Symptoms and General Pathology

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Respiratory Tract (Lung and Bronchial) Diseases

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Edema

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Lung Diseases

Respiratory Tract Diseases

Thoracic Injuries

Acute Graft Versus Host Disease

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Reproductive Control Agents

Respiratory System Agents

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Albuterol

Ipratropium

Bronchodilator Agents

Anti-Asthmatic Agents

Tocolytic Agents

Adrenergic Agents

Adrenergic beta-Agonists

Adrenergic Agonists

Neurotransmitter Agents

Cholinergic Antagonists

Cholinergic Agents

inhalation of salbutamol (5 mg)

ipratropium

Christoph Ellenberger, MD

Background :

Acute lung injury (ALI) occasionally occurs after pulmonary resection and carries a bad prognosis with a high mortality rate ranging from 20 to 100%.

Objectives :

1. to evaluate pre-, intra- and postoperative changes in hemodynamics, oxygenation indices as well as intra- and extravascular lung water using simple thermodilution technique and continuous arterial pressure analysis
2. to test the efficacy of inhaled beta2 -adrenergic agonist versus anticholinergic agents to reduce lung edema in patients undergoing thoracic surgery and in pigs subjected to lipolysacharide-induced ALI.

Design of the research protocol:

* Prospective controlled trial including surgical patients with high risk factors for ALI (n=60) allocated to receive inhaled drugs (randomised, double-blind, cross-over mode).
* Main measurements:

Intra-thoracic blood volume, intra- and extra-vascular lung water, hemodynamic parameters (CO, systolic arterial pressure/flow variations, dPmax, MAP, CVP), oxygenation indices (PaO2/FIO2), ventilatory parameters, clinical outcome data, histochemical and pathological data.

Glossary CO = cardiac output; dPmax = maximal arterial pressure slope; SAP-V = systolic arterial pressure variations; Flow-V = Flow variations; MAP = mean arterial pressure; CVP = central venous pressure; PaO2=arterial oxygen pressure; FIO2= oxygen inspiratory fraction

Material and Methods Patient selection Consecutive patients who require elective lung resection for cancer at the University Hospital of Geneva will be screened for the presence of risk factors for postoperative ALI or hydrostatic lung edema: age \> 60 yrs, history of chronic alcohol consumption (\>60g/day), prior radiation or chemotherapy, cardiac insufficiency (left ventricular ejection fraction \< 40%, or a history of past acute heart failure), coronary artery disease (history of myocardial infarct, Q wave on the ECG, positive stress test or coronary angiogram), recent pneumonia (within 6 weeks of hospital admission), reduced diffusion capacity for carbon monoxide (DLCO \< 60% of predicted values) and predicted postoperative lung perfusion of \< 55% of total lung perfusion. Patients with at least 3 risk factors for postoperative lung edema will be considered eligible for the study. Patients undergoing pneumonectomy or presenting with intracardiac shunts, valvular diseases or aortic abdominal aneurysm will all be excluded as these conditions preclude valid measurements of extravascular lung water volumes. In addition, chronic treatment with inhaled bronchodilators, a history of any adverse reaction to bronchodilators and liver or kidney insufficiencies will be considered exclusion criteria.

This randomized double blind, cross-over study has been approved by the local university hospital ethics committee and written informed consent has been obtained from all selected patients.

The same team of pneumonologists, thoracic surgeons and anesthesiologists/intensive care physicians will be involved in the perioperative medical management. In addition to history and clinical examination, a standardized preoperative assessment includes chest radiography, ECG, pulmonary function testing as well as computed tomography scans and positron emission tomographies of the chest, abdomen and brain. Quantitative lung perfusion/ventilation scanning, brain imaging, maximal aerobic capacity and myocardial stress testing will be performed when appropriate in intermediate-to-high risk surgical candidates.

Operative and anesthetic management Routinely, antimicrobial prophylaxis with cefazoline will be administered for 24 hours and an epidural catheter was inserted at the 4th-5th or at the 5th-6th vertebral interspace. Thoracic epidural anesthesia (TEA) will be initiated preoperatively with the administration of bupivacaïne 0.25% and continued postoperatively with a lower dosage (bupivacaine 0.1%) that was combined with opiates (fentanyl 2 mcg/ml).

Each patient will be equipped with a 4-French femoral artery catheter and an internal jugular venous line that will be connected to a pulse contour cardiac output monitor (PV2024L; Pulsion Medical Systems AG, Munich, Germany).

After anesthesia induction, a left sided double-lumen endotracheal tube will be inserted and pressure support ventilation will be adjusted to optimize gas exchanges and minimize lung hyperinflation with low tidal volume (5-6 ml/kg), high inspiratory oxygen fraction (50-80%) and positive end expiratory pressure levels (PEEP, 4-12 cm H2O). Periodically, lung recruitment maneuvers will also be performed to re-open alveolar collapsed areas. Anesthesia will be maintained by infusing propofol targeted to achieve bispectral electroencephalographic values between 40 and 60. Lung resection with systematic lymph node dissection will be performed through an anterolateral muscle-sparing thoracotomy.

During surgery, intravenous crystalloids (Ringer-lactate solution) will be infused at a rate of 2-3 ml/kg/h and blood losses will be compensated with colloids (poly(0-2-hydroxy-ethyl)amidon, HAES 6%) and with red blood cell concentrates if the hemoglobin levels decreased below 80-90 g/L. At the end of surgery, all patients will be extubated in the operating theater after reversing the residual neuromuscular blockade with anticholinesterase agents. An active physiotherapy program including incentive spirometry, deep diaphragmatic breathing exercises and mobilization will be started in the high-dependency care unit (HDU). A maximal fluid balance of 500 ml per day will be targeted during the first 48 hours after surgery, by limiting fluid intakes including i.v. crystalloids (glucose-saline 0.45% 1 ml/kg/h), i.v. colloids (1/1 compensation of fluid losses through thoracic drains and oral beverages (500 ml on the day of surgery and 1'000-1'200 ml over the next two days).

Study design Within the first 36 hours after surgery, patients will received in random order nebulized salbutamol and nebulized ipratropium bromide at 4 consecutive sessions conducted at least 6 hours apart (figure 1). The treatment order will be generated from random number tables by an independent observer and concealed in sealed envelopes. The investigators, attending physicians and nurses will be blinded to the treatment group.

Over 10 minutes, either salbutamol (5 mg diluted in 5 ml normal saline) or ipratropium bromide (0.5 mg diluted in 5 ml normal saline) will be administered via a Cirrus nebulizer and a compressor (Wokingham, UK).

Measurements In addition to arterial blood sampling, complete sets of hemodynamic measurements will be performed as shown in figure 1: (a) preoperatively, before and 30 min after initiation of TEA, (b) 2 and 8 hours after surgery (postoperative day 0, \[POD0\]), before and 30 min after administration of salbutamol or ipratropium (6 hours apart in random order), (c) on the morning of the first postoperative day (POD1) on two consecutive sessions (6 hours apart in random order), before and 30 min after administration of salbutamol or ipratropium bromide.

Cardiac output (CO) and volumetric pulmonary variables will be obtained by the simple transpulmonary indicator dilution technique. Three consecutive measurements with less than 10% variations will be averaged. A fifteen milliliters bolus of 0.9% saline at 4°C will be injected through the central venous catheter into the right atrium and the change in temperature will be measured with the femoral artery thermistor tipped catheter. Using the mean transit time methods, intrathoracic blood volume, extravascular lung water and global end-diastolic volume will be calculated and indexed for the patient body weight (ITBVI, EVLWI and GEDVI, respectively). Heart rate (HR), stroke volume (SV) and maximal change in arterial pressure will be determined by beat-to-beat analysis of the arterial pressure wave. The systemic vascular resistance index (SVRI) will be calculated using standard formula. The ratio of EVLWI to ITBVI will be calculated as an index reflecting the permeability of the alveolar-capillary barrier.

Arterial oxygen pressure (PaO2 in mmHg) will be measured using a blood gas analyzer (ABL-510 analyzer, Radiometer, Copenhagen, Denmark) and will be related to the inspiratory O2 fraction to express the oxygenation index (PaO2/FIO2). In addition, chest radiograph scores (number of quadrants with \>50% involvement with an alveolar filling process) will be recorded on POD0 (arrival in HDU) and POD1 (end of the study).

Outcomes The primary outcome measure will be a reduction in EVLWI within the first 24 hours after lung surgery. Secondary outcomes will be the PaO2/FIO2 ratio, hemodynamic data and radiological lung injury score.

Statistical analysis A sample size of 20 subjects provides the power (80%) to detect a 20% difference in EVLWI for a two-sided significance level of  = 0.05; in a preliminary study, we found a mean value of 9.1 ml/kg for EVLWI with a standard deviation (SD) of 2.2 ml/kg.

Results will be reported as M(SD), median (interquartile) or numbers (percentages). A p value of \< 0.05 was considered significant in all analyses. All data will be analyzed with the SPSS statistical software (version 9.0, SPP, Chicago, IL). ANOVA for repeated measurements will be used to compare baseline values (preoperative, POD0 and POD1) followed by Bonferroni post-hoc tests. Paired and unpaired Student t tests will be used to assess and to compare the effects of bronchodilators. Furthermore, the correlation between changes in EVLWI, CI, ITBVI and PaO2/FIO2 will be analyzed by linear regression.

Prevention of Lung Edema After Thoracic Surgery

Does Inhaled Salbutamol Prevent Lung Edema After Thoracic Surgery? A Randomized Controlled Study

University Hospital, Geneva

Nervous System Diseases

Pain, Postoperative

Chronic Pain

Pain

Postoperative Complications

Neurologic Manifestations

Chronic Graft Versus Host Disease

Thoracic surgery

Kasper Grosen, PhDS, MHScS, RN

Hans K Pilegaard, MD

Vibeke Hjortdal, MD, Professor, DMSc, PhD

Mogens P Jensen, MD, PhD

Pain that persists after the healing of a surgical wound has previously been described as an important, but often unrecognized clinical problem. Persistent postsurgical (chronic postoperative pain) is the consequence of either ongoing inflammation or more common neuropathic pain as a result of surgical damage to peripheral nerves.

Previous studies have shown that chronic pain is a frequent and serious complication following thoracic surgery. However, the prevalence of chronic pain following both thoracoscopy and anterior thoracotomy in patients with pulmonary malignancies is poorly characterized and the impact of this pain on patients' lives remains unclear. Thus, this study aims to investigate the prevalence of chronic pain following thoracoscopy or anterior thoracotomy, and the severity and impact of persistent post-surgical pain on daily life.

This study is working with several hypotheses: 1.) persistent postsurgical pain following lung cancer surgery is predominantly of neuropathic nature and the presence of neuropathic symptoms increases the severity of postsurgical pain and reduces the patient's quality of life, 2.) the prevalence of chronic pain is reduced over time, and 3.) less invasive thoracic surgical interventions reduces the risk of the development of chronic pain.

Chronic Pain Following Thoracic Surgery

Study of Persistent Postsurgical Pain Following Thoracic Surgery in Patients With Pulmonary Malignancies

University of Aarhus

PhD fellow, Master of Health Sciences, RN

Carcinoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

In the first cohort(20007-2009) almost all patients where operated through a thoracotomy.

In a second cohort, (2010-2011) the experience with vats was early.

In the third period (2012-2013), a standardized vats technique with extensive intrapulmonary and mediastinal lymphadenectomy was used.

Herbert Decaluwé, MD

Alessia Stanzi, MD

Christophe Dooms, MD, PhD

Paul De Leyn, MD, PhD

This study investigates peropeative nodal upstaging during anatomical resections for non-small-cell-lung-cancer in an era of rising numbers of VATS anatomical resections. In case of comparable study groups, unchanged pretreatment staging and equal quality of pathologic examination, lymph node upstaging is a marker of surgical quality and can be used to study the quality of a new surgical technique.

Vats lobectomy is becoming the standard of care for early stage lung cancer. Several studies have shown feasibility and safety in dedicated centres. Compared to thoracotomy the procedure is believed to achieve equal oncologic results and survival, perhaps better.

Publications have shown that mediastianal lymph node dissection during VATS is similar.

However, two recent reports have shown potential lower N1 (hilar and intrapulmonary) upstaging in VATS surgery After optimal staging the percentage of unforeseen N+ the percentage of unforeseen positive nodes can reach 15%

Nodal upstaging at final pathology is dependent on the quality of:

* pretreatment staging, the better, the less upstaging
* surgery, ie mediastinal, hilar and intrapulmonary lymphadenectomy
* pathologic examination If we accept that pretreatment staging and pathologic examination are equal in two comparable surgical cohorts, the finding of unforeseen N+ or nodal upstaging is a quality marker of surgery. When surgical techniques are changing, it is important to look at this marker.

In absence of a randomized trial, we believe a cohort analysis is useful. By including all patients, open or vats, and comparing cohorts instead of the surgical technique used, the selection bias is absent. We compare three cohorts. In the first (20007-2009) almost all patients where operated through a thoracotomy. In a second cohort, (2010-2011) the experience with vats was early. In the third period (2012-2013), a standardized vats technique with extensive intrapulmonary and mediastinal lymphadenectomy was used.

Nodal Upstaging in VATS Anatomical Resections for NSCLC

Cohort Analysis of Nodal Upstaging in the Era of Increase of VATS Anatomical Resections for NSCLC

clinical N0 to pathological N1 clinical N0 to pathological N2 clinical N1 to pathological N2

University Hospital, Gasthuisberg

RN, MScN

Pulmonary Disease, Chronic Obstructive

Pulmonary Emphysema

Emphysema

Lung Diseases, Interstitial

Chronic Disease

Disease Attributes

Lung Diseases, Obstructive

Patients undergoing thoracic surgery for suspected or confirmed lung cancer; including wedge resection, segmentectomy, lobectomy, bilobectomy or pneumonectomy. CTPVe will be modelled to predict postoperative lung function.

Patients undergoing assessment of emphysema/chronic obstructive pulmonary disease (COPD) for potential surgical intervention; including lung volume reduction surgery, endobronchial valve insertion or endobronchial coil insertion. CTPVe will be modelled to predict postoperative lung function.

Patients undergoing assessment or treatment of suspected or confirmed interstitial lung disease. CTPVe will be modelled to aid diagnosis of the subtype of interstitial lung disease confirmed by histological diagnosis.

Non contrast computed tomography (CTPVe) scan during end inspiration and end expiration in supine position

CTPVe

Babu Naidu, MBBS

This study uses CT scans to assess airflow in the lung, the scan is quick, cheap and painless. The information from the scan may help doctors tell which patients are suitable to have surgery to cure early stage lung cancer. It may also help doctors tell which patients would benefit from surgery for emphysema and diagnose types of lung disease. The investigators will follow up patients who go through surgery to test how well the scan predicts the function of the lung after surgery. The investigators will follow patients being investigated for lung disease to test how accurate the scan is at the getting the diagnosis right.

CT scans during breathing in and breathing out (CTPVe) can assess regional airflow within the lung, using newly developed software as described by Aliverti et al. This provides information about the function of each part of the lung. The investigators aim to assess the feasibility of a larger trial using CTPVe to guide treatment of lung diseases and develop the statistical models needed for use in these trials.

Surgery provides the best prospect of a cure in early Non-small cell lung cancer. In the UK only half of people with early lung cancer undergo surgery and poor lung function may be a barrier to removal of part of the lung. Many patients with lung cancer also have emphysema or other lung diseases that reduce lung function. Actual post-operative lung function is often better predicted by current methods. The investigators will assess regional airflow in the lung and compare the airflow to the patients lung function both before and after surgery to assess if CTPVe can predict postoperative lung function, enabling more people to be considered suitable for curative surgery,

Severe emphysema is debilitating, some surgical treatments can improve the symptoms of emphysema; these include lung volume reduction surgery, endobronchial valves and endobronchial coils. Each of these are only suitable for certain patients and it is difficult to predict who will benefit most. The investigators will assess regional airflow in the lung and compare the airflow to the patients lung function before and after these treatments for emphysema to assess if CTPVe can predict who will benefit from surgery.

There are hundreds of subtypes of interstitial lung disease that respond to different types of treatment but diagnosing the subtype can be very difficult. Patients may need to undergo surgery to get the diagnosis of their subtype and this is associated with major risks, including death. The investigators will assess the regional airflow in the lung and compare the pattern to the final subtype of interstitial lung disease to assess if CTPVe could mean future patients do not need surgery for diagnosis.

Computed Tomography Assessment of Regional Ventilation (CURVE)

An Observational Study of Non Contrast Computed Tomography in Assessment of Regional Ventilation of the Lung.

Change in gas transfer factor (DLCO) reported as percentage of predicted value.

Change in forced expiratory volume in 1 second reported as percentage of predicted value.

The histological or multidisciplinary team consensus diagnosis of subtype of interstitial lung disease (if applicable)

Change in the patient perception of breathlessness measured suing Borg scale 0-10

Regional ventilation of the lung as assessed on CTPVe scanning, reported in millilitres of air per gram of lung tissue

British Lung Foundation

Heart of England NHS Trust

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prevention of Lung Edema After Thoracic Surgery	NCT00498251	Lung Injury, Ac... Thoracotomy Anesthesia Intensive Care,... Extravascular L...	inhalation of s... ipratropium	-	University Hospital, Geneva
Chronic Pain Following Thoracic Surgery	NCT01144845	Pain, Postopera...	Thoracic surger...	-	University of Aarhus
Nodal Upstaging in VATS Anatomical Resections for NSCLC	NCT01985659	Carcinoma, Non-...		18 Years -	University Hospital, Gasthuisberg
Computed Tomography Assessment of Regional Ventilation (CURVE)	NCT02879773	Lung Neoplasms Emphysema Lung Diseases, ... Pulmonary Disea...	CTPVe	18 Years -	Heart of England NHS Trust

Spots Global Cancer Trial Database for thoracic surgical procedures