Validation of a novel donor lung scoring system based on the updated lung Composite Allocation Score.

Lung transplantation (LTx) continues to have lower rates of long-term graft survival compared with other organs. Additionally, lung utilization rates from brain-dead donors remain substantially lower compared with other solid organs, despite a growing need for LTx and the significant risk of waitlist mortality. This study aims to examine the effects of using a combination of the recently described novel lung donor (LUNDON) acceptability score and the newly adopted recipient lung Composite Allocation Score (CAS) to guide transplantation. We performed a review of nearly 18 000 adult primary lung transplants from 2015-2022 across the US with retroactive calculations of the CAS value. The medium-CAS group (29.6-34.5) had superior 1-year posttransplant survival. Importantly, the combination of high-CAS (> 34.5) recipients with low LUNDON score (≤ 40) donors had the worst survival at 1 year compared with any other combination. Additionally, we constructed a model that predicts 1-year and 3-year survival using the LUNDON acceptability score and CAS values. These results suggest that caution should be exercised when using marginally acceptable donor lungs in high-priority recipients. The use of the LUNDON score with CAS value can potentially guide clinical decision-making for optimal donor-recipient matches for LTx.

Intravenous Levothyroxine for Unstable Brain-Dead Heart Donors.

BACKGROUND: Hemodynamic instability and myocardial dysfunction are major factors preventing the transplantation of hearts from organ donors after brain death. Intravenous levothyroxine is widely used in donor care, on the basis of observational data suggesting that more organs may be transplanted from donors who receive hormonal supplementation. METHODS: In this trial involving 15 organ-procurement organizations in the United States, we randomly assigned hemodynamically unstable potential heart donors within 24 hours after declaration of death according to neurologic criteria to open-label infusion of intravenous levothyroxine (30 µg per hour for a minimum of 12 hours) or saline placebo. The primary outcome was transplantation of the donor heart; graft survival at 30 days after transplantation was a prespecified recipient safety outcome. Secondary outcomes included weaning from vasopressor therapy, donor ejection fraction, and number of organs transplanted per donor. RESULTS: Of the 852 brain-dead donors who underwent randomization, 838 were included in the primary analysis: 419 in the levothyroxine group and 419 in the saline group. Hearts were transplanted from 230 donors (54.9%) in the levothyroxine group and 223 (53.2%) in the saline group (adjusted risk ratio, 1.01; 95% confidence interval [CI], 0.97 to 1.07; P = 0.57). Graft survival at 30 days occurred in 224 hearts (97.4%) transplanted from donors assigned to receive levothyroxine and 213 hearts (95.5%) transplanted from donors assigned to receive saline (difference, 1.9 percentage points; 95% CI, -2.3 to 6.0; P<0.001 for noninferiority at a margin of 6 percentage points). There were no substantial between-group differences in weaning from vasopressor therapy, ejection fraction on echocardiography, or organs transplanted per donor, but more cases of severe hypertension and tachycardia occurred in the levothyroxine group than in the saline group. CONCLUSIONS: In hemodynamically unstable brain-dead potential heart donors, intravenous levothyroxine infusion did not result in significantly more hearts being transplanted than saline infusion. (Funded by Mid-America Transplant and others; ClinicalTrials.gov number, NCT04415658.).

Clinical outcomes of a prospective randomized comparison of bioreactance monitoring versus pulse-contour analysis in a stroke-volume based goal-directed fluid resuscitation protocol in brain-dead organ donors.

Eighty percent of brain-dead (BD) organ donors develop hypotension and are frequently hypovolemic. Fluid resuscitation in a BD donor is controversial. We have previously published our 4-h goal-directed stroke volume (SV)-based fluid resuscitation protocol which significantly decreased time on vasopressors and increased transplanting four or more organs. The SV was measured by pulse-contour analysis (PCA) or an esophageal doppler monitor, both of which are invasive. Thoracic bioreactance (BR) is a non-invasive portable technology that measures SV but has not been studied in BD donors. We performed a randomized prospective comparative study of BR versus PCA technology in our fluid resuscitation protocol in BD donors. Eighty-four donors (53.1%) were randomized to BR and 74 donors to PCA (46.8%). The two groups were well matched based on 24 demographic, social, and initial laboratory factors, without any significant differences between them. There was no difference in the intravenous fluid infused over the 4-h study period [BR 2271 ± 823 vs. PCA 2230 ± 962 mL; p = .77]. There was no difference in the time to wean off vasopressors [BR 108.8 ± 61.8 vs. PCA 150.0 ± 68 min p = .07], nor in the number of donors off vasopressors at the end of the protocol [BR 16 (28.6%) vs. PCA 15 (29.4%); p = .92]. There was no difference in the total number of organs transplanted per donor [BR 3.25 ± 1.77 vs. PCA 3.22 ± 1.75; p = .90], nor in any individual organ transplanted. BR was equivalent to PCA in clinical outcomes and provides a simple, non-invasive, portable technology to monitor fluid resuscitation in organ donors.

Utilizing computed tomography volumetry for size matching prior to lung transplantation: a case series.

Background: Appropriate size matching between donor and recipient is critical for successful pulmonary transplantation. Although surrogate measurements such as height and gender are often utilized to approximate predicted lung volume, these methods provide only a gross estimation with wide variability and poor predictive value. Case Description: A single center exploratory study was conducted in which four patients underwent lung transplantation (LT) with pre-operative computed tomography (CT) volumetry obtained in both the donor and recipient to facilitate decision making regarding organ size and suitability. In four cases in which CT volumetry was used, the lung volumes calculated using surrogate measurements significantly overestimated both donor and recipient lung volumes quantified by CT volumetric analysis. All recipients underwent successful LT without necessary graft downsizing. Conclusions: This is an initial report of prospectively utilizing CT volumetry as an adjunct to decision-making regarding suitability of donor lungs. In these cases, CT volumetry facilitated the confident acceptance of donor lungs that were initially predicted to be oversized based on other clinical measures.

Potential Role of Computed Tomography Volumetry in Size Matching in Lung Transplantation.

BACKGROUND: Accumulated knowledge on the outcomes related to size mismatch in lung transplantation derives from predicted total lung capacity equations rather than individualized measurements of donors and recipients. The increasing availability of computed tomography (CT) makes it possible to measure the lung volumes of donors and recipients before transplantation. We hypothesize that CT-derived lung volumes predict a need for surgical graft reduction and primary graft dysfunction. METHODS: Donors from the local organ procurement organization and recipients from our hospital from 2012 to 2018 were included if their CT exams were available. The CT lung volumes and plethysmography total lung capacity were measured and compared with predicted total lung capacity using Bland Altman methods. We used logistic regression to predict the need for surgical graft reduction and ordinal logistic regression to stratify the risk for primary graft dysfunction. RESULTS: A total of 315 transplant candidates with 575 CT scans and 379 donors with 379 CT scans were included. The CT lung volumes closely approximated plethysmography lung volumes and differed from the predicted total lung capacity in transplant candidates. In donors, CT lung volumes systematically underestimated predicted total lung capacity. Ninety-four donors and recipients were matched and transplanted locally. Larger donor and smaller recipient lung volumes estimated by CT predicted a need for surgical graft reduction and were associated with higher primary graft dysfunction grade. CONCLUSION: The CT lung volumes predicted the need for surgical graft reduction and primary graft dysfunction grade. Adding CT-derived lung volumes to the donor-recipient matching process may improve recipients' outcomes.

Characteristics of donor lungs declined on site and impact of lung allocation policy change.

OBJECTIVE: National and institutional data suggest an increase in organ discard rate (donor lungs procured but not implanted) after a new lung allocation policy was introduced in 2017. However, this measure does not include on-site decline rate (donor lungs declined intraoperatively). The objective of this study is to examine the impact of the allocation policy change on on-site decline. METHODS: We used a Washington University (WU) and our local organ procurement organization (Mid-America Transplant [MTS]) database to abstract data on all accepted lung offers from 2014 to 2021. An on-site decline was defined as an event in which the procuring team declined the organs intraoperatively, and the lungs were not procured. Logistic regression models were used to investigate potentially modifiable reasons for decline. RESULTS: The overall study cohort comprised 876 accepted lung offers, of which 471 donors were at MTS with WU or others as the accepting center and 405 at other organ procurement organizations with WU as the accepting center. At MTS, the on-site decline rate increased from 4.6% to 10.8% (P = .01) after the policy change. Given the greater likelihood of non-local organ placement and longer travel distance after policy change, the estimated cost of each on-site decline increased from $5727 to $9700. In the overall group, latest partial pressure of oxygen (odds ratio [OR], 0.993; 95% confidence interval [CI], 0.989-0.997), chest trauma (OR, 2.474; CI, 1.018-6.010), chest radiograph abnormality (OR, 2.902; CI, 1.289-6.532), and bronchoscopy abnormality (OR, 3.654; CI, 1.813-7.365) were associated with on-site decline, although lung allocation policy era was unassociated (P = .22). CONCLUSIONS: We found that nearly 8% of accepted lungs are declined on site. Several donor factors were associated with on-site decline, although lung allocation policy change did not have a consistent impact on on-site decline.

Development and validation of the lung donor (LUNDON) acceptability score for pulmonary transplantation.

There is a chronic shortage of donor lungs for pulmonary transplantation due, in part, to low lung utilization rates in the United States. We performed a retrospective cohort study using data from the Scientific Registry of Transplant Recipients database (2006-2019) and developed the lung donor (LUNDON) acceptability score. A total of 83 219 brain-dead donors were included and were randomly divided into derivation (n = 58 314, 70%) and validation (n = 24 905, 30%) cohorts. The overall lung acceptance was 27.3% (n = 22 767). Donor factors associated with the lung acceptance were age, maximum creatinine, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen, mechanism of death by asphyxiation or drowning, history of cigarette use (≥20 pack-years), history of myocardial infarction, chest x-ray appearance, bloodstream infection, and the occurrence of cardiac arrest after brain death. The prediction model had high discriminatory power (C statistic, 0.891; 95% confidence interval, 0.886-0.895) in the validation cohort. We developed a web-based, user-friendly tool (available at https://sites.wustl.edu/lundon) that provides the predicted probability of donor lung acceptance. LUNDON score was also associated with recipient survival in patients with high lung allocation scores. In conclusion, the multivariable LUNDON score uses readily available donor characteristics to reliably predict lung acceptability. Widespread adoption of this model may standardize lung donor evaluation and improve lung utilization rates.

Transplant of organs from donors with positive SARS-CoV-2 nucleic acid testing: A report from the organ procurement and transplantation network ad hoc disease transmission advisory committee.

BACKGROUND: Decisions to transplant organs from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test-positive (NAT+) donors must balance risk of donor-derived transmission events (DDTE) with the scarcity of available organs. METHODS: Organ Procurement and Transplantation Network (OPTN) data were used to compare organ utilization and recipient outcomes between SARS-CoV-2 NAT+ and NAT- donors. NAT+ was defined by either a positive upper or lower respiratory tract (LRT) sample within 21 days of procurement. Potential DDTE were adjudicated by OPTN Disease Transmission Advisory Committee. RESULTS: From May 27, 2021 (date of OTPN policy for required LRT testing of lung donors) to January 31, 2022, organs were recovered from 617 NAT+ donors from all OPTN regions and 53 of 57 (93%) organ procurement organizations. NAT+ donors were younger and had higher organ quality scores for kidney and liver. Organ utilization was lower for NAT+ donors compared to NAT- donors. A total of 1241 organs (776 kidneys, 316 livers, 106 hearts, 22 lungs, and 21 other) were transplanted from 514 NAT+ donors compared to 21 946 organs from 8853 NAT- donors. Medical urgency was lower for recipients of NAT+ liver and heart transplants. The median waitlist time was longer for liver recipients of NAT+ donors. The match run sequence number for final acceptor was higher for NAT+ donors for all organ types. Outcomes for hospital length of stay, 30-day mortality, and 30-day graft loss were similar for all organ types. No SARS-CoV-2 DDTE occurred in this interval. CONCLUSIONS: Transplantation of SARS-CoV-2 NAT+ donor organs appears safe for short-term outcomes of death and graft loss and ameliorates the organ shortage. Further study is required to assure comparable longer term outcomes.

The 20-year paradigm shift toward organ recovery centers: 2500 donors at Mid-America Transplant and broader adoption across the United States.

On March 1, 2001, Mid-America Transplant, the organ procurement organization (OPO) located in St Louis, Missouri, performed the first organ recovery of a brain-dead donor in a hospital-independent, free-standing, organ recovery center (ORC), with successful transplantation of a liver. This was the inception of a paradigm shift in donor management and organ procurement, moving away from the traditional method of using the donor hospital. In the last 20 years, many advances have occurred in the ORC. Brain-dead donors are moved within hours of authorization to fully equipped intensive care units. Some ORCs are equipped with computed tomography scanners, portable radiography, laboratory facilities, bronchoscopy, and a cardiac catheterization laboratory. ORCs have dedicated surgical suites, and operating time is frequently during the day and is rarely delayed. Donor management in an ORC is more consistent, efficient, and effective than that in a donor hospital, and studies have demonstrated increased organ yield. Multiple studies have demonstrated a cost benefit of an ORC as well as providing an ideal environment for donor research studies. Currently, there are 24 of 57 OPOs that are using an independent or hospital-based ORC to manage their donors. We review the history and describe the current state of ORCs.

The benefits of initiating continuous renal replacement therapy after brain death in organ donors with oligoanuric acute kidney injury.

Acute kidney injury (AKI) in deceased organ donors is increasing due to the escalation in anoxic brain-deaths. The management of an organ donor with oligoanuric AKI is frequently curtailed due to hemodynamic and electrolyte instability. Although continuous renal replacement therapy (CRRT) corrects the effects of AKI, it is rarely started after the diagnosis of brain-death (BD). Since 2017, we have initiated CRRT in organ donors with oligoanuric AKI to allow more time to stabilize the donor and improve the function of the thoracic organs. We now report our experience with the first 27 donors with oligoanuric AKI that received CRRT after the diagnosis of BD, with organs transplanted as the primary outcome. The average duration of CRRT was 30.1 ± 14.4 h and the mean ultrafiltration volume was 5141 ± 4272 ml. The time from BD declaration to cross clamp was significantly longer in the CRRT group versus a historical cohort with oligoanuric AKI that was not dialyzed (62.8 ± 18.3 vs. 37.1 ± 14.9 h; P < .01). The mean number of total organs transplanted per donor in the CRRT group was greater than the historical cohort, 2.9 ± 1.7 vs. 1.4 ± .6 (P = .< 01), respectively. The mean number of thoracic organs transplanted per donor also increased between the two groups, 1.4 ± 1.2 versus .6 ± .9 (P = .02). Thirty-seven percent of the kidneys were successfully transplanted with a mean serum creatinine of 1.4 mg/dl at 6 months. We suggest that OPOs consider starting CRRT in organ donors with oligoanuric AKI to possibly increase the number of organs transplanted.

Deceased Donor Procurement Biopsy Practices, Interpretation, and Histology-Based Decision-Making: A Survey of US Kidney Transplant Centers.

Introduction: The utility of kidney procurement biopsies is controversial. Understanding the current landscape of how clinicians obtain and use biopsies in organ evaluation may help inform consensus-building efforts. Methods: An electronic survey was distributed to clinicians at US kidney transplant programs (April 22, 2021-June 30, 2021) to evaluate donor biopsy indications, frequency, processing and interpretation, and impact of findings on practices. Results: Responses from staff involved in organ acceptance (73% surgeons, 20% nephrologists, 6% coordinators) at 95 transplant centers were analyzed, representing 40% of US transplant centers and 50% of recent deceased donor kidney transplant volume. More than a third of centers (35%) reported obtaining procurement biopsies on most-to-all kidneys. Most clinicians decided when to biopsy jointly with the Organ Procurement Organization (OPO) (82%) based on formal criteria for the decision (72%), although 41% reported having requested a biopsy outside of the criteria. Most respondents used a semiquantitative scoring system for interpretation (57%). Many respondents reported rarely or never having access to renal specialty pathologists (37%) or to telepathology (59%). Most respondents reported that a favorable biopsy result would encourage them to accept a "marginal" donor kidney (72%); nearly half (46%) indicated that an unfavorable biopsy result would lead to decline of a standard criteria kidney. Conclusion: Procurement biopsies are commonly used in organ acceptance decisions despite inconsistent access to experienced renal pathologists and heterogeneous approaches to criteria, scoring, and interpretation. Ongoing study and consensus building are needed to direct procurement biopsy practice toward increasing organ utilization and reducing allocation inefficiency.

Uncertainty analysis of chest X-ray lung height measurements and size matching for lung transplantation.

Background: Errors in measuring chest X-ray (CXR) lung heights could contribute to the occurrence of size-mismatched lung transplant procedures. Methods: We first used Bland-Altman analysis for repeated measures to evaluate contributors to measurement error of chest X-ray lung height. We then applied error propagation theory to assess the impact of measurement error on size matching for lung transplantation. Results: A total 387 chest X-rays from twenty-five donors and twenty-five recipients were measured by two raters. Individual standard deviation for lung height differences were independent of age, sex, donor vs. recipient, diagnostic group and race/ethnicity and all were pooled for analysis. Bias between raters was 0.27 cm (±0.03) and 0.22 cm (±0.06) for the right and left lung respectively. Within subject variability was the biggest contributor to error in measurement, 2.76 cm (±0.06) and 2.78 cm (±0.2) for the right and left lung height. A height difference of 4.4 cm or more (95% CI: ±4.2, ±4.6 cm) between the donor and the recipient right lung height has to be accepted to ensure matching for at least 95% of patients with the same true lung height. This difference decreases to ±1.1 cm (95% CI: ±0.9, ±1.3 cm) when the average from all available chest X-rays is used. The probability of matching a donor and a recipient decreases with increasing true lung height difference. Conclusions: Individual chest X-ray lung heights are imprecise for the purpose of size matching in lung transplantation. Averaging chest X-rays lung heights reduced uncertainty.

Dissemination and Implementation Science in Cardiothoracic Surgery: A Review and Case Study.

Dissemination and implementation (D&I) science is the practice of taking evidence-based interventions and sustainably incorporating them into routine clinical practice. As a relatively young field, D&I techniques are underutilized in cardiothoracic surgery. This review offers an overview of D&I science from the context of the cardiothoracic surgeon. First, we provide a general introduction to D&I science and basic terminology that is used in the field. Second, to illustrate D&I techniques in a real-world example, we discuss a case study for implementing lung protective management strategies for lung donor optimization nationally. Finally, we discuss challenges to successful implementation that are unique to cardiothoracic surgery and give several examples of evidence-based interventions that have been poorly implemented into surgical practice. We also provide examples of successful D&I interventions-including deimplementation strategies-from other surgical subspecialties. We hope that this review offers additional tools for cardiothoracic surgeons to explore when introducing evidence-based interventions into routine practice.

Specialized Donor Care Facility Model and Advances in Management of Thoracic Organ Donors.

BACKGROUND: Donor hearts and lungs are more susceptible to the inflammatory physiologic changes that occur after brain death. Prior investigations have shown that protocolized management of potential organ donors can rehabilitate donor organs that are initially deemed unacceptable. In this review we discuss advances in donor management models with particular attention to the specialized donor care facility model. In addition we review specific strategies to optimize donor thoracic organs and improve organ yield in thoracic transplantation. METHODS: We performed a literature review by searching the PubMed database for medical subject heading terms associated with organ donor management models. We also communicated with our local organ procurement organization to gather published and unpublished information first-hand. RESULTS: The specialized donor care facility model has been shown to improve the efficiency of organ donor management and procurement while reducing costs and minimizing travel and its associated risks. Lung protective ventilation, recruitment of atelectatic lung, and hormone therapy (eg, glucocorticoids and triiodothyronine/thyroxine) are associated with improved lung utilization rates. Stroke volume-based resuscitation is associated with improved heart utilization rates, whereas studies evaluating hormone therapy (eg, glucocorticoids and triiodothyronine/thyroxine) have shown variable results. CONCLUSIONS: Lack of high-quality prospective evidence results in conflicting practices across organ procurement organizations, and best practices remain controversial. Future studies should focus on prospective, randomized investigations to evaluate donor management strategies. The specialized donor care facility model fosters a collaborative environment that encourages academic inquiry and is an ideal setting for these investigations.

A multicenter randomized placebo-controlled trial of intravenous thyroxine for heart-eligible brain-dead organ donors.

BACKGROUND: Brain death frequently induces hemodynamic instability and cardiac stunning. Impairments in cardiac performance are major contributors to hearts from otherwise eligible organ donors not being transplanted. Deficiencies in pituitary hormones (including thyroid-stimulating hormone) may contribute to hemodynamic instability, and replacement of thyroid hormone has been proposed as a means of improving stability and increasing hearts available for transplantation. Intravenous thyroxine is commonly used in donor management. However, small controlled trials have not been able to demonstrate efficacy. METHODS: This multicenter study will involve organ procurement organizations (OPOs) across the country. A total of 800 heart-eligible brain-dead organ donors who require vasopressor support will be randomly assigned to intravenous thyroxine for at least 12 h or saline placebo. The primary study hypotheses are that thyroxine treatment will result in a higher proportion of hearts transplanted and that these hearts will have non-inferior function to hearts not treated with thyroxine. Additional outcome measures are the time to achieve hemodynamic stability (weaning off vasopressors) and improvement in cardiac ejection fraction on echocardiography. DISCUSSION: This will be the largest randomized controlled study to evaluate the efficacy of thyroid hormone treatment in organ donor management. By collaborating across multiple OPOs, it will be able to enroll an adequate number of donors and be powered to definitively answer the critical question of whether intravenous thyroxine treatment increases hearts transplanted and/or provides hemodynamic benefits for donor management. TRIAL REGISTRATION: ClinicalTrials.gov NCT04415658 . Registered on June 4, 2020.

Disparities in Deceased Organ Donor Research Authorization: Experience at One Organ Procurement Organization and Call for National Conversations.

INTRODUCTION: Research with deceased donor organs can provide an important platform for studying interventions to improve organ use and outcomes after authorization from the next-of-kin (NOK) or before death by the decedent (i.e., first-person authorization [FPA]). To date, information on authorization rates across donor subgroups is lacking. METHODS: We performed a retrospective chart review of all 690 deceased organ donors from January 2017 to December 2019 at a midsized Midwestern organ procurement organization (OPO). Multivariable logistic regression was used to assess associations between donor factors and research decline (adjusted odds ratio [aOR], 95% confidence interval [CI]). RESULTS: Electronic records for all 690 deceased donors were reviewed. Of these, 659 (95.5%) yielded at least one transplanted organ. Overall, research was declined in 10.8% of donations. Compared to White donors, research decline was higher for Black (16.0% vs. 8.9%; aOR, 1.87; 95% CI, 1.03-3.40; P = 0.04) and other non-White donors (24.0% vs. 8.9%; aOR, 4.21; 95% CI, 1.02-17.39; P = 0.05). Unadjusted research decline trended higher for Hispanic donors versus non-Hispanic donors (23.1% vs. 10.5%; P = 0.14). Compared to donors age <40 years, research decline trended higher for donors age ≥65 years (16.7% vs. 11.8%; aOR, 4.87; 95% CI, 1.12-21.05; P = 0.03), whereas research decline was 55% lower when donors provided FPA (7.3% vs 15.0%; aOR, 0.45; 95% CI, 0.27-0.76; P = 0.003). CONCLUSIONS: Deceased donor research authorization decline is higher for Black, other non-White, and older donors, but lower when the descendent provides FPA. Identification of disparities in research authorization may stimulate educational strategies to reduce barriers to scientific investigations directed at optimizing the outcomes of organ donation.