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PhD Defence Eline Oppersma

monitoring and regulation of supported breathing in intensive care

Eline Oppersma is a PhD student in the research group Biomedical Signals and Systems. Her supervisors are prof.dr.ir. P.H. Veltink from the faculty of Electrical Engineering, Mathematics and Computer Science, prof.dr. L.M.A. Heunks from the VU Medical Center Amsterdam and prof.dr. J.G. van der Hoeven from the Radboud University Medical Center. 

This thesis describes several chapters related to monitoring and regulation of breathing. The main goal is to provide better insight in the interaction between spontaneous breathing and mechanical ventilatory support. In chapter 2 we investigated the effect of metabolic alkalosis on the ventilatory response. In this intervention study the ventilatory response was assessed in 10 healthy subjects, using a hypercapnic ventilatory response (HCVR) test, before and after administration of high dose sodium bicarbonate. After bicarbonate administration Pdi, EAdi and VE were significantly lower for similar levels of inspired CO2. We demonstrated that the respiratory centers respond differently to inhaled CO2 when arterial bicarbonate levels are increased, probably as a result of the enhanced buffer capacity; more arterial bicarbonate supplies more capacity to buffer CO2 before the respiratory centers sense an increased arterial CO2. These findings could implicate that patients with metabolic alkalosis suffering from suppressed ventilation, and resulting weaning difficulties, could benefit from excreting bicarbonate to stimulate the respiratory centers. To analyze whether speckle tracking ultrasound can be used to noninvasively quantify diaphragm contractility, in chapter 3 this technique is used in healthy subjects undergoing a randomized stepwise threshold loading protocol. Speckle tracking ultrasound was used to assess strain and strain rate as measures of diaphragm tissue deformation and deformation velocity. Strain and strain rate increased with progressive loading of the diaphragm and were both highly correlated to transdiaphragmatic pressure and diaphragm electric activity. We concluded that speckle tracking ultrasound is superior to conventional ultrasound techniques to estimate diaphragm contractility under inspiratory threshold loading and, although this requires further research, might serve as a reliable tool to guide weaning at the bedside in the future.

Chapters 4, 5 and 6 of this thesis focus on the interaction between the two parallel systems involved in providing adequate ventilation: the patient and more specific its upper airway, and the ventilator. We studied this interaction in patients with an acute exacerbation of COPD during noninvasive ventilation. This topic is initiated by reviewing, in chapter 4, the effect of positive pressure ventilation on upper airway patency and its possible clinical implications during NIV. First we emphasized the importance of not only the interaction between the inspiratory muscle activity and the ventilator’s response, but during NIV mainly the synchrony between the ventilator and the upper airway muscles. Both pressure and flow receptors play an important role in muscle activity of the upper airway during respiration, whereas pulmonary C-fiber receptors, rapidly adapting receptors and slowly adapting pulmonary stretch receptors affect the patency of the upper airway. Although it is known in lambs and piglets that the patency of the upper airway is influenced by changes in pressure and flow during mechanical ventilation, we do not know whether this can be extrapolated to humans. In chapter 5 this is followed by studying the patency of the glottis during inspiration in patients with chronic obstructive pulmonary disease, during two modes and two levels of NIV. The electrical activity of the diaphragm, flow, pressure and video recordings of the glottis were synchronously acquired. From these video frames the angle of the vocal cords was calculated, as a measure of the patency of the upper airways. Patterns of glottis angle varied between and within patients. The median angle of the glottis during inspiration and at peak inspiratory effort were compared but no differences were found between PSV and NAVA at low and high levels of support. Although this pilot study showed no dependence of patency of the glottis on mode or level of NIV in COPD patients, it should be noted that COPD patients are prone to have harmed reflex pathways by CO2 exposure during smoking, and thereby incomparable to lambs or healthy subjects. The last chapter of this thesis, chapter 6, focused on patient-ventilator interaction. Synchrony between the patient and the ventilator, defined as a match between the patient and ventilator inspiratory and expiratory times, is at risk especially during NIV, due to the presence of leaks at the patient-mask interface. In NAVA mode, EAdi controls the ventilator and it has been shown that noninvasive NAVA improves patient-ventilator interaction relative to equal inspiratory pressures during noninvasive PSV. Increasing invasive NAVA has been shown to result in significantly lower trigger delays compared to increasing PSV. Patient-ventilator interaction was evaluated by comparing airway pressure and EAdi waveforms with automated computer algorithms. We showed a progressive mismatch between neural effort and pneumatic timing with increasing levels of PSV during NIV. During noninvasive NAVA the patient-ventilator interaction improved and this was independent of increasing NAVA levels.