Online Laboratory Investigations

Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung

Borges, João Batista MD, PhD^1,2; Costa, Eduardo L. V. MD, PhD^2,3; Bergquist, Maria MSc⁴; Lucchetta, Luca MD⁵; Widström, Charles MSc⁶; Maripuu, Enn MSc⁶; Suarez-Sipmann, Fernando MD, PhD^1,7; Larsson, Anders MD, PhD¹; Amato, Marcelo B. P. MD, PhD²; Hedenstierna, Göran MD, PhD⁴

Author Information

¹Hedenstierna Laboratory, Department of Surgical Sciences, Section of Anaesthesiology & Critical Care, Uppsala University, Uppsala, Sweden.

²Pulmonary Division, Cardio-Pulmonary Department, Heart Institute (Incor), University of São Paulo, São Paulo, Brazil.

³Research and Education Institute, Hospital Sirio-Libanês, São Paulo, Brazil.

⁴Hedenstierna Laboratory, Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden.

⁵Intensive Care Department, Hospital San Matteo, Pavia, Italy.

⁶Department of Medical Physics, University Hospital, Uppsala, Sweden.

⁷Centros de Investigación Biomédica en Red de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.

This work was performed at Hedenstierna Laboratory, Department of Surgical Sciences, Section of Anaesthesiology & Critical Care, Uppsala University, Uppsala, Sweden.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported, in part, by grants from Fundação de Amparo a Pesquisa do Estado de São Paulo (São Paulo State Research Support Foundation), Conselho Nacional de Desenvolvimento Científico e Tecnológico (National Council for Scientific and Technological Development), Financiadora de Estudos e Projetos (Studies and Projects Financial Support Provider), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Ministry of Education, Brazil, and also supported by grants from institutional funds from Uppsala University, Swedish Research Council (5315) and Swedish Heart-Lung Fund, Sweden.

Dr. Borges and his institution received grant support from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Ministry of Education, Brazil. Dr. Lucchetta is employed by the Universita di Pavia, Ospedale San Matteo. Dr. Suarez-Sipmann consulted for Maquet Critical Care. Dr. Larsson received support for travel from Maquet CC. His institution received grant support from the Swedish Heart and Lung Foundation. Dr. Amato received grant support from Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP) and Financiadora de Estudos e Projetos (FINEP). Dr. Amato’s institution received public grants (public grant agency: FAPESP, FINEP, Conselho Nacional de Desenvolvimento Científico e Tecnológico) and received grant support from New Port Medical. Dr. Hedenstierna received grant support from the Swedish Research Council, received support for travel from the Swedish Heart-Lung Fund, and received support for article research from the Swedish Research Council and the Swedish Heart-Lung Fund. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: [email protected]

Critical Care Medicine 43(5):p e123-e132, May 2015. | DOI: 10.1097/CCM.0000000000000926

Abstract

Objective:

PET with [¹⁸F]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We aimed at studying the location and evolution of inflammation by PET imaging, relating it to morphology (CT), during the first 27 hours of application of protective-ventilation strategy as suggested by the Acute Respiratory Distress Syndrome Network, in a porcine experimental model of acute respiratory distress syndrome.

Design:

Prospective laboratory investigation.

Setting:

University animal research laboratory.

Subjects:

Ten piglets submitted to an experimental model of acute respiratory distress syndrome.

Interventions:

Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. During 27 hours of controlled mechanical ventilation according to Acute Respiratory Distress Syndrome Network strategy, the animals were studied with dynamic PET imaging of [¹⁸F]fluoro-2-deoxy-D-glucose at two occasions with 24-hour interval between them.

Measurements and Main Results:

[¹⁸F]fluoro-2-deoxy-D-glucose uptake rate was computed for the total lung, four horizontal regions from top to bottom (nondependent to dependent regions) and for voxels grouped by similar density using standard Hounsfield units classification. The global lung uptake was elevated at 3 and 27 hours, suggesting persisting inflammation. In both PET acquisitions, nondependent regions presented the highest uptake (p = 0.002 and p = 0.006). Furthermore, from 3 to 27 hours, there was a change in the distribution of regional uptake (p = 0.003), with more pronounced concentration of inflammation in nondependent regions. Additionally, the poorly aerated tissue presented the largest uptake concentration after 27 hours.

Conclusions:

Protective Acute Respiratory Distress Syndrome Network strategy did not attenuate global pulmonary inflammation during the first 27 hours after severe lung insult. The strategy led to a concentration of inflammatory activity in the upper lung regions and in the poorly aerated lung regions. The present findings suggest that the poorly aerated lung tissue is an important target of the perpetuation of the inflammatory process occurring during ventilation according to the Acute Respiratory Distress Syndrome Network strategy.

Article Keywords

Keywords
[¹⁸F]fluoro-2-deoxy-D-glucose, acute pulmonary inflammation, acute respiratory distress syndrome, mechanical ventilation, positron emission tomography, ventilator-induced lung injury

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Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung