Noninvasive mechanical ventilation (NIV) is widely used in the acute care setting for acute respiratory failure (ARF) across a variety of aetiologies. This document provides European Respiratory ...Society/American Thoracic Society recommendations for the clinical application of NIV based on the most current literature.The guideline committee was composed of clinicians, methodologists and experts in the field of NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology for each actionable question. The GRADE Evidence to Decision framework in the guideline development tool was used to generate recommendations. A number of topics were addressed using technical summaries without recommendations and these are discussed in the supplementary material.This guideline committee developed recommendations for 11 actionable questions in a PICO (population-intervention-comparison-outcome) format, all addressing the use of NIV for various aetiologies of ARF. The specific conditions where recommendations were made include exacerbation of chronic obstructive pulmonary disease, cardiogenic pulmonary oedema,
hypoxaemic respiratory failure, immunocompromised patients, chest trauma, palliation, post-operative care, weaning and post-extubation.This document summarises the current state of knowledge regarding the role of NIV in ARF. Evidence-based recommendations provide guidance to relevant stakeholders.
The Sepsis-3 Task Force updated the clinical criteria for sepsis, excluding the need for systemic inflammatory response syndrome (SIRS) criteria. The clinical implications of the proposed flowchart ...including the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) and SOFA scores are unknown.
To perform a clinical decision-making analysis of Sepsis-3 in patients with community-acquired pneumonia.
This was a cohort study including adult patients with community-acquired pneumonia from two Spanish university hospitals. SIRS, qSOFA, the Confusion, Respiratory Rate and Blood Pressure (CRB) score, modified SOFA (mSOFA), the Confusion, Urea, Respiratory Rate, Blood Pressure and Age (CURB-65) score, and Pneumonia Severity Index (PSI) were calculated with data from the emergency department. We used decision-curve analysis to evaluate the clinical usefulness of each score and the primary outcome was in-hospital mortality.
Of 6,874 patients, 442 (6.4%) died in-hospital. SIRS presented the worst discrimination, followed by qSOFA, CRB, mSOFA, CURB-65, and PSI. Overall, overestimation of in-hospital mortality and miscalibration was more evident for qSOFA and mSOFA. SIRS had lower net benefit than qSOFA and CRB, significantly increasing the risk of over-treatment and being comparable with the "treat-all" strategy. PSI had higher net benefit than mSOFA and CURB-65 for mortality, whereas mSOFA seemed more applicable when considering mortality/intensive care unit admission. Sepsis-3 flowchart resulted in better identification of patients at high risk of mortality.
qSOFA and CRB outperformed SIRS and presented better clinical usefulness as prompt tools for patients with community-acquired pneumonia in the emergency department. Among the tools for a comprehensive patient assessment, PSI had the best decision-aid tool profile.
Patients with severe community-acquired pneumonia (SCAP) and life-threatening acute respiratory failure may require invasive mechanical ventilation (IMV). Since use of IMV is often associated with ...significant morbidity and mortality, we assessed whether patients invasively ventilated would represent a target population for interventions aimed at reducing mortality of SCAP.
We prospectively recruited consecutive patients with SCAP for 12 years. We assessed the characteristics and outcomes of patients invasively ventilated at presentation of pneumonia, compared with those without IMV, and determined the influence of risks factors on mortality with a multivariate weighted logistic regression using a propensity score.
Among 3,719 patients hospitalized with CAP, 664 (18%) had criteria for SCAP, and 154 (23%) received IMV at presentation of pneumonia; 198 (30%) presented with septic shock. In 370 (56%) cases SCAP was diagnosed based solely on the presence of 3 or more IDSA/ATS minor criteria. Streptococcus pneumoniae was the main pathogen in both groups. The 30-day mortality was higher in the IMV, compared to non-intubated patients (51, 33%, vs. 94, 18% respectively, p<0·001), and higher than that predicted by APACHE-II score (26%). IMV independently predicted 30-day mortality in multivariate analysis (adjusted odds-ratio 3·54, 95% confidence interval 1·45-8·37, p = 0·006). Other independent predictors of mortality were septic shock, worse hypoxemia and increased serum potassium.
Invasive mechanical ventilation independently predicted 30-day mortality in patients with SCAP. Patients invasively ventilated should be considered a different population with higher mortality for future clinical trials on new interventions addressed to improve mortality of SCAP.
Background and Purpose
No therapy is approved for vascular calcification or calcific uraemic arteriolopathy (calciphylaxis), which increases mortality and morbidity in patients undergoing dialysis. ...Deposition of hydroxyapatite (HAP) crystals in arterial walls is the common pathophysiologic mechanism. The mechanism of action of SNF472 to reduce HAP deposition in arterial walls was investigated.
Experimental Approach
We examined SNF472 binding features (affinity, release kinetics and antagonism type) for HAP crystals in vitro, inhibition of calcification in excised vascular smooth muscle cells from rats and bone parameters in osteoblasts from dogs and rats.
Key Results
SNF472 bound to HAP with affinity (KD) of 1–10 μM and saturated HAP at 7.6 μM. SNF472 binding was fast (80% within 5 min) and insurmountable. SNF472 inhibited HAP crystal formation from 3.8 μM, with complete inhibition at 30.4 μM. SNF472 chelated free calcium with an EC50 of 539 μM. Chelation of free calcium was imperceptible for SNF472 1–10 μM in physiological calcium concentrations. The lowest concentration tested in vascular smooth muscle cells, 1 μM inhibited calcification by 67%. SNF472 showed no deleterious effects on bone mineralization in dogs or in rat osteoblasts.
Conclusion and Implications
These experiments show that SNF472 binds to HAP and inhibits further HAP crystallization. The EC50 for chelation of free calcium is 50‐fold greater than a maximally effective SNF472 dose, supporting the selectivity of SNF472 for HAP. These findings indicate that SNF472 may have a future role in the treatment of vascular calcification and calcific uraemic arteriolopathy in patients undergoing dialysis.
Background Pseudomonas aeruginosa is not a frequent pathogen in community-acquired pneumonia (CAP). However, in patients with severe CAP, P aeruginosa can be the etiology in 1.8% to 8.3% of patients, ...with a case-fatality rate of 50% to 100%. We describe the prevalence, clinical characteristics, outcomes, and risk factors associated with CAP resulting from multidrug-resistant (MDR) and non-MDR P aeruginosa. Methods Prospective observational study of 2,023 consecutive adult patients with CAP with definitive etiology. Results P aeruginosa was found in 77 (4%) of the 2,023 cases with microbial etiology. In 22 (32%) of the 68 cases of P aeruginosa with antibiogram data, the isolates were MDR. Inappropriate therapy was present in 49 (64%) cases of P aeruginosa CAP, including 17/22 (77%) cases of MDR P aeruginosa CAP. Male sex, chronic respiratory disease, C-reactive protein <12.35 mg/dL, and pneumonia severity index risk class IV to V were independently associated with P aeruginosa CAP. Prior antibiotic treatment was more frequent in MDR P aeruginosa CAP compared with non-MDR P aeruginosa (58% vs 29%, P = .029), and was the only risk factor associated with CAP resulting from MDR P aeruginosa. In the multivariate analysis, age ≥65 years, CAP resulting from P aeruginosa , chronic liver disease, neurologic disease, nursing home, criteria of ARDS, acute renal failure, ICU admission, and inappropriate empiric treatment were the factors associated with 30-day mortality. Conclusions P aeruginosa is an individual risk factor associated with mortality in CAP. The risk factors described can help clinicians to suspect P aeruginosa and MDR P aeruginosa.
Most current information on hospital-acquired pneumonia (HAP) is extrapolated from patients with ventilator-associated pneumonia (VAP). No studies have evaluated HAP in the intensive care unit (ICU) ...in nonventilated patients.
To compare pneumonia acquired in the ICU by mechanically ventilated versus nonventilated patients.
We prospectively collected 315 episodes of ICU-acquired pneumonia. We compared clinical and microbiologic characteristics of patients with VAP (n = 164; 52%) and nonventilator ICU-acquired pneumonia (NV-ICUAP; n = 151; 48%). Among NV-ICUAP patients, 79 (52%) needed subsequent intubation.
Compared with NV-ICUAP, patients with VAP were more severe (APACHE-II 17 ± 6 vs. 15 ± 5; P < 0.001) and pneumonia occurred later in the ICU (8 ± 8 vs. 5 ± 6 d; P < 0.001). Etiologic diagnosis (117, 71% vs. 64, 42%; P < 0.001), nonfermenting (28% vs. 15%; P = 0.009) and enteric gram-negative bacilli (26% vs. 13%; P = 0.006), and methicillin-sensitive Staphylococcus aureus (14% vs. 6%; P = 0.031) were more frequent in VAP, likely caused by more patients with lower respiratory tract samples cultured (100% vs. 84%; P < 0.001). However, in patients with defined etiology only, the proportion of pathogens was similar between groups, except for a higher proportion of Streptococcus pneumoniae in NV-ICUAP (P = 0.045). The hospital mortality also was similar.
Despite a lower proportion of pathogens in NV-ICUAP compared with VAP, the type of isolates and outcomes are similar regardless of whether pneumonia is acquired or not during ventilation, indicating they may depend on patients' underlying severity rather than previous intubation. With the diagnostic techniques currently recommended by guidelines, both types of patients might receive similar empiric antibiotic treatment.
Data on the methods used for microbiological diagnosis of hospital-acquired pneumonia (HAP) are mainly extrapolated from ventilator-associated pneumonia. HAP poses additional challenges for ...respiratory sampling, and the utility of sputum or distal sampling in HAP has not been comprehensively evaluated, particularly in HAP admitted to the ICU.
We analyzed 200 patients with HAP from six ICUs in a teaching hospital in Barcelona, Spain. The respiratory sampling methods used were divided into non-invasive sputum and endotracheal aspirate (EAT) and invasive fiberoptic-bronchoscopy aspirate (FBAS), and bronchoalveolar lavage (BAL).
A median of three diagnostic methods were applied range 2-4. At least one respiratory sampling method was applied in 93% of patients, and two or more were applied in 40%. Microbiological diagnosis was achieved in 99 (50%) patients, 69 (70%) by only one method (42% FBAS, 23% EAT, 15% sputum, 9% BAL, 7% blood culture, and 4% urinary antigen). Seventy-eight (39%) patients underwent a fiberoptic-bronchoscopy when not receiving mechanical ventilation. Higher rates of microbiological diagnosis were observed in the invasive group (56 vs. 39%, p = 0.018). Patients with microbiological diagnosis more frequently presented changes in their empirical antibiotic scheme, mainly de-escalation.
A comprehensive approach might be undertaken for microbiological diagnosis in critically ill nonventilated HAP. Sputum sampling determined one third of microbiological diagnosis in HAP patients who were not subsequently intubated. Invasive methods were associated with higher rates of microbiological diagnosis.
Summary Background Non-invasive ventilation can prevent respiratory failure after extubation in individuals at increased risk of this complication, and enhanced survival in patients with hypercapnia ...has been recorded. We aimed to assess prospectively the effectiveness of non-invasive ventilation after extubation in patients with hypercapnia and as rescue therapy when respiratory failure develops. Methods We undertook a randomised controlled trial in three intensive-care units in Spain. We enrolled 106 mechanically ventilated patients with chronic respiratory disorders and hypercapnia after a successful spontaneous breathing trial. We randomly allocated participants by computer to receive after extubation either non-invasive ventilation for 24 h (n=54) or conventional oxygen treatment (n=52). The primary endpoint was avoidance of respiratory failure within 72 h after extubation. Analysis was by intention to treat. This trial is registered with clinicaltrials.gov , identifier NCT00539708. Findings Respiratory failure after extubation was less frequent in patients assigned non-invasive ventilation than in those allocated conventional oxygen therapy (8 15% vs 25 48%; odds ratio 5·32 95% CI 2·11–13·46; p<0·0001). In patients with respiratory failure, non-invasive ventilation as rescue therapy avoided reintubation in 17 of 27 patients. Non-invasive ventilation was independently associated with a lower risk of respiratory failure after extubation (adjusted odds ratio 0·17 95% CI 0·06–0·44; p<0·0001). 90-day mortality was lower in patients assigned non-invasive ventilation than in those allocated conventional oxygen (p=0·0146). Interpretation Early non-invasive ventilation after extubation diminished risk of respiratory failure and lowered 90-day mortality in patients with hypercapnia during a spontaneous breathing trial. Routine implementation of this strategy for management of mechanically ventilated patients with chronic respiratory disorders is advisable. Funding IDIBAPS, CibeRes, Fondo de Investigaciones Sanitarias, European Respiratory Society.
Hospital-acquired pneumonia is the second most frequent nosocomial infection and the first in terms of morbidity, mortality, and cost. In recent years, international societies and, most recently, the ...American Thoracic Society jointly with the Infectious Disease Society of America, have developed guidelines for the management of hospital-acquired pneumonia, health care-associated pneumonia, and ventilator-associated pneumonia. These guidelines include recommendations for risk stratification, initial and definitive antibiotic treatment, and prevention. The validation of these guidelines is important because it confirms that they can be used in clinical practice, as quality indicators, and as a standard of care. Several processes can be validated and are included in the guidelines, such as the accuracy of the prediction of microorganisms according to stratification criteria and the impact of guidelines on outcomes, including length of hospital and intensive care unit stay, duration of mechanical ventilation, complications, and in-hospital and 30-day mortality. Clinical studies have shown that the accuracy of predicting microorganisms according to risk stratification is reliable (∼80% and ∼90%). Three studies suggest that the implementation of guidelines, with a special emphasis on antibiotic treatment, improves several parameters of outcome. Only one study, using a before-and-after design, showed a decrease in 14-day mortality after guidelines implementation. A key issue for these studies is to modify recommendations according to local patterns of microbiology and drug resistance. In summary, implementation of guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia decreases the rate of initial inappropriate antibiotic treatment and decreased 14-day mortality in a study. More clinical studies to validate the influence of guidelines on outcome are warranted.
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