Ventilator-induced diaphragm dysfunction: translational mechanisms lead to therapeutical alternatives in the critically ill.

Mechanical ventilation [MV] is a life-saving technique delivered to critically ill patients incapable of adequately ventilating and/or oxygenating due to respiratory or other disease processes. This necessarily invasive support however could potentially result in important iatrogenic complications. Even brief periods of MV may result in diaphragm weakness [i.e., ventilator-induced diaphragm dysfunction [VIDD]], which may be associated with difficulty weaning from the ventilator as well as mortality. This suggests that VIDD could potentially have a major impact on clinical practice through worse clinical outcomes and healthcare resource use. Recent translational investigations have identified that VIDD is mainly characterized by alterations resulting in a major decline of diaphragmatic contractile force together with atrophy of diaphragm muscle fibers. However, the signaling mechanisms responsible for VIDD have not been fully established. In this paper, we summarize the current understanding of the pathophysiological pathways underlying VIDD and highlight the diagnostic approach, as well as novel and experimental therapeutic options.

Effect of Pressure Support vs T-Piece Ventilation Strategies During Spontaneous Breathing Trials on Successful Extubation Among Patients Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Importance: Daily spontaneous breathing trials (SBTs) are the best approach to determine whether patients are ready for disconnection from mechanical ventilation, but mode and duration of SBT remain controversial. Objective: To evaluate the effect of an SBT consisting of 30 minutes of pressure support ventilation (an approach that is less demanding for patients) vs an SBT consisting of 2 hours of T-piece ventilation (an approach that is more demanding for patients) on rates of successful extubation. Design, Setting, and Participants: Randomized clinical trial conducted from January 2016 to April 2017 among 1153 adults deemed ready for weaning after at least 24 hours of mechanical ventilation at 18 intensive care units in Spain. Follow-up ended in July 2017. Interventions: Patients were randomized to undergo a 2-hour T-piece SBT (n = 578) or a 30-minute SBT with 8-cm H2O pressure support ventilation (n = 557). Main Outcome and Measures: The primary outcome was successful extubation (remaining free of mechanical ventilation 72 hours after first SBT). Secondary outcomes were reintubation among patients extubated after SBT; intensive care unit and hospital lengths of stay; and hospital and 90-day mortality. Results: Among 1153 patients who were randomized (mean age, 62.2 [SD, 15.7] years; 428 [37.1%] women), 1018 (88.3%) completed the trial. Successful extubation occurred in 473 patients (82.3%) in the pressure support ventilation group and 428 patients (74.0%) in the T-piece group (difference, 8.2%; 95% CI, 3.4%-13.0%; P = .001). Among secondary outcomes, for the pressure support ventilation group vs the T-piece group, respectively, reintubation was 11.1% vs 11.9% (difference, -0.8%; 95% CI, -4.8% to 3.1%; P = .63), median intensive care unit length of stay was 9 days vs 10 days (mean difference, -0.3 days; 95% CI, -1.7 to 1.1 days; P = .69), median hospital length of stay was 24 days vs 24 days (mean difference, 1.3 days; 95% CI, -2.2 to 4.9 days; P = .45), hospital mortality was 10.4% vs 14.9% (difference, -4.4%; 95% CI, -8.3% to -0.6%; P = .02), and 90-day mortality was 13.2% vs 17.3% (difference, -4.1% [95% CI, -8.2% to 0.01%; P = .04]; hazard ratio, 0.74 [95% CI, 0.55-0.99]). Conclusions and Relevance: Among patients receiving mechanical ventilation, a spontaneous breathing trial consisting of 30 minutes of pressure support ventilation, compared with 2 hours of T-piece ventilation, led to significantly higher rates of successful extubation. These findings support the use of a shorter, less demanding ventilation strategy for spontaneous breathing trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02620358.

Extracorporeal membrane oxygenation (ECMO) in adults with acute respiratory distress syndrome (ARDS): A 6-year experience and case-control study.

PURPOSE: To evaluate the development of an extracorporeal membrane oxygenation (ECMO) program for the treatment of acute respiratory distress syndrome (ARDS) in adults. METHODS: a) Descriptive study of 15 cases treated since the program approval from 2010 to 2016. b) Case-control study matching the 15 ECMO cases with the 52 severe ARDS treated between 2005 and 2011 in which alternative rescue treatments (prone ventilation, tracheal gas insufflation (TGI) and/or the administration of inhaled nitric oxide (iNO)) were used. RESULTS: ECMO experience: Mortality 47% (7/15). Four patients died due to complications directly related to ECMO therapy. ICU stay 46.6 ± 45 days (range 4-138). Hospital stay 72.4 ± 98 days (range 4-320). Case-control: The mortality in the control group was 77% (44/52). The ECMO group practically doubled the mean days of ICU and hospital stay (p < 0.05). The multivariate analysis demonstrated an OR of 0.13 (0.02-0.73) for mortality associated with ECMO treatment. The following were also independent predictors of mortality: age (OR 1.05, 95% CI 1-11), SOFA score (OR 1.34, 95% CI 1.04-1.7), and the need for renal replacement therapy (OR 1.3, 95% CI 1.04-1.7). Economic analysis: The hospital cost per patient in the ECMO group doubled compared to that of the control group (USD 77,099 vs USD 37,660). However, the cost per survivor was reduced by 4% (USD 144,560 vs USD 150,640, respectively). CONCLUSIONS: Our results endorse the use of ECMO as a rescue therapy in adults with ARDS, although there are some risks associated with a learning curve as well as an important increase in the days of patient stay. The justification for the maintenance of an ECMO program in adults should be based on future studies of efficacy and cost effectiveness.

Clinical factors associated with inappropriate prophylaxis of venous thromboembolic disease in critically ill patients. A single day cross-sectional study.

PURPOSE: A poor implementation of VTE prophylactic measures recommended for critically ill patients has been observed in several epidemiological studies. The clinical factors associated with this have not been clearly established. The objective of our study was to identify which factors could be related to the inappropriate use of VTE prophylaxis. METHODS: Analytic epidemiological study based on different aspects of VTE prophylaxis performed on Spanish ICU patients. A multiple logistic regression analysis was conducted to identify the risk factors associated with inappropriate prophylaxis, according to the American College of Chest Physicians 2012 guidelines. RESULTS: We enrolled 777 patients. On admission, 62% presented medical, 30% surgical and 8% major trauma pathology. Of all patients, 41% were receiving an inappropriate prophylaxis, including 19% which did not receive any prophylaxis. The presence of a contraindication for pharmacological prophylaxis (OR 3.91, 95% CI 2.50-6.10) and non-medical pathology at ICU admission (OR 11.09; 95% CI 7.63-16.12) were associated with inappropriate prophylaxis. In contrast, mechanical ventilation (OR 0.70, 95% CI 0.45-0.98), bed rest>48h (OR 0.61, 95% CI 0.49-0.98), the use of a protocol for VTE prophylaxis (OR 0.66, 95% CI 0.45-0.98) and a VTE risk scoring system (OR 0.49, 95% CI 0.24-0.98) were associated with adequate prophylaxis. CONCLUSIONS: Our study highlighted a poor compliance with the VTE prophylaxis recommendations proposed for critical patients. The implementation of specific protocols for prophylaxis that include a correct evaluation according to VTE and haemorrhage risk, would allow for optimisation of mechanical and combined prophylaxis, improving adherence to the clinical practice guidelines.