Lung Transplantation


Recent advancements in lung transplantation have improved the chances, not only for survival, but for improved quality of life for individuals with end-stage lung disease. These include COPD, pulmonary fibrosis, cystic fibrosis, idiopathic pulmonary hypertension, alpha 1-antitrypsin deficiency, bronchiectasis, sarcoidosis, work and environmental lung disease, and congenital defects. Because of advancements, demand for lung transplantation has increased while lung procurement continues to have a low success rate.

According to the Organ Procurement and Transplantation Network,1 transplants performed in Ohio more than doubled from 2008 to 2009. According to those same figures, in the U.S. in 2009 the United Network for Organ Sharing reported 8,022 deceased solid organ donors. From those donors the total number of lungs procured was 2,955 showing a 36% lung procurement rate per donor. In 2010 there was a slightly higher procurement rate – out of the 7,943 donors 3,217 lungs were procured showing a 40% procurement rate per donor. In July, 2009, 1,802 patients were on the lung transplant list. With higher procurement rates, these patients might have received lungs. The purpose of this study was to determine if the introduction of combined techniques could increase procurement rates, also which techniques were associated with successful procurement.

A literature review revealed five trials reporting an established ability to improve lung procurement rates. These trials used interventions to improve rates including physiologic and pharmacologic strategies, APRV mode of ventilation, and vest therapy.2-5 Only one study used a large sample size.2

Staff at University of Cincinnati Medical Center (UCMC) began to capitalize on pulmonary physiology manipulation with lung recruitment and pulmonary toilet techniques used to increase lung function. The techniques included no other changes to the existing donor medical management protocols that were already in place. These variations were trialed at UCMC and have been used since March of 2009. Cincinnati’s only organ procurement organization has since adopted this practice. Specific interventions used are listed in Table 1. These interventions were instituted on a donor-by-donor basis determined by patient need.

The study had two specific aims:
1. To determine if there was a significant increase in procurement rate pre- and post-intervention, and if the procurement rate was significantly higher than national rates.
2. To determine what combinations of techniques were associated with successful lung procurement.

Materials & Methods
This study used a quasi-experimental retrospective pre/post chart review research design. The retrospective chart review was conducted on all UCMC solid organ donors over a three year period including pre- and post-implementation. The setting was UCMC’s intensive care units. UCMC is a large teaching hospital and a level 1 trauma center. The sample included all brain dead solid organ donors from Jan. 1, 2008 through Dec. 31, 2010. Lung procurement was attempted for 22 donors in 2008, 23 in 2009 and 23 in 2010, for a total of 68 donors.

The outcome variable for this study was successful lung procurement, defined as the procurement of at least one lung per donor. Two categories of variables associated with lung procurement were identified (Table 2). All data was collected from the medical chart.

Donor-related factors include demographic data (age, sex, race, height and weight), medical history and admitting diagnosis. The Major Diagnostic Category system of classification and the International Statistical Classification of Diseases and Related Health Problems, ninth edition, were used for history and diagnoses.

All respiratory-related factors were obtained from the patient’s chart (Table 2). Donors were classified by the new pulmonary manipulation techniques and which techniques they received. These techniques include recruitment maneuvers: higher inspiratory pressure holds (holding 40cm H2O for 40 seconds) and stair step pressure control ventilation (increasing inspiratory pressure and PEEP while simultaneously maintaining delta and monitoring lung compliance). Recruitment techniques were modified and instituted based on hemodynamic stability. Low-flow pressure volume loops (V1volumeloop) were done post-recruitment to optimize ventilation and maintain recruitment.

The donor criteria type was determined by the LifeCenter data bank. Information was collected on whether the donor met eligibility criteria established by United Network of Organ Sharing.

The pulmonary manipulation techniques (Table 1) were implemented in March 2009. Data were obtained for all donors from Jan. 1, 2008 through December 31, 2010, to allow comparison of the lungs procured per donor pre- and post-implementation of the techniques.

Results
To answer the first specific aim, we calculated frequencies, distribution and procurement rate.6 Successful procurement per 100 available lungs with and without intervention were calculated and compared. Rates with and without intervention were compared to the standard national UNOS rates.

Procurement was calculated using the Organ Procurement and Transplantation Network (OPTN) method. We divided the number of lungs procured by the number of donors and multiplied the result by 100 to obtain the lung procurement rate per 100 donors.

Data were collected on 26 donors who had not received the new procurement techniques and 31 who did. Eleven donors who received partial implementation during the transitional period were excluded. This period of transitional treatment occurred from March of 2009 through August of 2009 with full implementation after August 2009. The procurement rate prior to implementation of the new techniques was 69.2% (18 out of 26 lungs procured) compared to 83.9% (52 out of 62 lungs procured) after full implementation. When pre-implementation procurement rates were compared to post-implementation rates, a significant increase in the rate was determined by Fisher’s exact test (p= 0.007).

We compared the post-implementation procurement rate with the national procurement for the same year. The 2010 OPTN national procurement rate was 40.5% (number of lungs procured = 3,217; number of deceased donors = 7,943). UCMC’s post-implementation rate was significantly higher using Fisher’s exact text (p=0.0000009) and more than double the national rate.

To answer the second specific aim the data were scrutinized, beginning at the univariate level with descriptive statistics of location (e.g., mean, median, etc.) and shape (variance, skew, kurtosis, etc.). Each variable’s empirical distribution was visually inspected via histograms. The bivariate level was explored by calculating statistics of association (e.g., matrices of Pearson’s and Kendall’s correlations) and by visual inspection of the scatter plot matrices with smoothed (using the loess algorithm) regression lines drawn through each scatterplot. Smoothed regression lines allow curvilinear and threshold effects to be discerned via visual inspection.7

To predict success of the lung procurement program, two sets of predictors were examined (Table 3). The first set of variables (X1), including specific ventilator settings prior to the operating room suite, was common to both time periods examined in this study. The second set of variables (X2) was implemented only during the time period when the new lung procurement strategies were implemented. Each variable was examined as a separate predictor in a simple logistic regression model. The logistic regression models were calculated using either SPSS or LogXact, version 8. The result from each of these logistic regression models provided an odds ratio (OR). The OR is a ratio of two odds, ranging from zero to one, and one to positive infinity. An OR of one represents no effect, similar to a correlation of zero. The OR’s are presented for each variable in Table 4. To ease interpretation, all OR’s are given as greater than 1. None of the variables in X1 were significantly associated with lung procurement for either time period, with the single exception of V2PEEPDI. V2PEEPDI was strongly associated with successful procurement for each time period. In X2, four variables were significantly associated with lung procurement (Table 4). In rank order, these variables were: v2vest, v1volumeloop, v2recruit, and, v1recruit. Each of these variables was strongly associated with successful lung procurement.

Discussion
The lung procurement rate at UCMC significantly improved during the time period of this study. Demographic data were not identified as significant contributors to this increase. Five variables were strongly associated with successful lung procurement. Two of these variables, V1recruit and V2recruit, are recruitment maneuvers, performed at different times. Based on the statistical analysis, both the recruitment maneuvers and the low flow pressure volume loop interventions are important contributors to the success of donor management programs.

The fourth variable significantly associated with successful lung procurement was vest percussive therapy (V2vest). None of the five donors who went without this intervention donated lungs in this study. The only likely reason for withholding this intervention was if it was determined that there was no chance for lung procurement, including severe chest trauma, low lung compliance, or high lung resistance. It is therefore felt that this is not a significant intervention for improving lung procurement. Additional research to verify this opinion is recommended.

Finally, PEEP (V2PEEPDI) showed a statistically significant impact on lung procurement. Although PEEP settings are adjusted upward as part of the ventilator techniques employed at UCMC, they are also adjusted downward when assessing lung function, as during ABG tests. Additionally, PEEP settings are not adjusted downward in potential donors whose lungs have been determined to be unlikely to be procured, such as those with chest trauma or low lung compliance. This variable is therefore not felt to be a reliable indicator for lung procurement.

A shortcoming of this study is the lack of information regarding compliance with ventilation techniques prior to April 2010. UCMC replaced the registered nurse employed as an In-House Organ Donation Coordinator with a registered respiratory therapist (RRT) at that time. This RRT was tasked with overseeing the care of all solid organ donors, including their ventilation. Diligent application of the techniques described in this study, while making adjustments based on hemodynamic changes, certainly had an effect on the procurement rate but it is impossible to determine the degree of this effect. The importance of trained RRTs to institute the procedures is noteworthy.

Lung procurement is an important procedure in the fight to treat patients with end stage respiratory disease. This study demonstrates procedures that significantly improved lung procurement rates when applied by trained RRTs. The study was conducted at a large level 1 trauma center and rates may differ on the basis of geographic location as well as other moderating variables. The purpose of this study was to look at techniques to improve lung procurement at UCMC. The actual transplant procedure and care following transplantation have significant impact on survival rates. These issues are, however, beyond the scope of this study. Further study is indicated.

Kipp Leihgeber, RRT, NPS, is In House Organ Donation Coordinator, and John G. Pfeffer, IV, RRT is In House Organ Donation Coordination, at the University of Cincinnati Medical Center. Christine Savage, PhD, RN, FAAN, is professor and chair, Department of Community/Public Health, Johns Hopkins University, Baltimore. Misty M. Richmond, PhD(c), PMHNP-BC, is clinical program developer, UCMC; Doctoral candidate, University of Cincinnati College of Nursing, Jonas Scholar. John Schafer, PhD, is professor, University of Cincinnati College of Nursing. Jennifer Jackson, DNP, RN, is chief nursing officer and vice president of Patient Care Services, UCMC.

References
1. Organ Procurement and Transplantation Network. (2009). Organ procurement and transplantation rates [data file]. Retrieved from: http://optn.transplant.hrsa.gov/latestData/viewDataReports.asp
2. Angel, L.F., Levine, D.J., Restrepo, M.I., Johnson, S., Sako, E., Carpenter, A., Calhoon, J., Cornell, J.E., Adams, S.G., Chisholm, G.B., Nespral, J., Roberson, A., & Levine, S.M. (2006). Impact of a lung transplantation donor-management protocol on lung donation and recipient outcomes. AmJ Respir Crit Care Med, 174, 710-716.
3. Koch, R.L., Papadakos, P.J., & Lachmann, B. (2009). The use of APRV and open lung management for improving the outcome of lung procurement for transplantation. Critical Care and Shock, 12(4), 130-134.
4. Ganz, S.S., Levi, D.M., Nishida, S., Raines, J.K., Anton, M., Osorio, M., Hollingsworth, K., Bellinger, E.L., & Pham, S.M. (2004). Improving pulmonary function and lung recovery for transplantation using The LinkTM system during organ donor management. Poster presentation, Association of Organ Procurement Organizations Conference. Chicago, IL.
5. Eagan, C., Keller, C.A., Baz, M.A., & Thibault, M. (2009). Effects of administration of intravenous naloxone on gas exchange in brain-dead lung donors. Progress in Transplantation, 19(3), 267-71.
6. Fleiss, J.L., Levin, B. & Paik, M.C. (2003). Statistical Methods for Rates and Proportions. Hoboken, NJ: Wiley-InterScience.
7. Hardle, W. (1991). Smoothing Techniques: With Implementations in S. New York, NY: Springer-Verlag.

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