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Hemodynamic Effects of Lung Function Optimization in Experimental Acute Respiratory Distress Syndrome
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Acute Respiratory Distress Syndrome (ARDS) is a severe pulmonary inflammation affecting thousands of patients every year in Sweden and has a mortality of 30-50%. Mechanical ventilation (MV) is usually necessary, but could per se augment the inflammation and contribute to mortality. MV strategies protective for the lung parenchyma have been developed but without considering the pulmonary circulation or the right heart ventricle (RV) that also are affected in ARDS. MV should ideally be optimized to protect both the lung parenchyma and the RV/pulmonary vasculature. My hypothesis was that MV that prevents alveolar collapse and overdistension, i.e., the “open lung approach (OLA)” would be optimal. The aims of this project were 1) to carefully describe the pulmonary vascular mechanics (PVM) in ARDS compared with healthy lungs, 2) to assess how different ventilatory methods influence PVM, and 3) to propose a ventilatory method that protects both lung parenchyma and circulation.

In a porcine model, high fidelity pressure and flow sensors were applied directly on the main pulmonary artery to evaluate steady and oscillatory components of PVM.  In this way a complete PVM description was obtained for normal and injured lungs at different MV. In particular, the effects of OLA were compared with standard MV and, in addition, with MV methods where overdistension or collapse were present.

Results: 1) Compared with collapse or overdistension, OLA provided better PVM. 2) The effects on PVM of OLA and the standard protective MV were similar. 3) Early ARDS augmented the effects of pulse wave reflection on PVM leading to a situation in which the RV had to increase its work to maintain adequate blood flow. Thus, a part of this work was wasted by the effect of wave reflections, making the RV/pulmonary vasculature inefficient. 4) Tidal breathing affected PVM cyclically and this effect was enhanced in ARDS compared with healthy lungs.

In conclusion, ARDS and different ventilatory methods, as well as tidal ventilation per se, affected PVM. OLA improved PVM compared with other MV settings where significant collapse and overdistension were allowed. However, OLA was not superior to standard protective MV.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2018. , p. 60
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1419
Keywords [en]
Acute respiratory distress syndrome, Lung protective ventilation, Mechanical ventilation, Open lung approach, Pulmonary heart disease, Pulmonary vascular mechanics, Pulmonary vascular dysfunction, Pulse wave analysis, Right ventricular dysfunction
National Category
Physiology Anesthesiology and Intensive Care
Research subject
Anaesthesiology and Intensive Care; Physiology
Identifiers
URN: urn:nbn:se:uu:diva-338688ISBN: 978-91-513-0210-2 (print)OAI: oai:DiVA.org:uu-338688DiVA, id: diva2:1173455
Public defence
2018-03-08, Rosen, Akademiska sjukhuset 75185 Uppsala, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2018-02-13 Created: 2018-01-12 Last updated: 2018-03-07
List of papers
1. The Open Lung Approach Improves Pulmonary Vascular Mechanics in an Experimental Model of Acute Respiratory Distress Syndrome
Open this publication in new window or tab >>The Open Lung Approach Improves Pulmonary Vascular Mechanics in an Experimental Model of Acute Respiratory Distress Syndrome
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2017 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 3, p. e298-e305Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To test whether positive end-expiratory pressure consistent with an open lung approach improves pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressures in experimental acute respiratory distress syndrome.

DESIGN: Experimental study.

SETTING: Animal research laboratory.

SUBJECTS: Ten pigs, 35 ± 5.2 kg.

INTERVENTIONS: Acute respiratory distress syndrome was induced combining saline lung lavages with injurious mechanical ventilation. The positive end-expiratory pressure level resulting in highest compliance during a decremental positive end-expiratory pressure trial after lung recruitment was determined. Thereafter, three positive end-expiratory pressure levels were applied in a random order: hyperinflation, 6 cm H2O above; open lung approach, 2 cm H2O above; and collapse, 6 cm H2O below the highest compliance level. High fidelity pressure and flow sensors were placed at the main pulmonary artery for measuring pulmonary artery resistance (Z0), effective arterial elastance, compliance, and reflected pressure waves.

MEASUREMENTS AND MAIN RESULTS: After inducing acute respiratory distress syndrome, Z0 and effective arterial elastance increased (from 218 ± 94 to 444 ± 115 dyn.s.cm and from 0.27 ± 0.14 to 0.62 ± 0.22 mm Hg/mL, respectively; p < 0.001), vascular compliance decreased (from 2.76 ± 0.86 to 1.48 ± 0.32 mL/mm Hg; p = 0.003), and reflected waves arrived earlier (0.23 ± 0.07 vs 0.14 ± 0.05, arbitrary unit; p = 0.002) compared with baseline. Comparing the three positive end-expiratory pressure levels, open lung approach resulted in the lowest: 1) Z0 (297 ± 83 vs 378 ± 79 dyn.s.cm, p = 0.033, and vs 450 ± 119 dyn.s.cm, p = 0.002); 2) effective arterial elastance (0.37 ± 0.08 vs 0.50 ± 0.15 mm Hg/mL, p = 0.04, and vs 0.61 ± 0.12 mm Hg/mL, p < 0.001), and 3) reflection coefficient (0.35 ± 0.17 vs 0.48 ± 0.10, p = 0.024, and vs 0.53 ± 0.19, p = 0.005), comparisons with hyperinflation and collapse, respectively.

CONCLUSIONS: In this experimental setting, positive end-expiratory pressure consistent with the open lung approach resulted in the best pulmonary vascular mechanics compared with higher or lower positive end-expiratory pressure settings.

Keywords
Fluid responsiveness, Spontaneous breathing, Head-up tilt, Pulse pressure variation, Stroke volume variation, Systolic pressure variation
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-307915 (URN)10.1097/CCM.0000000000002082 (DOI)27763913 (PubMedID)
Available from: 2016-11-22 Created: 2016-11-22 Last updated: 2018-01-12Bibliographically approved
2. Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome
Open this publication in new window or tab >>Effects on Pulmonary Vascular Mechanics of Two Different Lung-Protective Ventilation Strategies in an Experimental Model of Acute Respiratory Distress Syndrome
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2017 (English)In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 45, no 11, p. e1157-e1164Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To compare the effects of two lung-protective ventilation strategies on pulmonary vascular mechanics in early acute respiratory distress syndrome.

DESIGN: Experimental study.

SETTING: University animal research laboratory.

SUBJECTS: Twelve pigs (30.8 ± 2.5 kg).

INTERVENTIONS: Acute respiratory distress syndrome was induced by repeated lung lavages and injurious mechanical ventilation. Thereafter, animals were randomized to 4 hours ventilation according to the Acute Respiratory Distress Syndrome Network protocol or to an open lung approach strategy. Pressure and flow sensors placed at the pulmonary artery trunk allowed continuous assessment of pulmonary artery resistance, effective elastance, compliance, and reflected pressure waves. Respiratory mechanics and gas exchange data were collected.

MEASUREMENTS AND MAIN RESULTS: Acute respiratory distress syndrome led to pulmonary vascular mechanics deterioration. Four hours after randomization, pulmonary vascular mechanics was similar in Acute Respiratory Distress Syndrome Network and open lung approach: resistance (578 ± 252 vs 626 ± 153 dyn.s/cm; p = 0.714), effective elastance, (0.63 ± 0.22 vs 0.58 ± 0.17 mm Hg/mL; p = 0.710), compliance (1.19 ± 0.8 vs 1.50 ± 0.27 mL/mm Hg; p = 0.437), and reflection index (0.36 ± 0.04 vs 0.34 ± 0.09; p = 0.680). Open lung approach as compared to Acute Respiratory Distress Syndrome Network was associated with improved dynamic respiratory compliance (17.3 ± 2.6 vs 10.5 ± 1.3 mL/cm H2O; p < 0.001), driving pressure (9.6 ± 1.3 vs 19.3 ± 2.7 cm H2O; p < 0.001), and venous admixture (0.05 ± 0.01 vs 0.22 ± 0.03, p < 0.001) and lower mean pulmonary artery pressure (26 ± 3 vs 34 ± 7 mm Hg; p = 0.045) despite of using a higher positive end-expiratory pressure (17.4 ± 0.7 vs 9.5 ± 2.4 cm H2O; p < 0.001). Cardiac index, however, was lower in open lung approach (1.42 ± 0.16 vs 2.27 ± 0.48 L/min; p = 0.005).

CONCLUSIONS: In this experimental model, Acute Respiratory Distress Syndrome Network and open lung approach affected pulmonary vascular mechanics similarly. The use of higher positive end-expiratory pressures in the open lung approach strategy did not worsen pulmonary vascular mechanics, improved lung mechanics, and gas exchange but at the expense of a lower cardiac index.

National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:uu:diva-334177 (URN)10.1097/CCM.0000000000002701 (DOI)000417107000007 ()28872540 (PubMedID)
Funder
Swedish Research Council, K2015-99X-22731-01-4Swedish Heart Lung FoundationEU, FP7, Seventh Framework Programme, 291820
Available from: 2017-11-21 Created: 2017-11-21 Last updated: 2018-03-09Bibliographically approved
3. Acute Respiratory Distress Syndrome deteriorates pulmonary vascular efficiency and increases cardiac energy wasting in a porcine model.
Open this publication in new window or tab >>Acute Respiratory Distress Syndrome deteriorates pulmonary vascular efficiency and increases cardiac energy wasting in a porcine model.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Right ventricle failure worsen outcomes in acute respiratory distress syndrome (ARDS). However, the pathophysiology of right ventricle failure and vascular dysfunction in ARDS is not completely understood. In this study we aim to evaluate the effects of early ARDS on pulmonary vascular efficiency for transmission of flow and pressure in an experimental animal model.  

Methods: ARDS was induced in 10 pigs (32.5±4.3 kg) combining saline lung-lavages with injurious mechanical ventilation. Pressure and flow sensors were placed at the main pulmonary artery for pulmonary vascular function evaluation, including arterial load parameters, cardiac power and energy transmission ratio.

Results: Compared to baseline healthy conditions, ARDS increased pulmonary vascular resistance (199±62 versus 524±154 dyn.s.cm-5, p <0.001), effective arterial elastance (0.65±0.26 versus 1.13±0.36 mmHg/ml, p <0.001) and total hydraulic power (195±60 to 266±87 mW, p =0.015), decreased pulmonary arterial compliance (from 2.34±0.86 to 1.00±0.25 ml/mmHg, p <0.001) and energy transmission ratio (68±15 versus 55±14%, p = 0.014), whereas oscillatory power did not change (17±6 versus 16±6%, p = 0.359).

Conclusions: In this experimental ARDS model, an increase in pulmonary arterial load was associated with a higher cardiac power and a decrease in the energy transmission ratio. These results suggest that right ventricle energy consumption is increased and part of this energy is wasted in pulmonary circulation worsening pulmonary vascular efficiency in the early course of ARDS. These findings may help to explain primary mechanisms leading to right ventricle dysfunction in ARDS.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-337402 (URN)
Available from: 2017-12-25 Created: 2017-12-25 Last updated: 2018-01-12
4. Cyclic Changes of Pulmonary Vascular Mechanics During mechanical ventilation in acute respiratory distress syndrome. A porcine experimental model.
Open this publication in new window or tab >>Cyclic Changes of Pulmonary Vascular Mechanics During mechanical ventilation in acute respiratory distress syndrome. A porcine experimental model.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objective: To test the hypothesis that acute respiratory syndrome (ARDS) worsens pulmonary vascular mechanics during the respiratory cycle under mechanical ventilation in an animal model.  

Design: Experimental study.

Setting: Animal research laboratory.

Subjects: 6 pigs, 31.7 ± 5.4 kg.

Interventions: ARDS was induced by combining saline lung-lavages with injurious mechanical ventilation. Pressure and flow sensors were placed at the main pulmonary artery (PA) and signals were collected simultaneously with airway pressure and flow. Pulmonary vascular mechanics and cardiac function parameters were calculates beat by beat during 2-3 minutes. We designed a novel method to quantify how the calculated variables behave during the whole respiratory cycle, i.e., during expiration and during inspiration. Results are expressed as the mean value during the corresponding phase of the respiratory cycle.

Measurements and Main Results: During the whole respiratory cycle and at expiration ARDS decreased SV and arterial compliance while increased mean and pulse PA pressure, effective arterial elastance and Dp/Dtmax when compared to baseline. At baseline and after ARDS, inspiration in positive pressure ventilation caused a decrease in stroke volume (-3±1ml, p<0.001 and -3±1ml, p<0.001), pulmonary mean (-0.5±0.3, p=0.007 and -0.7±0.3mmHg, p=0.002) and pulse pressure (-0.8±0.4, p=0.003 and -1,5±0.7mmHg, p=0.003) and compliance (-0.07±0.04 and -0.04±0.00ml/mmHg, p<0.001) and an increase in resistance (34±13, p=0.001 and 50±32dyn.s.cm-5, p=0.012) and in effective arterial elastance (0.04±0.01, p=0.001 and 0.08±0.04mmHg/ml, p=0.003). ARDS produced a more pronounced inspiratory increase in effective arterial elastance (p=0.041) when compared to baseline. Positive pressure ventilation caused a decrease in Dp/Dtmax at baseline (-15±9mmHg/s, p=0.010) but this was not significant during ARDS (-27±28mmHg/s, p=0.068).  

Conclusions: We found in this experimental model that MV induced tidal increase in arterial load and that this effect was higher during ARDS. This finding if transferred to patients, might partly explain the high rate of right heart failure clinically in ARDS.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-337405 (URN)
Available from: 2017-12-25 Created: 2017-12-25 Last updated: 2018-01-12

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