Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients without ARDS: A Randomized Clinical Trial.

This article by the Writing Group for the PReVENT Investigators was published in JAMA in November 2018.
Importance:  It remains uncertain whether invasive ventilation should use low tidal volumes in critically ill patients without acute respiratory distress syndrome (ARDS).
Objective:  To determine whether a low tidal volume ventilation strategy is more effective than an intermediate tidal volume strategy.
Design,Setting, and Participants:  A randomized clinical trial, conducted from September 1, 2014, through August 20, 2017,including patients without ARDS expected to not be extubated within 24 hours after start of ventilation from 6 intensive care units in the Netherlands.
Interventions:  Invasive ventilation using low tidal volumes(n = 477) or intermediate tidal volumes (n = 484).
Main Outcomes and Measures:  The primary outcome was the number of ventilator-free days and alive at day 28. Secondary outcomes included length of ICU and hospital stay; ICU, hospital, and 28- and 90-day mortality; and development of ARDS, pneumonia, severe atelectasis, orpneumothorax.
Results:  In total, 961 patients (65% male), with a median age of 68 years (interquartile range [IQR], 59-76), were enrolled. Atday 28, 475 patients in the low tidal volume group had a median of 21 ventilator-free days (IQR, 0-26), and 480 patients in the intermediate tidal volume group had a median of 21 ventilator-free days (IQR, 0-26) (mean difference, -0.27 [95% CI, -1.74 to 1.19]; P = .71). There was no significant difference in ICU (median, 6 vs 6 days; 0.39 [-1.09 to 1.89]; P = .58) and hospital (median, 14 vs 15 days; -0.60 [-3.52 to 2.31]; P = .68) length of stayor 28-day (34.9% vs 32.1%; hazard ratio [HR], 1.12 [0.90 to 1.40]; P = .30) and90-day (39.1% vs 37.8%; HR, 1.07 [0.87 to 1.31]; P = .54) mortality. There was no significant difference in the percentage of patients developing the following adverse events: ARDS (3.8% vs 5.0%; risk ratio [RR], 0.86 [0.59 to 1.24];P = .38), pneumonia (4.2% vs 3.7%; RR, 1.07 [0.78 to 1.47]; P = .67), severeatelectasis (11.4% vs 11.2%; RR, 1.00 [0.81 to 1.23]; P = .94), and pneumothorax (1.8% vs 1.3%; RR, 1.16 [0.73 to 1.84]; P = .55).  
Conclusions and Relevance:  In patients in the ICU without ARDS who were expected not to be extubated within 24 hours of randomization, a low tidal volume strategy did not result in a greater number of ventilator-free days than an intermediate tidal volume strategy.
The print copy of this issue JAMA is available in the Healthcare Library on D Level of Rotherham General Hospital.  The full text of the article should be available using a Rotherham NHS Athens password one month after publication via this link.

Risk Stratification in Pediatric Acute Respiratory Distress Syndrome

This study aims to describe the epidemiology of patients with PARDS across Asia and evaluate whether the Pediatric Acute Lung Injury Consensus Conference risk stratification accurately predicts outcome in PARDS | Critical Care Medicine

Objectives: The Pediatric Acute Lung Injury Consensus Conference developed a pediatric specific definition for acute respiratory distress syndrome (PARDS). In this definition, severity of lung disease is stratified into mild, moderate, and severe groups. We aim to describe the epidemiology of patients with PARDS across Asia and evaluate whether the Pediatric Acute Lung Injury Consensus Conference risk stratification accurately predicts outcome in PARDS.


Measurements and Main Results: Data on epidemiology, ventilation, adjunct therapies, and clinical outcomes were collected. Patients were followed for 100 days post diagnosis of PARDS. A total of 373 patients were included. There were 89 (23.9%), 149 (39.9%), and 135 (36.2%) patients with mild, moderate, and severe PARDS, respectively. The most common risk factor for PARDS was pneumonia/lower respiratory tract infection (309 [82.8%]). Higher category of severity of PARDS was associated with lower ventilator-free days (22 [17-25], 16 [0-23], 6 [0-19]; p < 0.001 for mild, moderate, and severe, respectively) and PICU free days (19 [11-24], 15 [0-22], 5 [0-20]; p < 0.001 for mild, moderate, and severe, respectively). Overall PICU mortality for PARDS was 113 of 373 (30.3%), and 100-day mortality was 126 of 317 (39.7%). After adjusting for site, presence of comorbidities and severity of illness in the multivariate Cox proportional hazard regression model, patients with moderate (hazard ratio, 1.88 [95% CI, 1.03-3.45]; p = 0.039) and severe PARDS (hazard ratio, 3.18 [95% CI, 1.68, 6.02]; p < 0.001) had higher risk of mortality compared with those with mild PARDS.

Conclusions: Mortality from PARDS is high in Asia. The Pediatric Acute Lung Injury Consensus Conference definition of PARDS is a useful tool for risk stratification.

Full reference: Wong, J, J-M. et al. (2017) Risk Stratification in Pediatric Acute Respiratory Distress Syndrome: A Multicenter Observational Study. Critical Care Medicine. Published online: July 26 2017


Incidence of Adult Respiratory Distress Syndrome in trauma patients

In trauma patients, acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality. Changes in diagnostics, management and treatment may have influenced the incidence of ARDS | Journal of Trauma and Acute Care Surgery

Background: The purpose of this manuscript is to evaluate whether there is a difference in the incidence of posttraumatic ARDS 1) over time, 2) attributable to geographic distribution, and 3) related to admitting surgical subspecialities.

Methods: A comprehensive search of articles published in English and German language was conducted using PubMed, MEDLINE, and the ISI Web of Science. Search terms included ARDS, acute respiratory distress syndrome, multiple trauma, polytrauma, and surgery. A meta-regression was performed to analyse differences between several decades of patient recruitment (decade 1: 1981-90; decade 2: 1991-2000; decade 3: 2001-2010), geographic location (North America and Europe), and the type of admitting surgical service (general vs orthopaedic trauma), respectively. Statistical analyses were performed with R (version 3.1.2, metafor package).

Conclusion: The results of this meta-analysis discard the assumption that the following factors have influenced the incidence of postraumatic ARDS: There was neither a change in the incidence over the last decades, nor a geographical difference within western societies, nor associated with the admitting surgical subspeciality.

Full reference: Pfeifer, R. et al. Incidence of Adult Respiratory Distress Syndrome (ARDS) in trauma patients: A systematic review and meta-analysis over a period of three decades. Journal of Trauma and Acute Care Surgery. Post Acceptance: June 6, 2017

Looking closer at acute respiratory distress syndrome: the role of advanced imaging techniques.

Bellani, G. et al. Current Opinion in Critical Care. Published online: 30 November 2016

Purpose of review: Advanced imaging techniques have provided invaluable insights in understanding of acute respiratory distress syndrome (ARDS) and the effect of therapeutic strategies, thanks to the possibility of gaining regional information and moving from simple ‘anatomical’ information to in-vivo functional imaging.

Summary: Progresses in lung imaging are key to individualize therapy, diagnosis, and pathophysiological mechanism at play in any patient at any specified time, helping to move toward personalized medicine for ARDS.

Read the full abstract here

Hydrocortisone treatment in early sepsis-associated acute respiratory distress syndrome

Tongyoo, S. et al.Critical Care. 20(329). Published online: 15 October 2016

Image source: LHcheM – Wikipedia // CC BY-SA 3.0

Background: Authors of recent meta-analyses have reported that prolonged glucocorticoid treatment is associated with significant improvements in patients with severe pneumonia or acute respiratory distress syndrome (ARDS) of multifactorial etiology. A prospective randomized trial limited to patients with sepsis-associated ARDS is lacking. The objective of our study was to evaluate the efficacy of hydrocortisone treatment in sepsis-associated ARDS.

Methods: In this double-blind, single-center (Siriraj Hospital, Bangkok), randomized, placebo-controlled trial, we recruited adult patients with severe sepsis within 12 h of their meeting ARDS criteria. Patients were randomly assigned (1:1 ratio) to receive either hydrocortisone 50 mg every 6 h or placebo. The primary endpoint was 28-day all-cause mortality; secondary endpoints included survival without organ support on day 28.

Results: Over the course of 4 years, 197 patients were randomized to either hydrocortisone (n = 98) or placebo (n = 99) and were included in this intention-to-treat analysis. The treatment group had significant improvement in the ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen and lung injury score (p = 0.01), and similar timing to removal of vital organ support (HR 0.74, 95 % CI 0.51–1.07; p = 0.107). After adjustment for significant covariates, day 28 survival was similar for the whole group (HR 0.80, 95 % CI 0.46–1.41; p = 0.44) and for the larger subgroup (n = 126) with Acute Physiology and Chronic Health Evaluation II score <25 (HR 0.57, 95 % CI 0.24–1.36; p = 0.20). With the exception of hyperglycemia (80.6 % vs. 67.7 %; p = 0.04), the rate of adverse events was similar. Hyperglycemia had no impact on outcome.

Conclusions: In sepsis-associated ARDS, hydrocortisone treatment was associated with a significant improvement in pulmonary physiology, but without a significant survival benefit.

Read the full article here

Reciprocal Risk of Acute Kidney Injury and Acute Respiratory Distress Syndrome in Critically Ill Burn Patients

Clemens, M. (2016) Critical Care Medicine. 44(10). pp.e915–e922

Objective: To evaluate the association between acute respiratory distress syndrome and acute kidney injury with respect to their contributions to mortality in critically ill patients.

Design: Retrospective analysis of consecutive adult burn patients requiring mechanical ventilation.

Setting: A 16-bed burn ICU at tertiary military teaching hospital.

Patients: Adult patients more than 18 years old requiring mechanical ventilation during their initial admission to our burn ICU from January 1, 2003, to December 31, 2011.

Measurements and Main Results: A total 830 patients were included, of whom 48.2% had acute kidney injury (n = 400). These patients had a 73% increased risk of developing acute respiratory distress syndrome after controlling for age, gender, total body surface area burned, and inhalation injury (hazard ratio, 1.73; 95% CI, 1.18–2.54; p = 0.005). In a reciprocal multivariate analysis, acute respiratory distress syndrome (n = 299; 36%) demonstrated a strong trend toward developing acute kidney injury (hazard ratio, 1.39; 95% CI, 0.99–1.95; p = 0.05). There was a 24% overall in-hospital mortality (n = 198). After adjusting for the aforementioned confounders, both acute kidney injury (hazard ratio, 3.73; 95% CI, 2.39–5.82; p < 0.001) and acute respiratory distress syndrome (hazard ratio, 2.16; 95% CI, 1.58–2.94; p < 0.001) significantly contributed to mortality. Age, total body surface area burned, and inhalation injury were also significantly associated with increased mortality.

Conclusions: Acute kidney injury increases the risk of acute respiratory distress syndrome in mechanically ventilated burn patients, whereas acute respiratory distress syndrome similarly demonstrates a strong trend toward the development of acute kidney injury. Acute kidney injury and acute respiratory distress syndrome are both independent risks for subsequent death. Future research should look at this interplay for possible early interventions.

Read the abstract here

Assessment of dead-space ventilation in patients with acute respiratory distress syndrome: a prospective observational study

Doorduin, J. et al. Critical Care2016. 20:121

Background: Physiological dead space (VD/VT) represents the fraction of ventilation not participating in gas exchange. In patients with acute respiratory distress syndrome (ARDS), VD/VT has prognostic value and can be used to guide ventilator settings. However, VD/VT is rarely calculated in clinical practice, because its measurement is perceived as challenging. Recently, a novel technique to calculate partial pressure of carbon dioxide in alveolar air (PACO2) using volumetric capnography (VCap) was validated. The purpose of the present study was to evaluate how VCap and other available techniques to measure PACO2 and partial pressure of carbon dioxide in mixed expired air (PeCO2) affect calculated VD/VT.

Methods: In a prospective, observational study, 15 post-cardiac surgery patients and 15 patients with ARDS were included. PACO2 was measured using VCap to calculate Bohr dead space or substituted with partial pressure of carbon dioxide in arterial blood (PaCO2) to calculate the Enghoff modification. PeCO2 was measured in expired air using three techniques: Douglas bag (DBag), indirect calorimetry (InCal), and VCap. Subsequently, VD/VT was calculated using four methods: Enghoff-DBag, Enghoff-InCal, Enghoff-VCap, and Bohr-VCap.

Results: PaCO2 was higher than PACO2, particularly in patients with ARDS (post-cardiac surgery PACO2 = 4.3 ± 0.6 kPa vs. PaCO2 = 5.2 ± 0.5 kPa, P < 0.05; ARDS PACO2 = 3.9 ± 0.8 kPa vs. PaCO2 = 6.9 ± 1.7 kPa, P < 0.05). There was good agreement in PeCO2 calculated with DBag vs. VCap (post-cardiac surgery bias = 0.04 ± 0.19 kPa; ARDS bias = 0.03 ± 0.27 kPa) and relatively low agreement with DBag vs. InCal (post-cardiac surgery bias = −1.17 ± 0.50 kPa; ARDS mean bias = −0.15 ± 0.53 kPa). These differences strongly affected calculated VD/VT. For example, in patients with ARDS, VD/VTcalculated with Enghoff-InCal was much higher than Bohr-VCap (VD/VT Enghoff-InCal = 66 ± 10 % vs. VD/VT Bohr-VCap = 45 ± 7 %; P < 0.05).

Conclusions: Different techniques to measure PACO2 and PeCO2 result in clinically relevant mean and individual differences in calculated VD/VT, particularly in patients with ARDS. Volumetric capnography is a promising technique to calculate true Bohr dead space. Our results demonstrate the challenges clinicians face in interpreting an apparently simple measurement such as VD/VT.

Read the full article here

Patients at high risk for psychiatric symptoms after a stay in the intensive care unit

Johns Hopkins Medicine. ScienceDaily. Published online: 20 April 2106

Results of a multi-institutional national study of nearly 700 people who survived life-threatening illness with a stay in an intensive care unit (ICU) suggest that a substantial majority of them are at high risk for persistent depression, anxiety and post-traumatic stress disorder — especially if they are female, young and unemployed.

The study, led by Johns Hopkins University researchers, found that two-thirds of study participants who survived a condition called acute respiratory distress syndrome (ARDS) and spent time in the ICU self-reported symptoms of at least one of these psychiatric disorders, and one-third of those patients with at least one psychiatric symptom said they experienced all three at the same time.

Contrary to the common risk factors associated with post-ARDS physical impairments and mortality, such as severity of illness and length of ICU stay, this study demonstrated that none of these risk factors had positive association with psychiatric symptoms.

Read the full commentary here

Acute respiratory distress syndrome: does histology matter?

Critical Care 2015, 19:337

Kao et al. have reported in Critical Care the histological findings of 101 patients with acute respiratory distress syndrome (ARDS) undergoing open lung biopsy. Diffuse alveolar damage (DAD), the histological hallmark of ARDS, was present in only 56.4 % of cases.

The presence of DAD was associated with higher mortality. Evidence from this and other studies indicates that the clinical criteria for the diagnosis of ARDS identify DAD in only about half of the cases.

On the contrary, there is evidence that the clinical course and outcome of ARDS differs in patients with DAD and in patients without DAD. The discovery of biomarkers for the physiological (increased alveolocapillary permeability) or histological (DAD) hallmarks of ARDS is thus of paramount importance.

via Critical Care | Full text | Acute respiratory distress syndrome: does histology matter?.