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.
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.
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.
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.
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.
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).
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.
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).
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 .
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
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.
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.
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.
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.
The published literature suggests a bidirectional independent relationship between T2DM and asthma, although we cannot exclude publication bias.
ObjectivesAccording to National Health Service England (NHSE) specialist respiratory commissioning specification for complex home ventilation, patients with weaning failure should be referred to a ...specialist centre. However, there are limited data reporting the clinical outcomes from such centres.SettingProspective observational cohort study of patients admitted to a UK specialist weaning, rehabilitation and home mechanical ventilation centre between February 2005 and July 2013.Participants262 patients admitted with a median age of 64.2 years (IQR 52.6–73.2 years). 59.9% were male.Results39.7% of patients had neuromuscular and/or chest wall disease, 21% were postsurgical, 19.5% had chronic obstructive pulmonary disease (COPD), 5.3% had obesity-related respiratory failure and 14.5% had other diagnoses. 64.1% of patients were successfully weaned, with 38.2% weaned fully from ventilation, 24% weaned to nocturnal non-invasive ventilation (NIV), 1.9% weaned to nocturnal NIV with intermittent NIV during the daytime. 21.4% of patients were discharged on long-term tracheostomy ventilation. The obesity-related respiratory failure group were most likely to wean (relative risk (RR) for weaning success=1.48, 95% CI 1.35 to 1.77; p<0.001), but otherwise weaning success rates did not significantly vary by diagnostic group. The median time-to-wean was 19 days (IQR 9–33) and the median duration of stay was 31 days (IQR 16–50), with no difference observed between the groups. Weaning centre mortality was 14.5%, highest in the COPD group (RR=2.15, 95% CI 1.19 to 3.91, p=0.012) and lowest in the neuromuscular and/or chest wall disease group (RR=0.34, 95% CI 0.16 to 0.75, p=0.007). Of all patients discharged alive, survival was 71.7% at 6 months and 61.8% at 12 months postdischarge.ConclusionsFollowing NHSE guidance, patients with weaning delay and failure should be considered for transfer to a specialist centre where available, which can demonstrate favourable short-term and long-term clinical outcomes.
PDF
