Published ahead of print on June 23, 2006, doi:10.1164/rccm.200603-432OC
© 2006 American Thoracic Society doi: 10.1164/rccm.200603-432OC
Impact of a Lung Transplantation Donor–Management Protocol on Lung Donation and Recipient OutcomesDivision of Pulmonary and Critical Care Medicine, Division of Cardiothoracic Surgery, and Center for Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio; Veterans Evidence-based Research, Dissemination, and Implementation Center (VERDICT) Center of Excellence, Audie L. Murphy VA Hospital; and the Texas Organ Sharing Alliance, San Antonio, Texas Correspondence and requests for reprints should be addressed to Luis F. Angel, M.D., 7703 Floyd Curl Drive, San Antonio, TX 78229. E-mail: angel{at}uthscsa.edu
Rationale: One of the limitations associated with lung transplantation is the lack of available organs. Objective: To determine whether a lung donor–management protocol could increase the number of lungs for transplantation without affecting the survival rates of the recipients. Methods: We implemented the San Antonio Lung Transplant protocol for managing potential lung donors according to modifications of standard criteria for donor selection and strategies for donor management. We then compared information gathered during a 4-yr period, during which the protocol was used with information gathered during a 4-yr period before protocol implementation. Primary outcome measures were the procurement rate of lungs and the 30-d and 1-yr survival rates of recipients. Main Results: We reviewed data from 711 potential lung donors. The mean rate of lung procurement was significantly higher (p < 0.0001) during the protocol period (25.5%) than during the pre-protocol period (11.5%), with an estimated risk ratio of 2.2 in favor of the protocol period. More patients received transplants during the protocol period (n = 121) than during the pre-protocol period (n = 53; p < 0.0001). Of 98 actual lung donors during the protocol period, 53 (54%) had initially been considered poor donors; these donors provided 64 (53%) of the 121 lung transplants. The type of donor was not associated with significant differences in recipients' 30-d and 1-yr survival rates or any clinical measures of adequate graft function. Conclusions: The protocol was associated with a significant increase in the number of lung donors and transplant procedures without compromising pulmonary function, length of stay, or survival of the recipients.
Key Words: lung recipients • lung transplantation • organ donation • organ donor • survival Lung transplantation is often the only available treatment option for patients with end-stage lung disease. Because of important advances in surgical techniques and pharmacologic management, lung transplantation offers many patients an improved quality of life and an increased likelihood of survival (1). Despite these advances, however, few patients benefit from transplantation because of the scarcity of lung donors. In 2005, nearly 3,000 patients were on the national waiting list for lung transplantation. Only 35% of these patients received transplants, and 10% died while awaiting a graft (2). Approximately half of the listed patients waited more than 2 yr before receiving a transplant. This trend worsens each year; the number of new additions to the waiting list annually is nearly double the number of patients who receive transplants (2). The lack of organ donors is most serious for patients awaiting lung transplantation, in part because lungs are procured from only 16% of organ donors (2). Multiple factors influence this low procurement rate; among them are acute lung injury after brain death, pneumonia, aspiration, and atelectasis (3, 4). In addition, many potentially usable organs are excluded because of current standard criteria for lung donors that have been in existence for more than two decades (4–8). Several strategies have been proposed for reducing the shortage of lung donors, including increasing communication between transplant centers and organ procurement organizations (OPOs), performing active medical management of potential lung donors, and modifying (or extending) the currently accepted criteria for donor selection (6, 7, 9–15). These published strategies contributed to our development of the San Antonio Lung Transplant (SALT) donor-management protocol. We hypothesized that implementing the SALT protocol would increase the lung procurement rate without adversely affecting the overall survival rate of lung transplant recipients. The principal aim of this study was to determine the impact of the SALT donor-management protocol on the rates of lung donation and the clinical outcomes of lung transplant recipients. Some of the results of this study have been previously presented in abstract form (16–19).
Methods, Patients, and Study Sites In September 2001, we implemented the SALT donor-management protocol for all potential organ donors evaluated for candidacy by the Texas Organ Sharing Alliance (TOSA) in San Antonio, Texas. The TOSA medical board and the Institutional Review Board of the University of Texas Health Science Center at San Antonio approved the research protocol. TOSA provided data regarding the procurement of donor organs for the period from September 1, 1997, through August 31, 2005; thus, we were able to compare data from the 4 yr before initiation of the SALT protocol with data from the 4 yr after its initiation. Donors older than 65 or younger than 10 yr of age and non–heart-beating donors were excluded from this review. The remaining donors were considered potential lung donors. Two of the investigators (J.E.C., G.B.C.), who were not involved with the care of any of the donors or recipients, applied our revised donor criteria and recipient outcomes to the appropriate databases.
SALT Protocol Components and Implementation
Active donor evaluation and management.
Modified donor selection criteria.
Revised donor classification.
Donor selection for lung transplantation.
Data Abstraction
Endpoints
Statistical Analyses Kaplan-Maier survival estimates were determined for lung transplant recipients during the pre-SALT and SALT periods. The recipients were classified by donor type: ideal, extended, poor to ideal, and poor to extended. Differences between the groups were assessed with a log-rank test; statistical significance was assigned at p < 0.05. A bootstrap multiple comparison procedure with Bonferroni adjustment was used to compare recipients for differences in intubation days, LOS in the ICU, total LOS in the hospital, 24-h PaO2/FIO2, and FEV1 at 12 mo. Analyses were performed with SAS statistical software (SAS Institute, Inc., Cary, NC), Stata (StataCorp LP, College Station, TX), and R (Free Software Foundation, Inc., Boston, MA).
We implemented the SALT protocol in September 2001. A total of 711 potential lung donors were evaluated for candidacy at 38 different medical centers during the 8-yr study period: 330 before the introduction of the SALT protocol (pre-SALT) and 381 after its initiation (SALT). Sixty-four percent of the potential lung donors were evaluated for candidacy at six large medical centers. The groups were similar in most baseline characteristics: The mean donor age was 36 yr, and the cause of brain death was equally divided between traumatic and medical conditions (Table 1). Approximately 60% of the donors underwent intubation at the hospital; the mean length of intubation before pronouncement of brain death was 2.5 d. The mean PaO2/FIO2 before brain death was significantly lower (p < 0.0001) for the SALT donor group than for the pre-SALT donor group (Table 1).
Endpoints: Lung Donation and Transplantation Rates The mean lung procurement rate from all potential donors was 11.5% (95% CI, 8.1–15.0) during the pre-SALT period and 25.5% (95% CI, 21.1–29.8) during the SALT period; there was an estimated risk ratio of 2.2 (95% CI, 1.1–4.4; p < 0.001) in favor of the SALT period (Figures 1 and 2). The number of potential lung donors who were consented for donation was significantly higher during the SALT period (87%) than during the pre-SALT period (76%; p < 0.001), as was the number of consented donors who became actual lung donors (15.2% pre-SALT; 29.2% SALT; p < 0.0001; Figure 1). The rate of lung offers from potential donors to transplant centers was 21% during the pre-SALT period and 57% during the SALT period (p < 0.001). Despite this increase in the rate of lung offers, there was no significant difference in the number of lungs rejected by transplant centers (43% pre-SALT; 55% SALT; p = 0.10). The procurement rate of lungs per lung donor was similar during both periods (1.57 lungs per donor pre-SALT; 1.7 lungs per donor SALT; p = 0.75). As a result of the increased number of donor lungs, the number of patients who received a lung transplant increased significantly, from 53 during the pre-SALT period to 121 during the SALT period (p < 0.0001; Figure 1). Thirty-eight percent of the lung transplantations were performed at eight transplant centers outside the TOSA region during the pre-SALT period, whereas 33% were performed at 14 transplant centers outside the region during the SALT period (p = 0.60).
Donor Classification After implementation of the SALT protocol, 254 (76%) lung donors were initially classified as poor, 37 (11%) as ideal, and 42 (13%) as extended donors (Table 2). The most frequently observed characteristic of the donors initially classified as poor donors was PaO2/FIO2 < 300 (67% of donors), followed by infiltrates on chest radiograph (58%) and abnormal results from bronchoscopy (28%). Sixteen poor donors had only abnormal results from bronchoscopy, with PaO2/FIO2 > 300 and no findings demonstrated by chest radiography.
Among the 124 extended donors, the most commonly seen extended characteristic was a positive result from Gram staining (80 of 124; 65%), followed by smoking status (23 of 124; 19%) and mechanical ventilation for more than 4 d (22 of 124; 18%). Of the 98 actual lung donors, 35 (36%) demonstrated only one extended characteristic, 13 (13%) demonstrated two extended characteristics, and 4 (4%) demonstrated more than two extended characteristics.
Impact of the SALT Protocol on Poor Donors
Impact of Donor Management on Oxygenation We found that the mean PaO2/FIO2 of 59% of all potential lung donors improved during the SALT period (PaO2/FIO2, 240–372; mean change, 131), whereas that of only 31% of the potential lung donors improved during the pre-SALT period (PaO2/FIO2, 263–351; mean change, 87; p < 0.0001). The mean final PaO2/FIO2 of the actual lung donors was significantly better during the SALT period (PaO2/FIO2, 463) than during the pre-SALT period (PaO2/FIO2, 416; p = 0.02). There were no significant differences in the final PaO2/FIO2 between the different donor groups (ideal, extended, poor to ideal, and poor to extended) during the SALT period (see Table 2). The impact of the SALT protocol on oxygenation was most substantial among the 105 poor donors with PaO2/FIO2 < 300 or with pulmonary infiltrates who underwent recruitment maneuvers (PaO2/FIO2, 236–320; mean change, 90). This change in oxygenation with recruitment maneuvers accounted for 31% (30 of 98) of the actual lung donors.
Recipient Outcomes
This study addresses one of the primary limitations of lung transplantation: the disparity between the number of actual donors and the number of patients awaiting lung transplantation. Our implementation of the SALT donor-management protocol was associated with significantly larger numbers of donors consented, lungs procured, and lungs transplanted. The key components of the SALT protocol were (1) improving communication between our transplant center and our local OPO, (2) providing direct involvement and active management of donors by our lung transplant physicians, and (3) establishing a donor classification system after management of potential donors. Furthermore, implementing the SALT protocol did not compromise the outcomes of the lung transplant recipients, as evidenced by comparable 30-d and 1-yr survival rates, oxygenation assessments, duration of mechanical ventilation, LOS in the ICU and in the hospital, and lung function. Improvements in lung procurement with donor-management strategies have also been reported by Gabbay and colleagues from Australia (27). These authors reported that the use of extended-donor organs and the institution of aggressive donor management increased procurement rates from 33 to 51%. A similar experience was reported by the California Organ Bank, where the use of a donor-management protocol has increased procurement rates by as much as 35% over the last few years (2, 28). In those studies, as in ours, the increase in organ donation was not associated with a change in the survival rates of recipients. A key strategy for increasing the number of useable donor lungs in our study was modifying donor criteria by reassessing oxygenation, chest radiography, and bronchoscopic findings as absolute criteria after active donor management. This study was not focused on the use of extended donors as much as on the successful optimization of potential lung donors. The use of extended donors has been retrospectively evaluated at other transplant centers, although these centers did not implement any specific protocol for managing potential donors. In 1993, Kron reported the first series of lung transplantation procedures using extended-donor lungs; there were no differences in the immediate postoperative results of 11 lung transplant recipients (29). Some large transplant centers have reported comparable short-term outcomes with similarly liberalized donor criteria (6, 7, 11, 12, 30–32). However, other centers have observed that the use of extended donors resulted in increased 30-d mortality rates among recipients of lungs with bilateral infiltrates, frankly purulent secretions, or both (7); the recipients also required prolonged stays in the ICU and the hospital (33). In contrast, our study found that neither the LOS in the ICU and in the hospital nor the 30-d and 1-yr mortality rates differed between recipients of lungs from the four donor groups. Good oxygenation among potential lung donors (final PaO2/FIO2 > 300) before donation is a required criterion in most transplant programs (3, 4, 20). During the SALT period, we were able to improve the oxygenation of potential lung donors by implementing the SALT donor-management protocol. In contrast, during the pre-SALT period, when no donor-management protocol was used, oxygenation decreased substantially. The significance of improving oxygenation is highlighted by the fact that in our study a final PaO2/FIO2 > 400 was the strongest donor variable associated with acceptance of lungs by transplant centers. Recruitment maneuvers were an important component of the SALT protocol; when these maneuvers were used, the condition of 21% of the donors who were initially classified as poor donors was improved sufficiently to allow them to become actual lung donors. This study has some limitations relating to preintervention and postintervention design. We used a retrospective comparison cohort to analyze the impact of the implementation of the SALT protocol. Additionally, organ bank personnel were not required to follow the SALT protocol; thus, compliance with all aspects of the protocol did not always occur. However, although this lack of compliance is considered a study limitation, it reflects the realities associated with any clinical change and increases the likelihood that similar protocols introduced at other local OPOs could have similar results. Finally, as is true of many other studies of lung transplantation, this study involved a relatively small recipient population, and we were unable to collect complete data from recipients undergoing transplantation at other institutions. However, with the observed survival rates among our SALT cohort, achieving the statistical power to detect a 10% difference in mortality rates between the recipient groups would have required the enrollment of nearly 300 patients in each group. In conclusion, our results demonstrate that implementing the SALT protocol was associated with a significant increase in the number of lung donors and in the number of lung transplantation procedures performed without increasing LOS in the hospital or the ICU and without compromising the pulmonary function or survival rates of the lung transplant recipients. A similar donor-management program, implemented on a large scale by organ banks around the country with a procurement rate approaching 25%, would nearly double the number of lung transplantation procedures, significantly decrease lengthy wait times, and potentially eliminate many of the deaths that occur among patients awaiting lung transplantation.
The authors thank Flo Witte, M.A., E.L.S., for editorial assistance.
Supported by the Division of Cardiothoracic Surgery, Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas. The views expressed in this article are those of the authors and do not necessarily represent the views of the University of Texas Health Science Center at San Antonio. Originally Published in Press as DOI: 10.1164/rccm.200603-432OC on June 23, 2006 Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the manuscript. Received in original form March 28, 2006; accepted in final form June 4, 2006
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ABSTRACT
METHODS
2 tests. Confidence intervals (CIs) for simpler proportions and means were calculated by using the Wald method. Exact Poisson methods were used to compute the means and 95% CIs for lung procurement rates. An interrupted time-series analysis was used to evaluate the effects of the SALT protocol in this situation because randomization was not feasible. This type of analysis is particularly suited to evaluate the impact of changes in health care policy or to evaluate the impact of interventions designed to change medical practices (
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Actual lung donors from consented donors (38 of 250 [15.2%] vs. 98 of 336 [29.2%]; p < 0.0001).
