| 1. |
- Jalde, Francesca Campoccia, et al.
(author)
-
Standardized Unloading of Respiratory Muscles during Neurally Adjusted Ventilatory Assist : A Randomized Crossover Pilot Study
- 2018
-
In: Anesthesiology. - 0003-3022 .- 1528-1175. ; 129:4, s. 769-777
-
Journal article (peer-reviewed)abstract
- Background: Currently, there is no standardized method to set the support level in neurally adjusted ventilatory assist (NAVA). The primary aim was to explore the feasibility of titrating NAVA to specific diaphragm unloading targets, based on the neuroventilatory efficiency (NVE) index. The secondary outcome was to investigate the effect of reduced diaphragm unloading on distribution of lung ventilation. Methods: This is a randomized crossover study between pressure support and NAVA at different diaphragm unloading at a single neurointensive care unit. Ten adult patients who had started weaning from mechanical ventilation completed the study. Two unloading targets were used: 40 and 60%. The NVE index was used to guide the titration of the assist in NAVA. Electrical impedance tomography data, blood-gas samples, and ventilatory parameters were collected. Results: The median unloading was 43% (interquartile range 32, 60) for 40% unloading target and 60% (interquartile range 47, 69) for 60% unloading target. NAVA with 40% unloading led to more dorsal ventilation (center of ventilation at 55% [51, 56]) compared with pressure support (52% [49, 56]; P = 0.019). No differences were found in oxygenation, CO2, and respiratory parameters. The electrical activity of the diaphragm was higher during NAVA with 40% unloading than in pressure support. Conclusions: In this pilot study, NAVA could be titrated to different diaphragm unloading levels based on the NVE index. Less unloading was associated with greater diaphragm activity and improved ventilation of the dependent lung regions.
|
|
| 2. |
- Kalzén, Håkan, et al.
(author)
-
Unnecessary harm is avoided by reliable paediatric index of mortality2 scores without arterial gas sampling
- 2019
-
In: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 108:4, s. 670-675
-
Journal article (peer-reviewed)abstract
- Aim: To investigate whether unnecessary harm could be avoided in children admitted to paediatric intensive care (PICU), we analysed the impact of arterial blood gas on the paediatric index of mortality score2 (PIM2) and the derived predicted death rate (PDR). Methods: From January 1, 2008 to December 31, 2010, 1793 consecutive admissions, newborn infants to 16 years of age (median 0.71 years) from a single, tertiary PICU in Gothenburg Sweden, were collected. Admission information on arterial oxygen tension (PaO2) and fraction of inspired oxygen (FiO2) was extracted from 990 admissions. Results: There was close agreement between PIM2 score and PDR regardless of whether the PaO2/FiO2 ratio was omitted or not. In the subgroup of admissions with a respiratory admission diagnosis, the inclusion of the PaO2/FiO2 ratio increased the accuracy of the PIM2 score as well as the PDR. The standard mortality ratio was slightly but not significantly overestimated by excluding the PaO2/FiO2 ratio. Conclusion: To avoid unnecessary harm to children admitted to PICU, an arterial blood gas analysis should only be performed if clinically indicated or if the child has a respiratory admission diagnosis. Estimation of the PIM2 score and PDR will not be less accurate by this approach.
|
|
| 3. |
- Ochala, Julien, et al.
(author)
-
Diaphragm muscle weakness in an experimental porcine intensive care unit model
- 2011
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6
-
Journal article (peer-reviewed)abstract
- In critically ill patients, mechanisms underlying diaphragm muscle remodeling and resultant dysfunction contributing to weaning failure remain unclear. Ventilator-induced modifications as well as sepsis and administration of pharmacological agents such as corticosteroids and neuromuscular blocking agents may be involved. Thus, the objective of the present study was to examine how sepsis, systemic corticosteroid treatment (CS) and neuromuscular blocking agent administration (NMBA) aggravate ventilator-related diaphragm cell and molecular dysfunction in the intensive care unit. Piglets were exposed to different combinations of mechanical ventilation and sedation, endotoxin-induced sepsis, CS and NMBA for five days and compared with sham-operated control animals. On day 5, diaphragm muscle fibre structure (myosin heavy chain isoform proportion, cross-sectional area and contractile protein content) did not differ from controls in any of the mechanically ventilated animals. However, a decrease in single fibre maximal force normalized to cross-sectional area (specific force) was observed in all experimental piglets. Therefore, exposure to mechanical ventilation and sedation for five days has a key negative impact on diaphragm contractile function despite a preservation of muscle structure. Post-translational modifications of contractile proteins are forwarded as one probable underlying mechanism. Unexpectedly, sepsis, CS or NMBA have no significant additive effects, suggesting that mechanical ventilation and sedation are the triggering factors leading to diaphragm weakness in the intensive care unit.
|
|
| 4. |
- Ochala, Julien, et al.
(author)
-
EMD 57033 partially reverses ventilator-induced diaphragm muscle fibre calcium desensitisation
- 2010
-
In: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 459:3, s. 475-483
-
Journal article (peer-reviewed)abstract
- In critically ill patients, ventilator-induced diaphragm muscle fibre dysfunction (VIDD) contributes to weaning problems, increasing hospitalisation time and related costs. VIDD pathophysiology remains partially unknown, especially the characterisation of the contractile dysfunction. In the present study, it was hypothesised that Ca(2+) activation is affected during VIDD. Ca(2+) sensitivity of contraction was therefore evaluated at the single skinned diaphragm muscle fibre level in piglets randomised into sham operation or 5-day mechanical ventilation. Ca(2+) sensitivities of force and stiffness in fibres were significantly impaired in all mechanically ventilated piglets compared with sham-operated controls, suggesting a less efficient Ca(2+) activation of cells, i.e. a lower relative number of strongly attached cross-bridges for each sub-maximal concentration of Ca(2+). In an attempt to test whether this negative effect of VIDD is reversible, single muscle fibres were exposed to the EMD 57033 Ca(2+) sensitiser. EMD 57033 (30 microM) improved the Ca(2+) sensitivity of force and stiffness in fibres from animals that were mechanically ventilated for 5 days as well as in sham-operated piglets. Thus, EMD 57033 partly restored the Ca(2+) activation of cells, reducing VIDD. This finding offers a strong basis for evaluating the effect of Ca(2+) sensitisers on diaphragm function in vivo.
|
|
| 5. |
- Ochala, Julien, et al.
(author)
-
Factors underlying the early limb muscle weakness in acute quadriplegic myopathy using an experimental ICU porcine model
- 2011
-
In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 6:6, s. e20876-
-
Journal article (peer-reviewed)abstract
- The basic mechanisms underlying acquired generalized muscle weakness and paralysis in critically ill patients remain poorly understood and may be related to prolonged mechanical ventilation/immobilization (MV) or to other triggering factors such as sepsis, systemic corticosteroid (CS) treatment and administration of neuromuscular blocking agents (NMBA). The present study aims at exploring the relative importance of these factors by using a unique porcine model. Piglets were all exposed to MV together with different combinations of endotoxin-induced sepsis, CS and NMBA for five days. Peroneal motor nerve conduction velocity and amplitude of the compound muscle action potential (CMAP) as well as biceps femoris muscle biopsy specimens were obtained immediately after anesthesia on the first day and at the end of the 5-day experimental period. Results showed that peroneal nerve motor conduction velocity is unaffected whereas the size of the CMAP decreases independently of the type of intervention, in all groups after 5 days. Otherwise, despite a preserved size, muscle fibre specific force (maximum force normalized to cross-sectional area) decreased dramatically for animals exposed to MV in combination with CS or/and sepsis. These results suggest that the rapid declines in CMAP amplitude and in force generation capacity are triggered by independent mechanisms with significant clinical and therapeutic implications.
|
|
| 6. |
- Radell, Peter J
(author)
-
Studies of diaphragm fatigue and dysfunction
- 2001
-
Doctoral thesis (other academic/artistic)abstract
- Diaphragm fatigue and dysfunction are important components of acute and chronic respiratory pump failure. We lack knowledge about the nature of diaphragm fatigue and the pathophysiological and morphological changes that occur in the diaphragm after prolonged mechanical ventilation. This thesis studied two aspects of diaphragm function. Diaphragm contractility and oxidative metabolism were studied during inspiratory resistive loaded breathing (IRB) and hypoxia, and diaphragm contractility, activation and morphology were examined during prolonged mechanical ventilation. Additionally, ultrasonography was evaluated as a quantitative measure of diaphragm function. Methods: Anesthetized piglets ages 4-6 weeks (studies I, II, III) or 2-4 months (studies IV, V) were studied. Diaphragm contractility was evaluated in all studies by measurement of transdiaphragmatic pressure, Pdi achieved by supramaximal phrenic nerve stimulation with transvenous stimulation electrodes. Intracellular high energy phosphates (ATP, phosphocreatine) were measured b y 31 phosphorus nuclear magnetic spectroscopy (NMS) following diaphragm fatigue induced by repetitive phrenic nerve stimulation and IRB (study I), as well as IRB and hypoxia (study II). Ultrasonography measurements of the posterior diaphragm were obtained in die transverse and lateral sagital planes, using 2D and m-modes, and were tested for agreement with measures of contractility before and after evoked diaphragm fatigue (study III). Combined diaphragm EMG, phrenic nerve- diaphragm electroneurogram and Pdi were obtained daily in studies of prolonged, controlled mechanical ventilation and evaluated along with repeated measures of dynamic lung compliance and airway resistance (study IV). Morphology, fiber type proportions and size were studied from diaphragm biopsies obtained from study animals and compared to controls (study V). Results: Spontaneous inspiratory resistive breathing led to respiratory failure (acidosis and hypercarbia) but preserved peripheral diaphragm contractility and oxidative metabolism. The addition of hypoxemia to ERB did result however, in decreased Pdi and signs of inadequate oxidative metabolism (rise in ratio of inorganic phosphate to phosphocreatine). Diaphragm fatigue induced by repetitive phrenic nerve stimulation was associated with a change in ultrasound m-mode measurement of mean inspiratory velocity of the right posterior hemidiaphragm. Prolonged mechanical ventilation and diapluagm inactivity over 5 days resulted in decreased Pdi over frequencies from 20 to 100 Hz and activation as measured by compound muscle action potential amplitude. Nerve conduction and neuromuscular transmission remained in tact. Morphologic signs of muscle adaptation or injury included areas of regeneration, micro-vacuolization and poor histologic staining for m-ATPase, which may be associated with loss of myosin. Conclusions: Acute respiratory failure in anesthetized piglets during spontaneous inspiratory resistive breathing is not caused by diaphragm fatigue due to decreased contractility or inadequate diaphragm oxidative metabolism. Ile addition of severe hypoxemia to inspiratory resistive breathing results, however, in inadequate oxidative metabolism and decreased contractility which may contribute to the respiratory failure seen. Utrasonography can be used to quantify diaphragm function and identify diaphragm fatigue in this setting. Prolonged controlled mechanical ventilation and diaphragm inactivity results in decreased diaphragm activation and contractility. Changes in neurophysiologic measures and diaphragm muscle fiber morphology indicate that the contractile dysfunction seen occurs at the level of diaphragm muscle rather than in nerve conduction or neuromuscular transmission.
|
|
