Lung protective ventilation based on donor size is associated with a lower risk of severe primary graft dysfunction after lung transplantation.

BACKGROUND: Mechanical ventilation immediately after lung transplantation may impact the development of primary graft dysfunction (PGD), particularly in cases of donor-recipient size mismatch as ventilation is typically based on recipient rather than donor size. METHODS: We conducted a retrospective cohort study of adult bilateral lung transplant recipients at our center between January 2010 and January 2017. We defined donor-based lung protective ventilation (dLPV) as 6 to 8 ml/kg of donor ideal body weight and plateau pressure <30 cm H2O. We calculated the donor-recipient predicted total lung capacity (pTLC) ratio and used logistic regression to examine relationships between pTLC ratio, dLPV and PGD grade 3 at 48 to 72 hours. We used Cox proportional hazards modelling to examine the relationship between pTLC ratio, dLPV and 1-year survival. RESULTS: The cohort included 373 recipients; 24 (6.4%) developed PGD grade 3 at 48 to 72 hours, and 213 (57.3%) received dLPV. Mean pTLC ratio was 1.04 ± 0.18. dLPV was associated with significantly lower risks of PGD grade 3 (OR = 0.44; 95% CI: 0.29-0.68, p < 0.001) and 1-year mortality (HR = 0.49; 95% CI: 0.29-0.8, p = 0.018). There was a significant association between pTLC ratio and the risk of PGD grade 3, but this was attenuated by the use of dLPV. CONCLUSIONS: dLPV is associated with decreased risk of PGD grade 3 at 48 to 72 hours and decreased 1-year mortality. Additionally, dLPV attenuates the association between pTLC and both PGD grade 3 and 1-year mortality. Donor-based ventilation strategies may help to mitigate the risk of PGD and other adverse outcomes associated with size mismatch after lung transplantation.

Management of chronic rejection after lung transplantation.

Outcomes after lung transplantation are limited by chronic lung allograft dysfunction (CLAD). The incidence of CLAD is high, and its clinical course tends to be progressive over time, culminating in graft failure and death. Indeed, CLAD is the leading cause of death beyond the first year after lung transplantation. Therapy for CLAD has been limited by a lack of high-quality studies to guide management. In this review, we will discuss the diagnosis of CLAD in light of the recent changes to definitions and will discuss the current clinical evidence available for treatment. Recently, the diagnosis of CLAD has been subdivided into bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). The current evidence for treatment of CLAD mainly revolves around treatment of BOS with more limited data existing for RAS. The best supported treatment to date for CLAD is the macrolide antibiotic azithromycin which has been associated with a small improvement in lung function in a minority of patients. Other therapies that have more limited data include switching immunosuppression from cyclosporine to tacrolimus, fundoplication for gastroesophageal reflux, montelukast, extracorporeal photopheresis (ECP), aerosolized cyclosporine, cytolytic anti-lymphocyte therapies, total lymphoid irradiation (TLI) and the antifibrotic agent pirfenidone. Most of these treatments are supported by case series and observational studies. Finally, we will discuss the role of retransplantation for CLAD.

Obstructive sleep apnea screening and postoperative mortality in a large surgical cohort.

OBJECTIVE: A recent investigation at Barnes-Jewish Hospital located in St. Louis, Missouri, found that an estimated 22% of adults presenting for inpatient surgery screened as high risk for obstructive sleep apnea (OSA). Surgical patients with OSA have multiple comorbidities and are at increased risk for perioperative complications. Our objective was to determine if a prior diagnosis of OSA or a positive screen for OSA was associated with increased risk for 30-day and one-year mortality. METHODS: B-J APNEAS (Barnes-Jewish Apnea Prevalence in Every Admission Study) was a prospective cohort study. Unselected adult surgical patients at Barnes Jewish Hospital were prospectively enrolled between February 2006 and April 2010. All patients completed preoperative OSA screening and those who were at risk for OSA according to a combination of the Berlin and Flemons screening tools received targeted postoperative interventions. STOP (loud Snoring, daytime Tiredness, Observed apneas, and high blood Pressure) and STOP-BANG (STOP, plus body mass index [BMI], age, neck circumference, and gender) scores also were obtained. RESULTS: Overall, the sample included 14,962 patients, of whom 1939 (12.9%) reported a history of OSA. All four screening tools identified a high prevalence of undiagnosed patients at risk for OSA (9.5%-41.6%), but agreement among screens was not strong with κ statistic ranging from 0.225 to 0.611. There was no significant difference in 30-day postoperative mortality between patients with possible OSA (based on their history or on a positive OSA screen with any of the four instruments) and the rest of the surgical population. Significant differences in one-year mortality were noted between the low-risk and high-risk groups as identified by the Flemons' (4.96% vs 6.91%; p<0.0001), STOP (5.28% vs 7.57%; p<0.0001) and STOP-BANG (4.13% vs 7.45%; p<0.0001) screens. After adjusting for risk factors, none of the OSA screening tools independently predicted mortality rate up to one year postoperatively. CONCLUSION: Neither a prior diagnosis of OSA nor a positive screen for OSA risk was associated with increased 30-day or one-year postoperative mortality. Differences in 1 year postoperative mortality were noted with three of the screening tools. The results of our study highlight uncertainties and research priorities for the medical community.