non-ARDS Patients Research Articles

DIFFERENCES IN LUNG PROTECTIVE VENTILATION USE IN FEMALE VS MALE ORGAN DONORS

SESSION TITLE: Transplantation SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 PM - 02:00 PM PURPOSE: Given that 15% of patients on the lung transplant list die waiting for a transplant, it is imperative that potential donors be managed optimally to preserve suitable organs. At present, the proportion of potential lungs judged suitable for transplant is only 15-25%. Lung protective ventilation strategies, largely focused on the use of lower tidal volumes (TVs), have been shown to improve outcomes in both ARDS and non-ARDS ICU patients, leading to the recommendation for TVs <=8ml/kg PBW for patients without lung injury, and <=6ml/kg PBW in ARDS. However, adherence to lung protective ventilation remains poor, with women and shorter patients receiving excessive TVs more frequently. With increasing evidence supporting the use of lung protective strategies in potential organ donors, we examined our institutions adherence to lung protective ventilation and whether similar sex disparities exist in this population. METHODS: We analyzed every patient accepted for organ donation at our institution from 2009-2016 (n=112) and a 2:1 randomly matched group of patients referred for donation but who were medically ruled out. We extracted ventilator data, demographic information and arterial blood gas data in 4-hour intervals for the 48 hours preceding the time of death. Data were analyzed to determine patient factors associated with receiving excessive TVs (>8cc/kg PBW). RESULTS: 65% of all subjects received excessive TVs during the 48 hours prior to death, and subjects received excessive TVs during 40% of all measured time points. Frequency of receiving excessive TVs did not differ between donors and rule-outs. 76% of women received excessive TVs at some point, compared to 57% of men (p<0.001). Women were also 50% more likely to receive excessive TVs of greater than 10ml/kg (12% vs 8%, p<0.001). Women received excessive TVs 46% of the time vs. 32% for men (p<0.001). Women also spent more time receiving excessive TVs (11h vs 7h, p<.001) than men. The association between female sex and excessive TVs remained significant after multiple regression analysis adjusting for height, BMI, trauma death and donation outcome (p=0.01). Other independent predictors of excessive TVs were morbid obesity, shorter height, and trauma as a cause of death (all p<0.001). CONCLUSIONS: We show that potential organ donors frequently did not receive appropriate low TV ventilation in the transplant evaluation period. Furthermore, women were less likely to receive lung protective tidal volumes. This association remains even after adjusting for other factors associated with receiving large TVs, including obesity and shorter height. CLINICAL IMPLICATIONS: While this is a single-center retrospective review, it suggests the possibility of an important disparity. Our findings suggest the need for larger, multi-center studies to determine the impact of excessive tidal volumes on organ suitability and outcomes. DISCLOSURES: No relevant relationships by Joaquin Chapa, source=Web Response No relevant relationships by Stephanie Nonas, source=Web Response

Risk factors and outcomes of acute respiratory distress syndrome in critically ill patients with cirrhosis.

Prior randomized controlled trials of acute respiratory distress syndrome (ARDS) excluded critically ill patients with cirrhosis. Data regarding risk factors for ARDS development and outcomes from ARDS in patients with cirrhosis are scarce. We sought to characterize outcomes from ARDS in patients with cirrhosis. An observational cohort of patients with cirrhosis admitted to an intensive care unit at a high-volume liver transplant center between 1 January 2012 and 31 December 2014 were reviewed. ARDS cases were identified according to the Berlin definition. Potential risk factors were examined in multivariable logistic regression analysis for ARDS development. Outcomes including in-hospital mortality were compared between ARDS and non-ARDS patients. A total of 559 patients met the inclusion criteria and 45 (8.1%) developed ARDS. Differences between ARDS and non-ARDS patients included sepsis, Model for End-Stage Liver Disease - Sodium score, and Sequential Organ Failure Assessment score. In-hospital mortality was higher in cirrhotic patients with ARDS compared with those without ARDS (82.2% vs. 27.6%, P < 0.001). In multivariable analysis, acute-on-chronic liver failure (OR 8.69, 95% CI 2.28-33.18, P < 0.01) and shock on intensive care unit admission (OR 3.13, 95% CI 1.57-6.24, P = 0.001) were associated with ARDS development, whereas etiology of cirrhosis or alcohol use were not. Acute-on-chronic liver failure and shock on intensive care unit admission were risk factors for ARDS development, whereas etiology of cirrhosis and alcohol were not. Mortality from ARDS was markedly increased in patients with cirrhosis. Early recognition and treatment for infection might be important for improving the high mortality in this group of patients.

Predictive Value of Combined LIPS and ANG-2 Level in Critically Ill Patients with ARDS Risk Factors.

To investigate the predictive value of the acute physiology and chronic health evaluation 2 (APACHE2) score and lung injury prediction score (LIPS) for acute respiratory distress syndrome (ARDS) when combined with biomarkers for this condition in patients with ARDS risk factors. In total, 158 Han Chinese patients with ARDS risk factors were recruited from the Respiratory and Emergency Intensive Care Units. The LIPS, APACHE2 score, primary diagnosis at admission, and ARDS risk factors were determined within 6 h of admission, and PaO2/FiO2 was determined on the day of admission. Blood was collected within 24 h of admission for the measurement of angiopoietin-2 (ANG-2), sE-selectin, interleukin-6 (IL-6), and interleukin-8 (IL-8) levels. ARDS was monitored for the next 7 days. Univariate and multivariate analyses and receiver operating characteristic (ROC) analyses were employed to construct a model for ARDS prediction. Forty-eight patients developed ARDS within 7 days of admission. Plasma ANG-2 level, sE-selectin level, LIPS, and APACHE2 score in ARDS patients were significantly higher than those in non-ARDS patients. ANG-2 level, LIPS, and APACHE2 score were correlated with ARDS (P < 0.001, P < 0.006, and P < 0.042, resp.). When the APACHE2 score was used in combination with the LIPS and ANG-2 level to predict ARDS, the area under the ROC curve (AUC) was not significantly increased. Compared to LIPS or ANG-2 alone, LIPS in combination with ANG-2 had significantly increased positive predictive value (PPV) and AUC for the prediction of ARDS. In conclusion, plasma ANG-2 level, LIPS, and APACHE2 score are correlated with ARDS. Combined LIPS and ANG-2 level displays favorable sensitivity, specificity, and AUC for the prediction of ARDS.

High-frequency power of heart rate variability can predict the outcome of thoracic surgical patients with acute respiratory distress syndrome on admission to the intensive care unit: a prospective, single-centric, case-controlled study

BackgroundThe morbidity and mortality of acute respiratory distress syndrome (ARDS) remains high, and the strategic focus of ARDS research has shifted toward identifying patients at high risk of mortality early in the course of illness. This study intended to identify the heart rate variability (HRV) measure that can predict the outcome of patients with ARDS on admission to the surgical intensive care unit (SICU).MethodsPatients who had lung or esophageal cancer surgery were included either in the ARDS group (n = 21) if they developed ARDS after surgery or in the control group (n = 11) if they did not. The ARDS patients were further stratified into survivors and non-survivors subgroups according to their outcomes. HRV measures of the patients were used for statistical analysis.ResultsThe mean RR interval (mRRI), high-frequency power (HFP) and product of low-/high-frequency power ratio tidal volume and tidal volume (LHR*VT) were significantly lower (p < 0.05), while the normalized HFP to VT ratio (nHFP/VT) was significantly higher in the ARDS patients (p = 0.011). The total power (TP), low-frequency power (LFP), HFP and HFP/VT were all significantly higher in the non-survived ARDS patients, whereas Richmond Agitation-Sedation Scale (RASS) was significantly lower in the non-survived ARDS patients. After adjustment for RASS, age and gender, firth logistic regression analysis identified the HFP, TP as the significant independent predictors of mortality for ARDS patients.ConclusionsThe vagal modulation of thoracic surgical patients with ARDS was enhanced as compared to that of non-ARDS patients, and the non-survived ARDS patients had higher vagal activity than those of survived ARDS patients. The vagal modulation-related parameters such as TP and HFP were independent predictors of mortality in patients with ARDS on admission to the SICU, and the HFP was found to be the best predictor of mortality for those ARDS patients. Increased vagal modulation might be an indicator for poor prognosis in critically ill patients following thoracic surgery.

Long-term outcome after the acute respiratory distress syndrome: different from general critical illness?

Purpose of reviewTo review the current research data on long-term outcome and health-related quality of life in survivors of the acute respiratory distress syndrome (ARDS) and to compare these findings with those from non-ARDS patients surviving critical illness.Recent findingsBetween 6 months and 2 years after discharge from ICU, survivors of ARDS present with substantial impairments of the levels of body function (muscle strength, walking capacity and/or physical activity (physical SF-36 score). In contrast to non-ARDS patients from surgical ICUs, a standardized intensified physical therapy during early course of illness in ARDS patients could not show an improvement of long-term physical function performance. Furthermore, a substantial part of further ARDS patients suffer from depression (26–33%), anxiety (38–44%) or posttraumatic stress disorder (22–24%). In general, the level of functional autonomy and daily life activities was reduced, and in one study, 6 months after ICU-discharge this level was significantly lower in ARDS patients compared with non-ARDS patients. In a recent study, 44% of ARDS survivors were jobless 1 year after critical illness, whereas half of previously employed patients returned to work within 4 months after hospital discharge. General health-related quality of life was significantly reduced compared with a matched population in all studies.SummarySurviving ARDS is associated with a long-term substantial reduction in health-related quality of life and such a reduction does not differ from findings in patients surviving other critical illness. In further research, a special attention should be paid to prevention measures of the ‘post intensive care syndrome’ as well as to patient important domains, which might better explain the patient's and families’ demands.

Protein C genetic variation was associated with the susceptibility to acute respiratory distress syndrome in Chinese Han population

Objective To investigate the genetic variants in the protein C (PC) and endothelial protein C receptor (EPCR) genes associated with the risk and outcome of acute respiratory distress syndrome (ARDS) patients in Chinese Han race. Methods Five tagSNPs (single nucleotide polymorphism, SNP) in the PC and EPCR genes were genotyped in patients with ARDS (n =275) and non-ARDS (n=337) in order to find the association between them in this case-control study. The SNPs were genotyped by SNPstream Beckman platform. Then, the correlation between the associated SNPs and plasma levels of activated protein C (APC) in patients with ARDS was investigated. The APC levels were measured using enzyme linked immunosorbent assay (ELISA) method. Results Association analysis revealed that two PC SNPs in perfect linkage disequilibrium, rs1799809 and rs1158867, were significantly associated with susceptibility to ARDS. T allele frequency of rs1799809 in ARDS patients was significantly higher than that in non-ARDS patients (OR=1.569, 95%CI: 1.192-2.066). And the genotype frequencies of rs1799809 were also significantly different between these two groups (P=0.007). The association remained significant after adjustment for multiple comparisons. Haplotype consisting of three SNPs in the PC gene was also associated with susceptibility to ARDS. The frequency of haplotype CCC in the ARDS samples was significantly lower than that in the non-ARDS group (P<0.01). Moreover, ARDS patients carrying rs1799809 TT genotype showed lower serum levels of APC than patients with TC and CC genotypes (Padj=0.02). However, genotype and allele analyses of EPCR did not show any significant difference between ARDS and non-ARDS patients. Conclusions These findings indicated that common genetic variation in the PC gene was significantly associated with susceptibility to ARDS in Chinese Han race. The PC genetic variation influenced plasma concentration of APC in patients with ARDS. Key words: PC; APC; EPCR; Genetic variation; SNPs; ARDS; Susceptibility; Prognosis

Safety of Percutaneous Dilatational Tracheostomy in Patients with Acute Brain Injury and Reduced PaO2/FiO2 Ratio-Retrospective Analysis of 54 Patients.

Percutaneous dilatational tracheostomy (PDT) is a commonly performed method in neurocritical care, and its safety has been proven in numerous studies. Nevertheless, data regarding the application in patients with acute brain injury and poor respiratory function are poor. The purpose of this study was to evaluate the incidence of hypoxemia and hypercapnia during PDT in those patients. In a retrospective analysis, we acquired data from 54 patients with an acute brain injury (ABI) and a reduced PaO2/FiO2 ratio (PaO2/FiO2 < 300 mm Hg). In all cases, blood gas analyses before, during, and approximately 12 hours after PDT were available. We reviewed the patients' ventilator settings, results of gas exchange, and radiographic signs of acute respiratory distress syndrome (ARDS). Patients with ARDS were defined using the Berlin criteria. We observed 2 cases (3.6%) of intraoperative hypoxemia (PaO2 < 60 mm Hg) and 4 cases (7.4%) of intraoperative hypercapnia (PaCO2 > 55 mm Hg). Twenty patients fulfilled the Berlin criteria for ARDS. While mean PaO2 did not differ significantly between ARDS and non-ARDS patients, intraoperative hypoxemia only occurred in the ARDS group (2/20). Mean PaCO2 was similar in the ARDS and non-ARDS groups, and cases of hypercapnia were apparent in both groups. The mean PaO2/FiO2 ratio of all patients improved from 229.1 mm Hg before PDT to 255.3 mm Hg. Regarding the intraoperative gas exchange, indication of PDT in patients with ABI and ARDS should be considered carefully. However, PDT in ABI patients with reduced PaO2/FiO2 ratio alone appears to be a safe procedure.

Involvement of the Bufadienolides in the Detection and Therapy of the Acute Respiratory Distress Syndrome.

The acute respiratory distress syndrome (ARDS) represents a major challenge for clinicians as well as basic scientists. The mortality rate for ARDS has been maintained within the range of 40-52%. The authors have examined the involvement of the "cardiotonic steroids" in the pathogenesis and therapy of ARDS. We have studied the possible role of the bufadienolide, marinobufagenin (MBG), in the pathogenesis of ARDS in both a rat model of ARDS and in patients afflicted with that disorder. In addition, the potential therapeutic benefit of an antagonist of MBG, resibufogenin (RBG), in an animal model has been evaluated. A syndrome resembling human ARDS was produced in the rat by exposing the animals to 100% oxygen for 48h. In other animals, RBG was administered to these "hyperoxic" rats, and the serum MBG was measured. In human ICU patients, urinary samples were examined for levels of MBG, and the values were compared to those obtained from other ICU patients admitted with diagnoses other than ARDS. (1) Exposure of rats to hyperoxia produced a histologic picture which resembled that of human ARDS. (2) Serum levels of MBG in the "hyperoxic" rats substantially exceeded those obtained in animals exposed to ambient oxygen levels and were reduced to normal by RBG. (3) In ARDS patients, substantial elevations in urinary MBG were obtained compared to those in non-ARDS ICU patients. MBG may serve as an important biomarker for the development of ARDS, and RBG may represent a preventative/therapy in this disorder.

Is Prone Positioning Effective for Atelectasis in Non-ARDS Patients?

Is Prone Positioning Effective for Atelectasis in Non-ARDS Patients?

A meta-analysis of low tidal volume on the outcome of adult patients without acute respiratory distress syndrome

Objective: To evaluate the effects of tidal volume on the survival in adult patients without acute respiratory distress syndrome (non-ARDS). Methods: We searched relevant clinical randomized controlled trials (RCT) from January 2000 to December 2015. Meta analyses related to the effects of tidal volume on mortality in non-ARDS adults were conducted using the methods recommended by the Cochrane Collaboration. Results: A total of nineteen RCTs (n=1 679) were finally included. There were 838 patients ventilated with low tidal volume, and the other 841 patients ventilated with normal tidal volume. The mortality rates were not significantly different between low tidal volume group and control group (5.87% vs 6.52%; RR=0.9, P=0.58). But respiratory complications were significantly lower in low tidal volume group, such as development of acute respiratory distress syndrome(RR=0.32, 95% CI 0.16-0.63, P=0.001), pneumonia (RR=0.48, 95%CI 0.29-0.78, P=0.003), while the incidence of atelectasis was quite comparable between two groups (RR=0.78, 95%CI 0.391-1.356, P=0.48). Conclusion: Non-ARDS patients ventilated with low tidal volume is associated with a lower risk of pulmonary complications, yet clinical outcome, mainly mortality is similar to that of patients with regular tidal volume.

Prehospital Aspirin Use and Acute Respiratory Distress Syndrome—A Case for Aspirin in the Drinking Water?*

Prehospital Aspirin Use and Acute Respiratory Distress Syndrome—A Case for Aspirin in the Drinking Water?*

The levels of angiopoietin-2 in patients with acute respiratory distress syndrome and its value on prognosis

To approach the correlation between angiopoietin-2 (Ang-2) levels and degree of lung injury and prognosis and its clinical significance in patients with acute respiratory distress syndrome (ARDS). A prospective observation was conducted. Fifty-three ARDS patients admitted to Department of Critical Care Medicine of Third Affiliated Hospital of Anhui Medical University from January 2012 to March 2014 were enrolled. According to the criteria of the Berlin Definition of ARDS, the patients were divided into mild group (n=15), moderate group (n=22) and severe group (n=16). Meanwhile, ARDS patients were further divided into survival group(n=29) and non-survival group(n=24) according to 28-day outcomes. Twenty cases of non-ARDS patients were served as control. The acute physiology and chronic health evaluation II(APACHEII) score, sequential organ failure assessment (SOFA) score, oxygenation index (PaO₂/FiO₂), lung injury score (LIS) were recorded within 24 hours after admission. And the plasma levels of Ang-2, interleukin-6 (IL-6) and C-reaction protein (CRP) were measured. The independent risk factors of ARDS were analyzed by univariate and multivariable logistic regression. Receiver operating characteristic curve (ROC) was plotted to evaluate the value of Ang-2 in predicting ARDS. Compared with non-ARDS group, APACHEII score, SOFA score, LIS score, mortality were significantly increased, PaO2/FiO2 was significantly decreased, and plasma Ang-2, IL-6, CRP were significantly elevated [APACHEII score: 20.7 ± 5.0 vs. 14.1 ± 5.3, SOFA score: 7.7 ± 3.5 vs. 3.5 ± 2.1, LIS score: 1.69 ± 0.71 vs. 0.28 ± 0.27, PaO₂/FiO₂(mmHg, 1 mmHg = 0.133 kPa): 159.5 ± 61.3 vs. 394.0 ± 3.2, mortality: 45.3% (24/53) vs. 20.0% (4/20), Ang-2(μg/L): 4.73(2.59, 6.99)vs. 1.22 (0.61, 1.52), IL-6(ng/L): 56.50 (27.15, 139.90)vs. 13.05 (4.38, 15.55), CRP (mg/L): 95.75(41.74, 189.72) vs. 10.56 (3.92, 21.36), P<0.05 or P<0.01]. Each index increased or decreased more significantly with the aggravation of the disease. It was shown by correlation analysis that the plasma levels of Ang-2 was significantly positive correlated with IL-6 (r=0.468,P=0.000), CRP(r = 0.492, P = 0.000), APACHEII score (r = 0.560, P = 0.000), SOFA score (r = 0.508, P = 0.000) and LIS score (r = 0.588, P = 0.000), significantly negatively correlated with PaO2/FiO2 (r=-0.685,P=0.000). Factors, APACHEII score, LIS score, PaO2/FiO2, Ang-2 and IL-6 founded statistical significance in univariate analysis were analyzed using multivariable logistic regression. High APACHEII score at admission [odds ratio (OR) = 1.316, 95% confidence interval (95% CI) = 1.040-1.633, P = 0.022] and increased plasma Ang-2 levels (OR = 1.287, 95% CI = 1.041-1.760, P = 0.038) were the independent prognostic factors for the 28-day mortality in ARDS. The area under the ROC curve of Ang-2 was 0.964, the optimal critical value of Ang-2 was 1.79 μg/L, the specificity was 90.0%, and sensitivity was 92.5%. Plasma levels of Ang-2 was better in predicting ARDS than APACHEII score, SOFA score and IL-6. The plasma level of Ang-2 was significantly increased in patients with ARDS. The plasma level of Ang-2 was correlated with the severity of acute lung injury and had important prognosis evaluation.

Lung inflammation and damage induced by extracellular histones.

Despite decades of research, acute respiratory distress syndrome (ARDS) remains an important clinical challenge due to an incomplete understanding of the pathophysiological mechanisms. No FDA-approved drug therapy currently exists for treatment of humans with ARDS. There is accumulating evidence in rodents and humans suggesting that extracellular histones are strong drivers of inflammation and tissue damage. We recently described an important role for extracellular histones during acute lung injury (ALI) in mice (Bosmann et al., FASEB J. 27:5010-5021 (2013)). Extracellular histones were detected in bronchoalveolar lavage fluids (BALF) from patients with ARDS but not in BALF from non-ARDS patients in intensive care units. Extracellular histones were also detected in BALF from mice during experimental ALI. The presence of extracellular histones was dependent on the two C5a receptors (C5aR and C5L2) and availability of neutrophils. Extracellular histones were highly pro-inflammatory, and caused severe damage to respiratory function. Intratracheal instillation of histones resulted in pro-inflammatory mediator production, epithelial cell damage, disturbances in alveolar-capillary gas exchange, lung consolidation, activation of the coagulation cascade, and in some cases, death. Antibody-mediated neutralization of extracellular histones attenuated C5a-induced ALI. Together, these data suggested a prominent role for extracellular histones in the pathophysiology of ALI. The predominant source of histones in ALI may be neutrophils that have been activated by C5a to form neutrophil extracellular traps (NETs). Therapeutic targeting of extracellular histones may provide a novel approach to combat ARDS in humans.

Mechanical ventilation in acute hypoxemic respiratory failure: a review of new strategies for the practicing hospitalist.

The goal of mechanical ventilation in acute hypoxemic respiratory failure is to support adequate gas exchange without harming the lungs. How patients are mechanically ventilated can significantly impact their ultimate outcomes. This review focuses on emerging evidence regarding strategies for mechanical ventilation in patients with acute hypoxemic respiratory failure including: low tidal volume ventilation in the acute respiratory distress syndrome (ARDS), novel ventilator modes as alternatives to low tidal volume ventilation, adjunctive strategies that may enhance recovery in ARDS, the use of lung-protective strategies in patients without ARDS, rescue therapies in refractory hypoxemia, and an evidence-based approach to weaning from mechanical ventilation. Once a patient is intubated and mechanically ventilated, low tidal volume ventilation remains the best strategy in ARDS. Adjunctive therapies in ARDS include a conservative fluid management strategy, as well as neuromuscular blockade and prone positioning in moderate-to-severe disease. There is also emerging evidence that a lung-protective strategy may benefit non-ARDS patients. For patients with refractory hypoxemia, extracorporeal membrane oxygenation should be considered. Once the patient demonstrates signs of recovery, the best approach to liberation from mechanical ventilation involves daily spontaneous breathing trials and protocolized assessment of readiness for extubation. Prompt recognition of ARDS and use of lung-protective ventilation, as well as evidence-based adjunctive therapies, remain the cornerstones of caring for patients with acute hypoxemic respiratory failure. In the absence of contraindications, it is reasonable to consider lung-protective ventilation in non-ARDS patients as well, though the evidence supporting this practice is less conclusive.

What is the future of acute respiratory distress syndrome after the Berlin definition?

To analyze recently published articles in the medical literature that studied distinct aspects of adult patients with acute respiratory distress syndrome (ARDS) after the new Berlin definition introduced in 2012. The degree of ARDS severity according to this new classification correlated well with extravascular lung water index, pulmonary vascular permeability index and the finding of diffuse alveolar damage on autopsy. The new possibility of bedside echocardiographic evaluation of biventricular cardiac function is indicating the necessity of including a subgroup of severity of patients with right ventricular dysfunction. High-resolution CT evaluation showed that signs of pulmonary fibroproliferation in early ARDS predict increased ventilator dependency, multiple organ failure and mortality. The median development of ARDS 1 or 2 days after hospital admission emphasizes the need for ARDS intrahospital prevention, especially protective ventilation in non-ARDS patients. The better outcome with the use of prone position in patients with PaO2/FIO2 below 150 recently observed questioned the Berlin definition thresholds to decide the future best treatment strategies according to the proposed degree of severity of the syndrome. The impact of the Berlin definition of ARDS on the incidence, better treatment stratification and mortality ratio of ARDS is still to be determined.

Association between autoimmune rheumatic diseases and the risk of dementia.

Aim. Autoimmune rheumatic diseases (ARD) are characterized by systemic inflammation and may affect multiple organs and cause vascular events such as ischemic stroke and acute myocardial infarction. However, the association between ARD and increased risk of dementia is uncertain. This is a retrospective cohort study to investigate and compare the risk of dementia between patients clinically diagnosed with ARD and non-ARD patients during a 5-year follow-up period. Methods. Data were obtained from the Longitudinal Health Insurance Database 2000 (LHID2000). We included 1221 patients receiving ambulatory or hospitalization care and 6105 non-ARD patients; patients were matched by sex, age, and the year of index use of health care. Each patient was studied for 5 years to identify the subsequent manifestation of dementia. The data obtained were analyzed by Cox proportional hazard regression. Results. During the 5-year follow-up period, 30 ARD (2.48%) and 141 non-ARD patients (2.31%) developed dementia. During the 5-year follow-up period, there were no significant differences in the risks of any type of dementia (adjusted hazard ratio (HR), 1.18; 95% CI, 0.79–1.76) in the ARD group after adjusting for demographics and comorbidities. Conclusions. Within the 5-year period, patients with and without ARD were found to have similar risks of developing dementia.

Predictors of Acute Respiratory Distress Syndrome in Patients with Paraquat Intoxication

IntroductionParaquat poisoning is characterized by acute lung injury, pulmonary fibrosis, respiratory failure, and multi-organ failure, resulting in a high rate of mortality and morbidity. The objectives of this study were to identify predictors of acute respiratory distress syndrome (ARDS) in cases of paraquat poisoning and determine the association between these parameters.Materials and MethodsIn total, 187 patients were referred for management of intentional paraquat ingestion between 2000 and 2010. Demographic, clinical, and laboratory data were recorded. Sequential organ failure assessment (SOFA) and Acute Kidney Injury Network (AKIN) scores were collected, and predictors of ARDS were analyzed.ResultsThe overall mortality rate for the entire population was 54% (101/187). Furthermore, the mortality rate was higher in the ARDS patients than in the non-ARDS patients (80% vs. 43.80%, P<0.001). Additionally, the ARDS patients not only had higher AKIN48-h scores (P<0.009), SOFA48-h scores (P<0.001), and time to ARDS/nadir PaO2 (P=0.008) but also suffered from lower nadir PaO2 (P<0.001), nadir AaDO2 (P<0.001), and nadir eGFR (P=0.001) compared to those in the non-ARDS patients. Moreover, pneumomediastinum episodes were more frequent in the ARDS patients than in the non-ARDS patients (P<0.001). A multivariate Cox regression model revealed that blood paraquat concentrations (P<0.001), SOFA48-h scores (P=0.001), and steroid and cyclophosphamide pulse therapies (P=0.024) were significant predictors of ARDS. The cumulative survival rates differed significantly (P<0.001) between patients with SOFA48-h scores <3 and SOFA48-h scores ≥3, with a sensitivity of 95.8%, specificity of 58.4%, and overall correctness of 67.6%. Finally, the area under the receiver operating characteristic (AUROC) analysis showed that SOFA48-h scores (P<0.001) had a better discriminatory power than blood paraquat concentrations (P=0.01) for predicting ARDS. ConclusionsThe analytical results indicate that SOFA48-h scores, blood paraquat concentrations, and steroid and cyclophosphamide pulse therapies are significantly associated with ARDS complications after paraquat intoxication.

Better Ventilator Settings Using a Computerized Clinical Tool

The Acute Respiratory Distress Syndome (ARDS) Network low tidal volume (VT) trial paved the ground for mechanically ventilating ARDS patients with a VT of 6 mL/kg ideal body weight (IBW). Although there is no consensus that a low VT is advantageous in non-ARDS patients,it is accepted that high VT should be avoided. Because compliance rates with ventilator recommendations are 30%, there is a need for process improvement. We postulated that a computerized screen prompt that recommended VT based on height would improve compliance with low VT.During ventilator order entry, the computerized decision tool prompts the clinician and encourages ventilation of patients at 8 mL/kg IBW, and 6 mL/kg IBW for patients with ARDS. A retrospective review was performed on patients who required volume controlled mechanical ventilation over a 3-y period. Subjects were chosen randomly from the respiratory records of 6 different ICUs at a single tertiary care academic center. Half of the charts selected were before intervention of on-screen prompt, and the other half were after implementation of the computerized decision tool. The initial set VT ranged from 6.26 to 13.45 mL/kg IBW, with a mean of 8.92 mL/kg. After implementation of the on-screen prompt, mean VT decreased by 0.84 mL/kg to 8.07 mL/kg (P= .001) with a lower range of 4.73-11.56 mL/kg IBW. We also noted a significant decrease in the number of subjects placed on an initial VT > 10 mL/kg IBW from 20% to 4% (P= .003). A computerized clinical decision tool with the preferred initial VT settings based on the patients' sex and height is a safe and reliable way to increase low VT strategy compliance across multiple ICUs. Its limitations are similar to those shared by other computer-generated prompts.

Neutrophils from critically ill septic patients mediate profound loss of endothelial barrier integrity

IntroductionSepsis is characterized by systemic immune activation and neutrophil-mediated endothelial barrier integrity compromise, contributing to end-organ dysfunction. Studies evaluating endothelial barrier dysfunction induced by neutrophils from septic patients are lacking, despite its clinical significance. We hypothesized that septic neutrophils would cause characteristic patterns of endothelial barrier dysfunction, distinct from experimental stimulation of normal neutrophils, and that treatment with the immunomodulatory drug β-glucan would attenuate this effect.MethodsBlood was obtained from critically ill septic patients. Patients were either general surgery patients (Primary Sepsis (PS)) or those with sepsis following trauma (Secondary Sepsis (SS)). Those with acute respiratory distress syndrome (ARDS) were identified. Healthy volunteers served as controls. Neutrophils were purified and aliquots were untreated, or treated with fMLP or β-glucan. Endothelial cells were grown to confluence and activated with tissue necrosis factor (TNF)-α . Electric Cell-substrate Impedance Sensing (ECIS) was used to determine monolayer resistance after neutrophils were added. Groups were analyzed by two-way analysis of variance (ANOVA).ResultsNeutrophils from all septic patients, as well as fMLP-normal neutrophils, reduced endothelial barrier integrity to a greater extent than untreated normal neutrophils (normalized resistance of cells from septic patients at 30 mins = 0.90 ± 0.04; at 60 mins = 0.73 ± 0.6 and at 180 mins = 0.56 ± 0.05; p < 0.05 vs normal). Compared to untreated PS neutrophils, fMLP-treated PS neutrophils caused further loss of barrier function at all time points; no additive effect was noted in stimulation of SS neutrophils beyond 30 min. Neutrophils from ARDS patients caused greater loss of barrier integrity than those from non-ARDS patients, despite similarities in age, sex, septic source, and neutrophil count. Neutrophils obtained after resolution of sepsis caused less barrier dysfunction at all time points. β-glucan treatment of septic patients’ neutrophils attenuated barrier compromise, rendering the effect similar to that induced by neutrophils obtained once sepsis had resolved.ConclusionsNeutrophils from septic patients exert dramatic compromise of endothelial barrier integrity. This pattern is mimicked by experimental activation of healthy neutrophils. The effect of septic neutrophils on the endothelium depends upon the initial inflammatory event, correlates with organ dysfunction and resolution of sepsis, and is ameliorated by β-glucan.

Non-invasive ventilation for acute hypoxemic respiratory failure: intubation rate and risk factors

IntroductionWe assessed rates and predictive factors of non-invasive ventilation (NIV) failure in patients admitted to the intensive care unit (ICU) for non-hypercapnic acute hypoxemic respiratory failure (AHRF).MethodsThis is an observational cohort study using data prospectively collected over a three-year period in a medical ICU of a university hospital.ResultsAmong 113 patients receiving NIV for AHRF, 82 had acute respiratory distress syndrome (ARDS) and 31 had non-ARDS. Intubation rates significantly differed between ARDS and non-ARDS patients (61% versus 35%, P = 0.015) and according to clinical severity of ARDS: 31% in mild, 62% in moderate, and 84% in severe ARDS (P = 0.0016). In-ICU mortality rates were 13% in non-ARDS, and, respectively, 19%, 32% and 32% in mild, moderate and severe ARDS (P = 0.22). Among patients with moderate ARDS, NIV failure was lower among those having a PaO2/FiO2 >150 mmHg (45% vs. 74%, p = 0.04). NIV failure was associated with active cancer, shock, moderate/severe ARDS, lower Glasgow coma score and lower positive end-expiratory pressure level at NIV initiation. Among intubated patients, ICU mortality rate was 46% overall and did not differ according to the time to intubation.ConclusionsWith intubation rates below 35% in non-ARDS and mild ARDS, NIV stands as the first-line approach; NIV may be attempted in ARDS patients with a PaO2/FiO2 > 150. By contrast, 84% of severe ARDS required intubation and NIV did not appear beneficial in this subset of patients. However, the time to intubation had no influence on mortality.