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Background: Physiological measures of heart failure are common in surgical patients, despite the absence of a diagnosis. Heart rate (HR) increases during exercise are frequently blunted in heart failure (termed chronotropic incompetence), which primarily reflects beta-adrenoreceptor dysfunction. We examined whether chronotropic incompetence was associated with myocardial injury after noncardiac surgery., Methods: This was a predefined analysis of an international cohort study where participants aged ≥40 yr underwent symptom-limited cardiopulmonary exercise testing before noncardiac surgery. Chronotropic incompetence was defined as the ratio of increase in HR during exercise to age-predicted maximal increase in HR <0.6. The primary outcome was myocardial injury within 3 days after surgery, defined by high-sensitivity troponin assays >99th centile. Explanatory variables were biomarkers for heart failure (ventilatory efficiency slope [minute ventilation/carbon dioxide production] ≥34; peak oxygen consumption ≤14 ml kg -1 min -1 ; HR recovery ≤6 beats min -1 decrease 1 min post-exercise; preoperative N-terminal pro-B-type natriuretic peptide [NT pro-BNP] >300 pg ml -1 ). Myocardial injury was compared in the presence or absence of sympathetic (i.e. chronotropic incompetence) or parasympathetic (i.e. impaired HR recovery after exercise) thresholds indicative of dysfunction. Data are presented as odds ratios (ORs) (95% confidence intervals)., Results: Chronotropic incompetence occurred in 396/1325 (29.9%) participants; only 16/1325 (1.2%) had a heart failure diagnosis. Myocardial injury was sustained by 162/1325 (12.2%) patients. Raised preoperative NT pro-BNP was more common when chronotropic incompetence was <0.6 (OR: 1.57 [1.11-2.23]; P=0.011). Chronotropic incompetence was not significantly associated with myocardial injury (OR: 1.05 [0.74-1.50]; P=0.78), independent of rate-limiting therapy. HR recovery <12 beats min -1 decrease after exercise was associated with myocardial injury in the presence (OR: 1.62 [1.05-2.51]; P=0.03) or absence (OR: 1.60 [1.06-2.39]; P=0.02) of chronotropic incompetence., Conclusions: Chronotropic incompetence is common in surgical patients. In contrast to parasympathetic dysfunction which was associated with myocardial injury, preoperative chronotropic incompetence (suggestive of sympathetic dysfunction) was not associated with postoperative myocardial injury., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Rationale: Survivors of acute respiratory failure commonly experience long-term psychological sequelae and impaired quality of life. For researchers interested in general mental health, using multiple condition-specific instruments may be unnecessary and inefficient when using the Medical Outcomes Study Short Form (SF)-36, a recommended outcome measure, may suffice. However, relationships between the SF-36 scores and commonly used measures of psychological symptoms in acute survivors of respiratory failure are unknown., Objectives: Our objective is to examine the relationship of the SF-36 mental health domain (MH) and mental health component summary (MCS) scores with symptoms of depression, anxiety, and post-traumatic stress disorder (PTSD) evaluated using validated psychological instruments., Methods: We conducted a cross-sectional analysis of 1,229 participants at 6- and 12-month follow-up assessment using data from five studies from the United States, the United Kingdom, and Australia., Measurements and Main Results: Symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS), Depression Anxiety Stress Scales, the Davidson Trauma Scale, Impact of Event Scale (IES), and IES-Revised (IES-R). At 6-month assessment there were moderate to strong correlations of the SF-36 MH scores with HADS depression and anxiety symptoms (r = -0.74 and -0.79) and with IES-R PTSD symptoms (r = -0.60) in the pooled analyses. Using the normalized population mean of 50 on the SF-36 MH domain score as a cut-off, positive predictive values were 16 and 55% for substantial depression; 20 and 68% for substantial anxiety (Depression Anxiety Stress Scales and HADS, respectively); and 40, 44, and 67% for substantial PTSD symptoms (IES-R, IES, and Davidson Trauma Scale, respectively). Negative predictive values were high. The area under the receiver operating characteristics curve of the SF-36 MH score was high for depression, anxiety, and PTSD symptoms (0.88, 0.91, and 0.84, respectively). All results were consistent for the MCS, across the individual studies, and for the 12-month assessment., Conclusions: For researchers interested in general mental health status, the SF-36 MH or MCS offers a strong measure of psychological symptoms prevalent among survivors of acute respiratory failure. For researchers interested in specific conditions, validated psychological instruments should be considered.

Background: The ability of medical teams to develop and maintain team situation awareness (team SA) is crucial for patient safety. Limited research has investigated team SA within clinical environments. This study reports the development of a method for investigating team SA during the intensive care unit (ICU) round and describes the results., Methods: In one ICU, a sample of doctors and nurses (n = 44, who combined to form 37 different teams) were observed during 34 morning ward rounds. Following the clinical review of each patient (n = 105), team members individually recorded their anticipations for expected patient developments over 48 h. Patient-outcome data were collected to determine the accuracy of anticipations. Anticipations were compared among ICU team members, and the degree of consensus was used as a proxy measure of team SA. Self-report and observational data measured team-member involvement and communication during patient reviews., Results: For over half of 105 patients, ICU team members formed conflicting anticipations as to whether patients would deteriorate within 48 h. Senior doctors were most accurate in their predictions. Exploratory analysis found that team processes did not predict team SA. However, the involvement of junior and senior trainee doctors in the patient decision-making process predicted the extent to which those team members formed team SA with senior doctors., Conclusions: A new method for measuring team SA during the ICU round was successfully employed. A number of areas for future research were identified, including refinement of the situation awareness and teamwork measures.

Background: A number of intensive care (ICU) patients experience significant problems with physical, psychological, and social functioning for some time after discharge from ICU. These problems have implications not just for patients, but impose a continuing financial burden for the National Health Service. To support recovery, a number of hospitals across the UK have developed Intensive Care follow-up clinics. However, there is a lack of evidence base to support these, and this study aims to test the hypothesis that intensive care follow up programmes are effective and cost-effective at improving physical and psychological quality of life in the year after intensive care discharge., Methods/design: This is a multi-centre, pragmatic, randomised controlled trial. Patients (n = 270) will be recruited prior to hospital discharge from three intensive care units in the UK, and randomised to one of two groups. The control group will receive standard in-hospital follow-up and the intervention group will participate in an ICU follow-up programme with clinic appointments 2-3 and 9 months after ICU discharge. The primary outcome measure is Health-related Quality of Life (HRQoL) 12 months after ICU discharge as measured by the Short Form-36. Secondary measures include: HRQoL at six months; Quality-adjusted life years using EQ-5D; posttraumatic psychopathology as measured by Davidson Trauma Scale; and anxiety and depression using the Hospital Anxiety and Depression Scale at both six and twelve months after ICU discharge. Contacts with health services in the twelve months after ICU discharge will be measured as part of the economic analysis., Discussion: The provision of intensive care follow-up clinics within the UK has developed in an ad hoc manner, is inconsistent in both the number of hospitals offering such a service or in the type of service offered. This study provides the opportunity to evaluate such services both in terms of patient benefit and cost-effectiveness. The results of this study therefore will inform clinical practice and policy with regard to the appropriate development of such services aimed at improving outcomes after intensive care., Trial Registration: ISRCTN24294750.

Objectives: To assess the clinical and cost-effectiveness of drotrecogin alfa (activated) for the treatment of adults with severe sepsis in a UK context., Data Sources: Electronic databases. Data from the commercial use of the drug up to April 2002. Data from the manufacturer submission to the National Institute for Clinical Excellence (NICE)., Review Methods: A systematic review of the literature and an economic evaluation were undertaken. Data were synthesised through a narrative review with full tabulation of results from included studies., Results: The evidence on the effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis came primarily from one large pivotal randomised controlled trial, the PROWESS study. This study demonstrated a statistically significant absolute reduction in 28-day mortality of 6.5%. Longer term survival benefit was maintained to 90 days. By 9 months, the trend towards increased median survival was non-significant, although the survival curves did not cross. Results presented by the number of organ dysfunctions were not statistically significant, but when mortality rates for those with two or more organ failures were combined, the relative risk of death was significantly lower in those treated with drotrecogin alfa (activated) compared with placebo. However, this report highlights a number of considerations relevant to the subgroup analyses reported for the PROWESS study. Published cost-effectiveness studies of treatment with drotrecogin alfa (activated) have applied a range of methods to the estimation of benefits, estimating an incremental gain per treated patient of between 0.38 and 0.68 life-years (for patients with severe sepsis). For patients with severe sepsis and multiple organ dysfunction, the manufacturer (Eli Lilly) estimated an incremental gain of 1.115 life-years per treated patient, compared to 1.351 life-years per treated patient estimated by the Southampton Health Technology Assessments Centre (SHTAC). These latter UK analyses are based on a patient group that is more severely affected by disease, where effectiveness is greater and the baseline risk of all-cause mortality is much higher (SHTAC analysis), these factors are associated with the noted difference in effect. The three published cost-effectiveness studies report cost for US and Canadian patient groups; for those patients with severe sepsis they report the additional cost per patient treated in a range around 10,000-16,000 dollars. The manufacturer's submission reports analysis for the UK, based on 28-day survival data in patients with severe sepsis and multiple organ dysfunction (the European licence indication), with the additional mean cost per treated patient estimated to be 5106 pounds. The analysis undertaken by SHTAC, for a UK group of patients with severe sepsis and multiple organ dysfunction, estimates an additional mean cost per patient treated of 6661 pounds. The manufacturer's submission to NICE presents cost-effectiveness estimates for drotrecogin alfa (activated) in the UK, in patients with severe sepsis and multiple organ dysfunction, at 6637 pounds per quality-adjusted life-year (QALY) based on 28-day effectiveness data, and 10,937 pounds per QALY based on longer term follow-up data. SHTAC developed an independent cost-effectiveness model and estimated a base-case cost per QALY of 8228 pounds in patients with severe sepsis and multiple organ failure (based on 28-day survival data). Simulation results indicate that where the NHS is willing to pay 20,000 pounds per QALY, drotrecogin alfa (activated) is a cost-effective use of resources in 98.7% of cases. Published economic evaluations report various sensitivity analyses, with results sensitive to changes in the measure of treatment effect, but otherwise studies reported that results were robust to variations in most assumptions used in the cost-effectiveness analysis., Conclusions: Drotrecogin alfa (activated) plus best supportive care appears clinically and cost-effective compared with best supportive care alone, in a UK cohort of severe sepsis patients, and in the subgroup of more severely affected patients with severe sepsis and multiple organ failure. The introduction of drotrecogin alfa (activated) will involve a substantial additional cost to the NHS. The treatment-eligible population in England and Wales may comprise up to 16,570 patients, with an estimated annual drug acquisition cost of over 80 million pounds, excluding VAT. Further research is required on the longer term impact of drotrecogin alfa (activated) on both mortality and morbidity in UK patients with severe sepsis, on the clinical and cost-effectiveness of drotrecogin alfa (activated) in children (under 18 years) with severe sepsis, and on the effect of the timing of dosage and duration of treatment on outcomes in severe sepsis.

Surgical patients make up 60-70% of the work load of intensive care units in the UK. There is a recognised short fall in the resource allocation for high dependency units (HDUs) and intensive care units (ICUs) in this country, despite repeated national audits urging that this resource be increased. British ICUs admit patients later and with higher severity of illness scores than elsewhere and this leads to higher ICU mortality. How can this situation be improved? Scoring systems that allow selection of appropriate patients for admission to ICU and avoid inappropriate admission are still in development. Pre-operative admission and optimisation in ICU is rare in this country despite increasing evidence to support this practice in high risk surgical patients. Early admission to ICU, with potential improvement in outcomes, could also be achieved using multi-disciplinary medical emergency teams. These teams would be alerted by ward staff in response to set specific conditions and physiological criteria. These proposals are still under trial but may offer benefit by reducing mortality in critically ill surgical patients.

Objective: Although unlicensed, inhaled nitric oxide (NO) therapy is now widely used in the United Kingdom. Our aim was to produce guidelines for the clinical application of inhaled NO in adult intensive care practice, based upon the current level of published information., Methods: The published data regarding the use of inhaled NO in the acute respiratory distress syndrome and right-sided cardiac failure was presented, analysed and discussed. Recommendations based on these data as well as on current experience in the United Kingdom were formulated., Design: An expert group comprising intensive care specialists from within the United Kingdom, representatives from the European Society of Intensive Care Medicine and the Society of Critical Care Medicine and individuals from the Departments of Health and Industry related to the field was assembled., Results: United Kingdom guidelines for the indications, contraindications, dose, delivery, monitoring and scavenging of inhaled NO therapy were produced., Conclusions: The need for additional quality research to establish evidence of efficacy and safety was emphasized. The guidelines are designed to act within the context of current practice and knowledge and should be revised as further data emerge.