23 research outputs found
Mortality in adult intensive care patients with severe systemic inflammatory response symdroles is strongly associated with the hypoimmune TNF-238A polymorphism
No full textAbstract The systemic inflammatory response syndrome (SIRS) is associated with activation of innate immunity. We studied the association between mortality and measures of disease severity in the intensive care unit (ICU) and functional polymorphisms in genes coding for Toll-like receptor 4 (TLR4), macrophage migratory inhibitory factor (MIF), tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA). Two hundred thirty-three patients with severe SIRS were recruited from one general adult ICU in a tertiary centre in the UK. DNA from patients underwent genotyping by 5? nuclease assay. Genotype was compared to phenotype. Primary outcome was mortality in ICU. Minor allele frequencies were TLR4 +896G 7%, MIF 173C 16%, TNF ?238A 10% and LTA +252G 34%. The frequency of the hypoimmune minor allele TNF ?238A was significantly higher in patients who died in ICU compared to those who survived (p?=?0.0063) as was the frequency of the two haplotypes LTA +252G, TNF ?1031T, TNF ?308G, TNF ?238A and LTA +252G, TNF?1031T, TNF?308A and TNF?238A (p? =?0.0120 and 0.0098, respectively). These findings re-enforce the view that a balanced inflammatory/anti-inflammatory response is the most important determinant of outcome in sepsis. Genotypes that either favour inflammation or its counter-regulatory anti-inflammatory response are likely to influence mortality and morbidity
Multifrequency methods for Electrical Impedance Tomography
No full textMultifrequency Electrical Impedance Tomography (MFEIT) is an emerging imaging modality which exploits the dependence of tissue impedance on frequency to recover images of conductivity. Given the low cost and portability of EIT scanners, MFEIT could provide emergency diagnosis of pathologies such as acute stroke, brain injury and breast cancer. Whereas time-difference, or dynamic, EIT is an established technique for monitoring lung ventilation, MFEIT has received less attention in the literature, and the imaging methodology is at an early stage of development. MFEIT holds the unique potential to form images from static data, but high sensitivity to noise and modelling errors must be overcome. The subject of this doctoral thesis is the investigation of novel techniques for including spectral information in the image reconstruction process. The aim is to improve the ill-posedness of the inverse problem and deliver the first imaging methodology with sufficient robustness for clinical application. First, a simple linear model for the conductivity is defined and a simultaneous multifrequency method is developed. Second, the method is applied to a realistic numerical model of a human head, and the robustness to modelling errors is investigated. Third, a combined image reconstruction and classification method is developed, which allows for the simultaneous recovery of the conductivity and the spectral information by introducing a Gaussian-mixture model for the conductivity. Finally, a graph-cut image segmentation technique is integrated in the imaging method. In conclusion, this work identifies spectral information as a key resource for producing MFEIT images and points to a new direction for the development of MFEIT algorithms
Mycobacterium tuberculosis and trypanosoma brucei as models for the TLR-dependent activation of the innate immune system
No full textIncludes bibliographical references
Epidemiological characteristics, practice of ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international, multicentre, prospective study
No full textBackground Scant information exists about the epidemiological characteristics and outcome of patients in the intensive care unit (ICU) at risk of acute respiratory distress syndrome (ARDS) and how ventilation is managed in these individuals. We aimed to establish the epidemiological characteristics of patients at risk of ARDS, describe ventilation management in this population, and assess outcomes compared with people at no risk of ARDS. Methods PRoVENT (PRactice of VENTilation in critically ill patients without ARDS at onset of ventilation) is an international, multicentre, prospective study undertaken at 119 ICUs in 16 countries worldwide. All patients aged 18 years or older who were receiving mechanical ventilation in participating ICUs during a 1-week period between January, 2014, and January, 2015, were enrolled into the study. The Lung Injury Prediction Score (LIPS) was used to stratify risk of ARDS, with a score of 4 or higher defining those at risk of ARDS. The primary outcome was the proportion of patients at risk of ARDS. Secondary outcomes included ventilatory management (including tidal volume [VT] expressed as mL/kg predicted bodyweight [PBW], and positive end-expiratory pressure [PEEP] expressed as cm H2O), development of pulmonary complications, and clinical outcomes. The PRoVENT study is registered at ClinicalTrials.gov, NCT01868321. The study has been completed. Findings Of 3023 patients screened for the study, 935 individuals fulfilled the inclusion criteria. Of these critically ill patients, 282 were at risk of ARDS (30%, 95% CI 27–33), representing 0·14 cases per ICU bed over a 1-week period. VT was similar for patients at risk and not at risk of ARDS (median 7·6 mL/kg PBW [IQR 6·7–9·1] vs 7·9 mL/kg PBW [6·8–9·1]; p=0·346). PEEP was higher in patients at risk of ARDS compared with those not at risk (median 6·0 cm H2O [IQR 5·0–8·0] vs 5·0 cm H2O [5·0–7·0]; p<0·0001). The prevalence of ARDS in patients at risk of ARDS was higher than in individuals not at risk of ARDS (19/260 [7%] vs 17/556 [3%]; p=0·004). Compared with individuals not at risk of ARDS, patients at risk of ARDS had higher in-hospital mortality (86/543 [16%] vs 74/232 [32%]; p<0·0001), ICU mortality (62/533 [12%] vs 66/227 [29%]; p<0·0001), and 90-day mortality (109/653 [17%] vs 88/282 [31%]; p<0·0001). VT did not differ between patients who did and did not develop ARDS (p=0·471 for those at risk of ARDS; p=0·323 for those not at risk). Interpretation Around a third of patients receiving mechanical ventilation in the ICU were at risk of ARDS. Pulmonary complications occur frequently in patients at risk of ARDS and their clinical outcome is worse compared with those not at risk of ARDS. There is potential for improvement in the management of patients without ARDS. Further refinements are needed for prediction of ARDS
The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis
No full textThe ISOS study was funded through an unrestricted research
grant from Nestle Health Sciences. T.E.F.A. is supported by a
Medical Research Council/British Journal of Anaesthesia clinical
research training fellowship. B.B. is funded by a National
Research Foundation rating grant and an MRC (SA) selfinitiated
research grant. M.G. is a Chief Scientist Office (Scotland)
NHS Research Scheme Clinician. R.P. is a UK National
Institute for Health Research Professor
Intraoperative ventilator settings and their association with postoperative pulmonary complications in neurosurgical patients: Post-hoc analysis of LAS VEGAS study
No full textBackground: Limited information is available regarding intraoperative ventilator settings and the incidence of postoperative pulmonary complications (PPCs) in patients undergoing neurosurgical procedures. The aim of this post-hoc analysis of the 'Multicentre Local ASsessment of VEntilatory management during General Anaesthesia for Surgery' (LAS VEGAS) study was to examine the ventilator settings of patients undergoing neurosurgical procedures, and to explore the association between perioperative variables and the development of PPCs in neurosurgical patients. Methods: Post-hoc analysis of LAS VEGAS study, restricted to patients undergoing neurosurgery. Patients were stratified into groups based on the type of surgery (brain and spine), the occurrence of PPCs and the assess respiratory risk in surgical patients in Catalonia (ARISCAT) score risk for PPCs. Results: Seven hundred eighty-four patients were included in the analysis; 408 patients (52%) underwent spine surgery and 376 patients (48%) brain surgery. Median tidal volume (VT) was 8 ml [Interquartile Range, IQR = 7.3-9] per predicted body weight; median positive end-expiratory pressure (PEEP) was 5 [3 to 5] cmH20. Planned recruitment manoeuvres were used in the 6.9% of patients. No differences in ventilator settings were found among the sub-groups. PPCs occurred in 81 patients (10.3%). Duration of anaesthesia (odds ratio, 1.295 [95% confidence interval 1.067 to 1.572]; p = 0.009) and higher age for the brain group (odds ratio, 0.000 [0.000 to 0.189]; p = 0.031), but not intraoperative ventilator settings were independently associated with development of PPCs. Conclusions: Neurosurgical patients are ventilated with low VT and low PEEP, while recruitment manoeuvres are seldom applied. Intraoperative ventilator settings are not associated with PPCs
Associations of intraoperative end–tidal CO2 levels with postoperative outcome–secondary analysis of a worldwide observational study
No full textBackground: Patients receiving intraoperative ventilation during general anesthesia often have low end–tidal CO2 (etCO2). We examined the association of intraoperative etCO2 levels with the occurrence of postoperative pulmonary complications (PPCs) in a conveniently–sized international, prospective study named ‘Local ASsessment of Ventilatory management during General Anesthesia for Surgery’ (LAS VEGAS). Methods: Patients at high risk of PPCs were categorized as ‘low etCO2’ or ‘normal to high etCO2’ patients, using a cut–off of 35 mmHg. The primary endpoint was a composite of previously defined PPCs; the individual PPCs served as secondary endpoints. The need for unplanned oxygen was defined as mild PPCs and severe PPCs included pneumonia, respiratory failure, acute respiratory distress syndrome, barotrauma, and new invasive ventilation. We performed propensity score matching and LOESS regression to evaluate the relationship between the lowest etCO2 and PPCs. Results: The analysis included 1843 (74 %) ‘low etCO2’ patients and 648 (26 %) ‘normal to high etCO2’ patients. There was no difference in the occurrence of PPCs between ‘low etCO2’ and ‘normal to high etCO2’ patients (20 % vs. 19 %; RR 1.00 [95 %–confidence interval 0.94 to 1.06]; P = 0.84). The proportion of severe PPCs among total occurring PPCs, were higher in ‘low etCO2’ patients compared to ‘normal to high etCO2’ patients (35 % vs. 18 %; RR 1.16 [1.08 to 1.25]; P < 0.001). Propensity score matching did not change these findings. LOESS plot showed an inverse relationship of intraoperative etCO2 levels with the occurrence of PPCs. Conclusions: In this cohort of patients at high risk of PPCs, the overall occurrence of PPCs was not different between ‘low etCO2’ patients and ‘normal to high etCO2’ patients, but severe PPCs occurred more often in ‘low etCO2’, with an inverse dose–dependent relationship between intraoperative etCO2 levels and PPCs. Funding: This analysis was performed without additional funding. LAS VEGAS was partially funded and endorsed by the European Society of Anesthesiology and Intensive Care (ESAIC) and the Amsterdam University Medical Centers, location ‘AMC’. Registration: LAS VEGAS was registered at Clinicaltrials.gov (NCT01601223), first posted on May 17, 2012
Prospective observational cohort study on grading the severity of postoperative complications in global surgery research
No full textNestle Health Sciences
Association of preoperative smoking with the occurrence of postoperative pulmonary complications: A post hoc analysis of an observational study in 29 countries
No full textIntroduction: While smoking has been consistently identified as a significant contributor to postoperative complications, the existing literature on its association with postoperative pulmonary complications remains conflicting. Aim: We examined the association of preoperative smoking with the occurrence of postoperative pulmonary complications (PPCs). Methods: Post hoc analysis of an observational study in 146 hospitals across 29 countries. We included patients at increased risk of PPCs, according to the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score (≥ 26 points). The primary endpoint was the occurrence of one or more predefined PPCs in the first five postoperative days, including unplanned postoperative need for supplementary oxygen, respiratory failure, unplanned need for invasive ventilation, ARDS, pneumonia and pneumothorax. Secondary endpoints included length of hospital stay and in–hospital mortality. We performed propensity score matching to correct for factors with a known association with postoperative outcomes. Results: Out of 2632 patients, 531 (20.2 %) patients were smokers and 2102 (79.8 %) non-smokers. At five days after surgery, 101 (19.0 %) smokers versus 404 (19.2) non–smokers had developed one or more PPCs (P = 0.95). Respiratory failure was more common in smokers (5.1 %) than non–smokers (3.0 %) (P = 0.02), while rates of other PPCs like need for supplementary oxygen, invasive ventilation, ARDS, pneumonia, or pneumothorax did not differ between the groups. Length of hospital stay and mortality was not different between groups. Propensity score matching did not change the findings. Conclusion: The occurrence of PPCs in smokers is not different from non–smokers. Funding: This analysis was performed without additional funding. LAS VEGAS was partially funded and endorsed by the European Society of Anaesthesiology through their Clinical Trial Network and the Amsterdam University Medical Centers, Amsterdam, The Netherlands. Registration: LAS VEGAS was registered at Clinicaltrials.gov (NCT01601223). Prior presentation: Preliminary study results have been presented at the Euroanaesthesia 2024 International Congress, in Munich, Germany
Association of preoperative smoking with the occurrence of postoperative pulmonary complications: A post hoc analysis of an observational study in 29 countries
No full textIntroduction: While smoking has been consistently identified as a significant contributor to postoperative complications, the existing literature on its association with postoperative pulmonary complications remains conflicting. Aim: We examined the association of preoperative smoking with the occurrence of postoperative pulmonary complications (PPCs). Methods: Post hoc analysis of an observational study in 146 hospitals across 29 countries. We included patients at increased risk of PPCs, according to the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score (≥ 26 points). The primary endpoint was the occurrence of one or more predefined PPCs in the first five postoperative days, including unplanned postoperative need for supplementary oxygen, respiratory failure, unplanned need for invasive ventilation, ARDS, pneumonia and pneumothorax. Secondary endpoints included length of hospital stay and in–hospital mortality. We performed propensity score matching to correct for factors with a known association with postoperative outcomes. Results: Out of 2632 patients, 531 (20.2 %) patients were smokers and 2102 (79.8 %) non-smokers. At five days after surgery, 101 (19.0 %) smokers versus 404 (19.2) non–smokers had developed one or more PPCs (P = 0.95). Respiratory failure was more common in smokers (5.1 %) than non–smokers (3.0 %) (P = 0.02), while rates of other PPCs like need for supplementary oxygen, invasive ventilation, ARDS, pneumonia, or pneumothorax did not differ between the groups. Length of hospital stay and mortality was not different between groups. Propensity score matching did not change the findings. Conclusion: The occurrence of PPCs in smokers is not different from non–smokers. Funding: This analysis was performed without additional funding. LAS VEGAS was partially funded and endorsed by the European Society of Anaesthesiology through their Clinical Trial Network and the Amsterdam University Medical Centers, Amsterdam, The Netherlands. Registration: LAS VEGAS was registered at Clinicaltrials.gov (NCT01601223). Prior presentation: Preliminary study results have been presented at the Euroanaesthesia 2024 International Congress, in Munich, Germany
