Evaluation of Bivalirudin as the Primary Anticoagulant in Patients Receiving Extracorporeal Membrane Oxygenation for SARS-CoV-2-Associated Acute Respiratory Failure.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a potential option for the management of severe acute respiratory failure secondary to COVID-19. Conflicting the use of this therapy is the known coagulopathy within COVID-19, leading to an incidence of venous thrombotic events of 25% to 49%. To date, limited guidance is available on optimal anticoagulation strategies in this population. OBJECTIVE: The purpose of this study was to evaluate the utilization of a pharmacist-driven bivalirudin dosing protocol for anticoagulation in the setting of ECMO for COVID-19-associated respiratory failure. METHODS: This was a single-center retrospective chart review over a 9-month period of patients receiving bivalirudin while on ECMO. All patients with acute respiratory failure requiring ECMO with a positive SARS-CoV-2 polymerase chain reaction were included. Bivalirudin was dosed via aPTT monitoring after a starting dose of 0.2 or 0.3 mg/kg/h. RESULTS: There were 33 patients included in this study, all receiving mechanical ventilation. The most common starting dose of bivalirudin was 0.2 mg/kg/h, with an average time to therapeutic range of 20 hours. Compared to previous reports, rates of bleeding were low at 15.1%, and 6.1% of patients developed a new venous thromboembolic event while on ECMO. ECMO survival was 51.5%, with an ICU mortality rate of 48.5%. CONCLUSION AND RELEVANCE: In the first published report of its use within this population, bivalirudin was found to be a viable choice for anticoagulation in those patients on ECMO for severe respiratory failure secondary to COVID-19.

Gait-speed and oxygen flow during six-minute walk test predicts mortality in patients with advanced lung disease.

The six-minute walk test (6MWT) is a useful tool to predict outcomes in patients with advanced lung diseases. Greater distance walked has been shown to have more favorable prognostic value compared to other recorded variables.  We reviewed the medical records of 164 patients with advanced lung disease who underwent lung transplant evaluation. Results of the 6MWT (distance walked, oxygen required, and mean gait speed) were recorded and analyzed with respect to mortality. 6MWT mean oxygen (O2) flow via nasal cannula was 3.5 ± 3.7 L/min. The distance walked in meters (m) and % predicted were inversely associated with mortality, OR: 0.995 (0.992-0.998) and 0.970 (0.950-0.990), respectively. Patients who walked < 200 meters (OR: 2.1 (1.1-4.0)) or < 45% of predicted, OR: 2.7 (1.2-5.7) had higher mortality. O2 flow during the test had a direct association with mortality (OR: 1.1 (1.0-1.2). In multivariate analysis, O2 flow > 3.5 L/min remained predictive of mortality, OR: 1.1 (1.0-1.2). Mean gait speed was higher in patient who lived compared with patients who died (mean 0.83 ± 0.35 m/mim vs mean 0.69 ± 0.33 m/min, respectively, p= 0.03). Gait speed was a predictor of survival, OR 3.4 (1.1, 10.6). O2 flow during the 6MWT was an independent predictor of mortality in patients with advanced lung disease. The patients that required more than 3.5 L/m of O2 had a higher mortality. Faster gait speed during the 6MWT was also associated with better survival.

Increased blood transfusion and its impact in patients having tracheostomy while on extracorporeal membrane oxygenation.

INTRODUCTION: Tracheostomy has been utilized in combination with venovenous extracorporeal membrane oxygenation (VV-ECMO) to enable early spontaneous breathing and minimize sedation requirements. Tracheostomy has been previously reported to be safe in patients supported on VV-ECMO; however, the impact of tracheostomy on blood loss in VV-ECMO patients is unknown. METHODS: We analyzed VV-ECMO patients with and without tracheostomy over a 5-year period. In order to avoid other potential sources of blood loss not related to tracheostomy or ECMO-related blood loss, patients who underwent a recent surgery prior to ECMO or during ECMO (other than tracheostomy) were excluded. RESULTS: Sixty-three patients meeting the inclusion criteria were identified (tracheostomy n=30, non-tracheostomy n=33). Tracheostomy patients were found to require more daily transfusions of red blood cells (RBC) (0.47 [0.20-1.0] vs. 0.23 [0.06-0.40] units/day, p=0.02) and total blood products (0.60 [0.32-1.0] vs. 0.31 [0.10-0.50] units/day, p=0.01). CONCLUSIONS: These results suggest that tracheostomy while on VV-ECMO predisposes patients to increased transfusion burden. Based on previous research, this increased transfusion burden could potentially be linked to increased complications and mortality.

Impact of donor lung pathogenic bacteria on patient outcomes in the immediate post-transplant period.

BACKGROUND: Patient outcomes post-lung transplant remain inferior to other types of solid organ transplantation. We investigated whether the presence of potentially pathogenic bacteria (PPB) in donor lung bronchial cultures was associated with adverse outcomes postoperatively. METHODS: All patients who underwent lung transplantation between August 2015 and April 2017 at the University of Kentucky Medical Center were retrospectively reviewed. Retransplants, patients with bronchiectasis (including cystic fibrosis), and individuals who received organs from donation after cardiac death (DCD) donors were excluded. The remaining subjects were separated into two groups: individuals whose donor bronchial cultures grew PPB, and those whose cultures either returned negative for PPB or were sterile. 30-day mortality rates as well as the incidence of grade 3 primary graft dysfunction (PGD) and acute kidney injury (AKI) at both 24 and 72 hours post-transplant were calculated. The duration of mechanical ventilation postoperatively was also recorded. RESULTS: Thirty two subjects comprised the study population. 20 patients (63%) had growth of PPB on donor cultures, while 12 (37%) did not. Patients with PPB had a significantly greater number of days on the ventilator postoperatively compared to those with no PPB (mean = 11.3 and median = 5.0 vs mean = 5.8 and median = 3.0, respectively, P = 0.0232). Subsequent regression analysis revealed this association to not be influenced by recipient lung allocation score (LAS), donor age, donor smoking history, recipient mean pulmonary artery pressure (mPAP) value, and/or use of cardiopulmonary bypass at the time of transplantation. Neither 30-day survival nor incidence of Grade 3 PGD and AKI at 24 or 72 hours post-transplant differed between the two groups (P > 0.05). CONCLUSION: The recovery of PPB in donor lung cultures was associated with a longer duration of mechanical ventilation postoperatively in lung transplant recipients.

Chromoblastomycosis: A Potential Mimic of Squamous Cell Carcinoma in Transplant Recipients.

Chromoblastomycosis (CBM), also known as chromomycosis is a chronic, granulomatous fungal infection of the skin and subcutaneous tissue. It usually occurs by the traumatic inoculation of various dematiaceous fungi and is more common in the developing world. This condition is rare in North America and the developed world. Herein, we present a case of a 75-year-old man who received a bilateral lung transplant 4 months prior and presented for evaluation of a painful, erythematous papule on the elbow which was diagnosed as CBM. This case highlights that immunosuppression used in patients who undergo solid organ transplantation not only increases the risk of opportunistic infections like CBM but can also be confused for cutaneous squamous cell carcinoma as both these entities share many overlapping clinical and histopathologic features and may be a potential source of misdiagnosis.

Assessing Right Ventricle Over Time in Patients on Veno-Venous Extracorporeal Membrane Oxygenation: Insights From Serial Echocardiography.

Extracorporeal membrane oxygenation (ECMO) is often used in acute respiratory distress syndrome (ARDS) with refractory hypoxemia. There is limited literature highlighting the development of right ventricular (RV) failure while on ECMO. We conducted a retrospective multicenter observational study including 70 patients who were placed on veno-venous (VV)-ECMO for respiratory failure at Mayo Clinic, Jacksonville, and Mayo Clinic, Rochester, between January 2018 and June 2022 and had at least two post-ECMO transthoracic echoes. The primary outcomes were the incidence and progression of RV dysfunction and dilatation. The secondary outcome was in-patient mortality. Among 70 patients in our cohort, 60.6% had a normal RV function at the time of ECMO placement, whereas only 42% had a normal RV function at the second post-ECMO echo. On multinomial regression, a moderate decrease in RV function was associated with ECMO flow (odds ratio [OR] = 2.32, p = 0.001) and ECMO duration (OR = 1.01, p = 0.01). A moderately dilated RV size was also associated with ECMO flow (OR = 2.62, p < 0.001) and ECMO duration (OR = 1.02, p = 0.02). An increasing degree of RV dysfunction was associated with worse outcomes. Our study showed that the increasing duration and flow of VV-ECMO correlated with progressive RV dilatation and dysfunction, which were associated with poor survival.

Pulmonary hypertension before first and second lung transplantation.

BACKGROUND: Pulmonary hypertension (PH) is frequently encountered in patients with advanced lung disease before the first and second lung transplantation. We sought to determine whether there is any relationship between pulmonary hemodynamics obtained before first and second lung transplantation. We also assessed whether PH has prognostic implications in lung transplant patients going for second transplantation. METHODS: We included consecutive adult (16-yr-old or older) patients who underwent lung re-transplantation, between 1997 and 2009, and had right heart catheterization before their first and second lung transplantation. RESULTS: Eighteen patients were included in the study. Age at first transplantation was 50.4 (SD 10.4) yr, and bronchiolitis obliterans syndrome (BOS) in the transplanted lung was the only indication for re-transplantation. PH was observed in 39% of the patients before the first lung transplant and in 56% of the subjects before re-transplantation (p = 0.91). Pre-capillary PH was present in 28% (n = 5) and 33% (n = 6) of the patients before first and second lung transplantation, respectively. None of the hemodynamic variables obtained before the first transplant predicted the development of PH before re-transplantation. PH before re-transplantation did not predict survival or development of BOS after re-transplantation. CONCLUSIONS: PH before initial lung transplantation did not predict the development of PH before the second transplantation. In our cohort, PH before second lung transplantation did not predict outcomes after re-transplantation.

Comparison of sirolimus with azathioprine in a tacrolimus-based immunosuppressive regimen in lung transplantation.

RATIONALE: Lung transplantation has evolved into a life-saving therapy for select patients with end-stage lung diseases. However, long-term survival remains limited because of chronic rejection. Sirolimus is beneficial in preventing cardiac rejection and may decrease rejection after lung transplantation. OBJECTIVES: To determine the potential benefit versus risk of sirolimus in lung transplantation. METHODS: We conducted a multicenter randomized, open label controlled trial comparing sirolimus (SIR) with azathioprine (AZA) in a tacrolimus-based immunosuppressive regimen in lung transplantation. The primary end point was the incidence of acute rejection at 1 year after transplantation between the two study groups. MEASUREMENTS AND MAIN RESULTS: One hundred eighty-one patients were randomized to be included in this study. At 1 year after transplantation, there was no significant difference in the incidence of grade A acute rejection between the two study groups. Similarly, the incidence of chronic rejection and graft survival was no different between the two study groups. Cytomegalovirus infection was decreased in the SIR arm compared with the AZA arm (relative risk, 0.67 [95% confidence interval, 0.55, 0.82]; P < 0.01). There was a higher rate of adverse events leading to early discontinuation of SIR (64%) compared with AZA (49%) during the course of this study. CONCLUSIONS: Sirolimus, an mTOR inhibitor, did not decrease the incidence of acute rejection at 1 year compared with azathioprine in lung transplantation. These results differ from previous results in cardiac and renal transplantation and emphasize the need for multicenter randomized controlled trials in lung transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT 00321906).

Plasma protein biomarkers for primary graft dysfunction after lung transplantation: a single-center cohort analysis.

The clinical use of circulating biomarkers for primary graft dysfunction (PGD) after lung transplantation has been limited. In a prospective single-center cohort, we examined the use of plasma protein biomarkers as indicators of PGD severity and duration after lung transplantation. The study comprised 40 consecutive lung transplant patients who consented to blood sample collection immediately pretransplant and at 6, 24, 48, and 72 h after lung transplant. An expert grader determined the severity and duration of PGD and scored PGD at T0 (6 h after reperfusion), T24, T48, and T72 h post-reperfusion using the 2016 ISHLT consensus guidelines. A bead-based multiplex assay was used to measure 27 plasma proteins including cytokines, growth factors, and chemokines. Enzyme-linked immunoassay was used to measure cell injury markers including M30, M65, soluble receptor of advanced glycation end-products (sRAGE), and plasminogen activator inhibitor-1 (PAI-1). A pairwise comparisons analysis was used to assess differences in protein levels between PGD severity scores (1, 2, and 3) at T0, T24, T48, and T72 h. Sensitivity and temporal analyses were used to explore the association of protein expression patterns and PGD3 at T48-72 h (the most severe, persistent form of PGD). We used the Benjamini-Hochberg method to adjust for multiple testing. Of the 40 patients, 22 (55%) had PGD3 at some point post-transplant from T0 to T72 h; 12 (30%) had PGD3 at T48-72 h. In the pairwise comparison, we identified a robust plasma protein expression signature for PGD severity. In the sensitivity analysis, using a linear model for microarray data, we found that differential perioperative expression of IP-10, MIP1B, RANTES, IL-8, IL-1Ra, G-CSF, and PDGF-BB correlated with PGD3 development at T48-72 h (FDR < 0.1 and p < 0.05). In the temporal analysis, using linear mixed modeling with overlap weighting, we identified unique protein patterns in patients who did or did not develop PGD3 at T48-72 h. Our findings suggest that unique inflammatory protein expression patterns may be informative of PGD severity and duration. PGD biomarker panels may improve early detection of PGD, predict its clinical course, and help monitor treatment efficacy in the current era of lung transplantation.

Technical pearls for swine lung transplantation.

BACKGROUND: Since the advent of ex vivo lung perfusion (EVLP), there has been increased focus on swine models of lung transplantation; however, the anatomic differences between human and swine lungs and the technical challenges in performing porcine lung transplantation are not well described in the surgical literature. METHODS: Surgically important anatomic variations are described, and the technical measures taken to address them during harvest and transplantation are introduced. RESULTS: There are three surgically important anatomic variations in pigs. First, the right cranial lobe bronchus arises directly from the trachea, which makes right lung transplantation technically challenging if not prohibitive. Second, the left hemi-azygos vein is fully developed and courses upward through the posterior mediastinum, where it crosses the left pulmonary hilum and drains directly into the coronary sinus. During transplantation, this vein is ligated and dissected away to expose the underlying left pulmonary hilar structures. Third, the right inferior pulmonary vein crosses the midline to drain into the left atrium immediately adjacent to the left inferior pulmonary vein. During donor lung preparation, the right inferior pulmonary vein is ligated distally from the left atrium, which leaves an adequate atrial cuff around the left sided pulmonary veins for later anastomosis. CONCLUSION: Experimental porcine lung transplantation is technically demanding. We have found recognition of the above described anatomical differences and technical nuances facilitate transplantation and provide reproducible results.

Inspiratory muscle strength training improves weaning outcome in failure to wean patients: a randomized trial.

INTRODUCTION: Most patients are readily liberated from mechanical ventilation (MV) support, however, 10% - 15% of patients experience failure to wean (FTW). FTW patients account for approximately 40% of all MV days and have significantly worse clinical outcomes. MV induced inspiratory muscle weakness has been implicated as a contributor to FTW and recent work has documented inspiratory muscle weakness in humans supported with MV. METHODS: We conducted a single center, single-blind, randomized controlled trial to test whether inspiratory muscle strength training (IMST) would improve weaning outcome in FTW patients. Of 129 patients evaluated for participation, 69 were enrolled and studied. 35 subjects were randomly assigned to the IMST condition and 34 to the SHAM treatment. IMST was performed with a threshold inspiratory device, set at the highest pressure tolerated and progressed daily. SHAM training provided a constant, low inspiratory pressure load. Subjects completed 4 sets of 6-10 training breaths, 5 days per week. Subjects also performed progressively longer breathing trials daily per protocol. The weaning criterion was 72 consecutive hours without MV support. Subjects were blinded to group assignment, and were treated until weaned or 28 days. RESULTS: Groups were comparable on demographic and clinical variables at baseline. The IMST and SHAM groups respectively received 41.9 ± 25.5 vs. 47.3 ± 33.0 days of MV support prior to starting intervention, P = 0.36. The IMST and SHAM groups participated in 9.7 ± 4.0 and 11.0 ± 4.8 training sessions, respectively, P = 0.09. The SHAM group's pre to post-training maximal inspiratory pressure (MIP) change was not significant (-43.5 ± 17.8 vs. -45.1 ± 19.5 cm H2O, P = 0.39), while the IMST group's MIP increased (-44.4 ± 18.4 vs. -54.1 ± 17.8 cm H2O, P < 0.0001). There were no adverse events observed during IMST or SHAM treatments. Twenty-five of 35 IMST subjects weaned (71%, 95% confidence interval (CI) = 55% to 84%), while 16 of 34 (47%, 95% CI = 31% to 63%) SHAM subjects weaned, P = .039. The number of patients needed to be treated for effect was 4 (95% CI = 2 to 80). CONCLUSIONS: An IMST program can lead to increased MIP and improved weaning outcome in FTW patients compared to SHAM treatment. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00419458.

Lung Transplantation in a Patient With COVID-19-Associated Acute Respiratory Failure.

Coronavirus disease 2019 (COVID-19) is currently a significant cause of acute respiratory failure worldwide, leading to irreversible fibrotic lung disease. In patients with persistent respiratory failure after acute COVID-19 infection, lung transplant is an emerging option. Here, we have presented a case where the patient required venovenous extracorporeal membrane oxygenation (VV-ECMO) support for 33 days until a bilateral lung transplant was performed on day 71 after the initial COVID-19 infection. The early outcomes have been favorable. Currently, no guidelines exist for an acceptable time period after initial COVID-19 infection, duration of negative COVID polymerase chain reaction (PCR) testing, or negative Vero cell culture in the setting of persistent positive COVID PCR testing before listing for a lung transplant. Due to a lack of standardized guidelines, this patient was not listed for a lung transplant until the COVID-19 PCRs came negative on days 47 and 49 after the infection.

Ambulatory extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation.

Ambulatory extracorporeal membrane oxygenation (ECMO) has shown promise as a bridge to lung transplantation. The primary goal of ambulatory ECMO is to provide enough gas exchange to allow patients to participate in preoperative physical therapy. Various strategies of ambulatory ECMO are utilized depending upon patients' need. A wide spectrum of ECMO configurations is available to tackle this situation. We discuss those configurations in this article.

Physical Function Measured Prior to Lung Transplantation Is Associated With Posttransplant Patient Outcomes.

INTRODUCTION: The primary objective of this study was to determine whether pretransplant physical function is correlated with posttransplantation outcomes. METHODS: We performed a retrospective study of patients that participated in pretransplantation screening and subsequently underwent lung transplantation. Pretransplant variables of interest included demographics, muscle mass, body composition, physical function, and physical frailty. Correlation tests were performed to assess relationships with significance set at 0.05. RESULTS: Twenty-five patients with a mean age of 57 ± 13 years (68% male) with pretransplant lung allocation score of 45 ± 14 were included. This cohort had a 3-year mortality rate of 32% (n = 8). Pretransplant 4-m gait speed was significantly related to performance on the Short Physical Performance Battery (r = 0.74, P = .02) and distance ambulated on the 6-minute walk test (r = 0.62, P = .07) at hospital discharge. Older age was associated with slower gait speed and worse performance on sit-to-stand testing at hospital discharge (r = -0.76, P = .01 and r = -0.75, P = .01, respectively). Statistically, only diagnosis of cystic fibrosis was associated with 3-year mortality. DISCUSSION: Our study demonstrates that demographic, clinical, and physical function assessed prior to lung transplantation may be indicators of functional recovery.

Discrepancies between clinical and autopsy diagnoses in lung transplant recipients.

We sought to investigate the role of autopsy diagnoses in lung transplantation by comparing the clinically derived cause of death with autopsy deduced cause of death in a cohort of lung transplant recipients. We retrospectively reviewed all consecutive autopsy findings on lung transplant recipients transplanted between March 1994 and March 2007. We reviewed medical records and our lung transplant database to determine the clinical diagnosis of cause of death based on the clinical assessment and discharge summary at the time of death. Our study showed that 21% of the autopsies performed on lung transplant recipients at our institution revealed findings unsuspected at the time of death. Myocardial infarction, pulmonary embolism, high grade acute cellular rejection and infections were the most frequently missed diagnoses. The autopsy remains a useful tool in confirming diagnostic accuracy in lung transplant recipients.

Pregabalin-Induced Myopathy in a Double Lung Transplant Recipient.

Pregabalin is a gamma-aminobutyric acid (GABA) derivative that was commercially approved by the Food and Drug Administration (FDA) in 2004. It is commonly used in the treatment of diabetic neuropathy, peripheral neuropathy, and spinal cord injury. We present the case of a 36-year-old Caucasian male double lung transplant recipient who presented with an 18-month history of fatigue and muscle weakness. He had elevated creatinine kinase level and his muscle biopsy showed evidence of drug-induced myopathy that improved after the cessation of pregabalin. We present a case of drug-induced myopathy as a rare complication of pregabalin therapy in a double lung transplant recipient.

Pleural mesothelial cell transformation into myofibroblasts and haptotactic migration in response to TGF-beta1 in vitro.

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by the development of subpleural foci of myofibroblasts that contribute to the exuberant fibrosis noted in the pulmonary parenchyma. Pleural mesothelial cells (PMC) are metabolically dynamic cells that cover the lung and chest wall as a monolayer and are in intimate proximity to the underlying lung parenchyma. The precise role of PMC in the pathogenesis of pulmonary parenchymal fibrosis remains to be identified. Transforming growth factor (TGF)-beta1, a cytokine known for its capacity to induce proliferative and transformative changes in lung cells, is found in significantly higher quantities in the lungs of patients with IPF. High levels of TGF-beta1 in the subpleural milieu may play a key role in the transition of normal PMC to myofibroblasts. Here we demonstrate that PMC activated by TGF-beta1 undergo epithelial-mesenchymal transition (EMT) and respond with haptotactic migration to a gradient of TGF-beta1 and that the transition of PMC to myofibroblasts is dependent on smad-2 signaling. The EMT of PMC was marked by upregulation of alpha-smooth muscle actin (alpha-SMA), fibroblast specific protein-1 (FSP-1), and collagen type I expression. Cytokeratin-8 and E-cadherin expression decreased whereas vimentin remained unchanged over time in transforming PMC. Knockdown of smad-2 gene by silencing small interfering RNA significantly suppressed the transition of PMC to myofibroblasts and significantly inhibited the PMC haptotaxis. We conclude that PMC undergo EMT when exposed to TGF-beta1, involving smad-2 signaling, and PMC may be a possible source of myofibroblasts in IPF.

Obliterative bronchiolitis in lung allografts removed at retransplant for intractable airway problems.

BACKGROUND AND OBJECTIVE: The role of large airway ischaemia, with resultant airway narrowing, in the development of post-lung transplant bronchiolitis obliterans has not been defined. A determination of clinical bronchiolitis obliterans syndrome (BOS), which is defined as a decline in FEV(1) from a stable post-transplant baseline, is difficult in the setting of airway complications. The aim of this study was to assess the evidence for histological bronchiolitis obliterans in lung allografts removed during retransplantation for severe recurrent airway narrowing. METHODS: Case records and histological findings in allograft lungs removed at retransplantation were retrospectively reviewed. RESULTS: Five lung transplant recipients, who had undergone retransplantation because of severe recalcitrant airway stenosis, were identified. In each case, explant allograft lung pathology revealed evidence of bronchiolitis obliterans. CONCLUSIONS: There is a possible link between airway ischaemia, large airway stenosis and the development of bronchiolitis obliterans, which is the most common cause of death in lung transplant recipients after the first year. These findings may provide an impetus for evaluation of the role of bronchial artery revascularization techniques in the prevention of bronchiolitis obliterans.

Effects of administration of intravenous naloxone on gas exchange in brain-dead lung donors.

OBJECTIVE: To observe the effect of naloxone on the lung function of potential lung transplant donors with neurogenic pulmonary edema. DESIGN AND INTERVENTIONS: Donors aged 16 to 55 years without any factors to contraindicate lung donation (pneumonia, pulmonary contusion, etc) were included. Ventilator settings were standardized to a tidal volume of 10 to 12 mL/kg, an FIO2 of 0.40, and a respiratory rate that kept PCO2 between 35 and 45 mm Hg. Chest physiotherapy, nebulizer treatments, and frequent suctioning were undertaken. Baseline arterial blood gas analysis and an oxygen challenge were performed. The patients were then given 8 to 10 mg of naloxone. Oxygen challenges and arterial blood gas analyses were repeated every 4 to 6 hours. The data were analyzed by using a paired t test, and each patient served as his or her own control. SETTING: These interventions were performed on the 19 LifeQuest donors who met the set criteria from July 2002 to July 2004. RESULTS: The PaO2 on the oxygen challenge immediately after administration of naloxone increased from 329 (SD 177) to 363 (SD 191) mm Hg, although the increase from baseline was not significant. The PaO2 from the second oxygen challenge (median time, 7 hours after administration of naloxone) increased to 413 (SD 177) mm Hg (P<.01).

Outcomes of Lung Transplantation for Cystic Fibrosis in the Setting of Extensively Drug-Resistant Organisms.

INTRODUCTION: Since the largest study on extensively drug-resistant organisms and lung transplantation in patients with cystic fibrosis, there have been innovations and advancements in the treatment of Pseudomonas aeruginosa. RESEARCH QUESTION: What differences exist for patients with cystic fibrosis with a history of extensively drug-resistant infections who undergo lung transplantation despite treatment advances with antimicrobial therapy? STUDY DESIGN: Two-center, retrospective, cohort study conducted in 44 patients with cystic fibrosis chronically infected with extensively drug-resistant organisms who received a lung transplant from January 2008 through August 2016. Patients in the resistant cohort were chronically infected with pan-resistant P aeruginosa, polymyxin-sensitive only, or sensitive to 2 antibiotic classes (polymyxin plus one other); remaining patients with more susceptible P aeruginosa or no P aeruginosa remained in the control cohort. The primary outcome is a composite of patient survival, retransplantation, chronic lung allograft dysfunction, and acute rejection 12 months posttransplant. Categorical variables were analyzed using χ2 testing. The independent samples t test was utilized for continuous variables. RESULTS: There was no difference in the primary outcome (40% vs 37%, P = .831). Differences between patient survival (84% vs 95%, P = .487), the incidence of acute rejection (20% vs 33%, P = .323), and the incidence of chronic lung allograft rejection (12% vs 5%, P = .441) were not different between groups. DISCUSSION: Recipients chronically infected with an extensively resistant P aeruginosa had similar outcomes compared to those infected with more sensitive organisms.