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Early rehabilitation relieves diaphragm dysfunction induced by prolonged mechanical ventilation: a randomised control study.

ABSTRACT:

Background

Prolonged mechanical ventilation (MV) induces diaphragm dysfunction in patients in the intensive care units (ICUs). Our study aimed to explore the therapeutic efficacy of early rehabilitation therapy in patients with prolonged MV in the ICU.

Methods

Eighty eligible patients who underwent MV for > 72 h in the ICU from June 2019 to March 2020 were enrolled in this prospective randomised controlled trial. The patients were randomly divided into a rehabilitation group (n = 39) and a control group (n = 41). Rehabilitation therapy included six levels of rehabilitation exercises. Diaphragm function was determined using ultrasound (US).

Results

Diaphragmatic excursion (DE) and diaphragm thickening fraction (DTF) were significantly decreased in all patients in both groups after prolonged MV (p < 0.001). The rehabilitation group had significantly higher DTF (p = 0.008) and a smaller decrease in DTF (p = 0.026) than the control group after 3 days of rehabilitation training. The ventilator duration and intubation duration were significantly shorter in the rehabilitation group than in the control group (p = 0.045 and p = 0.037, respectively). There were no significant differences in the duration of ICU stay, proportion of patients undergoing tracheotomy, and proportion of recovered patients between the two groups.

Conclusions

Early rehabilitation is feasible and beneficial to ameliorate diaphragm dysfunction induced by prolonged MV and advance withdrawal from the ventilator and extubation in patients with MV. Diaphragm US is suggested for mechanically ventilated patients in the ICU. Trial registration Chinese Clinical Trial Registry, ID: ChiCTR1900024046, registered on 2019/06/23.

SUBMITTER: Dong Z

PROVIDER: S-EPMC8006630 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

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Project description:BackgroundIn intensive care unit (ICU) patients, diaphragmatic dysfunction (DD) can occur on admission or during the subsequent stay. The respective incidence of these two phenomena has not been previously studied in humans. The study was designed to describe temporal trends in diaphragm function in mechanically ventilated (MV) patients.MethodsAncillary study of a prospective, 6-month, observational cohort study conducted in two ICUs. MV patients were studied within 24 h following intubation (day-1) and every 48-72 h thereafter. Diaphragm function was assessed by twitch tracheal pressure (Ptr,stim) in response to bilateral anterior magnetic phrenic nerve stimulation. Diaphragm dysfunction was defined as Ptr,stim < 11 cmH2O. Patients who received MV for at least 5 days were retained, and the first and the last measures were analysed.ResultsForty-three patients were included. Overall, 79 % of patients developed DD at some point during their ICU stay: 23 (53 %) patients presented DD on initiation of mechanical ventilation, 14 (33 %) of whom had persistent DD, while diaphragm function improved in 9 (21 %). Among the remaining 20 (47 %) patients who did not present DD on initiation of MV, 11 (26 %) developed DD during the ICU stay, while 9 (21 %) did not. Mortality was higher in patients with DD either on initiation of mechanical ventilation or during the subsequent ICU stay than in those who never developed DD (35 vs. 0 %, p = 0.04). Duration of MV was higher in patients with DD on initiation of MV that subsequently persisted than in patients who never exhibited diaphragm dysfunction (18 vs. 5 days, p = 0.04). Factors associated with a change in Ptr,stim were: age [linear coefficient regression (Coeff.) -0.097, standard error (SD) 0.047, p = 0.046], PaO2/FiO2 ratio (Coeff. 0.014, SD 0.006, p = 0.0211) and the proportion of the time under MV with sedation (per 10 %, Coeff. -5.359, SD 2.451, p = 0.035).ConclusionsDD is observed in a large majority of MV patients ≥5 days at some point of their ICU stay. Various patterns of DD are observed, including DD on initiation of mechanical ventilation and ICU-acquired DD. Trial registration clinicaltrials.gov Identifier # NCT00786526.

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