Interventions to promote family member involvement in adult critical care settings: a systematic review.

OBJECTIVE: To identify, appraise and synthesise evidence of interventions designed to promote family member involvement in adult critical care units; and to develop a working typology of interventions for use by health professionals and family members. DESIGN: Mixed-method systematic review. DATA SOURCES: Bibliographic databases were searched without date restriction up to June 2019: MEDLINE, EMBASE and CINAHL; the Cochrane Central Register of Controlled Trials, Joanna Briggs and Cochrane Libraries. Back issues of leading critical care and patient experience journals were manually searched, as were the reference lists of included studies. All evaluation studies of relevant intervention activities were included; all research designs and outcome measures were eligible. Due to heterogeneity in interventions, designs and outcome measures, the synthesis followed a narrative approach. Service users met with the research team termly. RESULTS: Out of 4962 possible citations, a total of 20 studies were included. The overall evidence base was assessed as moderate to weak. Six categories of interventions were identified: environmental unit changes (n=2), web-based support (n=4), discussion-based support (n=6), multicomponent support (n=4), participation in rounds (n=3) and participation in physical care (n=1). Clinical and methodological heterogeneity across studies hindered meta-analysis, hence a narrative synthesis was pursued. Six main outcomes were identified, grouped under two categories: (i) involvement outcomes: communication (mean difference ranged from 6.39 to 8.83), decision-making (mean difference ranged from -0.8 to 5.85), satisfaction (mean difference ranged from 0.15 to 2.48); and (ii) health outcomes: family trauma (mean difference ranged from -7.12 to 0.9), family well-being (mean difference ranged from -0.7 to -4), patient outcomes (relative risk ranged from 1.27 to 4.91). The findings from the qualitative studies were thematically analysed to identify features of the interventions that participants perceived to influence effectiveness. Synthesised into five overarching categories (practicality, development, interaction, reflexivity and bridging), these can serve as principles to inform the future design and development of more refined family member involvement interventions. CONCLUSIONS: Future interventions should be developed with much closer family member input and designed by considering the key features we identified. We call for future interventions to be multilayered and allow for a greater or lesser level, and different kinds, of involvement for family members. Choice of intervention should be informed by a baseline diagnostic of family members' needs, readiness and preparedness for involvement. PROSPERO REGISTRATION: CRD42018086325.

Healthcare stakeholders' perceptions and experiences of factors affecting the implementation of critical care telemedicine (CCT): qualitative evidence synthesis.

BACKGROUND: Critical care telemedicine (CCT) has long been advocated for enabling access to scarce critical care expertise in geographically-distant areas. Additional advantages of CCT include the potential for reduced variability in treatment and care through clinical decision support enabled by the analysis of large data sets and the use of predictive tools. Evidence points to health systems investing in telemedicine appearing better prepared to respond to sudden increases in demand, such as during pandemics. However, challenges with how new technologies such as CCT are implemented still remain, and must be carefully considered. OBJECTIVES: This synthesis links to and complements another Cochrane Review assessing the effects of interactive telemedicine in healthcare, by examining the implementation of telemedicine specifically in critical care. Our aim was to identify, appraise and synthesise qualitative research evidence on healthcare stakeholders' perceptions and experiences of factors affecting the implementation of CCT, and to identify factors that are more likely to ensure successful implementation of CCT for subsequent consideration and assessment in telemedicine effectiveness reviews. SEARCH METHODS: We searched MEDLINE, Embase, CINAHL, and Web of Science for eligible studies from inception to 14 October 2019; alongside 'grey' and other literature searches. There were no language, date or geographic restrictions. SELECTION CRITERIA: We included studies that used qualitative methods for data collection and analysis. Studies included views from healthcare stakeholders including bedside and CCT hub critical care personnel, as well as administrative, technical, information technology, and managerial staff, and family members. DATA COLLECTION AND ANALYSIS: We extracted data using a predetermined extraction sheet. We used the Critical Appraisal Skills Programme (CASP) qualitative checklist to assess the methodological rigour of individual studies. We followed the Best-fit framework approach using the Consolidated Framework for Implementation Research (CFIR) to inform our data synthesis.  We classified additional themes not captured by CFIR under a separate theme. We used the GRADE CERQual approach to assess confidence in the findings. MAIN RESULTS: We found 13 relevant studies. Twelve were from the USA and one was from Canada. Where we judged the North American focus of the studies to be a concern for a finding's relevance, we have reflected this in our assessment of confidence in the finding. The studies explored the views and experiences of bedside and hub critical care personnel; administrative, technical, information technology, and managerial staff; and family members. The intensive care units (ICUs) were from tertiary hospitals in urban and rural areas. We identified several factors that could influence the implementation of CCT. We had high confidence in the following findings: Hospital staff and family members described several advantages of CCT. Bedside and hub staff strongly believed that the main advantage of CCT was having access to experts when bedside physicians were not available. Families also valued having access to critical care experts. In addition, hospital staff described how CCT could support clinical decision-making and mentoring of junior staff.  Hospital staff greatly valued the nature and quality of social networks between the bedside and CCT hub teams. Key issues for them were trust, acceptance, teamness, familiarity and effective communication between the two teams. Interactions between some bedside and CCT hub staff were featured with tension, frustration and conflict. Staff on both sides commonly described disrespect of their expertise, resistance and animosity. Hospital staff thought it was important to promote and offer training in the use of CCT before its implementation. This included rehearsing every step in the process, offering staff opportunities to ask questions and disseminating learning resources. Some also complained that experienced staff were taken away from bedside care and re-allocated to the CCT hub team. Hospital staff's attitudes towards, knowledge about and value placed on CCT influenced acceptance of CCT. Staff were positive towards CCT because of its several advantages. But some were concerned that the CCT hub staff were not able to understand the patient's situation through the camera. Some were also concerned about confidentiality of patient data. We also identified other factors that could influence the implementation of CCT, although our confidence in these findings is moderate or low. These factors included the extent to which telemedicine software was adaptable to local needs, and hub staff were aware of local norms; concerns about additional administrative work and cost; patients' and families' desire to stay close to their local community; the type of hospital setting; the extent to which there was support from senior leadership; staff access to information about policies and procedures; individuals' stage of change; staff motivation, competence and values; clear strategies for staff engagement; feedback about progress; and the impact of CCT on staffing levels. AUTHORS' CONCLUSIONS: Our review identified several factors that could influence the acceptance and use of telemedicine in critical care. These include the value that hospital staff and family members place on having access to critical care experts, staff access to sufficient training, and the extent to which healthcare providers at the bedside and the critical care experts supporting them from a distance acknowledge and respect each other's expertise. Further research, especially in contexts other than North America, with different cultures, norms and practices will strengthen the evidence base for the implementation of CCT internationally and our confidence in these findings. Implementation of CCT appears to be growing in importance in the context of global pandemic management, especially in countries with wide geographical dispersion and limited access to critical care expertise. For successful implementation, policymakers and other stakeholders should consider pre-empting and addressing factors that may affect implementation, including strengthening teamness between bedside and hub teams; engaging and supporting frontline staff; training ICU clinicians on the use of CCT prior to its implementation; and ensuring staff have access to information and knowledge about when, why and how to use CCT for maximum benefit.

Interventions to promote patients and families' involvement in adult intensive care settings: a protocol for a mixed-method systematic review.

BACKGROUND: There has been an identified need for greater patient and family member involvement in healthcare. This is particularly relevant in an intensive care unit (ICU), as the family provides a key communicative and practical link between patient and clinician. Family members have been deemed a positive beneficial influence on ICU care and recovery processes, yet they themselves are often emotionally affected after discharge. There has been no standardised evidenced-based approach which explores research on family member involvement and the range and quality of contributions remain unclear. This project will undertake a systematic review to assess the evidence base for interventions designed to promote patient and family member involvement in adult intensive care settings and develop a comprehensive typology of interventions for use by clinicians, patients and carers. METHODS: The following databases will be searched without date restriction: MEDLINE, EMBASE and CINAHL, as well as the Cochrane Central Register of Controlled Trials, Joanna Briggs and Cochrane Libraries. Manual searches of recent back issues of leading ICU and patient experience journals will also be undertaken, as will the reference lists of included studies. Unpublished literature will be sought through grey literature databases, including GreyLit and OpenGrey. All evaluation studies that consider intervention activities to promote patient and family member involvement in adult ICUs will be included; all research designs will be eligible. We will seek to include studies that report on a mixture of relevant outcomes for patients and family members. Abstracts and papers will be independently screened by at least two members of the team to determine their inclusion. Included papers will be assessed for methodological rigour using a standard rating approach, which assesses 'quality of study' and 'quality of information'. Quality assessment will be completed by at least two members of the team. Data on interventions, evaluation methods and outcomes will be collated using a predetermined extraction table. These are likely to be heterogeneous in nature, which will mean that the review will follow a narrative approach to synthesis. DISCUSSION: The review will provide valuable and rigorous insight into the range and quality of interventions available to promote patient and family member involvement in ICU. This is the first step towards addressing the absence of a synthesis of research for this context, and will, in addition, develop a typology of available interventions that will help service users and clinicians make informed decisions about the approaches to patient and family member involvement which they might want to adopt. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42018086325).

Exploring fasting practices for critical care patients - A web-based survey of UK intensive care units.

BACKGROUND: Enteral nutrition delivery in the critically ill is frequently interrupted for surgical and airway procedures to avoid aspiration of stomach contents. Recurrent fasting leads to under delivery of enteral nutrition and this underfeeding is associated with worse outcomes. International fasting recommendations do not provide guidance for intubated patients receiving enteral nutrition. This study aimed to gain a detailed perspective of UK critical care fasting practices. METHODS: A web-based survey was sent to 232 UK intensive care units consisting of questions relating to fasting practices, presence of guidelines, average fasting times for common procedures and dietitian time per intensive care unit bed. RESULTS: A total of 176 intensive care units responded. Only 20% of units had guidelines and respondents stated that they were not consistently adhered to (mean compliance 66%). Units with greater dietetic involvement were more likely to have guidelines (p = 0.04). Fasting times were shorter for abdominal surgery (p = 0.002), non-abdominal surgery (p = 0.016) and radiology (p = 0.015) if a guideline was present. Fasting for extubation and tracheostomy was similar irrespective of the presence of a guideline. Considerable variation in fasting times was reported, usually due to inconsistencies in clinical decision-making. CONCLUSIONS: This survey of national practice demonstrates that fasting times are varied and inconsistent, which may lead to under-delivery of enteral nutrition. More dietetic input was associated with increased likelihood of a fasting guideline.

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.

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.

A web-based survey of United Kingdom sedation practice in the intensive care unit.

PURPOSE: The purpose of this work was to obtain a detailed perspective of sedation practice. Sedation included sedative and opioid choice, presence of local guidelines, and use of scoring systems. METHODS: A Web-based survey was designed. The aim was to gain sufficient detail of UK sedation while also being succinct enough to complete in 15 minutes. It was composed of relevant demographics, policy, sedative choice, and analgesia. The survey was piloted before launch. The investigators selected the intensive care unit (ICU) pharmacist as the respondent. RESULTS: One hundred fifty-seven ICUs responded. Eighty-nine (59%) reported use of sedation guidelines, 78% undertook sedation holds, and 87% use sedation scores. Only 42% used a daily sedation target. Seventy (43%) assess for delirium; 27 of those use a validated tool. Propofol (89%) use was common, followed by midazolam (49%). Morphine (49%), fentanyl (34%), and alfentanil (34%) were the most frequently used opioids. CONCLUSION: This survey confirmed expected variation in UK sedation practice. Recognized strategies such as target sedation score and sedation policy are underused. A 43% uptake in delirium screening suggests that larger engagement is required to meet national standards.

The influence of statin exposure on inflammatory markers in patients with early bacterial infection: pilot prospective cohort study.

BACKGROUND: In the context of infection, progressive illness resulting in acute organ dysfunction is thought to be secondary to inflammatory response. Our aims were to determine risk factors for progressive illness following infection in a low-risk hospitalised cohort, including the impact of prior stain therapy. METHODS: We performed a prospective observational cohort study on two adult acute medical wards of a single tertiary academic hospital. We screened drug prescription charts of all adult acute medical admissions for inclusion criteria of inpatient administration of antibiotics for more than 24 hours for a microbiologically confirmed or clinically suspected infection. Patients were followed until admission to a high dependency unit (HDU) or intensive care unit (ICU), discharge from hospital, or to a maximum of 10 days. Outcomes were evolution of systemic inflammatory response syndrome (SIRS) criteria, white cell count and C-reactive protein measurements, and adverse clinical outcomes. We constructed multivariable models accounting for repeated within-patient measurements to determine associations between a priori selected predictors (days since admission, age, gender, Charlson score, prior statin exposure) and selected outcomes. RESULTS: We enrolled 209 patients; 27.8% were statin users and the commonest infection was pneumonia (51.0%). Most (88.0%) had at least 1 SIRS criterion on admission, and 76 (37.3%) manifested additional SIRS criteria over time. Risks of admission to HDU/ICU (3.3%) and of 30-day mortality (5.7%) were low. The proportion of patients with at least 1 SIRS criterion, mean CRP, and mean WBC all decreased over time. Multivariable regression models identified days since hospital admission as the only variable associated with daily presence of SIRS criteria, WCC, or CRP (adjusted OR <1 and p < 0.0001 in all analyses). Statin exposure was not a significant predictor. CONCLUSIONS: This cohort of ward patients treated for infection had a low risk of clinical deterioration, inflammatory markers improved over time, and statin exposure was not associated with any outcome. Future larger studies may identify risk factors for progression of illness in this population and plausible surrogate endpoints for evaluation in clinical trials.

An observational cohort study to determine efficacy, adherence and outcome of the early initiation of pressure support ventilation during mechanical ventilation.

BACKGROUND: Timely initiation of weaning from mechanical ventilation (MV) is important. Non-validated screening criteria may delay weaning if too prescriptive. This study observed physician-led utilisation of pressure support ventilation (PSV), referenced to four reported conventional screening criteria hypothesising that these criteria would have delayed the weaning progress. METHODS: A prospective observational cohort study of adult patients receiving MV in a 30-bed university hospital intensive care unit (ICU). Logistic regression analysis identified factors associated with PSV failure. Outcome is reported according to adherence to the screening criteria. RESULTS: 209 patients were included (age 62.6±15.9 years, male:female 115:94, Acute Physiology and Chronic Health Evaluation (APACHE) II 16.7±6.1). Median (IQR) time to initiate PSV was 11.0 (5.0-22.0) h, and duration of weaning to extubation was 43.0 (13.0-121.5) h. PSV weaning was initiated despite significant hypoxia (partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) 35.8±15.9 kPa), moderate positive end-expiratory pressure levels (7.5±2.5 cm H2O), deep sedation (44% Richmond Agitation and Sedation Scale (RASS) ≤-3) and cardiovascular instability (48.8%). At PSV initiation, 85% of patients violated at least one screening criterion, yet 74.6% of patients remained stable for 24 h and 25.4% of patients were successfully extubated within 12 h. There was no association between individual screening criteria and PSV failure. Failure to sustain a PSV trial was associated with ventilation >7 days (RR=2.12 (1.33 to 3.38), p=0.002) and ICU mortality (RR=2.94 (1.46 to 5.94), p=0.002). CONCLUSIONS: Physician-led transition to PSV and weaning was often initiated early and successfully before patients fulfilled conventional screening criteria. Failure to sustain a PSV trial could be an early indicator of prolonged MV and ICU mortality and warrants further investigation. These data support the view that current screening criteria may delay initiation of weaning.

Redox state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis.

In an endotoxaemic mouse model of sepsis, a tissue-based proteomics approach for biomarker discovery identified long pentraxin 3 (PTX3) as the lead candidate for inflamed myocardium. When the redox-sensitive oligomerization state of PTX3 was further investigated, PTX3 accumulated as an octamer as a result of disulfide-bond formation in heart, kidney, and lung-common organ dysfunctions seen in patients with sepsis. Oligomeric moieties of PTX3 were also detectable in circulation. The oligomerization state of PTX3 was quantified over the first 11 days in critically ill adult patients with sepsis. On admission day, there was no difference in the oligomerization state of PTX3 between survivors and non-survivors. From day 2 onward, the conversion of octameric to monomeric PTX3 was consistently associated with a greater survival after 28 days of follow-up. For example, by day 2 post-admission, octameric PTX3 was barely detectable in survivors, but it still constituted more than half of the total PTX3 in non-survivors (p < 0.001). Monomeric PTX3 was inversely associated with cardiac damage markers NT-proBNP and high-sensitivity troponin I and T. Relative to the conventional measurements of total PTX3 or NT-proBNP, the oligomerization of PTX3 was a superior predictor of disease outcome.

The interaction of vasopressin and corticosteroids in septic shock: a pilot randomized controlled trial.

OBJECTIVES: Vasopressin and corticosteroids are both commonly used adjunctive therapies in septic shock. Retrospective analyses have suggested that there may be an interaction between these drugs, with higher circulating vasopressin levels and improved outcomes in patients treated with both vasopressin and corticosteroids. We aimed to test for an interaction between vasopressin and corticosteroids in septic shock. DESIGN: Prospective open-label randomized controlled pilot trial. SETTING: Four adult ICUs in London teaching hospitals. PATIENTS: Sixty-one adult patients who had septic shock. INTERVENTIONS: Initial vasopressin IV infusion titrated up to 0.06 U/min and then IV hydrocortisone (50 mg 6 hourly) or placebo. Plasma vasopressin levels were measured at 6-12 and 24-36 hours after hydrocortisone/placebo administration. MEASUREMENTS AND MAIN RESULTS: Thirty-one patients were allocated to vasopressin + hydrocortisone and 30 patients to vasopressin + placebo. The hydrocortisone group required a shorter duration of vasopressin therapy (3.1 d; 95% CI, 1.1-5.1; shorter in hydrocortisone group) and required a lower total dose of vasopressin (ratio, 0.47; 95% CI, 0.32-0.71) compared with the placebo group. Plasma vasopressin levels were not higher in the hydrocortisone group compared with the placebo group (64 pmol/L difference at 6- to 12-hour time point; 95% CI, -32 to 160 pmol/L). Early vasopressin use was well tolerated with only one serious adverse event possibly related to study drug administration reported. There were no differences in mortality rates (23% 28-day mortality in both groups) or organ failure assessments between the two treatment groups. CONCLUSIONS: Hydrocortisone spared vasopressin requirements, reduced duration, and reduced dose, when used together in the treatment of septic shock, but it did not alter plasma vasopressin levels. Further trials are needed to assess the clinical effectiveness of vasopressin as the initial vasopressor therapy with or without corticosteroids.

Statin therapy in critical illness: an international survey of intensive care physicians' opinions, attitudes and practice.

BACKGROUND: Pleotropic effects of statins on inflammation are hypothesised to attenuate the severity of and possibly prevent the occurrence of the host inflammatory response to pathogen and infection-related acute organ failure. We conducted an international survey of intensive care physicians in Australia, New Zealand (ANZ) and United Kingdom (UK). The aims of the survey were to assess the current prescribing practice patterns, attitudes towards prescribing statin therapy in critically ill patients and opinions on the need for an interventional trial of statin therapy in critically ill patients. METHODS: Survey questions were developed through an iterative process. An expert group reviewed the resulting 26 items for face and content validity and clarity. The questions were further refined following pilot testing by ICU physicians from Australia, Canada and the UK. We used the online Smart SurveyTM software to administer the survey. RESULTS: Of 239 respondents (62 from ANZ and 177 from UK) 58% worked in teaching hospitals; most (78.2%) practised in 'closed' units with a mixed medical and surgical case mix (71.0%). The most frequently prescribed statins were simvastatin (77.6%) in the UK and atorvastatin (66.1%) in ANZ. The main reasons cited to explain the choice of statin were preadmission prescription and pharmacy availability. Most respondents reported never starting statins to prevent (65.3%) or treat (89.1%) organ dysfunction. Only a minority (10%) disagreed with a statement that the risks of major side effects of statins when prescribed in critically ill patients were low. The majority (84.5%) of respondents strongly agreed that a clinical trial of statins for prevention is needed. More than half (56.5%) favoured rates of organ failure as the primary outcome for such a trial, while a minority (40.6%) favoured mortality. CONCLUSIONS: Despite differences in type of statins prescribed, critical care physicians in the UK and ANZ reported similar prescription practices. Respondents from both communities agreed that a trial is needed to test whether statins can prevent the onset of new organ failure in patients with sepsis.

Risk factors for acute organ failure in intensive care unit patients who receive respiratory support in the absence of non-respiratory organ failure: an international prospective cohort study.

INTRODUCTION: Many supposed low-risk intensive care unit (ICU) admissions develop acute organ failure (AOF). Identifying patients at high risk of developing AOF and targeting them with preventative strategies may be effective. Our study question was: in a population of ICU patients receiving positive pressure respiratory support (invasive or non-invasive) in the absence of non-respiratory AOF, what is the 14-day incidence of, risk factors for and time to acute organ failure? METHODS: In an international prospective cohort study, patients receiving positive pressure respiratory support (invasive or non-invasive) in the absence of non-respiratory AOF were enrolled and followed for 14 days. The primary outcome measure was the incidence of any AOF (defined as SOFA 3 to 4) during follow-up. RESULTS: A total of 123 of 766 screened patients (16.1%) were enrolled. Data are reported for 121 patients. In total, 45 out of 121 patients (37.2%) developed AOF. Mortality rates were higher in those with AOF: 17.8% versus 4.0% OR 5.11, P = 0.019) for ICU mortality; and 28.9% versus 11.8% (OR 2.80, P = 0.019) for hospital mortality. Median ICU length of stay was also longer in those with AOF (11 versus 3.0 days; P < 0.0001). Hypoxemic respiratory failure (P = 0.001) and cardiovascular dysfunction (that is, SOFA 1 to 2; P = 0.03) were associated with AOF. The median time to first AOF was two days. CONCLUSIONS: Patients receiving positive (invasive or non-invasive) pressure respiratory support in the absence of non-respiratory AOF are commonly admitted to ICU; AOF is frequent in these patients. Organ failure developed within a short period after admission. Hypoxemic respiratory failure and cardiovascular dysfunction were strongly associated with AOF.

Statins do not prevent acute organ failure in ventilated ICU patients: single-centre retrospective cohort study.

INTRODUCTION: Observational studies suggest statin therapy reduces incident sepsis, but few studies have examined the impact on new organ failure. We tested the hypothesis that statin therapy, administered for standard clinical indications to ventilated intensive care unit patients, prevents acute organ failure without harming the liver. METHODS: We performed a retrospective, single-centre cohort study in a tertiary mixed medical/surgical intensive care unit. Mechanically ventilated patients without nonrespiratory organ failure within 24 hours after admission were assessed (during the first 15 days) for new acute organ failure (defined as Sequential Organ Failure Assessment (SOFA) score 3 or 4), liver failure (defined as new hepatic SOFA ≥ 3, or a 1.5 times increase of bilirubin from baseline to a value ≥ 20 mmol/l), and alanine transferase (ALT) > 165 IU/l. The effect of statin administration was explored in generalised linear mixed models. RESULTS: A total of 1,397 patients were included. Two hundred and nineteen patients received a median (interquartile range) of three (two, eight) statin doses. Patients receiving statins were older (67.4 vs. 55.5 years, P < 0.0001), less likely female (25.1% vs. 37.9%, P = 0.0003) and sicker (Acute Physiology and Chronic Health Evaluation (APACHE) II score 20.3 vs. 17.8, P < 0.0001). Considering outcome events at least 1 day after statin administration, statin patients were equally likely to develop acute organ failure (28.4% vs. 22.3%, P = 0.29) and hepatic failure (9.5% vs. 7.6%, P = 0.34), but were more likely to experience an ALT increase to > 165 IU/l ((11.2% vs. 4.8%, P = 0.0005). Multivariable analysis showed that APACHE II score (odds ratio (OR) = 1.05 per point; 95% confidence interval (CI) = 1.03 to 1.07) and APACHE II admission category (P < 0.0001), but not statin administration (OR = 1.21; 95% CI = 0.92 to 1.62), were significantly associated with acute organ failure occurring on or after the day of first statin administration. Statin administration was not associated with liver impairment (OR = 1.08; 95% CI = 0.66 to 1.77) but was associated with a rise in ALT > 165 IU/l (OR = 2.25; 95% CI = 1.32 to 3.84), along with APACHE II score (P = 0.016) and admission ALT (P = 0.0001). CONCLUSIONS: Concurrent statin therapy does not appear to protect against the development of new acute organ failure in critically ill, ventilated patients. The lack of effect may be due to residual confounding, a relatively low number of doses received, or an absence of true effect. Randomised controlled trials are needed to confirm a protective effect.

Potential metabolic consequences of statins in sepsis.

OBJECTIVE: Statins may be important for the prevention and management of sepsis; however, through their impact on ubiquinone synthesis, they may impair mitochondrial and organ function in the septic patient. Here we provide a narrative review of the function and roles of ubiquinone in cellular metabolism, the interactions with statins, and the potential consequences in the critically ill. DATA SOURCE: Literature search using the PubMed database. Search terms included statins, mitochondria, ubiquinone, and sepsis. CONCLUSION: Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and act by decreasing mevalonate levels, a precursor for cholesterol synthesis. However, mevalonate is also a precursor for ubiquinone, an integral component of the mitochondrial respiratory chain and an important antioxidant. Plasma ubiquinone is inversely related to statin levels, and impaired statin metabolism or excretion can decrease ubiquinone levels markedly. This is potentially important as critical illness markedly impairs statin metabolism. As mitochondrial dysfunction may be a major contributor to sepsis-induced organ failure, it is plausible that low ubiquinone levels may exacerbate mitochondrial and organ dysfunction. Furthermore, although the clinical relevance of low ubiquinone levels is currently unknown in the critically ill, this is often cited as a possible cause of the myopathy and rhabdomyolysis associated with statin use.

Tissue saturation measurement--exciting prospects, but standardisation and reference data still needed.

Sepsis and shock result in disturbances in microcirculatory perfusion and tissue oxygen utilisation that may not be reflected in global measures of haemodynamics. Near-infrared spectroscopy enables measurement of tissue oxygen saturation (StO2) and provides information on local microvascular and mitochondrial function. This measure could be incorporated with existing targets of goal-directed therapy to provide an integrated approach to haemodynamic resuscitation of both the macro- and microcirculation in various shock states. However, key methodological factors must be addressed before widespread clinical application.