Noninvasive ventilation has been studied as a means of reducing complications among patients being weaned from invasive mechanical ventilation. We sought to summarize evidence comparing noninvasive ...and invasive weaning and their effects on mortality.
We identified relevant randomized and quasirandomized trials through searches of databases, conference proceedings and grey literature. We included trials comparing extubation and immediate application of noninvasive ventilation with continued invasive weaning in adults on mechanical ventilation. Two reviewers each independently screened citations, assessed trial quality and abstracted data. Our primary outcome was mortality.
We identified 16 trials involving 994 participants, most of whom had chronic obstructive pulmonary disease (COPD). Compared with invasive weaning, noninvasive weaning significantly reduced mortality (risk ratio RR 0.53, 95% confidence interval CI 0.36 to 0.80), weaning failures (RR 0.63, 95% CI 0.42 to 0.96), ventilator-associated pneumonia (RR 0.25, 95% CI 0.15 to 0.43), length of stay in the intensive care unit (mean difference MD -5.59 d, 95% CI -7.90 to -3.28) and in hospital (MD -6.04 d, 95% CI -9.22 to -2.87), and total duration of mechanical ventilation (MD -5.64 d, 95% CI -9.50 to -1.77). Noninvasive weaning had no significant effect on the duration of ventilation related to weaning, but significantly reduced rates of tracheostomy (RR 0.19, 95% CI 0.08 to 0.47) and reintubation (RR 0.65, 95% CI 0.44 to 0.97). Mortality benefits were significantly greater in trials enrolling patients with COPD than in trials enrolling mixed patient populations (RR 0.36 95% CI 0.24 to 0.56 v. RR 0.81 95% CI 0.47 to 1.40).
Noninvasive weaning reduces rates of death and pneumonia without increasing the risk of weaning failure or reintubation. In subgroup analyses, mortality benefits were significantly greater in patients with COPD.
Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to ...underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile the microbial composition of critically ill mechanically ventilated patients, and to determine whether microbial diversity is associated with illness severity and mortality.
We conducted a prospective, observational study of mechanically ventilated critically ill patients with a high incidence of pneumonia in 2 intensive care units (ICUs) in Hamilton, Canada, nested within a randomized trial for the prevention of healthcare-associated infections. The microbial profiles of specimens from 3 anatomical sites (respiratory, and upper and lower gastrointestinal tracts) were characterized using 16S ribosomal RNA gene sequencing.
We collected 65 specimens from 34 ICU patients enrolled in the trial (29 endotracheal aspirates, 26 gastric aspirates and 10 stool specimens). Specimens were collected at a median time of 3 days (lower respiratory tract and gastric aspirates; interquartile range IQR 2-4) and 6 days (stool; IQR 4.25-6.75) following ICU admission. We observed a loss of biogeographical distinction between the lower respiratory tract and gastrointestinal tract microbiota during critical illness. Moreover, microbial diversity in the respiratory tract was inversely correlated with APACHE II score (r = - 0.46, p = 0.013) and was associated with hospital mortality (Median Shannon index: Discharged alive; 1.964 vs. Deceased; 1.348, p = 0.045).
The composition of the host-associated microbial communities is severely perturbed during critical illness. Reduced microbial diversity reflects high illness severity and is associated with mortality. Microbial diversity may be a biomarker of prognostic value in mechanically ventilated patients.
ClinicalTrials.gov ID NCT01782755 . Registered February 4 2013.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The optimal approach to titrate vasopressor therapy is unclear. Recent sepsis guidelines recommend a mean arterial pressure (MAP) target of 65 mmHg and higher for chronic hypertensive patients. As ...data emerge from clinical trials comparing blood pressure targets for vasopressor therapy, an accurate description of usual care is required to interpret study results. Our aim was to measure MAP values during vasopressor therapy in Canadian intensive care units (ICUs) and to compare these with stated practices and guidelines.
In a multicenter prospective cohort study of critically ill adults with severe hypotension, we recorded MAP and vasopressor doses hourly. We investigated variability across patients and centres using multivariable regression models and Analysis of variance (ANOVA), respectively.
We included data from 56 patients treated in 6 centers. The mean (standard deviation SD) age and Acute Physiology and Chronic Health Evaluation (APACHE) II score were 64 (14) and 25 (8). Half (28 of 56) of the patients were at least 65 years old, and half had chronic hypertension. The patient-averaged MAP while receiving vasopressors was 75 mm Hg (6) and the median (1st quartile, 3rd quartile) duration of vasopressor therapy was 43 hours (23, 84). MAP achieved was not associated with history of underlying hypertension (p = 0.46) but did vary by center (p<0.001).
In this multicenter, prospective observational study, the patient-level average MAP while receiving vasopressors for severe hypotension was 75 mmHg, approximately 10 mmHg above current recommendations and stated practices. Moreover, our results do not support the notion that clinicians tailor vasopressor therapy to individual patient characteristics such as underlying chronic hypertension but MAP achieved while receiving vasopressors varied by site.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective To review the literature on the use of inhaled nitric oxide to treat acute lung injury/acute respiratory distress syndrome (ALI/ARDS) and to summarise the effects of nitric oxide, compared ...with placebo or usual care without nitric oxide, in adults and children with ALI or ARDS.Design Systematic review and meta-analysis.Data sources Medline, CINAHL, Embase, and CENTRAL (to October 2006), proceedings from four conferences, and additional information from authors of 10 trials.Review methods Two reviewers independently selected parallel group randomised controlled trials comparing nitric oxide with control and extracted data related to study methods, clinical and physiological outcomes, and adverse events.Main outcome measures Mortality, duration of ventilation, oxygenation, pulmonary arterial pressure, adverse events. Results 12 trials randomly assigning 1237 patients met inclusion criteria. Overall methodological quality was good. Using random effects models, we found no significant effect of nitric oxide on hospital mortality (risk ratio 1.10, 95% confidence interval 0.94 to 1.30), duration of ventilation, or ventilator-free days. On day one of treatment, nitric oxide increased the ratio of partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2 ratio) (13%, 4% to 23%) and decreased the oxygenation index (14%, 2% to 25%). Some evidence suggested that improvements in oxygenation persisted until day four. There was no effect on mean pulmonary arterial pressure. Patients receiving nitric oxide had an increased risk of developing renal dysfunction (1.50, 1.11 to 2.02).Conclusions Nitric oxide is associated with limited improvement in oxygenation in patients with ALI or ARDS but confers no mortality benefit and may cause harm. We do not recommend its routine use in these severely ill patients.
With expansion of the pool of kidney grafts, through the use of higher-risk donors, and increased attention to donor management strategies, the 1-year graft survival rate is subject to change. It is, ...therefore, useful to elucidate 1-year graft survival rates by dissecting the characteristics of the low-risk and high-risk kidney transplant cases. The objective of our study was to evaluate factors purported to influence the risk of 1-year graft loss in kidney transplant recipients.
We searched bibliographic databases from 2000 to 2017 and included observational studies that measured the association between donor, recipient, the transplant operation, or early postoperative complications, and 1-year death-censored graft loss.
We identified 35 eligible primary studies, with 20 risk factors amenable to meta-analysis. Six factors were associated with graft loss, with moderate to high degree of certainty: donor age (hazard ratio HR, 1.11 per 10-year increase; 95% confidence interval 95% CI, 1.04 to 1.18), extended criteria donors (HR, 1.35; 95% CI, 1.28 to 1.42), deceased donors (HR, 1.54; 95% CI, 1.32 to 1.82), number of HLA mismatches (HR, 1.08 per one mismatch increase; 95% CI, 1.07 to 1.09), recipient age (HR, 1.17 per 10-year increase; 95% CI, 1.09 to 1.25), and delayed graft function (HR, 1.89; 95% CI, 1.46 to 2.47) as risk factors for 1-year graft loss. Pooled analyses also excluded, with a high degree of certainty, any associations of cold ischemia time, recipient race, pretransplant body mass index, diabetes, and hypertension with 1-year graft loss.
Recipient age, donor age, standard versus extended criteria donor, living versus deceased donor, HLA mismatch, and delayed graft function all predicted 1-year graft survival. The effect of each risk factor is small.
Higher positive end-expiratory pressure (PEEP) levels may reduce atelectrauma, but increase over-distention lung injury. Whether higher PEEP improves clinical outcomes among patients with acute ...respiratory distress syndrome (ARDS) is unclear.
To compare clinical outcomes of mechanical ventilation strategies using higher PEEP levels versus lower PEEP strategies in patients with ARDS.
We performed a systematic review and meta-analysis of clinical trials investigating mechanical ventilation strategies using higher versus lower PEEP levels. We used random effects models to evaluate the effect of higher PEEP on 28-day mortality, organ failure, ventilator-free days, barotrauma, oxygenation, and ventilation.
We identified eight randomized trials comparing higher versus lower PEEP strategies, enrolling 2,728 patients with ARDS. Patients were 55 (±16) (mean ± SD) years old and 61% were men. Mean PEEP in the higher PEEP groups was 15.1 (±3.6) cm H
O as compared with 9.1 (±2.7) cm H
O in the lower PEEP groups. Primary analysis excluding two trials that did not use lower Vt ventilation in the lower PEEP control groups did not demonstrate significantly reduced mortality for patients receiving higher PEEP as compared with a lower PEEP (six trials; 2,580 patients; relative risk, 0.91; 95% confidence interval CI = 0.80-1.03). A higher PEEP strategy also did not significantly decrease barotrauma, new organ failure, or ventilator-free days when compared with a lower PEEP strategy (moderate-level evidence). Quality of evidence for primary analyses was downgraded for precision, as CIs of outcomes included estimates that would result in divergent recommendations for use of higher PEEP. Secondary analysis, including trials that did not use low Vt in low-PEEP control groups, showed significant mortality reduction for high-PEEP strategies (eight trials; 2,728 patients; relative risk, 0.84; 95% CI = 0.71-0.99), with greater mortality benefit observed for high PEEP in trials that did not use lower Vts in the low-PEEP control group (P = 0.02). Analyses stratifying by use of recruitment maneuvers (P for interaction = 0.69), or use of physiological targets to set PEEP versus PEEP/Fi
tables (P for interaction = 0.13), did not show significant effect modification.
Use of higher PEEP is unlikely to improve clinical outcomes among unselected patients with ARDS.
There are conflicting data regarding the safety and efficacy of recruitment maneuvers (RMs) in patients with acute lung injury (ALI).
To summarize the physiologic effects and adverse events in adult ...patients with ALI receiving RMs.
Systematic review of case series, observational studies, and randomized clinical trials with pooling of study-level data.
Forty studies (1,185 patients) met inclusion criteria. Oxygenation (31 studies; 636 patients) was significantly increased after an RM (PaO2): 106 versus 193 mm Hg, P = 0.001; and PaO2/FiO2 ratio: 139 versus 251 mm Hg, P < 0.001). There were no persistent, clinically significant changes in hemodynamic parameters after an RM. Ventilatory parameters (32 studies; 548 patients) were not significantly altered by an RM, except for higher PEEP post-RM (11 versus 16 cm H2O; P = 0.02). Hypotension (12%) and desaturation (9%) were the most common adverse events (31 studies; 985 patients). Serious adverse events (e.g., barotrauma 1% and arrhythmias 1%) were infrequent. Only 10 (1%) patients had their RMs terminated prematurely due to adverse events.
Adult patients with ALI receiving RMs experienced a significant increase in oxygenation, with few serious adverse events. Transient hypotension and desaturation during RMs is common but is self-limited without serious short-term sequelae. Given the uncertain benefit of transient oxygenation improvements in patients with ALI and the lack of information on their influence on clinical outcomes, the routine use of RMs cannot be recommended or discouraged at this time. RMs should be considered for use on an individualized basis in patients with ALI who have life-threatening hypoxemia.
Severe traumatic brain injury often leads to death from withdrawal of life-sustaining therapy, although prognosis is difficult to determine.
To evaluate variation in mortality following the ...withdrawal of life-sustaining therapy and hospital mortality in patients with critical illness and severe traumatic brain injury, we conducted a two-year multicentre retrospective cohort study in six Canadian level-one trauma centres. The effect of centre on hospital mortality and withdrawal of life-sustaining therapy was evaluated using multivariable logistic regression adjusted for baseline patient-level covariates (sex, age, pupillary reactivity and score on the Glasgow coma scale).
We randomly selected 720 patients with traumatic brain injury for our study. The overall hospital mortality among these patients was 228/720 (31.7%, 95% confidence interval CI 28.4%-35.2%) and ranged from 10.8% to 44.2% across centres (χ(2) test for overall difference, p < 0.001). Most deaths (70.2% 160/228, 95% CI 63.9%-75.7%) were associated with withdrawal of life-sustaining therapy, ranging from 45.0% (18/40) to 86.8% (46/53) (χ(2) test for overall difference, p < 0.001) across centres. Adjusted odd ratios (ORs) for the effect of centre on hospital mortality ranged from 0.61 to 1.55 (p < 0.001). The incidence of withdrawal of life-sustaining therapy varied by centre, with ORs ranging from 0.42 to 2.40 (p = 0.001). About one half of deaths that occurred following the withdrawal of life-sustaining therapies happened within the first three days of care.
We observed significant variation in mortality across centres. This may be explained in part by regional variations in physician, family or community approaches to the withdrawal of life-sustaining therapy. Considering the high proportion of early deaths associated with the withdrawal of life-sustaining therapy and the limited accuracy of current prognostic indicators, caution should be used regarding early withdrawal of life-sustaining therapy following severe traumatic brain injury.
High-frequency oscillatory ventilation (HFOV) is theoretically beneficial for lung protection, but the results of clinical trials are inconsistent, with study-level meta-analyses suggesting no ...significant effect on mortality.
The aim of this individual patient data meta-analysis was to identify acute respiratory distress syndrome (ARDS) patient subgroups with differential outcomes from HFOV.
After a comprehensive search for trials, two reviewers independently identified randomized trials comparing HFOV with conventional ventilation for adults with ARDS. Prespecified effect modifiers were tested using multivariable hierarchical logistic regression models, adjusting for important prognostic factors and clustering effects.
Data from 1,552 patients in four trials were analyzed, applying uniform definitions for study variables and outcomes. Patients had a mean baseline Pa
/Fi
of 114 ± 39 mm Hg; 40% had severe ARDS (Pa
/Fi
<100 mm Hg). Mortality at 30 days was 321 of 785 (40.9%) for HFOV patients versus 288 of 767 (37.6%) for control subjects (adjusted odds ratio, 1.17; 95% confidence interval, 0.94-1.46; P = 0.16). This treatment effect varied, however, depending on baseline severity of hypoxemia (P = 0.0003), with harm increasing with Pa
/Fi
among patients with mild-moderate ARDS, and the possibility of decreased mortality in patients with very severe ARDS. Compliance and body mass index did not modify the treatment effect. HFOV increased barotrauma risk compared with conventional ventilation (adjusted odds ratio, 1.75; 95% confidence interval, 1.04-2.96; P = 0.04).
HFOV increases mortality for most patients with ARDS but may improve survival among patients with severe hypoxemia on conventional mechanical ventilation.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life threatening clinical conditions seen in critically ill patients with diverse underlying illnesses. Lung injury may be ...perpetuated by ventilation strategies that do not limit lung volumes and airway pressures. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing pressure and volume-limited (PVL) ventilation strategies with more traditional mechanical ventilation in adults with ALI and ARDS.
We searched Medline, EMBASE, HEALTHSTAR and CENTRAL, related articles on PubMed™, conference proceedings and bibliographies of identified articles for randomized trials comparing PVL ventilation with traditional approaches to ventilation in critically ill adults with ALI and ARDS. Two reviewers independently selected trials, assessed trial quality, and abstracted data. We identified ten trials (n = 1,749) meeting study inclusion criteria. Tidal volumes achieved in control groups were at the lower end of the traditional range of 10-15 mL/kg. We found a clinically important but borderline statistically significant reduction in hospital mortality with PVL relative risk (RR) 0.84; 95% CI 0.70, 1.00; p = 0.05. This reduction in risk was attenuated (RR 0.90; 95% CI 0.74, 1.09, p = 0.27) in a sensitivity analysis which excluded 2 trials that combined PVL with open-lung strategies and stopped early for benefit. We found no effect of PVL on barotrauma; however, use of paralytic agents increased significantly with PVL (RR 1.37; 95% CI, 1.04, 1.82; p = 0.03).
This systematic review suggests that PVL strategies for mechanical ventilation in ALI and ARDS reduce mortality and are associated with increased use of paralytic agents.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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