Serial measurement of pancreatic stone protein for the early detection of sepsis in intensive care unit patients: a prospective multicentric study.

BACKGROUND: The early recognition and management of sepsis improves outcomes. Biomarkers may help in identifying earlier sub-clinical signs of sepsis. We explored the potential of serial measurements of C-reactive protein (CRP), procalcitonin (PCT) and pancreatic stone protein (PSP) for the early recognition of sepsis in patients hospitalized in the intensive care unit (ICU). METHODS: This was a multicentric international prospective observational clinical study conducted in 14 ICUs in France, Switzerland, Italy, and the United Kingdom. Adult ICU patients at risk of nosocomial sepsis were included. A biomarker-blinded adjudication committee identified sepsis events and the days on which they began. The association of clinical sepsis diagnoses with the trajectories of PSP, CRP, and PCT in the 3 days preceding these diagnoses of sepsis were tested for markers of early sepsis detection. The performance of the biomarkers in sepsis diagnosis was assessed by receiver operating characteristic (ROC) analysis. RESULTS: Of the 243 patients included, 53 developed nosocomial sepsis after a median of 6 days (interquartile range, 3-8 days). Clinical sepsis diagnosis was associated with an increase in biomarkers value over the 3 days preceding this diagnosis [PSP (p = 0.003), PCT (p = 0.025) and CRP (p = 0.009)]. PSP started to increase 5 days before the clinical diagnosis of sepsis, PCT 3 and CRP 2 days, respectively. The area under the ROC curve at the time of clinical sepsis was similar for all markers (PSP, 0.75; CRP, 0.77; PCT, 0.75). CONCLUSIONS: While the diagnostic accuracy of PSP, CRP and PCT for sepsis were similar in this cohort, serial PSP measurement demonstrated an increase of this marker the days preceding the onset of signs necessary to clinical diagnose sepsis. This observation justifies further evaluation of the potential clinical benefit of serial PSP measurement in the management of critically ill patients developing nosocomial sepsis. Trial registration The study has been registered at ClinicalTrials.gov (no. NCT03474809), on March 16, 2018. https://www.clinicaltrials.gov/ct2/show/NCT03474809?term=NCT03474809&draw=2&rank=1 .

Lung Ultrasound Findings in the Postanesthesia Care Unit Are Associated With Outcome After Major Surgery: A Prospective Observational Study in a High-Risk Cohort.

BACKGROUND: Postoperative pulmonary complications are associated with increased morbidity. Identifying patients at higher risk for such complications may allow preemptive treatment. METHODS: Patients with an American Society of Anesthesiologists (ASA) score >1 and who were scheduled for major surgery of >2 hours were enrolled in a single-center prospective study. After extubation, lung ultrasound was performed after a median time of 60 minutes by 2 certified anesthesiologists in the postanesthesia care unit after a standardized tracheal extubation. Postoperative pulmonary complications occurring within 8 postoperative days were recorded. The association between lung ultrasound findings and postoperative pulmonary complications was analyzed using logistic regression models. RESULTS: Among the 327 patients included, 69 (19%) developed postoperative pulmonary complications. The lung ultrasound score was higher in the patients who developed postoperative pulmonary complications (12 [7-18] vs 8 [4-12]; P < .001). The odds ratio for pulmonary complications in patients who had a pleural effusion detected by lung ultrasound was 3.7 (95% confidence interval, 1.2-11.7). The hospital death rate was also higher in patients with pleural effusions (22% vs 1.3%; P < .001). Patients with pulmonary consolidations on lung ultrasound had a higher risk of postoperative mechanical ventilation (17% vs 5.1%; P = .001). In all patients, the area under the curve for predicting postoperative pulmonary complications was 0.64 (95% confidence interval, 0.57-0.71). CONCLUSIONS: When lung ultrasound is performed precociously <2 hours after extubation, detection of immediate postoperative alveolar consolidation and pleural effusion by lung ultrasound is associated with postoperative pulmonary complications and morbi-mortality. Further study is needed to determine the effect of ultrasound-guided intervention for patients at high risk of postoperative pulmonary complications.

Definitions and pathophysiology of vasoplegic shock.

Vasoplegia is the syndrome of pathological low systemic vascular resistance, the dominant clinical feature of which is reduced blood pressure in the presence of a normal or raised cardiac output. The vasoplegic syndrome is encountered in many clinical scenarios, including septic shock, post-cardiac bypass and after surgery, burns and trauma, but despite this, uniform clinical definitions are lacking, which renders translational research in this area challenging. We discuss the role of vasoplegia in these contexts and the criteria that are used to describe it are discussed. Intrinsic processes which may drive vasoplegia, such as nitric oxide, prostanoids, endothelin-1, hydrogen sulphide and reactive oxygen species production, are reviewed and potential for therapeutic intervention explored. Extrinsic drivers, including those mediated by glucocorticoid, catecholamine and vasopressin responsiveness of the blood vessels, are also discussed. The optimum balance between maintaining adequate systemic vascular resistance against the potentially deleterious effects of treatment with catecholamines is as yet unclear, but development of novel vasoactive agents may facilitate greater understanding of the role of the differing pathways in the development of vasoplegia. In turn, this may provide insights into the best way to care for patients with this common, multifactorial condition.

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.

A service evaluation of measuring fluid responsiveness in acutely unwell hypotensive patients outside of critical care.

INTRODUCTION: Early recognition and prompt, appropriate management may reduce mortality in patients with sepsis. The Surviving Sepsis Campaign's guidelines suggest the use of dynamic measurements to guide fluid resuscitation in sepsis; although these methods are rarely employed to monitor cardiac output in response to fluid administration outside intensive care units. This service evaluation investigated the introduction of a nurse led protocolised goal-directed fluid management using a non-invasive cardiac output monitor to the standard assessment of hypotensive ward patients. METHODS: We introduced the use of a goal-directed fluid management protocol into our critical care outreach teams' standard clinical assessment. Forty-nine sequential patients before and thirty-nine after its introduction were included in the assessment. RESULTS: Patients in the post-intervention cohort received less fluid in the 6 h following outreach assessment (750mls vs 1200mls). There were no differences in clinical background or rates of renal replacement therapy, but rates of invasive and non-invasive ventilation were reduced (0% vs 31%). Although the groups were similar, the post-intervention patients had lower recorded blood pressures. CONCLUSION: IV fluid therapy in the patient with hypotension complicating sepsis can be challenging. Excessive IV fluid administration is commonplace and associated with harm, and the use of advanced non-invasive haemodynamic monitoring by trained nurses can provide objective evaluation of individualised response to treatment. Avoiding excessive IV fluid and earlier institution of appropriate vasopressor therapy may improve patient outcomes. IMPLICATIONS FOR CLINICAL PRACTICE: Adoption of dynamic measures of cardiac output outside of critical care by trained critical care nurses is feasible and may translate into improved patient outcomes. In hospitals with a nurse-led critical care outreach service, consideration should be given to such an approach.

Timing and burden of persistent critical illnessin UK intensive care units: An observational cohort study.

Background: Persistent critical illness is a recognisable clinical syndrome defined conceptually as when the patient's reason for being in the intensive care unit (ICU) is more related to their ongoing critical illness than their original reason for admission. Our objectives were: (1) to assess the day in ICU on which chronic factors (e.g., age, gender and comorbidities) were more predictive of survival than acute factors (e.g. admission diagnosis, physiological derangements) measured on the day of admission; (2) to assess the consistency of this finding across major patient subgroups and over time and (3) to compare case mix characteristics and outcomes for patients determined to develop persistent critical illness (based on ICU length of stay) with other patients. Methods: Observational cohort study using a high-quality clinical database from the national clinical audit of adult critical care. 217 adult ICUs in England, Wales and Northern Ireland. 835,946 adult patients admitted to participating ICUs between 1 April 2009 and 31 March 2016. The main outcome measure was mortality at discharge from acute hospital. Results: We fitted two statistical models ('chronic' and 'acute') and updated these based upon patients with an ICU length of stay of at least 1, 2, etc., up to 28 days. The discrimination of the chronic model first exceeded that of the acute model on day 11. Patients with longer stays (>10 days) comprised 9% of admissions but used 45% of ICU bed-days. After a mean ICU length of stay of 22 days and a subsequent 28 days in hospital, 30% died. Conclusions: Persistent critical illness is commonly encountered in clinical practice and is associated with increased healthcare utilisation and adverse outcomes. Improvements in our understanding of the longer term outcomes and in the development of tools to aid prognostication are urgently required - for humane as well as health economic reasons.

Efficacy of remote ischaemic preconditioning on outcomes following non-cardiac non-vascular surgery: a systematic review and meta-analysis.

BACKGROUND: Remote ischaemic preconditioning (RIPC) has been investigated as a simple intervention to potentially mitigate the ischaemic effect of the surgical insult and reduce postoperative morbidity. This review systematically evaluates the effect of RIPC on morbidity, including duration of hospital stay and parameters reflective of cardiac, renal, respiratory, and hepatic dysfunction following non-cardiac non-vascular (NCNV) surgery. METHODS: The electronic databases PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from their inception date to November 2021. Studies investigating the effect of local preconditioning or postconditioning were excluded. Methodological quality and risk of bias were determined according to the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2). Calculation of the odds ratios and a random effects model was used for dichotomous outcomes and mean differences or standardised mean differences as appropriate were used for continuous outcomes. The primary outcomes of interest were cardiac and renal morbidity, and the secondary outcomes included other organ function parameters and hospital length of stay. RESULTS: A systematic review of the published literature identified 36 randomised controlled trials. There was no significant difference in postoperative troponin or acute kidney injury. RIPC was associated with lower postoperative serum creatinine (9 studies, 914 patients, mean difference (MD) - 3.81 µmol/L, 95% confidence interval (CI) - 6.79 to - 0.83, p = 0.01, I2 = 5%) and lower renal stress biomarker (neutrophil gelatinase-associated lipocalin (NGAL), 5 studies, 379 patients, standardized mean difference (SMD) - 0.66, 95% CI - 1.27 to - 0.06, p = 0.03, I2 = 86%). RIPC was also associated with improved oxygenation (higher PaO2/FiO2, 5 studies, 420 patients, MD 51.51 mmHg, 95% CI 27.32 to 75.69, p < 0.01, I2 = 89%), lower biomarker of oxidative stress (malondialdehyde (MDA), 3 studies, 100 patients, MD - 1.24 µmol/L, 95% CI - 2.4 to - 0.07, p = 0.04, I2 = 91%)) and shorter length of hospital stay (15 studies, 2110 patients, MD - 0.99 days, 95% CI - 1.75 to - 0.23, p = 0.01, I2 = 88%). CONCLUSIONS: This meta-analysis did not show an improvement in the primary outcomes of interest with the use of RIPC. RIPC was associated with a small improvement in certain surrogate parameters of organ function and small reduction in hospital length of stay. Our results should be interpreted with caution due to the limited number of studies addressing individual outcomes and the considerable heterogeneity identified. TRIAL REGISTRATION: PROSPERO CRD42019129503.

The incidence of postoperative vasopressor usage: protocol for a prospective international observational cohort study (SQUEEZE).

BACKGROUND: Postoperative hypotension is common after major non-cardiac surgery, due predominantly to vasodilation. Administration of infused vasopressors postoperatively may often be considered a surrogate indicator of vasodilation. The incidence of postoperative vasopressors has never been described for non-cardiac surgery, nor have outcomes associated with their use. This paper presents a protocol for a prospective international cohort study to address these gaps in knowledge. The primary objectives are to estimate the proportion of patients who receive postoperative vasopressor infusions (PVI) and to document the variation in this proportion between hospitals and internationally. Furthermore, we will identify factors in variation of care (patient, condition, surgery, and intraoperative management) associated with receipt of PVI and investigate how PVI use is associated with patient outcomes, including organ dysfunction, length of hospital stay, and 30-day in-hospital mortality. METHOD: This will be a prospective, international, multicentre cohort study that includes all adult (≥ 18 years) non-cardiac surgical patients in participating centres. Patients undergoing cardiac, obstetric, or day-case surgery will be excluded. We will recruit two cohorts of patients: cohort A will include all eligible patients admitted to participating hospitals for seven consecutive days. Cohort B will include 30 sequential patients per hospital, with the single additional inclusion criterion of postoperative vasopressor usage. We expect to collect data on approximately 40,000 patients for cohort A and 12,800 patients for cohort B. DISCUSSION: While in cardiac surgery, clinical trials have informed the choice of vasopressors used to treat postoperative vasoplegia; there remains equipoise over the best approach in non-cardiac surgery. Our study will represent the first large-scale assessment of the use of vasopressors after non-cardiac surgery. These data will inform future studies, including trials of different vasopressors and potential management options to improve outcomes and reduce resource use after surgery. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03805230, 15 January 2019.

Remote Ischaemic Preconditioning in Intra-Abdominal Cancer Surgery (RIPCa): A Pilot Randomised Controlled Trial.

There is limited evidence on the effect of remote ischaemic preconditioning (RIPC) following non-cardiac surgery. The aim of this study was to investigate the effect of RIPC on morbidity following intra-abdominal cancer surgery. We conducted a double blinded pilot randomised controlled trial that included 47 patients undergoing surgery for gynaecological, pancreatic and colorectal malignancies. The patients were randomized into an intervention (RIPC) or control group. RIPC was provided by intermittent inflations of an upper limb tourniquet. The primary outcome was feasibility of the study, and the main secondary outcome was postoperative morbidity including perioperative troponin change and the urinary biomarkers tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 (TIMP-2*IGFBP-7). The recruitment target was reached, and the protocol procedures were followed. The intervention group developed fewer surgical complications at 30 days (4.5% vs. 33%), 90 days (9.5% vs. 35%) and 6 months (11% vs. 41%) (adjusted p 0.033, 0.044 and 0.044, respectively). RIPC was a significant independent variable for lower overall postoperative morbidity survey (POMS) score, OR 0.79 (95% CI 0.63 to 0.99) and fewer complications at 6 months including pulmonary OR 0.2 (95% CI 0.03 to 0.92), surgical OR 0.12 (95% CI 0.007 to 0.89) and overall complications, OR 0.18 (95% CI 0.03 to 0.74). There was no difference in perioperative troponin change or TIMP2*IGFBP-7. Our pilot study suggests that RIPC may improve outcomes following intra-abdominal cancer surgery and that a larger trial would be feasible.

Epidemiology and age-related mortality in critically ill patients with intra-abdominal infection or sepsis: an international cohort study.

OBJECTIVE: To describe epidemiology and age-related mortality in critically ill older adults with intra-abdominal infection. METHODS: A secondary analysis was undertaken of a prospective, multi-national, observational study (Abdominal Sepsis Study, ClinicalTrials.gov #NCT03270345) including patients with intra-abdominal infection from 309 intensive care units (ICUs) in 42 countries between January and December 2016. Mortality was considered as ICU mortality, with a minimum of 28 days of observation when patients were discharged earlier. Relationships with mortality were assessed by logistic regression analysis. RESULTS: The cohort included 2337 patients. Four age groups were defined: middle-aged patients [reference category; 40-59 years; n=659 (28.2%)], young-old patients [60-69 years; n=622 (26.6%)], middle-old patients [70-79 years; n=667 (28.5%)] and very old patients [≥80 years; n=389 (16.6%)]. Secondary peritonitis was the predominant infection (68.7%) and was equally prevalent across age groups. Mortality increased with age: 20.9% in middle-aged patients, 30.5% in young-old patients, 31.2% in middle-old patients, and 44.7% in very old patients (P<0.001). Compared with middle-aged patients, young-old age [odds ratio (OR) 1.62, 95% confidence interval (CI) 1.21-2.17], middle-old age (OR 1.80, 95% CI 1.35-2.41) and very old age (OR 3.69, 95% CI 2.66-5.12) were independently associated with mortality. Other independent risk factors for mortality included late-onset hospital-acquired intra-abdominal infection, diffuse peritonitis, sepsis/septic shock, source control failure, liver disease, congestive heart failure, diabetes and malnutrition. CONCLUSIONS: For ICU patients with intra-abdominal infection, age >60 years was associated with mortality; patients aged ≥80 years had the worst prognosis. Comorbidities and overall disease severity further compromised survival. As all of these factors are non-modifiable, it remains unclear how to improve outcomes.

The need for post-operative vasopressor infusions after major gynae-oncologic surgery within an ERAS (Enhanced Recovery After Surgery) pathway.

BACKGROUND: Hypotension following major abdominal surgery is common, and once hypovolaemia has been optimally treated, is often due to vasodilation which can be treated with vasopressor infusions. There is unpredictability in the dose and duration of post-operative vasopressor infusions, and factors associated with this have not been determined. METHODS: We present a case series of consecutive patients who received major gynae-oncology surgery delivered within an Enhanced Recovery After Surgery (ERAS) pathway at a single institution. Patients were electively admitted from theatre directly to the intensive care unit (ICU). Data was collected prospectively into electronic databases (Philips ICCA, Wardwatcher) and then retrospectively collated and appropriate statistical analyses were performed. In the absence of a consensus definition of vasoplegia, we, necessarily arbitrarily, chose a noradrenaline dose of > 0.1 mcg/kg/min at 08:00 on the first post-operative day. The rationale is that this would be more than would typically be expected to counteract the vasodilatory effects of epidural analgesia, which is commonly used at our institution. RESULTS: Data was collected from 324 patients, all treated between February 2014 and July 2016. The average age was 67 years and 39% received neoadjuvant chemotherapy. The commonest tumour type was ovarian (58%). The median estimated blood loss was 800 ml and epidural analgesia was used in 71%. Fifty per cent received post-operative vasopressor infusions: factors associated with this included epidural use and estimated blood loss. Nineteen per cent met our criteria for vasoplegia: factors associated with this included CRP on post-operative day 1 and P-POSSUM morbidity score. Hospital and ICU length of stay was prolonged in those who had vasoplegia. CONCLUSIONS: Patients commonly receive vasopressors following major gynae-oncologic surgery, and this can be at relatively high doses. Clinical factors only accounted for a minority of the variability in vasopressor usage-suggesting considerable biological variability. Optimal care of patients having major abdomino-pelvic surgery may include advanced haemodynamic monitoring and ready availability of infused vasopressors, in a suitable environment.

Type 2 Diabetes and Asthma: Systematic Review of the Bidirectional Relationship.

BACKGROUND AND OBJECTIVE: Obesity is an important contributor to the risk of both asthma and Type 2 Diabetes (T2DM). However, it has been suggested that T2DM and asthma are also independently associated. The aim of this systematic review was to synthesize the evidence for an independent relationship between T2DM and asthma. METHODS: MEDLINE and EMBASE were searched for studies reporting the relationship between asthma and T2DM in adults. Given a potential bidirectional relationship, articles relating to T2DM as a risk factor for asthma, and asthma as a risk factor for T2DM were examined separately. RESULTS: Eight studies were identified for inclusion in the review (n=2,934,399 participants). Four studies examined incident diabetes in those with asthma. The pooled (random effects model) adjusted hazard ratio for incident T2DM in asthma was 1.37 (95%CI 1.12-1.69; p <0.001) after controlling for BMI. Four studies reported prevalence or incidence rates of asthma in people with T2DM; higher rates of asthma in those with T2DM were reported in all four studies. Meta-analysis of results was not possible due to methodological heterogeneity. The quality of included studies was good, but due to small numbers, publication bias cannot be excluded. CONCLUSION: The published literature suggests a bidirectional independent relationship between T2DM and asthma, although we cannot exclude publication bias.

Manipulating the Microcirculation in Sepsis - the Impact of Vasoactive Medications on Microcirculatory Blood Flow: A Systematic Review.

BACKGROUND: Sepsis is life-threatening organ dysfunction because of a dysregulated host response to infection. Disturbed microvascular blood flow is associated with excess mortality and is a potential future target for interventions. This review addresses the evidence for pharmacological manipulation of the microcirculation in sepsis assessed by techniques that evaluate the sublingual microvasculature. METHODS: Systematic review using a published protocol. Eligibility criteria were studies of septic patients published from January 2000 to February 2018. Interventions were drugs aimed at improving perfusion. Outcome was improvement in microvascular flow using orthogonal polarization spectral, sidestream dark field, or incident dark field imaging (Grades of Recommendation, Assessment, Development, and Evaluation criteria used). RESULTS: Two thousand six hundred and six articles were screened and 22 included. (6 randomized controlled trials, 12 interventional, 3 observational, and 1 pilot, n = 572 participants). Multiple measurement techniques were described, including: automated analyses, subjective, and composite scoring systems. Norepinephrine was not found to improve microvascular flow (low-grade evidence, n = 6 studies); except in chronic hypertension (low, n = 1 study). Addition of arginine vasopressin or terlipressin to norepinephrine maintained flow while decreasing norepinephrine requirements (high, n = 2 studies). Neither dobutamine nor glyceryl trinitrate consistently improved flow (low, n = 6 studies). A single study (n = 40 participants) demonstrated improved flow with levosimendan (high). In a risk of bias assessment 16/16 interventional, pilot and observational studies were found to be high risk. CONCLUSIONS: There is no robust evidence to date that any one agent can reproducibly lead to improved microvascular flow. Furthermore, no study demonstrated outcome benefit of one therapeutic agent over another. Updated consensus guidelines could improve comparable reporting of measurements and reduce bias, to enable meaningful comparisons around the effects of individual pharmacological agents.

The impact of therapy on the risk of asthma in type 2 diabetes.

BACKGROUND AND OBJECTIVES: There are limited data about the risk of asthma in people with diabetes. We examined the incidence of asthma in subjects with type 2 diabetes (T2DM) compared to controls, and the association with metformin, sulphonylureas and insulin therapy. MATERIALS AND METHODS: We conducted a retrospective cohort study using a representative UK primary care database (N = 894 646 adults). We used 1:1 propensity score matching (age, gender, socio-economic deprivation, body mass index and smoking status) to match 29 217 pairs of T2DM cases and controls. We used Cox proportional hazard regression to compare the incidence of asthma in both groups over 8 years of follow-up. In those with T2DM, we used Cox proportional hazard regression to assess for any impact of antidiabetic medications on asthma incidence. RESULTS: Individuals with T2DM were less likely to develop asthma than matched controls (hazard ratio [HR] 0.85, 95% CI 0.77-0.93). Insulin increased the risk of incident asthma (HR 1.25, 95% CI 1.01-1.56), whilst metformin and sulphonylureas were associated with reduced risk (HR 0.80, 95% CI 0.69-0.93 and HR 0.76, 95% CI 0.60-0.97, respectively). There was no association with diabetes duration, complications or glycaemic control. CONCLUSIONS: T2DM may have a protective effect against asthma development. Insulin use was associated with an increased risk of asthma, while metformin and sulphonylureas reduced the risk in those with T2DM.

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: "AbSeS", a multinational observational cohort study and ESICM Trials Group Project.

PURPOSE: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). METHODS: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. RESULTS: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. CONCLUSION: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection.

The promise of next generation colloids.

The aim of perioperative haemodilution is to reduce loss of red blood cells during elective surgery. The oncotic and molecular characteristics of the various plasma substitutes employed determine how effectively normovolaemia is maintained, and their non-oncotic effects include alterations in microvascular perfusion. In the previous issue of Critical Care, Martini and colleagues assessed the effects of haemodilution with either polyethylene glycol (PEG)ylated albumin or a commercially available hydroxyethyl starch-based colloid in a hamster haemorrhage model. PEGylated albumin was superior to hydroxyethyl starch, as reflected by survival, haemodynamic parameters and assessment of the microcirculation using intravital microscopy.

An under-recognized complication of treatment of acute severe asthma.

A 39-year-old man presented to the emergency department (ED) in severe respiratory distress. He had a prior diagnosis of brittle asthma and had been admitted on several occasions but never previously ventilated. Therapy given in the first 3 hours of arrival included nebulized salbutamol (5 mg, x5), ipratropium bromide (0.5 mg), intravenous hydrocortisone (200 mg), and magnesium sulfate (2 g). His arterial blood gases continued to deteriorate. He was then given an intravenous bolus of salbutamol (250 microg) and heliox via facemask. His worsening status necessitated invasive ventilation. His hypercapnia and resultant respiratory acidosis improved rapidly, but there was a concurrent accumulation of lactic acid resulting in acidemia. This patient had lactic acidosis as a direct effect of administration of salbutamol. The development of hazardous salbutamol-induced toxicity in acute severe asthma is discussed.

Type 2 diabetes: A protective factor for COPD?

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2DM) are common comorbidities. COPD is a known risk factor for incident T2DM, however few studies have examined the relationship in reverse. The primary aim of this study was to compare the incidence of COPD in people with and without T2DM. MATERIALS AND METHODS: We conducted a retrospective case-control study using a long-established English general practice network database (n=894,646). We matched 29,217 cases of T2DM with controls, adjusting for age, gender, smoking status, BMI and social deprivation, to achieve 1:1 propensity matching and compared the rate of incident COPD over eight years of follow-up. We performed a secondary analysis to investigate the effect of insulin, metformin and sulphonylureas on COPD incidence. RESULTS: People with T2DM had a reduced risk of COPD compared to matched controls over the follow-up period (HR 0.89, 95%CI 0.79-0.93). 48.5% of those with T2DM were ex-smokers compared with 27.3% of those without T2DM. Active smoking rates were 20.4% and 23.7% respectively. Insulin, metformin and sulphonylureas were not associated with incident COPD. CONCLUSIONS: People with T2DM are less likely to be diagnosed with COPD than matched controls. This may be due to positive lifestyle changes, such as smoking cessation in those with T2DM.

What are the optimum components in a care bundle aimed at reducing post-operative pulmonary complications in high-risk patients?

BACKGROUND: Post-operative pulmonary complications (POPC) are common, predictable and associated with increased morbidity and mortality, independent of pre-operative risk. Interventions to reduce the incidence of POPC have been studied individually, but the use of a care bundle has not been widely investigated. The purpose of our work was to use Delphi consensus methodology and an independently chosen expert panel to formulate a care bundle for patients identified as being at high of POPC, as preparation towards an evaluation of its effectiveness at reducing POPC. METHODS: We performed a survey of members of the ESICM POIC section to inform a Delphi consensus and to share their opinions on a care bundle to reduce POPC, the POPC-CB. We formed a team of 36 experts to participate in and complete an email-based Delphi consensus over three rounds, leading to the formulation of the POPC-CB. RESULTS: The survey had 362 respondents and informed the design of the Delphi consensus. The Delphi consensus resulted in a proposed POPC-CB that incorporates components before surgery-supervised exercise programmes and inspiratory muscle training, during surgery, low tidal volume ventilation with individualised PEEP (positive end-expiratory pressure), use of routine monitoring to avoid hyperoxia and efforts made to limit neuromuscular blockade, and post-operatively, deep breathing exercises and elevation of the head of the bed. CONCLUSION: A care bundle has been suggested for evaluation in surgical patients at high risk of POPC. Evaluation of feasibility of both implementation and effectiveness is now indicated.