Is “lung repair centre” a possible answer to organ shortage? Transplantation of left and right lung at two different centres after evlp evaluation and repair: case report

Introduction. Ex vivo lung perfusion (EVLP) has become a reality as a technique to evaluate and recondition lungs from marginal donors (1), opening the door to clinical and organizational progresses. In this scenario, the Toronto group has firstly shown the feasibility of the \u2018EVLP Centre\u2019 approach in a case of emergent transplantation (2). Objectives. We report a successful case on the use of EVLP followed by separate transplantation in two different centres. Methods. The local organ procurement organization proposed the lungs of a 53 years old male nonsmoker donor who died from cerebral haemorrhage. The chest X-ray showed hilar reinforcement and basal dysventilation; secretions of moderate quantity were present; P/F ratio was 294 after lung recruitment maneuvers. Oto score was 10. Two centres accepted the grafts for two single transplantations under the condition of EVLP evaluation. After usual retrieval, the bi-pulmonary block was transferred to Milan transplantation centre and EVLP was run as previously described (3). At the end of the procedure the two lungs were evaluated separately and both judged suitable for transplantation. After cooling and storage on ice, the block was separated on the back table. The left lung was transplanted in a patient with pulmonary fibrosis (LAS 35); surgery was complicated by cardiac arrhythmias that required several defibrillations. The right lung was transferred on ice to Padua transplantation centre, 250 Km away from Milan, and transplanted in a patient with idiopathic pulmonary fibrosis (LAS 50). The ischemic times from cross-clamping to revascularization were 18 hours for the patient in Milan and 15 hours for the patient in Padua. None of the recipients suffered from PGD. The former patient, despite KPC infection, is alive after 14 months, in good condition (FEV1 75%). The other patient had an uneventful post-operative period, and was discharged after 27 days. At the 14th months follow-up he is alive, in good condition (FEV1 51%). Conclusions. This is the first report of the separate use of lungs after EVLP for non urgent recipients in two different centres with good results. This experience opens the door to a new allocation model with great potentials on organ shortage. The limitations are transportation times, costs, complex logistics and the prolonged cold ischemia. We demonstrated that the perspective of a \u2018lung repair centre\u2019 is feasible and effective. We expect the results of the Perfusix protocol in order to confirm of this new scenario (4). References. 1. Van Raemdonck D, et al. Ex-Vivo Lung Perfusion. Transplant Int 2015;28(6):643-56. 2. Wigfield CH, et al. Successful emergent lung transplantation after remote ex vivo perfusion optimization and transportation of donor lungs. Am J Transplant 2012;12:2838-44. 3. Valenza F, et al. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation. Transplant International 2014; 27: 553-561. 4. NCT02234128, www.ClinicalTrial.go

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications

BACKGROUND Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN This was a prospective international 1-week observational study using the ‘Assess Respiratory Risk in Surgical Patients in Catalonia risk score’ (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (VT) size was 500 ml, or 7 to 9 ml kg1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P < 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P < 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. CONCLUSION The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high VT and low PEEP levels. PPCs occur frequently in patients at increased risk, with worse clinical outcome

Epidemiology, practice of ventilation and outcome for patients at increased risk of postoperative pulmonary complications: LAS VEGAS - An observational study in 29 countries

BACKGROUND Limited information exists about the epidemiology and outcome of surgical patients at increased risk of postoperative pulmonary complications (PPCs), and how intraoperative ventilation was managed in these patients. OBJECTIVES To determine the incidence of surgical patients at increased risk of PPCs, and to compare the intraoperative ventilation management and postoperative outcomes with patients at low risk of PPCs. DESIGN This was a prospective international 1-week observational study using the ‘Assess Respiratory Risk in Surgical Patients in Catalonia risk score’ (ARISCAT score) for PPC for risk stratification. PATIENTS AND SETTING Adult patients requiring intraoperative ventilation during general anaesthesia for surgery in 146 hospitals across 29 countries. MAIN OUTCOME MEASURES The primary outcome was the incidence of patients at increased risk of PPCs based on the ARISCAT score. Secondary outcomes included intraoperative ventilatory management and clinical outcomes. RESULTS A total of 9864 patients fulfilled the inclusion criteria. The incidence of patients at increased risk was 28.4%. The most frequently chosen tidal volume (V T) size was 500 ml, or 7 to 9 ml kg−1 predicted body weight, slightly lower in patients at increased risk of PPCs. Levels of positive end-expiratory pressure (PEEP) were slightly higher in patients at increased risk of PPCs, with 14.3% receiving more than 5 cmH2O PEEP compared with 7.6% in patients at low risk of PPCs (P ˂ 0.001). Patients with a predicted preoperative increased risk of PPCs developed PPCs more frequently: 19 versus 7%, relative risk (RR) 3.16 (95% confidence interval 2.76 to 3.61), P ˂ 0.001) and had longer hospital stays. The only ventilatory factor associated with the occurrence of PPCs was the peak pressure. CONCLUSION The incidence of patients with a predicted increased risk of PPCs is high. A large proportion of patients receive high V T and low PEEP levels. PPCs occur frequently in patients at increased risk, with worse clinical outcome.</p

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P &lt; 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P &lt; 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Lung pre-conditioning during ex-vivo lung perfusion: results of an experimental study

Background: Clinical data suggest a benefit of transplanting lungs after Ex-Vivo Lung Perfusion (EVLP). Objective: To explore the bio-molecular and cellular mechanisms that might explain a role of EVLP on lung pre-conditioning. Material and methods: EVLP was run for 180 min on Sprague-Dawley rat lungs (Hugo Sachs System). Cytokine and chemokine release in the perfusate was assayed by Luminex xMAP\uae Technology. Cells recovered in the perfusate were counted, characterized (May-Gr\ufcnwald Giemsa staining), and cultured to assess viability (Trypan blue exclusion). Gene expression was investigated using custom low-density arrays. Hierarchical cluster analysis was performed with DNA-chip program. Differentially expressed genes were identified using Significance Analysis of Microarrays (SAM), considering lungs from naive (Native) or from sham-operated rats (Sham) as controls. Western blot analysis (SDS-PAGE) was performed to explore activation of signaling pathways. Results: A total of 15 animals were investigated: Native, Sham, EVLP (n=5 each). The EVLP system was stable over time, with no signs of lung edema (W/D: 5.3\ub10.5). At 180 min, mediators in the perfusate with highest median value were: TIMP-1, MIP-2, MCP-1, and IL-6. A total of 11.03\ub11.43x10^6 cells were recovered after EVLP: 91\ub11% lymphocytes with 82% viability after 24 h of culture. Unsupervised analysis revealed that EVLP induced a specific transcriptional signature (P=0.003). Pattern of genes up-regulated included inflammation, resolution of inflammation, antiapoptosis/survival, heat-shock/redox while neutrophil related genes were down-regulated (q=0). STAT3, MAP kinase (ERK1/2, p38), and NFKB signaling pathways were activated after EVLP. Conclusion: EVLP is associated with a number of bio-molecular and cellular mechanisms compatible with pre-conditioning of the lung