required extensive reorganisation of critical care services with expansion of ICU capacity from 69 to 129 beds, redeployment of staff from other hospital areas, and coordinated hospital-level effort. CONCLUSIONS: COVID-19 is associated with a high burden of mortality for patients treated on the ward and the ICU and required substantial reconfiguration of critical care services. This has significant implications for planning and resource utilisation.

The Utility of ICU Readmission as a Quality Indicator and the Effect of Selection.

OBJECTIVES: Intensive care readmission rates are used to signal quality, yet it is unclear whether they represent poor quality in the transition of care from the ICU to the ward, patient factors, or differences in survival of the initial admission. This study aims to measure the selection effect of surviving the initial ICU admission on readmission rates. DESIGN: Retrospective cohort study of adult patients admitted to ICUs participating in the Case Mix Program database from the Intensive Care National Audit Research Centre. SETTINGS: The study includes 262 ICUs in the United Kingdom. PATIENTS: The study includes 682,975 patients admitted to ICUs between 2010 and 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study includes 682,975 patients admitted to ICUs in the United Kingdom. There were 591,710 patients discharged alive, of which 9,093 (1.53%) were readmitted within the first 2 days of ICU discharge. Post-ICU admission hospital mortality and ICU readmission were poorly correlated (r = 0.130). The addition of a selection model resulted in a weaker correlation (r = 0.082). CONCLUSIONS: ICU readmission performed poorly as a performance metric. The selection process by which only patients who survive their index admission are eligible for readmission has a significant effect on ICU readmission rankings, particularly the higher ranked ICUs. Failure to consider this selection bias gives misleading signals about ICU performance and leads to faulty design of incentive schemes.

Relationship between multidisciplinary critical care and burn patients survival: A propensity-matched national cohort analysis.

OBJECTIVE: The aims of this study are: firstly, to investigate if admission to specialized burn critical care units leads to better clinical outcomes; secondly, to elucidate if the multidisciplinary critical care contributes to this superior outcome. METHODS: A multi-centre cohort analysis of a prospectively collected national database of 1759 adult burn patients admitted to 13 critical care units in England and Wales between 2005 and 2011. Units were contacted via telephone to establish frequency and constitution of daily ward rounds. Critical care units were categorized into 3 settings: specialized burns critical care units, generalized critical care units and 'visiting' critical care units. Multivariate logistic regression analysis and propensity dose-response analysis were used to calculate risk adjusted mortality. RESULTS: Multivariate logistic regression analysis shows that admission to a specialized burn critical care service is independently associated with significant survival benefit compared to generalized critical care unit (adjusted OR for in-hospital death 1.81, [95% CI, 1.24, 2.66]) and 'visiting' critical care services (adjusted OR for in-hospital death 2.24 [95% CI, 1.49, 3.38]). Further analysis using propensity dose-response analysis demonstrates that risk-adjusted in-hospital mortality rate decreased as the dose of multidisciplinary care increased, with an adjusted odds ratio of 1 (specialized burn critical care units), 1.81 (generalized critical care units) and 2.24 ('visiting' critical care units). CONCLUSIONS: Admission to a specialized burn critical care service is independently associated with significant survival benefit. This is, at least in part, due to care being provided by a fully integrated multidisciplinary team.

Telemedicine with clinical decision support for critical care: a systematic review.

BACKGROUND: Telemedicine applications aim to address variance in clinical outcomes and increase access to specialist expertise. Despite widespread implementation, there is little robust evidence about cost-effectiveness, clinical benefits, and impact on quality and safety of critical care telemedicine. The primary objective was to determine the impact of critical care telemedicine (with clinical decision support available 24/7) on intensive care unit (ICU) and hospital mortality and length of stay in adults and children. The secondary objectives included staff and patient experience, costs, protocol adherence, and adverse events. METHODS: Data sources included MEDLINE, EMBASE, CINAHL, Cochrane Library databases, Health Technology Assessment Database, Web of Science, OpenGrey, OpenDOAR, and the HMIC through to December 2015. Randomised controlled trials and quasi-experimental studies were eligible for inclusion. Eligible studies reported on differences between groups using the telemedicine intervention and standard care. Two review authors screened abstracts and assessed potentially eligible studies using Cochrane guidance. RESULTS: Two controlled before-after studies met the inclusion criteria. Both were assessed as high risk of bias. Meta-analysis was not possible as we were unable to disaggregate data between the two studies. One study used a non-randomised stepped-wedge design in seven ICUs. Hospital mortality was the primary outcome which showed a reduction from 13.6 % (CI, 11.9-15.4 %) to 11.8 % (CI, 10.9-12.8 %) during the intervention period with an adjusted odds ratio (OR) of 0.40 (95 % CI, 0.31-0.52; p = .005). The second study used a non-randomised, unblinded, pre-/post-assessment of telemedicine interventions in 56 adult ICUs. Hospital mortality (primary outcome) reduced from 11 to 10 % (adjusted hazard ratio (HR) = 0.84; CI, 0.78-0.89; p = <.001). CONCLUSIONS: This review highlights the poor methodological quality of most studies investigating critical care telemedicine. The results of the two included studies showed a reduction in hospital mortality in patients receiving the intervention. Further multi-site randomised controlled trials or quasi-experimental studies with accompanying process evaluations are urgently needed to determine effectiveness, implementation, and associated costs. TRIAL REGISTRATION: PROSPERO CRD42014007406.

Rapid response systems: a systematic review and meta-analysis.

INTRODUCTION: Although rapid response system teams have been widely adopted by many health systems, their effectiveness in reducing hospital mortality is uncertain. We conducted a meta-analysis to examine the impact of rapid response teams on hospital mortality and cardiopulmonary arrest. METHOD: We conducted a systematic review of studies published from January 1, 1990, through 31 December 2013, using PubMed, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and the Cochrane Library. We included studies that reported data on the primary outcomes of ICU and in-hospital mortality or cardiopulmonary arrests. RESULTS: Twenty-nine eligible studies were identified. The studies were analysed in groups based on adult and paediatric trials that were further sub-grouped on methodological design. There were 5 studies that were considered either cluster randomized control trial, controlled before after or interrupted time series. The remaining studies were before and after studies without a contemporaneous control. The implementation of RRS has been associated with an overall reduction in hospital mortality in both the adult (RR 0.87, 95 % CI 0.81-0.95, p<0.001) and paediatric (RR=0.82 95 % CI 0.76-0.89) in-patient population. There was substantial heterogeneity in both populations. The rapid response system team was also associated with a reduction in cardiopulmonary arrests in adults (RR 0.65, 95 % CI 0.61-0.70, p<0.001) and paediatric (RR=0.64 95 % CI 0.55-0.74) patients. CONCLUSION: Rapid response systems were associated with a reduction in hospital mortality and cardiopulmonary arrest. Meta-regression did not identify the presence of a physician in the rapid response system to be significantly associated with a mortality reduction.

Improving critical care discharge summaries: a collaborative quality improvement project using PDSA.

Around 110,000 people spend time in critical care units in England and Wales each year. The transition of care from the intensive care unit to the general ward exposes patients to potential harms from changes in healthcare providers and environment. Nurses working on general wards report anxiety and uncertainty when receiving patients from critical care. An innovative form of enhanced capability critical care outreach called 'iMobile' is being provided at King's College Hospital (KCH). Part of the remit of iMobile is to review patients who have been transferred from critical care to general wards. The iMobile team wished to improve the quality of critical care discharge summaries. A collaborative evidence-based quality improvement project was therefore undertaken by the iMobile team at KCH in conjunction with researchers from King's Improvement Science (KIS). Plan, Do, Study, Act (PDSA) methodology was used. Three PDSA cycles were undertaken. Methods adopted comprised: a scoping literature review to identify relevant guidelines and research evidence to inform all aspects of the quality improvement project; a process mapping exercise; informal focus groups / interviews with staff; patient story-telling work with people who had experienced critical care and subsequent discharge to a general ward; and regular audits of the quality of both medical and nursing critical care discharge summaries. The following behaviour change interventions were adopted, taking into account evidence of effectiveness from published systematic reviews and considering the local context: regular audit and feedback of the quality of discharge summaries, feedback of patient experience, and championing and education delivered by local opinion leaders. The audit results were mixed across the trajectory of the project, demonstrating the difficulty of sustaining positive change. This was particularly important as critical care bed occupancy and through-put fluctuates which then impacts on work-load, with new cohorts of staff regularly passing through critical care. In addition to presenting the results of this quality improvement project, we also reflect on the lessons learned and make suggestions for future projects.

Extravascular lung water and acute lung injury.

Acute lung injury carries a high burden of morbidity and mortality and is characterised by nonhydrostatic pulmonary oedema. The aim of this paper is to highlight the role of accurate quantification of extravascular lung water in diagnosis, management, and prognosis in "acute lung injury" and "acute respiratory distress syndrome". Several studies have verified the accuracy of both the single and the double transpulmonary thermal indicator techniques. Both experimental and clinical studies were searched in PUBMED using the term "extravascular lung water" and "acute lung injury". Extravascular lung water measurement offers information not otherwise available by other methods such as chest radiography, arterial blood gas, and chest auscultation at the bedside. Recent data have highlighted the role of extravascular lung water in response to treatment to guide fluid therapy and ventilator strategies. The quantification of extravascular lung water may predict mortality and multiorgan dysfunction. The limitations of the dilution method are also discussed.

Vasopressors and the search for the optimal trial design.

Despite several advances in the care of critically ill patients, sepsis and septic shock continue to carry the largest burden of mortality and morbidity. Trials comparing vasopressors in shock have been disappointing and several key issues in methodology may need to be explored. There has been substantial progress in evolving adaptive trial methodology, however these have seldom been translated to clinical trials. This paper discusses some of the issues relevant to critical illness. To illustrate the potential contribution of adaptive trials we discuss fixed sample size design including event and time to event studies. We then explore group sequential and adaptive trial design, enrichment strategies and sample size re-estimation. An attractive feature of responsive adaptive designs is the flexibility to deal with unanticipated treatment effect size. If the observed effect size is larger than expected, early stopping is permitted. If the effect size is smaller than expected, sample size recalculation would be a reasonable choice in the face of an underpowered study. This allows for optimal efficiency in trial design. Reservations about adaptive trial design centre on issues of validity, feasibility and integrity of the study and are discussed in this paper.

Levosimendan and mortality after coronary revascularisation: a meta-analysis of randomised controlled trials.

INTRODUCTION: Patients undergoing coronary revascularization often require inotropic support that has been associated with an increased risk for death and morbidity. The purpose of this study was to evaluate the effect of levosimendan versus control on survival after coronary revascularization. METHODS: A systemic review and meta-analysis of the literature was carried out on published randomized controlled clinical trials that investigated the efficacy of levosimendan compared to other therapy in patients having coronary revascularisaion. The databases searched were Pubmed, EMBASE, the Cochrane Registry of Clinical Trials and the metaRegister of Controlled Trials. Studies that compared levosimendan to any other therapy for coronary revascularisation in adult humans and reported at least one outcome of interest were considered for inclusion. Both percutaneous coronary intervention and cardiac surgery were included. Data extraction was performed independently by two reviewers using predefined criteria. Relevant outcomes included mortality, cardiac index, cardiac enzymes, length of stay and post-procedural atrial fibrillation. RESULTS: The meta-analysis included 729 patients from 17 studies. Levosimendan was associated with a mortality reduction after coronary revascularization, (19/386 in the levosimendan group vs 39/343 in the control arm) odds ratio (OR) 0.40 (95% confidence interval (CI) 0.21 to 0.76, P for overall effect 0.005, P for heterogeneity = 0.33, I2 = 12% with a total of 729 patients. Levosimendan also had a favourable effect on cardiac index (standardised mean difference 1.63, 95% CI 1.43 to 1.83, P for overall effect < 0.00001), length of intensive care stay (random effects model, mean difference - 26.18 hours 95% CI 46.20 to 6.16, P for heterogeneity < 0.00001, I2 = 95%, P for overall effect P = 0.01), reductions in the rate of atrial fibrillation (OR 0.54, 95% CI 0.36 to 0.82, P for effect = 0.004, P for heterogeneity 0.84, I2 = 0% for 465 patients) and troponin I levels group (mean difference -1.59, 95% CI 1.78 to 1.40, P for overall effect < 0.00001, P for heterogeneity < 0.00001, I2 = 95%). Limitations of this analysis are discussed. CONCLUSIONS: Levosimendan is associated with a significant improvement in mortality after coronary revascularization. There are also improvements in several secondary endpoints. A suitably powered randomised controlled trial is required to confirm these findings and to address the unresolved questions about the timing and dosing of levosimendan.