Abstract
Patients undergoing mechanical ventilation (MV) often experience respiratory muscle dysfunction, which complicates the weaning process. There is no simple means to predict or diagnose respiratory muscle dysfunction because diagnosis depends on measurements in muscle diaphragmatic fibre. As oxidative stress is a key mechanism contributing to MV-induced respiratory muscle dysfunction, the aim of this study was to determine if differences in blood measures of oxidative stress in patients who had success and failure in a spontaneous breathing trial (SBT) could be used to predict the outcome of MV. This was a prospective analysis of MV-dependent patients (≥72 hrs; n = 34) undergoing a standard weaning protocol. Clinical, laboratory and oxidative stress analyses were performed. Measurements were made on blood samples taken at three time-points: immediately before the trial, 30 min. into the trial in weaning success (WS) patients, or immediately before return to MV in weaning failure (WF) patients, and 6 hrs after the trial. We found that blood measures of oxidative stress distinguished patients who would experience WF from patients who would experience WS. Before SBT, WF patients presented higher oxidative damage in lipids and higher antioxidant levels and decreased nitric oxide concentrations. The observed differences in measures between WF and WS patients persisted throughout and after the weaning trial. In conclusion, WF may be predicted based on higher malondialdehyde, higher vitamin C and lower nitric oxide concentration in plasma.
Highlights
Reactive oxygen species exert significant influence on contractile function of skeletal muscles of the respiratory system and the limbs [1]
Laboratory findings obtained on samples procured prior to spontaneous breathing trial (SBT) showed that weaning failure (WF) patients exhibited damage in lipids [MDA in WF: 0.39 lmol/l (0.14–0.80) versus MDA in weaning success (WS): 0.16 lmol/l (0.06–0.39); Fig. 1]; higher antioxidant levels [vitamin C in WF: 1.78 lmol/l (0.52– 10.85) versus vitamin C in WS: 0.81 lmol/l (0.26–1.20); Fig. 2]; and decreased nitric oxide concentrations [nitrite in WF: 1.66 mmol NaNO2/g protein (0.87–6.46) versus nitrite in WS: 2.29 mmol NaNO2/ g protein (1.11–4.27); Fig. 3]
Evaluations of enzymatic (SOD, CAT and glutathione peroxidase (GPx)), and other nonenzymatic defences, as well as of damage in plasma proteins and iron status were similar in WS and WF patients (Table 2)
Summary
Reactive oxygen species exert significant influence on contractile function of skeletal muscles of the respiratory system and the limbs [1]. In MV-subjects, Jaber et al [13] showed tissue atrophy and increased expression of ubiquitinated proteins, nuclear factor-jB and calpain isoforms measured in diaphragmatic muscle; Levine et al [14] found marked muscle atrophy and increased diaphragmatic proteolysis (reduced glutathione concentration and increased active caspase-3). Both groups made measurements in muscle diaphragmatic fibre during MV-support. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine
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