Acute lung injury associated with thoracic surgery

Shelley, Benjamin Guy (2015) Acute lung injury associated with thoracic surgery. MD thesis, University of Glasgow.

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Lung cancer is the most common cause of cancer death in the UK. In suitable cases, the best chance of cure is surgical resection. Due to high levels of co-morbidity seen in this population, lung resection is associated with high cardio-respiratory complication rates. One such complication is the development of Acute Lung Injury / Acute Respiratory Distress Syndrome (ALI/ARDS). ALI/ARDS is reported to occur in four to 11% of patients undergoing lung resection and is the major cause of hospital mortality following lung resection.

ALI/ARDS occurring following lung resection is widely interpreted to be a variant of ALI/ARDS and follows an identical clinical and pathophysiological course to that seen in the wider critical care environment. The pathophysiology of lung injury following lung resection is complex and can be broadly conceptualised as occurring secondary to insults specific to both the ipsilateral (surgical) lung, the contralateral (anaesthetic) lung in addition to those insults common to both lungs. Increased recognition of the role of ventilator induced lung injury, and peri-operative fluid prescribing in the pathogenesis of lung injury in this population has brought the prevention of lung injury to the attention of the thoracic anaesthetist. Though high quality evidence is lacking, expert opinion widely favours the adoption of lung protective ventilatory strategies and restriction of peri-operative fluids in patients undergoing lung resection.

This thesis presents the rationale, methodology and results of four discrete studies concerning the development of lung injury in the thoracic surgical population undergoing resection of primary lung cancer.

Investigation I is a survey of contemporary UK thoracic anaesthetic practice when anaesthetising for thoracic surgery and lung resection, with specific reference to strategies designed to prevent lung injury. Though implementation of the techniques described is far from universal, the survey results suggest that aspects of lung protective ventilation are widespread within UK thoracic anaesthetic practice.

Investigation II seeks to examine the impact of increased adoption of such strategies over time. A random effects meta-analysis and meta-regression analysis was performed to examine the trends in the incidence of and mortality from ALI and/or ARDS over time. The main findings of this study are that whilst there is no evidence to suggest the incidence of ALI and/or ARDS post-lung resection is falling, mortality due to ARDS (but not ALI) does appear to be falling over time.

Investigations III and IV examine the utility of two clinical monitoring methodologies which have potential to provide bedside clinical monitoring of lung injury development in the thoracic surgical population in order to guide clinical decision making, monitor patient progress and serve as a surrogate end point in future clinical studies.

Investigation III examines the utility of a single lung injury biomarker (long chain Pentraxin 3 – PTX3) and a panel of multiple lung injury biomarkers in the early post-operative period following lung resection. The properties of the ‘ideal’ lung injury biomarker are defined, against which PTX3 and the multiple biomarker panel are compared. PTX3 compared favourably to properties of the ‘ideal’ lung injury biomarker and appeared to identify a population of patients with elevated post-operative Lung Injury Score with high sensitivity. Conversely there is no evidence from the results presented that a ‘risk of lung injury score’ derived from a panel of 7 candidate lung injury biomarkers (as previously defined in a cohort of critically ill patients with ALI/ARDS) has any utility in the lung resection population.

Investigation IV tests the reproducibility and construct validity of transpulmonary thermodilution derived measurements of extravascular lung water and pulmonary vascular permeability index in patients undergoing lung resection. The study’s findings are largely supportive of the reproducibility and construct validity of extravascular lung water measurement and pulmonary vascular permeability measurements after lung resection.

In combination, it is hoped that the studies presented provide greater insight into the syndrome of post lung resection lung injury. More accurate definition of standard anaesthetic practice and the incidence of and mortality from ALI/ARDS following lung resection should serve to inform future clinical studies seeking to prevent, treat, or better understand this important clinical syndrome. The biomarker PTX3 and transpulmonary thermodilution derived measurement of extravascular lung water and pulmonary vascular permeability index are presented as surrogate endpoints suitable for use in such studies.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Keywords: Acute lung injury, acute respiratory distress syndrome, thoracic surgery, lung resection
Subjects: R Medicine > RD Surgery
R Medicine > RZ Other systems of medicine
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities
Supervisor's Name: Kinsella, Prof. John
Date of Award: 2015
Depositing User: Dr Benjamin Shelley
Unique ID: glathesis:2015-6469
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 18 Jun 2015 09:04
Last Modified: 12 Aug 2015 08:29

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