The disadvantages of chronic high-intensity noninvasive ventilation in severe stable COPD: results ventilator-induced lung and diaphragm injury to worse outcomes before and after lung transplantation?

lung transplantation Non-invasive ventilation

Prof. dr. M.L. Duiverman
Tji Gan

Nature of the research:
Retrospective analysis of data of patients with severe COPD who received and lung transplantation, comparing patients who were priorly treated with chronic noninvasive ventilation to patients that were not treated with chronic noninvasive ventilation.

Fields of study:
pulmonology intensive care

Background / introduction
Chronic nocturnal noninvasive ventilation (NIV) has become evidence based care in patients with severe chronic obstructive pulmonary disease (COPD) and chronic respiratory failure.1,2 In some patients, NIV might be used a “a bridge” to lung transplant. However, to achieve efficient ventilatory support, a ventilatory mode is often needed with high inspiratory pressure (IPAP) and a probably also a high backup respiratory rate (BURR). This mode is called high-intensity NIV.3
At the intensive care unit, last years, there has become increasing attention for prevention of ventilator-induced lung injury (VILI) caused by over distension at high lung volumes and consequent release of inflammatory mediators.4 Clinical trials showed that ventilation with lower tidal volumes decreased mortality in patients with the acute respiratory distress syndrome (ARDS).5 Although with high-intensity NIV in the chronic state, high inspiratory pressures are applied, it is not known how large the actual volumes applied are and whether this strategy leads to VILI.
Secondly, it is known that mechanical ventilation may lead to respiratory muscle atrophy.6 It is generally thought that this occurs soon6 and both with controlled ventilation and with high pressure support levels.7 Most patients on chronic NIV use their ventilator only nocturnally, however, with progressive disease the use may increase. Furthermore, with the high-intensity strategy, high inspiratory pressures and minimisation of the patients’ respiratory efforts are applied. Therefore, it is very well possible that high-intensity NIV induces respiratory muscle atrophy. This might lead to increasing dependence on the ventilator, reduced quality of life and in patients who are awaiting a lung transplant, difficulties with weaning postoperatively.
The aim of the overall proposal is to get insight in VILI and respiratory muscle atrophy in severe COPD patients on chronic NIV. As a first step, we will compare clinical outcomes of patients that received a lung transplantation while on chronic NIV before with patients with similar severity of COPD who were not treated with chronic NIV before receiving a lung transplant.
Research question / problem definition
Are short- and long-term clinical outcomes after lung transplantation for severe COPD influenced by prior use of chronic non-invasive ventilation?
The student will perform a retrospective analysis of data of patients with COPD who received a lung transplant the last 5 years, comparing patients who were treated with chronic non-invasive ventilation prior to transplantation with patients that were not using chronic non-invasive ventilation. The student will search for outcome parameters in the electronic patient records and will perform the statistical analyses to answer the research question.
The current project is a part of a larger research project, investigating VILI and diaphragm atrophy in these patients. We will also set-up an analysis of VILI in explant material already available and finally will perform a prospective study in which we will gather fresh lung material and diaphragm biopsies in the lung transplanted patients to investigate VILI and diaphragm changes thoroughly. Thus, if the student is interested, the project can be expanded to a project combining clinical research with pathology and even an MD PhD project with the prospective study.
The student will participate in the team of the home mechanical ventilation (HMV) centre Groningen and the lung transplant team. To get feeling with the treatment, the student may participate in the outpatient clinics and inpatient care of patients on HMV. Furthermore, the student may be involved in running research projects. Furthermore, the student will get the unique opportunity to learn about HMV and lung transplantation, very specialized area of care, more in general and research in this field.
1. Duiverman ML, Wempe JB, Bladder G, et al. Two-year home-based nocturnal noninvasive ventilation added to rehabilitation in chronic obstructive pulmonary disease patients: A randomized controlled trial. Respir Res. 2011;12:112-9921-12-112.
2. Kohnlein T, Windisch W, Kohler D, et al. Non-invasive positive pressure ventilation for the treatment of severe stable chronic obstructive pulmonary disease: A prospective, multicentre, randomised, controlled clinical trial. Lancet Respir Med. 2014;2(9):698-705.
3. Windisch W, Storre JH, Kohnlein T. Nocturnal non-invasive positive pressure ventilation for COPD. Expert Rev Respir Med. 2015;9(3):295-308.
4. Curley GF, Laffey JG, Zhang H, Slutsky AS. Biotrauma and ventilator-induced lung injury: Clinical implications. Chest. 2016;150(5):1109-1117.
5. Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301-1308.
6. Levine S, Nguyen T, Taylor N, et al. Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans. N Engl J Med. 2008;358(13):1327-1335.
7. Hudson MB, Smuder AJ, Nelson WB, Bruells CS, Levine S, Powers SK. Both high level pressure support ventilation and controlled mechanical ventilation induce diaphragm dysfunction and atrophy. Crit Care Med. 2012;40(4):1254-1260.
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Laatst gewijzigd: 23 februari 2012