Didier Schneiter

Anesthetic-induced improvement of the inflammatory response to one-lung ventilation.

Background:Although one-lung ventilation (OLV) has become an established procedure during thoracic surgery, sparse data exist about inflammatory alterations in the deflated, reventilated lung. The aim of this study was to prospectively investigate the effect of OLV on the pulmonary inflammatory response and to assess possible immunomodulatory effects of the anesthetics propofol and sevoflurane. Methods:Fifty-four adults undergoing thoracic surgery with OLV were randomly assigned to receive either anesthesia with intravenously applied propofol or the volatile anesthetic sevoflurane. A bronchoalveolar lavage was performed before and after OLV on the lung side undergoing surgery. Inflammatory mediators (tumor necrosis factor &agr;, interleukin 1&bgr;, interleukin 6, interleukin 8, monocyte chemoattractant protein 1) and cells were analyzed in lavage fluid as the primary endpoint. The clinical outcome determined by postoperative adverse events was assessed as the secondary endpoint. Results:The increase of inflammatory mediators on OLV was significantly less pronounced in the sevoflurane group. No difference in neutrophil recruitment was found between the groups. A positive correlation between neutrophils and mediators was demonstrated in the propofol group, whereas this correlation was missing in the sevoflurane group. The number of composite adverse events was significantly lower in the sevoflurane group. Conclusions:This prospective, randomized clinical study suggests an immunomodulatory role for the volatile anesthetic sevoflurane in patients undergoing OLV for thoracic surgery with significant reduction of inflammatory mediators and a significantly better clinical outcome (defined by postoperative adverse events) during sevoflurane anesthesia.

Accelerated treatment for early and late postpneumonectomy empyema

BACKGROUND Postpneumonectomy empyema is a rare but serious complication of pneumonectomy. Despite use of various therapeutic approaches and techniques during the last five decades, successful therapy remains difficult and is often associated with high morbidity and prolonged hospitalization. METHODS We evaluated a concept for accelerated treatment, which consists of radical debridement of the pleural cavity and packing with wet dressings of povidoneiodine. This was repeated in the operating theater every second day, until the chest cavity was macroscopically clean. If present, bronchial stump insufficiency was closed and secured by omentopexy. Finally, the pleural space was obliterated with antibiotic solution. RESULTS Twenty patients, 13 with early postpneumonectomy empyema (10 to 89 days; mean, 37 days) and 7 with late postpneumonectomy empyema (124 to 7,200 days; mean, 1,126 days) were treated. Fifteen patients presented with bronchopleural fistula (11 right, 4 left), which developed after chemotherapy (n = 6) or after radiotherapy (n = 3) (unknown cause in 4 patients). Six patients were referred after previously unsuccessful surgical attempts. Pleural cultures were positive in 17 cases for one or several bacteria including fungoides (n = 2). The average number of interventions was 3.5 (3 to 5). The chest was definitively closed in all patients within 8 days. Mean hospitalization time was 17 days (7 to 35 days). During the same hospitalization, 2 patients needed reoperation because of an undetected bronchopleural fistula. Postpneumonectomy empyema was successfully treated in all patients. There was no in-hospital or 3-month postoperative mortality. CONCLUSIONS Repeated surgical debridement combined with closure of bronchopleural fistula and antimicrobial therapy enables successful treatment of early and late postpneumonectomy empyema within a short period and is a well-tolerated concept.

Bronchoscopic radioisotope injection for sentinel lymph-node mapping in potentially resectable non-small-cell lung cancer

OBJECTIVE Prospective study to evaluate the feasibility of a preoperative bronchoscopic radioisotope application, followed by conventional sentinel lymph-node (SLN) identification and to investigate the occurrence and distribution of micrometastases in relation to SLN activity. METHODS Twenty patients with a mean age of 63 years and proven clinical stage T1-3 N0-1 non-small-cell lung cancer (NSCLC) were included. A dosage of 80MBq radiolabeled technetium-99m nanocolloid was endoscopically administrated on intubated patients in the operation theatre. At thoracotomy, scintigraphic readings of both the primary tumor and hilar and mediastinal lymph-node stations were obtained with a hand-held gamma-counter. Patients underwent lung resection and mediastinal lymphadenectomy. Radiolabeled nodes were also examined separately on back-table. SLNs were defined as the hottest nodes or nodes with at least one-tenth of the radioactivity of the hottest nodes. SLNs pathologic assessment included standard examination using hematoxylin and eosin staining on step sections and immunohistochemistry (ICH) for cytokeratins. RESULTS Identification of SLNs was possible in 19/20 (95%) patients after bronchoscopic radioisotope application. In 7/19 (37%) patients, a unique SLN was identified, whereas in 12/19 (63%) patients, nodes from two different stations could be classified as SLNs. Metastatic nodal disease was found in 9/19 (47%) patients. ICH revealed micrometastases in 2/12 (17%) patients, initially classified nodal negative. Pathologic negative SLNs were a predictor for absence of metastatic nodal disease after mediastinal lymphadenectomy. No complication related to the procedure was observed. CONCLUSION Our preliminary results suggest that preoperative bronchoscopic radioisotope injection for SLN identification is a safe and simple method, improving accuracy of SLN detection in comparison to intraoperative technique. The absence of metastases in the SLNs seems to predict a negative nodal status accurately.

Accelerated treatment of postpneumonectomy empyema : a binational long-term study

OBJECTIVE Postpneumonectomy empyema remains a clinical challenge. We proposed an accelerated therapy without an open chest window 5 years ago. This concept was evaluated on a larger scale in 2 centers in 2 different countries. METHODS Between July 1995 and October 2005, 75 consecutive patients with postpneumonectomy empyema were treated in Szczecin, Poland (n = 35), and Zurich, Switzerland (n = 40). The therapy consisted of repeated open surgical debridement of the pleural cavity after achievement of general anesthesia, a negative pressure wound therapy of the temporarily closed chest cavity filled with povidone-iodine-soaked towels, and continuous suction and systemic antimicrobial therapy. If present, bronchopleural fistulae were closed and reinforced either with a muscle flap or the omentum. Finally, the pleural space was filled with an antibiotic solution and definitively closed. RESULTS Of 75 patients (63 men; median age, 59 years; age range, 19-82 years), postpneumonectomy empyema was present on the right in 46 patients (32 with bronchopleural fistula) and in 29 patients (12 with bronchopleural fistula) on the left. Median time between pneumonectomy and postpneumonectomy empyema was 131 days (range, 7-7200 days). Bronchopleural fistulae have been closed and additionally reinforced by means of different methods (omentum, 18; muscle, 11; pericardial fat, 5; azygos vein, 1). The chest was definitively closed within 8 days in 94.6% of patients. The median hospitalization time was 18 days (range, 9-134 days). Postpneumonectomy empyema was successfully treated in 97.3% of patients, including 10 (13%) patients who needed a second treatment cycle. Three (4%) patients died within 90 days. The median follow-up time was 29.5 moths (range, 3-107 months). CONCLUSIONS Treatment of postpneumonectomy empyema with the accelerated treatment is effective and safe. Our results are superior compared with those in reported series using a (temporary) chest fenestration. Patients appreciate the physical integrity of the chest.

Long-term outcomes of bilateral lobar lung transplantation

OBJECTIVES Lobar lung transplantation is an option that provides the possibility of transplanting an urgent listed recipient of small size with a size-mismatched donor lung by surgically reducing the size of the donor lung. We report our short- and long-term results with bilateral lobar lung transplantation (BLLT) and compare it with the long-term outcomes of our cohort. METHODS Retrospective analyses of 75 lung transplant recipients who received downsized lungs with a special focus on 23 recipients with BLLT performed since January 2000. Postoperative surgical complications, lung function tests, late complications and survival were analyzed. The decision to perform lobar transplantation was considered during allocation and finally decided prior to implantation. RESULTS Cystic fibrosis was the most common indication (43.5%) followed by pulmonary fibrosis (35%). Median age at transplantation was 41 (range 13-66) years. Fifteen were females. Nineteen of the transplantations (83%) were done with extracorporeal membrane oxygenation (ECMO) support; 3 of them were already on ECMO prior to transplantation. There was no 30-day or in-hospital mortality. No bronchial complications occurred. The most common early complication was haematothorax (39%), which required surgical intervention. The rate of postoperative atrial arrhythmias was 30%. Forced expiratory volumes in 1 s (% predicted) at 1 and 2 years were 76 ± 23 and 76 ± 22, respectively (mean ± standard deviation). By 2-year follow-up, bronchiolitis obliterans syndrome was documented in 3 patients with a median follow-up of 1457 days. Overall survivals at 1 and 5 years were 82 ± 8 and 64 ± 11%, respectively and were comparable with those of 219 other recipients who received bilateral lung transplantation during the same period (log rank test, P = 0.56). CONCLUSIONS This study demonstrates that BLLT has short- and long-term outcomes comparable with those of standard bilateral lung transplantation. The limitation of lung transplantation due to size-mismatch, particularly in smaller recipients, could be overcome by utilizing lobar lung transplantation.

Melatonin in vivo prolongs cardiac allograft survival in rats.

Abstract:  Melatonin, secreted by the pineal gland, is a multifunctional agent which (i) protects tissues from damage through free radical scavenging and attenuates ischemia/reperfusion injury in organ grafts; (ii) acts synergistically with cellular antioxidants; and (iii) displays complex, dose‐dependent immunoenhancing and suppressing effects in vitro and in vivo. We analyzed the immunomodulatory effect of melatonin on acute allograft rejection. Cardiac grafts were transplanted from LBNF1 to LEW rats and anastomosed to the abdominal great vessels. The effect of low‐dose (LD; 20 mg/kg/day) and high‐dose (HD; 200 mg/kg/day) melatonin treatment in recipients compared with untreated controls was investigated. HD melatonin therapy abrogated acute rejection, significantly prolonging allograft survival (mean survival: 12.3 ± 1 days S.D., n = 8, P < 0.0001) compared with untreated controls, which rapidly reject the transplant (6.3 ± 1 days n = 12). LD therapy did not extend survival significantly (7.3 ± 1.1 days, n = 12). Allospecific IgM showed a significant decrease in animals receiving HD therapy versus untreated recipients at days 10 and 14 post‐transplantation (P < 0.01), whereas in the LD group at day 10, a significant increase in allospecific IgM (P < 0.01) over the HD cohort was demonstrated. HD treatment markedly reduced lymphocyte proliferative capacity compared with controls and the LD group. HD melatonin treatment abrogated acute allograft rejection and significantly prolonged graft survival. Our results suggest an involvement of melatonin in humoral and cellular immune pathways following perfused organ transplantation. These findings may indicate a novel therapeutic approach, based on modulation of the neuroendocrine/immune axis through melatonin as a possible future immunosuppressant in organ transplantation.

Acute Amiodarone-Induced Pulmonary Toxicity following Lung Resection

Amiodarone-induced pulmonary toxicity has been described mostly in patients receiving large doses of the drug over prolonged periods. In this report, we describe the early onset of acute pulmonary toxicity leading to acute respiratory distress syndrome after a short course of amiodarone treatment following middle-lobe non-small-cell lung cancer resection.

Outcome of Extracorporeal Membrane Oxygenation as a Bridge To Lung Transplantation: An Institutional Experience and Literature Review.

Background Extracorporeal life support (ECLS) as a bridge to lung transplantation (LuTx) is a promising option for patients with end-stage lung disease on the transplant waiting list. We investigated the outcome of patients bridged to lung transplantation on ECLS technologies, mainly extracorporeal membrane oxygenation (ECMO). Methods Between January 2007 and October 2013, ECLS was implanted in 30 patients with intention to bridge to LuTx. Twenty-six patients (26/30) were successfully bridged to LuTx on ECLS. The most common diagnosis was cystic fibrosis (N = 12). Venovenous ECMO was used in 10, venoarterial in 4, interventional lung assist in 5, and stepwise combination of them in 7 recipients. Results Two patients weaned from ECMO, and 2 patients died on ECMO on the waiting list. Median duration of ECLS was 21 days (1-81 years). Six patients were awake and spontaneously breathing during ECLS support. Thirty-day, 1-year, and 2-year survivals were 89%, 68%, and 53%, respectively, for bridged patients and 96%, 85%, and 79%, respectively, for control group (P = 0.001). Three months conditional survivals were 89% and 69% at 1 and 2 years for ECLS group, compared to 92% and 86% for control group (P = 0.03). Cystic fibrosis recipients had 82% survival rate at 1 and 2 years. All recipients bridged to LuTx on awake ECLS (N = 6) are alive with a median follow-up of 10.8 months (range, 6-21 months). Conclusions Our data show significantly lower survival in this high-risk group compared to patients transplanted without preoperative ECLS. Awake and ambulatory ECLS provides the best prognosis for these high-risk patients.

Survival of patients treated surgically for synchronous single-organ metastatic NSCLC and advanced pathologic TN stage

INTRODUCTION Patients with stage IV metastatic non-small cell lung cancer (NSCLC) are generally not considered for surgery due to their poor median survival ranging from 4 to 11 months. However published results suggested that carefully selected patients with oligometastatic disease may benefit from resection of both the primary and metastatic sites in a multidisciplinary treatment approach. The aim of the study was to analyze and detect prognostic factors in surgically treated patients with synchronous single-organ metastasis from NSCLC. METHODS This is a retrospective single-center study including 29 patients with synchronous single-organ metastatic NSCLC who underwent lung resection and local treatment of the metastasis between 2002 and 2008. Overall survival was estimated from the date of lung surgery until last follow-up. The impact on survival of nine variables (age, pT, pN, site of metastasis, presence of solitary metastasis, R-resection status, presence of neoadjuvant or adjuvant treatment, tumor histology) were further assessed. RESULTS Twenty-nine patients (20 males, 69%) with a median age of 62 (from 44 to 77) were included. Site of metastatic disease was the brain in 19, the lung in 8 and the adrenal glands in 2 patients. Histology was adenocarcinoma in 21, large-cell carcinoma in 3, squamous-cell carcinoma in 2 and other in 3 patients. Type of lung resection performed for primary tumors were pneumonectomy in 3, bilobar resection in 3, lobar resection in 17 and sublobar resection in 6 patients. Survival at 1 and 5 years for the overall population reached 65% and 36%, respectively. Median survival was 20.5 months. Univariate regression model analysis identified pathologic T stage as a predictor of survival. Patients with pT1-2 behaved statistically significantly better (p=0.007) compared to patients with pT3-4 tumors. No impact on survival for the other 8 variables has been shown. CONCLUSIONS The 5-year survival rate of 36% confirms that multimodality treatment including surgical lung resection should be considered in the therapy of single-site metatastatic NSCLC for selected patients. Pathologic T stage appeared to have significant impact on predicting patient survival.

Lung Volume Reduction Surgery and Improvement of Endothelial Function and Blood Pressure in Patients with Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial

RATIONALE Cardiovascular disease is a major cause of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Preliminary studies have shown that both airflow obstruction and systemic inflammation may contribute to endothelial dysfunction in COPD. Lung volume reduction surgery (LVRS) is a treatment option in selected patients with COPD with emphysema that improves breathing mechanics and lung function. OBJECTIVES To determine the effect of LVRS on endothelial function and systemic inflammation. METHODS We conducted a randomized controlled trial in 30 patients scheduled for LVRS. In the intervention group, immediate LVRS was performed after baseline evaluation followed by reassessment 3 months later. In the control group, reassessment followed 3 months after baseline evaluation, and thereafter LVRS was performed. MEASUREMENTS AND MAIN RESULTS The primary outcome measures were the treatment effect on endothelial function and systemic inflammation. In the LVRS group 14 patients completed the trial and 13 in the control group. LVRS led to a relative reduction in mean (SD) residual volume/total lung capacity of -12% (12%) and an increase in FEV1 of 29% (27%). Flow-mediated dilatation of the brachial artery increased in the intervention group as compared with the control group (+2.9%; 95% confidence interval, +2.1 to +3.6%; P < 0.001), whereas there was no significant change in systemic inflammation. A significant treatment effect on mean blood pressure was observed (-9.0 mm Hg; 95% confidence interval, -17.5 to -0.5; P = 0.039). CONCLUSIONS Endothelial function and blood pressure are improved 3 months after LVRS in patients with severe COPD and emphysema. LVRS may therefore have beneficial effects on cardiovascular outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT 01020344).