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Development of a Non–Heart-Beating Donor Program and ResultsAfter the First Year

J.C. Meneses, P. Gámez, A. Mariscal, C. Marrón, V. Díaz-Hellín, M. Cortes, A. de Pablo, E. Lopez,V. Perez, O. Gonzalez, L. Juarros, I. Martinez, F. Hermoso, R. Ávila, M. Zuluaga, and J.L.M. de Nicolás

ABSTRACT

Our lung transplant unit began activity in October 2008. We have performed 37 lungtransplants with a hospital mortality of 2.7% (n � 1). The need for a greater number ofdonors and the presence of an already existent non–heart-beating donor (NHBD)program for abdominal grafts and tissues encouraged us to consider assessing lung graftsfrom these donors. It was necessary to develop a new multiorgan preservation methodol-ogy, “bithermia preservation.” The clinical experience with which during the first year June2010 to July 2011, including 15 NHBDs is presented herein. The chest x-ray was normal in6 donors (40%) and 7 had pulmonary infiltrates. Bronchoscopy was normal in 8 donors(53%) but 3 had abundant bleeding airway secretions and signs of bronchoaspiration.Preservation procedures were performed in 6 donors. Pulmonary functional evaluation in4 donors showed gas measurements to be adequate in 75% of cases. Three double-lunggrafts were judged to be valid for implantation, among which we performed 3 lungtransplantations, 1 bilateral and 2 unilaterals, while 2 grafts were offered to the NationalTransplant Organization for other units. No transplant suffered primary graft dysfunction;all 3 showed excellent function allowing early extubation in 2 cases. There was noin-hospital mortality. All 3 patients are alive and leading normal lives; none hasbronchiolitis obliterans syndrome. In conclusion, the “bithermia preservation” methodol-ogy achieved adequate lung preservation in NHBDs, allowing liver, kidneys, and lungs to

be obtained from the same donor.

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SINCE the first organ donation in 1933 by Voronoy1 andthe first lung transplant from a heart attack deceased

onor in 1963 by Hardy,2 most lungs have been obtainedfrom brain-dead donors, particularly since 1971 when forthe first time the legal entity of a brain-dead donor wasdefined in Finland. Subsequently, owing to the donorshortage, attention has turned to cardiac death donors withthe creation in 1993 of a non–heart-beating donor (NHBD)protocol.3

Since beginning its activity in 2008, our lung transplantunit has performed 37 lung transplants up to October 2011.Hospital mortality was 2.7% (n � 1); 1- and 3-year survivalswere 94% and 87%, respectively. According to data fromthe Spanish national registry of lung transplantation, theoverall survival is 71% at 1 year and 59% at 3 years.

The need for a greater number of donors and thepresence of an already existing NHBD program for abdom-inal grafts and tissues since January 20064 prompted us to

onsider assessing lungs from these donors. After a 1-year

© 2012 by Elsevier Inc. All rights reserved.360 Park Avenue South, New York, NY 10010-1710

Transplantation Proceedings, 44, 2047–2049 (2012)

reclinical phase we evaluated 17 donors 4 of them werereserved, evaluated, and implanted (23.5%) beginning inune 2010. Abdominal organs were preserved normother-ically using cardiopulmonary bypass, and the thoracic

rgans were maintained in hypothermia using continuousirculation of cold Perfadex; the technique was calledbithermia preservation.”

From the Department of Thoracic Surgery (J.C.M., P.G., A.M.,C.M., V.D.-H., I.M., F.H., R.A., M.Z., J.L.M.D.N.), Department ofAnesthesiology (M.C., E.L., O.G.), Department of Pulmonology(A.d.P., V.P.), and Department of Rehabilitation (L.J.), Hospital12 de Octubre, Madrid, Spain.

Address reprint requests to Jose Carlos Meneses, Departmentof Thoracic Surgery, Hospital 12 de Octubre, Calle Campo de laEstrella, numero 7, Portal L, 5°B, CP: 28050, Madrid, Spain.

E-mail: jcmenesesp@gmail.com

0041-1345/–see front matterhttp://dx.doi.org/10.1016/j.transproceed.2012.07.092

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2048 MENESES, GÁMEZ, MARISCAL ET AL

MATERIALS AND METHODS

After a witnessed extrahospital cardiac arrest, cardiopulmonaryresuscitation (CPR) must be quickly initiated (within the first fewminutes) and continued. When CPR is not effective the NHBDprogram is initiated. The transplant coordinator notifies surgicalteams at the hospital while the donor is being transfered. Oncethere, the absence of cardiac activity is certified and the donor istaken to the operating room to have abdominal and thoracicprocedures for preservation performed. Unlike other NHBD pro-grams, our abdominal organ preservation procedure is performedin normothermia.

Because it is necessary to cool donor lungs topically to obtainviable pulmonary grafts, we developed a pleural cooling systemwith a closed circuit of cold recirculating pleural preservationsolution without interfering with the abdominal normothermia, ie,“bithermia preservation.” The cooled preservation solution entersthe pleural cavities through 2 apical chest tubes and exits through2 basal chest tubes. The topical cooling of the lungs must beperformed no later than 3 hours after the cardiac arrest. Acceptedinclusion criteria are: age �55 years, known time of cardiac arrest,CPR within 15 minutes of cardiac arrest, normal chest x-ray, timefrom cardiac arrest to topical cooling �180 minutes, and pulmo-nary preservation �240 minutes. Exclusion criteria are the same asthose for a brain-dead donor regarding medical history and serol-ogies, with the addition of severe head injury with loss of the brain.5

If there is no legal impediment and the family agrees, pulmonaryextraction is performed within the first 4 hours of cooling. Organfunction assessment is performed by pulmonary vein blood gasdetermination after perfusion through the pulmonary artery ofdonor venous blood. The lungs under mechanical ventilation mustshow the fraction of inspired oxygen (FIO2) of 1 and a positivend-expiratory pressure of 5. This evaluation methodology usingonor blood was previously tested in an experimental study per-ormed by the lung transplant unit.

The criteria to consider a pulmonary graft to be valid are: normalhest x-ray; compliance with established times; bronchoscopy witho signs of bronchoaspiration, pulmonary edema, significant hemer purulent secretions, or airway lesions; normal macroscopiculmonary evaluation; negative virus serologies; and a partialxygen pressure (pO2) obtained from the left atrium or pulmonary

veins �400 mm Hg.We performed a 1-year preclinical project to assess the organ

viability and possible influence on already active renal and hepaticprograms. Once tested and with the consent of the other programswe initiated the clinical phase.

RESULTS

Since the first pulmonary transplant from an NHBD per-formed in June 2010, we have evaluated 15 candidatedonors up to September 2011. The average age was 43 years(SD 7.8), predominantly male (86.7%). The most frequentblood type was A (45%), followed by O (27%); less

Table 1. Fir

DonorAge

RecipientAge

RecipientDisease

TransplantType WIT

38 y 49 y Emphysema Bilateral 2 h 45 min39 y 62 y COPD-IV Unilateral 2 h 20 min40 y 60 y COPD-IV Unilateral 2 h 30 min

WIT, warm ischemia time; TIT, total ischemia time; PGD, primary graft dysfunction

requent were blood types B (18%) and AB (9%). Fiftyercent of the candidate donors were smokers and 17%x-smokers; 44.4% had comorbid conditions, such as arte-ial hypertension, bronchiolitis, acute myocardial infarction,ypothyroidism, dyslipidemia, extrahospital pneumonia,nd gunshot wound.

During the assessment before preservation, chest x-raysere obtained in 14/15 cases showing no pathologic findings

n 40% (n � 6). In 47% (n � 7) there were pulmonaryinfiltrates. In 1 case, the x-ray was inconclusive. A bron-choscopy was performed in 13 subjects, with normal resultsin 53% (n � 8), 2 with bronchoaspiration (13%), and 3 withbloody secretions (20%).

Based on the background, waiting lists, x-ray results,and bronchoscopy, pulmonary preservation was per-formed in 6 cases with a warm ischemia time of 152.5 �3.5 minutes. Sternotomy and subsequent pulmonaryfunctional assessment was performed in 4⁄6. In 1 case theright lung was injured, and in the other instance we didnot obtain family consent for transplantation. In 3 cases,the functional assessment was optimal, with an averageleft atrial pO2 of 572 mm Hg (corrected for tempera-ture). The average temperature reached by the leftatrium was 15.25 � 2.2°C (59.45 � 3.96°F). In these 3cases the bipulmonary block was extracted for implanta-tion with excellent results (Table 1).

The first pulmonary transplantation from the NHBDprogram using the “bithermia preservation” methodologywas performed on a 49-year-old woman with pulmonaryemphysema due to alfa-1 antitrypsin deficiency. The donorwas a 38-year-old man with a warm ischemia time of 165minutes. A bipulmonary transplant was performed with atotal ischemia time of 12 hours 40 minutes. The pO2/FiO2

quotient upon arrival at the postoperative care unit was 243.The patient was extubated within 120 hours of intervention.

The second case was a unipulmonary transplant per-formed on a 62-year-old man with chronic obstructivepulmonary disease (COPD). The graft was from a 39-year-old with a warm ischemia time of 140 minutes. The totalischemia time was 11 hours 15 minutes; the pO2/FiO2

quotient was 391 after the intervention. The patient wasextubated 3 hours after the intervention.

The third and most recent case was a 60-year-old manwith COPD. The donor was a 40-year-old man with awarm ischemia time of 150 minutes. The total ischemiatime was 11 hours 44 minutes; the pO2/FiO2 quotient was

02. The patient was extubated 4 hours after the trans-lantation.

ar Results

TIT PO2/FiO2 Extubation PGDHospital

StayHospitalMortality

40 min 243 120 h No 127 d No15 min 391 3 h No 15 d No44 min 402 4 h No 26 d No

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12 h11 h11 h

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NON–HEART-BEATING DONOR PROGRAM 2049

None of these 3 cases developed primary graft dysfunc-tion; all were discharged home. The first patient presentedclinical signs of possible clinical rejection without patho-logic confirmation. None of the 3 have shown long-termsigns of bronchiolitis obliterans syndrome. All have experi-enced a significant improvements in their quality of life,being able to perform normal daily activities.

DISCUSSION

Non–heart-beating donor organ transplantation is a world-wide practice, providing surgical teams with an additionalsource of organs. However, it was not until recently that thistype of donor acquired significant importance in Spain. Thefirst pulmonary transplant from an extrahospital NHBD inSpain was performed in 2002 by the Puerta de HierroHospital, Madrid.6

Our NHBD program for abdominal grafts and tissuesbegan in January 2006.4 In 2010, the Lung Transplant Unitbegan an NHBD program based on this infrastructure. TheNHBD program has supplied the hospital with 8% of thetransplanted lungs, representing 20% of the NHBD assess-ments. Aware of the uncertainty inherent to this type ofdonor, we sought to scientifically demonstrate the validityof the pulmonary functional assessment using an animalmodel.7

The NHBD program includes a medical and surgicalmultidisciplinary staff who are physically present in theoperating room (OR) upon the arrival of the donor. Thisteam includes nephrologists, general surgeons, anesthesiol-ogists, perfusionists, urologists, thoracic surgeons, and ORnurses. Preservation procedures and early assessments areperformed by these specialists. The perfusionist constantlymonitors the correct function of the extracorporeal circu-lation system, taking special care to preserve the abdominalorgans. This strict normothermic control of the abdominalorgans by the perfusionists has allowed the addition of

cooling of the thoracic organs without hampering the

bdominal preservation. The perfusionist also controls theulmonary cooling. This effort has greatly contributed tohe excellent results achieved, with none of the 3 recipientshowing signs of primary graft dysfunction, contrary to whatas been recorded in other studies.8 These positive results

are in addition to the other abdominal grafts and tissuespreserved by normothermia.

This “bithermia preservation” method offers an innova-tive effective method to harvest lungs from uncontrolledNHBDs, providing greater control of the entire organpreservation and assessment process as well as the possibil-ity to harvest other abdominal grafts and tissues in normo-thermia with thoracic organs in hypothermia.

REFERENCES

1. Hamilton DN, Reid WA, Yu Y: Voronoy and the first humankidney allograft. Surg Gynecol Obstet 159:289–94, 1984

2. Hardy J, Webb WR, Dalton MR, et al: Lung homotrasplan-tation in man. JAMA 186, 1963

3. DeVita MA, Snyder JV. Development of the University ofPittsburgh Medical Center policy for the care of terminally illpatients who may become organ donors after death following theremoval of life support. Kennedy Inst Ethics J 3:131, 1993

4. Jiménez-Galanes S, Meneu-Díaz MJ, Elola Olaso-AM, et al:Liver transplantation using uncontrolled non–heart-beating donorsunder normothermic extracorporeal membrane oxygenation. LiverTranspl 15:1110, 2009

5. Aigner C, Seebacher G, Klepetko W: Lung transplantation.Donor selection. Chest Surg Clin North Am 13:429, 2003

6. Gámez P, Córdoba M, Ussetti P, et al, Lung TransplantGroup of the Puerta de Hierro Hospital: Lung Transplantationfrom out-of-hospital non–heart-beating lung donors. One yearexperience and results. J Heart Lung Transplant 24:1098, 2005

7. Meneses JC, Gámez AP, Mariscal MA, et al: Comparativeexperimental study of pulmonary function evaluation in outpatientNHBLD among exanguinating donors and sudden death donors.ISHLT 31st Annual Meeting and Scientific Sessions, San Diego,California, 2011

8. Rodríguez DA, del Río F, Fuentes ME, et al: Lung transplan-tation with uncontrolled non–heart-beating donors. Transplanta-

tion. Donor prognostic factor and immediate evolution post trans-plant. Arch Bronconeumol 47:403, 2011