Early Extubation: Who Qualifies Postoperatively in Lung Transplantation?

INTRODUCTION: Early extubation has been adopted in many settings within cardiothoracic surgery, with several advantages for patients. We sought to determine the association of timing of extubation in lung transplant recipients' short- and long-term outcomes. METHODS: Adult, primary lung transplants were identified from the United Network for Organ Sharing database. Recipients were stratified based on the duration of postoperative ventilation: 1) None (NV); 2) <5 Days (<5D); and 3) 5+ Days (5+D). Comparative statistics were performed, and both unadjusted and adjusted survival were analyzed with Kaplan-Meier Methods and a Cox proportional hazard model. A multivariable model including recipient, donor, and transplant characteristics was created to examine factors associated with NV. RESULTS: 28,575 recipients were identified (NV = 960, <5D = 21,959, 5+D = 5656). The NV group had shorter median length of stay (P < 0.01) and lower incidence of postoperative dialysis (P < 0.01). The NV and <5D groups had similar survival, while 5+D recipients had decreased survival (P < 0.01). The multivariable model demonstrated increased donor BMI, center volume, ischemic time, single lung transplant, and transplantation between 2011 and 2015 were associated with NV (P < 0.01 for all). Use of donation after cardiac death donors and transplantation between 2016 and 2021 was associated with postoperative ventilator use. CONCLUSIONS: Patients extubated early after lung transplantation have a shorter median length of stay without an associated increase in mortality. While not all patients are appropriate for earlier extubation, it is possible to extubate patients early following lung transplant. Further efforts are necessary to help expand this practice and ensure its' success for recipients.

Insights into early postoperative acute kidney injury following lung transplantation.

BACKGROUND: Acute kidney injury (AKI) is a common complication after lung transplantation (LT) and is associated with higher cost and mortality. We sought to evaluate the incidence of postoperative AKI, defined as AKI within 14 days of transplant, and identify associated perioperative factors. METHODS: We conducted a single-center, retrospective review of 153 lung transplant recipients. Postoperative AKI was determined using the RIFLE (Risk, Injury, Failure, Loss, End Stage) criteria. Perioperative covariates and their association with postoperative AKI were analyzed using Cox proportional hazards. Kaplan-Meier survival curves were constructed to evaluate patient survival at 1 year and data finalization. A sub-analysis was performed evaluating factors associated with early AKI (within 48 h of transplant) and late AKI. RESULTS: Postoperative AKI occurred in 36.6% of patients with 51.8% of cases occurring within 48 h of LT. Recipient race, transplant type, cardiopulmonary support, and red blood cell administration were associated with postoperative AKI. Survival was significantly lower in patients with postoperative AKI following LT. CONCLUSIONS: Postoperative AKI within 2 weeks of lung transplant is associated with lower short- and long-term survival. Perioperative factors associated with postoperative AKI may be potential points of intervention to minimize AKI development in the future.

Lung transplantation in the septuagenarian can be successfully performed though long-term results impacted by diseases of aging.

BACKGROUND: Advanced age is considered a risk factor for lung transplantation (LTX). We sought to evaluate the long-term outcomes of LTX in the septuagenarian. METHODS: LTX recipients in the UNOS transplant registry (May 1, 2005-June 12, 2020) were stratified into 18-59, 60-69, and > = 70 years of age. Recipient and transplant characteristics were evaluated for survival, cause of death (COD), length of stay (LOS), and complications. A Kaplan-Meier analysis examined long-term survival for all patients stratified by age, specifically looking at cause of death. RESULTS: A total of 27 632 recipients were identified. As recipients aged, we found a decrease in proportion of cystic fibrosis and an increase in restrictive disease while obstructive disease peaked in the 60-69yo cohort (P < .001). Septuagenarians had higher rates of single LTX, male gender, and white race (P < .001). Older recipients had significantly longer donor recovery distances traveled with paradoxical shorter ischemic times, shorter hospital LOS and were transplanted at higher volume centers. There was no difference with in-hospital mortality among groups (P = .5). Acute rejection during initial hospitalization, rejection within 1 year, and post-transplant dialysis incidence decreased with age. Graft failure was a common COD in younger patients while malignancy and cardio/cerebrovascular diseases were common COD in > = 70yo. CONCLUSION: Select septuagenarian LTX candidates may be safely transplanted with relatively few complications. Immunosenescence and conditions of the aged are likely contributing factors to the decreased rejection and graft failure observations. Septuagenarians should not be excluded from LTX consideration based solely on age. Transplantation in septuagenarians should only be done in very selected patients (screened for malignancies and atherosclerotic disease) and these recipients should be carefully followed after transplantation because of these risk factors.

Ex Vivo Lung Perfusion and Primary Graft Dysfunction Following Lung Transplantation: A Contemporary United Network for Organ Sharing Database Analysis.

Background: Primary graft dysfunction (PGD) has detrimental effects on recipients following lung transplantation. Here, we determined the contemporary trends of PGD in a national database, factors associated with the development of PGD grade 3 (PGD3) and ex vivo lung perfusion's (EVLP) effect on this harmful postoperative complication. Methods: The United Network for Organ Sharing database was queried from 2015 to 2023, and recipients were stratified into No-PGD, PGD1/2, or PGD3. The groups were analyzed with comparative statistics, and survival was determined with Kaplan-Meier methods. Multivariable Cox regression was used to determine factors associated with increased mortality. PGD3 recipients were then stratified based on EVLP use prior to transplantation, and a 3:1 propensity match was performed to determine outcomes following transplantation. Finally, logistic regression models based on select criteria were used to determine risk factors associated with the development of PGD3 and mortality within 1 year. Results: A total of 21.4% of patients were identified as having PGD3 following lung transplant. Those with PGD3 suffered significantly worse perioperative morbidity, mortality, and had worse long-term survival. PGD3 was also independently associated with increased mortality. Matched EVLP PGD3 recipients had significantly higher use of ECMO postoperatively; however, they did not suffer other significant morbidity or mortality as compared to PGD3 recipients without EVLP use. Importantly, EVLP use prior to transplantation was significantly associated with decreased likelihood of PGD3 development, while having no significant association with early mortality. Conclusions: EVLP is associated with decreased PGD3 development, and further optimization of this technology is necessary to expand the donor pool.

Thoracic retransplantation: Does time to retransplantation matter?

OBJECTIVE: For some individuals, chronic allograft failure is best treated with retransplantation. We sought to determine if time to retransplantation impacts short- and long-term outcomes for heart or lung retransplant recipients with a time to retransplantation more than 1 year. METHODS: The United Network for Organ Sharing/Organ Procurement and Transplantation Network STAR file was queried for all adult, first-time heart (June 1, 2006, to September 30, 2020) and lung (May 1, 2005, to September 30, 2020) retransplantations with a time to retransplantation of at least 1 year. Patients were grouped according to the tertile of time to retransplantation (tertile 1: 1-7.7 years, tertile 2: 7.7-14.7 years, tertile 3: 14.7+ years; lung: tertile 1: 1-2.8 years, tertile 2: 2.8-5.6 years, tertile 3: 5.6+ years). The primary outcome was survival after retransplantation. Comparative statistics identified differences in groups, and Kaplan-Meier methods and a Cox proportional hazard model were used for survival analysis. RESULTS: After selection, 908 heart and 871 lung retransplants were identified. Among heart retransplant recipients, tertile 1 was associated with male sex, smoking history, higher listing status, and increased mechanical support pretransplant. Tertile 3 had the highest rate of concomitant kidney transplant; however, the incidence of morbidity and in-hospital mortality was similar among the groups. Unadjusted and adjusted analyses revealed no survival difference among all groups. Regarding lung retransplant recipients, tertile 1 was associated with increased lung allocation score, pretransplant hospitalization, and mechanical support. Unadjusted and adjusted survival analyses revealed decreased survival in tertile 1. CONCLUSIONS: Time to retransplant does not appear to affect heart recipients with a time to retransplantation of more than 1 year; however, shorter time to retransplantation for prior lung recipients is associated with decreased survival. Potential lung retransplant candidates with a time to retransplantation of less than 2.8 years should be carefully evaluated before retransplantation.

Clinical Validation of a Plasma Donor-derived Cell-free DNA Assay to Detect Allograft Rejection and Injury in Lung Transplant.

Background: Lung transplant patients are vulnerable to various forms of allograft injury, whether from acute rejection (AR) (encompassing acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), chronic lung allograft dysfunction (CLAD), or infection (INFXN). Previous research indicates that donor-derived cell-free DNA (dd-cfDNA) is a promising noninvasive biomarker for the detection of AR and allograft injury. Our aim was to validate a clinical plasma dd-cfDNA assay for detection of AR and other allograft injury and to confirm and expand on dd-cfDNA and allograft injury associations observed in previous studies. Methods: We measured dd-cfDNA fraction using a novel single-nucleotide polymorphism-based assay in prospectively collected plasma samples paired with clinical-pathologic diagnoses. dd-cfDNA fraction was compared across clinical-pathologic cohorts: stable, ACR, AMR, isolated lymphocytic bronchiolitis, CLAD/neutrophilic-responsive allograft dysfunction (NRAD), and INFXN. Performance characteristics were calculated for AR and combined allograft injury (AR + CLAD/NRAD + INFXN) versus the stable cohort. Results: The study included 195 samples from 103 patients. Median dd-cfDNA fraction was significantly higher for ACR (1.43%, interquartile range [IQR]: 0.67%-2.32%, P = 5 × 10-6), AMR (2.50%, IQR: 2.06%-3.79%, P = 2 × 10-5), INFXN (0.74%, IQR: 0.46%-1.38%, P = 0.02), and CLAD/NRAD (1.60%, IQR: 0.57%-2.60%, P = 1.4 × 10-4) versus the stable cohort. Area under the receiver operator characteristic curve for AR versus stable was 0.91 (95% confidence interval [CI]: 0.83-0.98). Using a ≥1% dd-cfDNA fraction threshold, sensitivity for AR was 89.1% (95% CI: 76.2%-100.0%), specificity 82.9% (95% CI: 73.3%-92.4%), positive predictive value, 51.9% (95% CI: 37.5%-66.3%), and negative predictive value, 97.3% (95% CI: 94.3%-100%). For combined allograft injury area under the receiver operator characteristic curve was 0.76 (95% CI: 0.66-0.85), sensitivity 59.9% (95% CI: 46.0%-73.9%), specificity 83.9% (95% CI: 74.1%-93.7%), positive predictive value, 43.6% (95% CI: 27.6%-59.6%), and negative predictive value, 91.0% (95% CI: 87.9%-94.0%). Conclusions: These results indicate that our dd-cfDNA assay detects AR and other allograft injury. dd-cfDNA monitoring, accompanied by standard clinical assessments, represents a valuable precision tool to support lung transplant health and is appropriate for further assessment in a prospective randomized-controlled study.

Lung transplantation for pulmonary hypertension.

From its identification as a distinct disease entity, understanding and management of pulmonary hypertension has continuously evolved. Diagnostic and therapeutic interventions have greatly improved the prognostic implications of this devastating disease, previously rapidly and uniformly fatal to one chronically managed by multi-disciplinary teams. Improved diagnostic algorithms and active research into biochemical signatures of pulmonary hypertension (PH) have led to earlier diagnosis of PH. Medical therapy has moved from upfront use of continuous intravenous prostaglandins to administration of combinations of oral medications targeting multiple pathways underlying this disease process. In addition to improved medical therapies, recently introduced interventions such as pulmonary endarterectomy and pulmonary artery balloon angioplasty for chronic thromboembolic pulmonary hypertension (CTEPH) give patients an increasing array of treatment options. Despite these many advances, lung transplantation remains the definitive treatment for patients with disease refractory to or progressing on best medical therapy. As our understanding of medical therapy has advanced, so to have best practices for lung transplantation. Recipient selection and approach to organ transplantation techniques have continuously evolved. Mechanical circulatory support has become increasingly employed to bridge patients through lung transplantation in the immediate post transplantation recovery. In this review, we give a history of lung transplantation for PH, an overview of PH, discuss current best practices and look to the future for insights into the care of these patients.

Nalbuphine-induced psychosis treated with naloxone.

PURPOSE: A case of nalbuphine-induced psychosis, which resolved after the administration of naloxone, is described. SUMMARY: A 25-year-old African-American woman with a history of systemic lupus erythematosus was admitted to the hospital for management of cholecystitis. A laparoscopic cholecystectomy was performed, and the patient received multiple doses of i.v. hydromorphone for postoperative pain management. Four days later, shortly after receiving a dose of i.v. nalbuphine for opioid-induced pruritus, she experienced an acute psychotic event, with symptoms including intense headache, akathisia, altered mental status, and formication (a hallucinatory sensation of insects crawling on the skin). The neuropsychiatric symptoms abated within 5 minutes of two consecutively administered doses of i.v. naloxone. During this event, which lasted 25-30 minutes, there was no evidence of metabolic abnormalities and were no signs of infection. The patient did not have a history of mental illness or substance abuse. The patient did not receive further doses of nalbuphine and did not experience similar events during her hospital stay; she was discharged home 10 days later without further complications. According to the algorithm of Naranjo et al., the case was assigned a score of 6, indicating a probable adverse reaction to nalbuphine. CONCLUSION: A patient developed an acute psychotic reaction that was probably secondary to administration of i.v. nalbuphine for opioid-induced pruritus. Evidence supporting this diagnosis included correlation between the timing of administration of nalbuphine and symptom onset and the marked improvement in mentation following the administration of naloxone.