Diaphragm dysfunction during weaning from mechanical ventilation: an underestimated phenomenon with clinical implications.
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ABSTRACT:
SUBMITTER: Dres M
PROVIDER: S-EPMC5861656 | biostudies-literature | 2018 Mar
REPOSITORIES: biostudies-literature
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Diaphragm dysfunction during weaning from mechanical ventilation: an underestimated phenomenon with clinical implications.
Dres Martin M Demoule Alexandre A
Critical care (London, England) 20180320 1
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2018 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 . ...[more]
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Project description:BACKGROUND:Diaphragm dysfunction is defined by a value of twitch tracheal pressure in response to magnetic phrenic stimulation (twitch pressure) amounting to less than 11 cmH2O. This study assessed whether this threshold or a lower one would predict accurately weaning failure from mechanical ventilation. Twitch pressure was compared to ultrasound measurement of diaphragm function. METHODS:In patients undergoing a first spontaneous breathing trial, diaphragm function was evaluated by twitch pressure and by diaphragm ultrasound (thickening fraction). Receiver operating characteristics curves were computed to determine the best thresholds predicting failure of spontaneous breathing trial. RESULTS:Seventy-six patients were evaluated, 48 (63%) succeeded and 28 (37%) failed the spontaneous breathing trial. The optimal thresholds of twitch pressure and thickening fraction to predict failure of the spontaneous breathing trial were, respectively, 7.2 cmH2O and 25.8%, respectively. The receiver operating characteristics curves were 0.80 (95% CI 0.70-0.89) for twitch pressure and 0.82 (95% CI 0.73-0.93) for thickening fraction. Both receiver operating characteristics curves were similar (p?=?0.83). A twitch pressure value lower than 11 cmH2O (the traditional cutoff for diaphragm dysfunction) predicted failure of the spontaneous breathing trial with a sensitivity of 89% (95% CI 72-98%) and a specificity of 45% (95% CI 30-60%). CONCLUSIONS:Failure of spontaneous breathing trial can be predicted with a lower value of twitch pressure than the value defining diaphragm dysfunction. Twitch pressure and thickening fraction had similar strong performance in the prediction of failure of the spontaneous breathing trial.
| S-EPMC5913054 | biostudies-literature
Project description:BackgroundDiaphragm weakness occurs rapidly in adult animals treated with mechanical ventilation (MV), but the effects of MV on the neonatal diaphragm have not been determined. Furthermore, it is unknown whether co-existent lung disease exacerbates ventilator-induced diaphragmatic dysfunction (VIDD). We investigated the impact of MV (mean duration = 7.65 h), either with or without co-existent respiratory failure caused by surfactant deficiency, on the development of VIDD in newborn lambs.MethodsNewborn lambs (1-4 days) were assigned to control (CTL, non-ventilated), mechanically ventilated (MV), and MV + experimentally induced surfactant deficiency (MV+SD) groups. Immunoblotting and quantitative PCR assessed inflammatory signaling, the ubiquitin-proteasome system, autophagy, and oxidative stress. Immunostaining for myosin heavy chain (MyHC) isoforms and quantitative morphometry evaluated diaphragm atrophy. Contractile function of the diaphragm was determined in isolated myofibrils ex vivo.ResultsEqual decreases (25-30%) in myofibrillar force generation were found in MV and MV+SD diaphragms compared to CTL. In comparison to CTL, both MV and MV+SD diaphragms also demonstrated increased STAT3 transcription factor phosphorylation. Ubiquitin-proteasome system (Atrogin1 and MuRF1) transcripts and autophagy indices (Gabarapl1 transcripts and the ratio of LC3B-II/LC3B-I protein) were greater in MV+SD relative to MV alone, but fiber type atrophy was not observed in any group. Protein carbonylation and 4-hydroxynonenal levels (indices of oxidative stress) also did not differ among groups.ConclusionsIn newborn lambs undergoing controlled MV, there is a rapid onset of diaphragm dysfunction consistent with VIDD. Superimposed lung injury caused by surfactant deficiency did not influence the severity of early diaphragm weakness.
| S-EPMC6469194 | biostudies-literature
Project description:Controlled mechanical ventilation (CMV) is associated with the development of diaphragm atrophy and contractile dysfunction, and respiratory muscle weakness is thought to contribute significantly to delayed weaning of patients. Therefore, therapeutic strategies for preventing these processes may have clinical benefit. The aim of the current study was to investigate the role of the Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) signaling pathway in CMV-mediated diaphragm wasting and weakness in rats. CMV-induced diaphragm atrophy and contractile dysfunction coincided with marked increases in STAT3 phosphorylation on both tyrosine 705 (Tyr705) and serine 727 (Ser727). STAT3 activation was accompanied by its translocation into mitochondria within diaphragm muscle and mitochondrial dysfunction. Inhibition of JAK signaling during CMV prevented phosphorylation of both target sites on STAT3, eliminated the accumulation of phosphorylated STAT3 within the mitochondria, and reversed the pathologic alterations in mitochondrial function, reduced oxidative stress in the diaphragm, and maintained normal diaphragm contractility. In addition, JAK inhibition during CMV blunted the activation of key proteolytic pathways in the diaphragm, as well as diaphragm atrophy. These findings implicate JAK/STAT3 signaling in the development of diaphragm muscle atrophy and dysfunction during CMV and suggest that the delayed extubation times associated with CMV can be prevented by inhibition of Janus kinase signaling.-Smith, I. J., Godinez, G. L., Singh, B. K., McCaughey, K. M., Alcantara, R. R., Gururaja, T., Ho, M. S., Nguyen, H. N., Friera, A. M., White, K. A., McLaughlin, J. R., Hansen, D., Romero, J. M., Baltgalvis, K. A., Claypool, M. D., Li, W., Lang, W., Yam, G. C., Gelman, M. S., Ding, R., Yung, S. L., Creger, D. P., Chen, Y., Singh, R., Smuder, A. J., Wiggs, M. P., Kwon, O.-S., Sollanek, K. J., Powers, S. K., Masuda, E. S., Taylor, V. C., Payan, D. G., Kinoshita, T., Kinsella, T. M. Inhibition of Janus kinase signaling during controlled mechanical ventilation prevents ventilation-induced diaphragm dysfunction.
| S-EPMC4062832 | biostudies-other
Project description:Prolonged use of mechanical ventilation (MV) leads to atrophy and dysfunction of the major inspiratory muscle, the diaphragm, contributing to ventilator dependence. Numerous studies have shown that proteolysis and oxidative stress are among the major effectors of ventilator-induced diaphragm muscle dysfunction (VIDD), but the upstream initiator(s) of this process remain to be elucidated. We report here that periodic diaphragm contraction via phrenic nerve stimulation (PNS) substantially reduces MV-induced proteolytic activity and oxidative stress in the diaphragm. We show that MV rapidly induces phosphorylation of Smad3, and PNS nearly completely prevents this effect. In cultured cells, overexpressed Smad3 is sufficient to induce oxidative stress and protein degradation, whereas inhibition of Smad3 activity suppresses these events. In rats subjected to MV, inhibition of Smad3 activity by SIS3 suppresses oxidative stress and protein degradation in the diaphragm and prevents the reduction in contractility that is induced by MV. Smad3's effect appears to link to STAT3 activity, which we previously identified as a regulator of VIDD. Inhibition of Smad3 suppresses STAT3 signaling both in vitro and in vivo. Thus, MV-induced diaphragm inactivity initiates catabolic changes via rapid activation of Smad3 signaling. An early intervention with PNS and/or pharmaceutical inhibition of Smad3 may prevent clinical VIDD.
| S-EPMC5673963 | biostudies-literature
Project description:Weaning is the process of successfully liberating the patient from mechanical ventilation. The majority of patients will separate from the ventilator after a successful spontaneous breathing trial (SBT).1 In a minority of patients, weaning can be challenging and prolonged. Finding the cause of weaning difficulty is crucial to minimize the rates of extubation failure and prolonged ventilation. Diaphragm dysfunction (DD) has been described as a separate entity responsible for weaning failure with an incidence of 23–80%. It has also been associated with difficult weaning, prolonged intensive care unit (ICU) stay and mechanical ventilation, and increased ICU and hospital mortality.2 Sepsis, shock, and ventilator induced diaphragm dysfunction are important risk factors of DD. Diaphragm dysfunction has several mechanisms. Disuse atrophy and microstructural changes of the diaphragm have been described as the two cardinal pathophysiologic features. Establishing the diagnosis of DD can be complex in critically ill patients. Bilateral anterior magnetic phrenic stimulation is widely considered as the gold standard but is only available in large research centers with limited availability. Ultrasonography of the diaphragm is a promising tool given its wide availability, affordability, and non-invasive nature. Ultrasound is operator dependent, however and it does not provide continuous monitoring capabilities. The diaphragm thickening fraction (DTF) can be calculated from measuring the end-expiratory and end-inspiratory diaphragm thickness at the bedside. It correlates well with transdiaphragmatic pressure.3 Electromyography of the diaphragm may overcome the limitation of ultrasound by offering a continuous assessment of the diaphragmatic electrical activity, but it requires the placement of a specialized nasogastric tube. Management of DD is better approached by implementing a preventive and a curative strategy. From animal studies, allowing for spontaneous breathing on mechanical ventilation may prevent the problem. The degree of the recommended patient effort and ventilator assistance to achieve optimal balance between diaphragmatic loading and unloading are yet to be defined. Monitoring DTF while finding the optimal ventilator support level can be useful in this context. Another modality to prevent DD is diaphragm pacing applied through a transvenous phrenic nerve pacing system. Animal studies in pigs showed that this modality resulted in less diaphragm atrophy when pacing was synchronized with ventilation.4 There is an ongoing study to assess the role of diaphragm pacing to recondition and strengthen the diaphragm in difficult to wean mechanically ventilated patients (Clinicaltrials.gov NCT03107949). Once diaphragm dysfunction is established, no specific treatments exist at this time. Other causes of weaning failure like cardiac dysfunction have to be excluded and treated. Improving respiratory load and respiratory muscle weakness imbalance is also crucial. While it appears to improve inspiratory muscle strength parameters, inspiratory muscle training has not consistently shown improvements in weaning success.5 Levosemindan showed some benefit in improving diaphragm contractility and efficiency in healthy volunteers but was later found to increase likelihood of weaning failure in septic patients. Anabolic steroids were not found to be effective in treating diaphragm dysfunction in several studies. More evidence is needed before recommending non-invasive ventilation post-extubation in all DD patients.
| S-EPMC6851905 | biostudies-literature
Project description:BackgroundLung and diaphragm ultrasound methods have recently been introduced to predict the outcome of weaning from mechanical ventilation (MV). The aim of this study is to assess the reliability and accuracy of these techniques for predicting successful weaning in critically ill adults.MethodsWe conducted two studies: a cross-sectional interobserver agreement study between two sonographers and a prospective cohort study to assess the accuracy of lung and diaphragm ultrasound for predicting weaning and extubation outcome. For the interobserver agreement study, we included 50 general critical care patients who were consecutively admitted to the ICU. For the predictive accuracy study, we included consecutively 69 patients on MV who were ready for weaning. We assessed interobserver agreement of ultrasound measurements, using the weighted kappa coefficient for LUSm score (modified lung ultrasound score) and the intraclass correlation coefficient (ICC) and Bland-Altman method for TI (diaphragm thickening index). We assessed the predictive value of LUSm and TI in weaning outcome by plotting the corresponding ROC curves.ResultsWe found adequate interobserver agreement for both LUSm (weighted kappa 0.95) and TI (ICC 0.78, difference according to Bland-Altman analysis?±?12.5%). LUSm showed good-moderate discriminative power for successful weaning and extubation (area under the ROC curve (AUC) for successful weaning 0.80, and sensitivity and specificity at optimal cut-off point 0.76 and 0.73, respectively; AUC for successful extubation 0.78, and optimal sensitivity and specificity 0.76 and 0.47, respectively. TI was more sensitive but less specific for predicting successful weaning (AUC 0.71, optimal sensitivity and specificity 0.93 and 0.48) and successful extubation (AUC 0.76, optimal sensitivity and specificity 0.93 and 0.58). The area under the ROC curve for predicting weaning success was 0.83 for both ultrasound measurements together.ConclusionsInterobserver agreement was excellent for LUSm and moderate-good for TI. A low TI value or high LUSm value indicates high risk of weaning failure.
| S-EPMC6004341 | biostudies-literature
Project description:BackgroundDiaphragmatic dysfunction is a major factor responsible for weaning failure in patients that underwent prolonged invasive mechanical ventilation for acute severe respiratory failure from COVID-19. This study hypothesizes that ultrasound measured diaphragmatic thickening fraction (DTF) could provide corroborating information for weaning COVID-19 patients from mechanical ventilation.MethodsThis was an observational, pragmatic, cross-section, multicenter study in 6 Italian intensive care units. DTF was assessed in COVID-19 patients undergoing weaning from mechanical ventilation from 1st March 2020 to 30th June 2021. Primary aim was to evaluate whether DTF is a predictive factor for weaning failure.ResultsFifty-seven patients were enrolled, 25 patients failed spontaneous breathing trial (44%). Median length of invasive ventilation was 14 days (IQR 7-22). Median DTF within 24 h since the start of weaning was 28% (IQR 22-39%), RASS score (- 2 vs - 2; p = 0.031); Kelly-Matthay score (2 vs 1; p = 0.002); inspiratory oxygen fraction (0.45 vs 0.40; p = 0.033). PaO2/FiO2 ratio was lower (176 vs 241; p = 0.032) and length of intensive care stay was longer (27 vs 16.5 days; p = 0.025) in patients who failed weaning. The generalized linear regression model did not select any variables that could predict weaning failure. DTF was correlated with pH (RR 1.56 × 1027; p = 0.002); Kelly-Matthay score (RR 353; p < 0.001); RASS (RR 2.11; p = 0.003); PaO2/FiO2 ratio (RR 1.03; p = 0.05); SAPS2 (RR 0.71; p = 0.005); hospital and ICU length of stay (RR 1.22 and 0.79, respectively; p < 0.001 and p = 0.004).ConclusionsDTF in COVID-19 patients was not predictive of weaning failure from mechanical ventilation, and larger studies are needed to evaluate it in clinical practice further. Registered: ClinicalTrial.gov (NCT05019313, 24 August 2021).
| S-EPMC9392990 | biostudies-literature
Project description:This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
| S-EPMC7092676 | biostudies-literature
Project description:Previous workers have demonstrated that controlled mechanical ventilation results in diaphragm inactivity and elicits a rapid development of diaphragm weakness as a result of both contractile dysfunction and fiber atrophy. Limited data exist regarding the impact of pressure support ventilation, a commonly used mode of mechanical ventilation-that permits partial mechanical activity of the diaphragm-on diaphragm structure and function. We carried out the present study to test the hypothesis that high-level pressure support ventilation decreases the diaphragm pathology associated with CMV.Sprague-Dawley rats were randomly assigned to one of the following five groups:1) control (no mechanical ventilation); 2) 12 hrs of controlled mechanical ventilation (12CMV); 3) 18 hrs of controlled mechanical ventilation (18CMV); 4) 12 hrs of pressure support ventilation (12PSV); or 5) 18 hrs of pressure support ventilation (18PSV).We carried out the following measurements on diaphragm specimens: 4-hydroxynonenal-a marker of oxidative stress, active caspase-3 (casp-3), active calpain-1 (calp-1), fiber type cross-sectional area, and specific force (sp F). Compared with the control, both 12PSV and 18PSV promoted a significant decrement in diaphragmatic specific force production, but to a lesser degree than 12CMV and 18CMV. Furthermore, 12CMV, 18PSV, and 18CMV resulted in significant atrophy in all diaphragm fiber types as well as significant increases in a biomarker of oxidative stress (4-hydroxynonenal) and increased proteolytic activity (20S proteasome, calpain-1, and caspase-3). Furthermore, although no inspiratory effort occurs during controlled mechanical ventilation, it was observed that pressure support ventilation resulted in large decrement, approximately 96%, in inspiratory effort compared with spontaneously breathing animals.High levels of prolonged pressure support ventilation promote diaphragmatic atrophy and contractile dysfunction. Furthermore, similar to controlled mechanical ventilation, pressure support ventilation-induced diaphragmatic atrophy and weakness are associated with both diaphragmatic oxidative stress and protease activation.
| S-EPMC3308123 | biostudies-literature
Project description:Weaning from mechanical ventilation (MV) may be impeded by the occurrence of agitation. Loxapine has the ability to control agitation without affecting spontaneous ventilation. The aim of this study was to establish whether loxapine would reduce MV weaning duration in agitated patients.We performed a multicentre, double-blind, placebo-controlled, parallel group, randomised trial. Patients who were potential candidates for weaning but exhibited agitation (Richmond Agitation-Sedation Scale score???2) after sedation withdrawal were randomly assigned to receive either loxapine or placebo. In case of severe agitation, conventional sedation was immediately resumed. The primary endpoint was the time between first administration of loxapine or placebo and successful extubation.The trial was discontinued after 102 patients were enrolled because of an insufficient inclusion rate. Median times to successful extubation were 3.2 days in the loxapine group and 5 days in the placebo group (relative risk 1.2, 95% CI 0.75-1.88, p?=?0.45). During the first 24 h, sedation was more frequently resumed in the placebo group (44% vs 17%, p?=?0.01).In this prematurely stopped trial, loxapine did not significantly shorten weaning from MV. However, loxapine reduced the need for resuming sedation.Clinicaltrials.gov, NCT01193816 ?. Registered on 26 August 2010.
| S-EPMC5586048 | biostudies-literature