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.

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.

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.

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.

Whole Blood Thiamine in Organ Donors After the Neurologic Determination of Death.

INTRODUCTION: Metabolic resuscitation of organ donors and the attenuation of oxidative stress incurred by organs following brain death and transplantation have the potential to improve organ yield and allograft function. Thiamine (vitamin B1) is a vital coenzyme in both energy metabolism and the production of antioxidants that has not been studied in the donor population. RESEARCH AIM: To determine the frequency of subclinical thiamine deficiency in brain-dead organ donors and its correlation with demographics, length of hospitalization, donor management, lactic acidosis, and the requirement for vasoactive support. DESIGN: Prospective cohort study of brain-dead donors managed at a single organ procurement organization's organ recovery facility. RESULTS: A total 64 donors were enrolled; 24 donors had thiamine levels drawn upon arrival and 40 donors had levels drawn at the time of organ procurement. Whole blood thiamine levels were inversely correlated with the time from death (P = .007) and 20% (8/40) of donors had levels below the normal range at the time of organ procurement. Demographic features of the donor were not associated with thiamine levels although longer hospital stays prior to death were associated with lower levels (P < .05). The presence and resolution of lactic acidosis was not associated with whole blood thiamine level. Higher thiamine levels were associated with earlier discontinuation of vasoactive support (P = .04). DISCUSSION: Whole blood thiamine deficiency was not uncommon at the time of organ procurement. Thiamine may be associated with the requirement for hemodynamic support.

Different-team procurements: A potential solution for the unintended consequences of change in lung allocation policy.

The new lung allocation policy has led to an increase in distant donors and consequently enhanced logistical burden of procuring organs. Though early single-center studies noted similar outcomes between same-team transplantation (ST, procuring team from transplanting center) and different-team transplantation (DT, procuring team from different center), the efficacy of DT in the contemporary era remains unclear. In this study, we evaluated the trend of DT, rate of transplanting both donor lungs, 1-year graft survival, and risk of Grade 3 primary graft dysfunction (PGD) using the Scientific Registry of Transplant Recipient (SRTR) database from 2006 to 2018. A total of 21619 patients (DT 2085, 9.7%) with 19837 donors were included. Utilization of DT decreased from 15.9% in 2006 to 8.5% in 2018. Proportions of two-lung donors were similar between the groups, and DT had similar 1-year graft survival as ST for both double (DT, HR 1.108, 95% CI 0.894-1.374) and single lung transplants (DT, HR 1.094, 95% CI 0.931-1.286). Risk of Grade 3 PGD was also similar between ST and DT. Given our results, expanding DT may be a feasible option for improving lung procurement efficiency in the current era, particularly in light of the COVID-19 pandemic.

Ventilation in the prone position improves oxygenation and results in more lungs being transplanted from organ donors with hypoxemia and atelectasis.

BACKGROUND: Hypoxemia is the most common barrier to lungs being transplanted from eligible organ donors who are brain dead (BD). Atelectasis is the principal reversible contributing factor to hypoxemia after brain death. We evaluated prospectively whether ventilation in the prone position in donors who are BD would reverse atelectasis, improve oxygenation, and result in more lungs being transplanted. METHODS: Organ donors managed at the recovery center of 1 organ procurement organization over a 2-year period who exhibited hypoxemia (partial pressure of arterial oxygen [PaO2]/fraction of inspired oxygen of <300 mm Hg) and had evidence of atelectasis were ventilated in the prone position for 12 hours or longer during donor management. A subset underwent computed tomography (CT) imaging to quantify the degree of atelectasis before and after prone positioning. Outcomes were compared with those of a control group with hypoxemia and atelectasis managed similarly but in the supine position in the previous 2 years. RESULTS: A total of 40 lung-eligible donors who were BD with hypoxemia and atelectasis were managed in a prone position and compared with 79 donors in supine position. Baseline PaO2 was similar between the prone and the supine groups (194 ± 78 vs 177 ± 77 mm Hg, p = 0.26) but increased more in the prone group at 4 hours (by 113 vs 54 mm Hg, p = 0.001) and remained 74-mm Hg higher at 12 hours (340 vs 266 mm Hg, p = 0.0006). CT-graded atelectasis was significantly reduced after ventilation in the prone position but persisted in the supine group (p = 0.001). Final PaO2 was not significantly higher (344 vs 306, p = 0.12), but lungs were more often transplanted in the prone group (45% vs 24%, p = 0.03). CONCLUSIONS: Ventilation in the prone position reverses atelectasis and rapidly and sustainably improves oxygenation in organ donors who are BD with hypoxemia. This effect appears to translate into more lungs being transplanted.

Donor management using a specialized donor care facility is associated with higher organ utilization from drug overdose donors.

Drug overdoses have tripled in the United States over the last two decades. With the increasing demand for donor organs, one potential consequence of the opioid epidemic may be an increase in suitable donor organs. Unfortunately, organs from donors dying of drug overdose have poorer utilization rates than other groups of brain-dead donors, largely due to physician and recipient concerns about viral disease transmission. During the study period of 2011 to 2016, drug overdose donors (DODs) account for an increasingly greater proportion of the national donor pool. We show that a novel model of donor care, known as specialized donor care facility (SDCF), is associated with an increase in organ utilization from DODs compared to the conventional model of hospital-based donor care. This is likely related to the close relationship of the SDCF with the transplant centers, leading to improved communication and highly efficient donor care.

Point-of-care blood gas analyzers have an impact on the acceptance of donor lungs for transplantation.

An organ donor PaO2 above 40 kPa is generally required for lung transplantation. Point-of-care (POC) blood gas analyzers are commonly used by organ procurement organizations (OPO) but may underestimate the PaO2 at high levels. We hypothesized that changing to a more accurate blood gas analyzer would result in additional lungs transplanted. All PaO2 measurements on organ donors managed at one OPO's recovery center were performed on an i-STAT POC analyzer prior to October 2015, and on a GEM 4000 subsequently. For 24 weeks, all blood gases were tested simultaneously on both analyzers. We compared lung outcomes of 147 donors in the year prior to this change (using the i-STAT) with 56 donors in the 24-week study period (using the GEM 4000 for lung allocation). When the PaO2 was above 40 kPa, the i-STAT PaO2 was 7.2 kPa lower on average than the GEM 4000. When the GEM PaO2 measured between 40 and 50 kPa, the corresponding i-STAT PaO2 value registered less than 40 kPa 25 out of 48 times (52%), with an average difference of 7.3 kPa (SD = 2.9). The rate of lungs transplanted using the GEM 4000 was 48% compared with 35% in the year prior using the i-STAT (p = .11), with equivalent recipient outcomes. The i-STAT analyzer underestimated the PaO2 above 40 kPa and changing to a more accurate PaO2 analyzer may increase lungs transplanted.

Shipping Lungs Greater Distances Increases Costs Without Cutting Waitlist Mortality.

BACKGROUND: On November 24, 2017, a change in lung allocation policy was initiated to replace the donor service area with a 250-nautical-mile radius circle around the donor hospital. We aim to analyze the consequences of this change, including organ acquisition cost and transplant outcomes, at the national level. METHODS: Data on adult patients undergoing lung transplantation between April 27, 2017, and June 22, 2018 (30 weeks before to 30 weeks after allocation policy change) were extracted from the Scientific Registry of Transplant Recipients database. Patients were classified into pre-change and post-change subgroups. Six-month overall survival was evaluated by Kaplan-Meier analysis. Organ acquisition costs were compared between the pre-change and post-change groups. RESULTS: Of the 3317 adult patients removed from the waiting list during the study period (pre-change 1637 vs post-change 1680), 2734 underwent transplantation (pre-change 1371 of 1637 [83.8%] vs post-change 1363 of 1680 [81.1%]), and 382 died or became too sick to be transplanted (pre-change 168 of 1637 [10.3%] vs post-change 214 of 1680 [12.7%], P = .077). Six-month survival rates of transplanted patients were similar between the two groups. However, average organ acquisition costs increased after policy change (pre-change $50,735 ± $10,858 vs post-change $53,440 ± $10,247, P < .001) with an increase in nonlocal donors (pre-change 44.3% vs post-change 68.9%, P < .001). CONCLUSIONS: Organ acquisition costs and resource utilization increased with the new lung allocation policy, whereas deaths on the waiting list or after transplantation did not decrease. Further optimization of the allocation policy is necessary to balance access to transplant and proper stewardship of human and financial resources.

A stroke volume-based fluid resuscitation protocol decreases vasopressor support and may increase organ yield in brain-dead donors.

Brain-dead donors are frequently hypovolemic and hypotensive requiring vasopressor support. We studied a stroke volume-based fluid resuscitation and vasopressor weaning protocol prospectively on 64 hypotensive donors, with a recent control cohort of 30 hypotensive donors treated without a protocol. Stroke volume was measured every 30 minutes for 4 hours by pulse contour analysis or esophageal Doppler. A 500 mL saline fluid bolus was infused over 30 minutes and repeated if the stroke volume increased by 10%. No fluid was infused if the stroke volume did not increase by 10%. Vasopressors were weaned every 10 minutes if the mean arterial pressure was greater than 65 mm Hg. The protocol group received 1937 ± 906 mL fluid compared to 1323 ± 919 mL in the control group (P = .003). Mean time on vasopressors was decreased from 957.6 ± 586.2 to 176.3 ± 82.2 minutes (P<.001). Donors in the protocol group were more likely to donate four or more organs than donors in the control group (OR = 4.114, 95% Confidence Interval (CI) = 1.003-16.876). While more organs were transplanted per donor in the protocol group (3.39 ± 1.52) than in the control group (2.93 ± 1.44) (P = .268), the difference did not reach statistical significance. A goal-directed fluid resuscitation protocol decreased organ ischemia and may increase organs transplanted.

Unintended consequences of changes to lung allocation policy.

Organ allocation for transplantation aims to balance the principles of justice and medical utility to optimally utilize a scarce resource. To address practical considerations, the United States is divided into 58 donor service areas (DSA), each constituting the first unit of allocation. In November 2017, in response to a lawsuit in New York, an emergency action change to lung allocation policy replaced the DSA level of allocation for donor lungs with a 250 nautical mile circle around the donor hospital. Similar policy changes are being implemented for other organs including heart and liver. Findings from a recent US Department of Health and Human Services report, supplemented with data from our institution, suggest that the emergency policy has not resulted in a change in the type of patients undergoing lung transplantation (LT) or early postoperative outcomes. However, there has been a significant decline in local LT, where donor and recipient are in the same DSA. With procurement teams having to travel greater distances, organ ischemic time has increased and median organ cost has more than doubled. We propose potential solutions for consideration at this critical juncture in the field of transplantation. Policymakers should choose equitable and sustainable access for this lifesaving discipline.