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Aprotinin decreases reperfusion injury and allograft dysfunction in clinical lung transplantation.
Eur J Cardiothorac Surg 2006; 29(2):210-5EJ

Abstract

OBJECTIVE

Primary graft dysfunction caused by ischemia-reperfusion injury is one of the most frequent causes of early morbidity and death after lung transplantation. We hypothesized that the perioperative management with aprotinin decreases the incidence of allograft reperfusion injury and dysfunction after clinical lung transplantation.

METHODS

Lung transplant databases of two transplant centers were used to investigate the incidence of severe post-transplant reperfusion injury (PTRI). We examined data of 142 patients who underwent either single lung (81) or bilateral sequential lung (61) transplantation for COPD, idiopathic pulmonary fibrosis, cystic fibrosis, and miscellaneous lung disorders between 1997 and 2000. Thirty patients were excluded due to heart-lung transplantation or lung transplantation for Eisenmenger's disease, re-transplantation, rejection, or deviation from the standardized triple immunosuppression protocol. The data of remaining 112 patients (control group, 64% single lung, 36% sequential bilateral lung transplants) were compared to the prospectively collected data of 59 lung transplant patients over the last 5 years. All of these 59 patients were managed perioperatively with aprotinin infusion. In addition, Euro-Collins-aprotinin procurement solution (Apt-EC group) was used for 50 donor lungs (58% single lung, 42% sequential bilateral lung transplants). Aprotinin in combination with low-potassium dextran (LPD) flush solution (Apt-LPD group) was used for the procurement of 34 lungs (59% single lung, 41% sequential bilateral lung transplants). The International Society of Heart and Lung Transplantation (ISHLT) grade III injury score was used for the diagnosis of severe PTRI, which is based on a PaO(2)-FIO(2) ratio of less than 200 mmHg.

RESULTS

Severe reperfusion injury grade III was observed in 18% of the control group. ECMO support was required in 25% of these patients. The associated mortality rate was 40%. Correlating factors for PTRI were donor age greater than 35 years (45%, p=0.01, mean age 38+/-8) and recipient pulmonary artery systolic pressure greater than 60 mmHg (48%, p<0.05). Lung graft ischemic times (231+/-14 min) and intraoperative techniques (cardiopulmonary bypass in 12%) were not associated with negative outcomes. Despite longer ischemic times (258+/-36 min and 317+/-85 min, respectively) and older donors (42+/-12 years and 46+/-12 years, respectively) in the aprotinin patient groups (Apt-EC and Apt-LPD group), the incidence of PTRI was markedly lower (6% and 9%, respectively). There was no mortality in the Apt-EC group and one patient died in the Apt-LPD group due to PTRI-induced graft failure.

CONCLUSIONS

Severe PTRI increased short-term morbidity and mortality. The incidence of reperfusion injury was not dependent upon the duration of donor organ ischemia. The use of aprotinin in the perioperative patient management in lung transplantation had strong beneficial effects on the patient outcomes and decreased the incidence of post-transplant ischemia-reperfusion injury significantly.

Authors+Show Affiliations

Division of Thoracic and Cardiovascular Surgery, Heart Center Leipzig of the University of Leipzig, Struempell Strasse 39, 04289 Leipzig, Germany. hartmuth.bittner@medizin.uni-leipzig.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study

Language

eng

PubMed ID

16386921

Citation

Bittner, Hartmuth B., et al. "Aprotinin Decreases Reperfusion Injury and Allograft Dysfunction in Clinical Lung Transplantation." European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery, vol. 29, no. 2, 2006, pp. 210-5.
Bittner HB, Richter M, Kuntze T, et al. Aprotinin decreases reperfusion injury and allograft dysfunction in clinical lung transplantation. Eur J Cardiothorac Surg. 2006;29(2):210-5.
Bittner, H. B., Richter, M., Kuntze, T., Rahmel, A., Dahlberg, P., Hertz, M., & Mohr, F. W. (2006). Aprotinin decreases reperfusion injury and allograft dysfunction in clinical lung transplantation. European Journal of Cardio-thoracic Surgery : Official Journal of the European Association for Cardio-thoracic Surgery, 29(2), pp. 210-5.
Bittner HB, et al. Aprotinin Decreases Reperfusion Injury and Allograft Dysfunction in Clinical Lung Transplantation. Eur J Cardiothorac Surg. 2006;29(2):210-5. PubMed PMID: 16386921.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aprotinin decreases reperfusion injury and allograft dysfunction in clinical lung transplantation. AU - Bittner,Hartmuth B, AU - Richter,Markus, AU - Kuntze,Thomas, AU - Rahmel,Axel, AU - Dahlberg,Peter, AU - Hertz,Marshall, AU - Mohr,Friedrich W, PY - 2005/10/17/received PY - 2005/11/26/revised PY - 2005/12/02/accepted PY - 2006/1/3/pubmed PY - 2006/5/26/medline PY - 2006/1/3/entrez SP - 210 EP - 5 JF - European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery JO - Eur J Cardiothorac Surg VL - 29 IS - 2 N2 - OBJECTIVE: Primary graft dysfunction caused by ischemia-reperfusion injury is one of the most frequent causes of early morbidity and death after lung transplantation. We hypothesized that the perioperative management with aprotinin decreases the incidence of allograft reperfusion injury and dysfunction after clinical lung transplantation. METHODS: Lung transplant databases of two transplant centers were used to investigate the incidence of severe post-transplant reperfusion injury (PTRI). We examined data of 142 patients who underwent either single lung (81) or bilateral sequential lung (61) transplantation for COPD, idiopathic pulmonary fibrosis, cystic fibrosis, and miscellaneous lung disorders between 1997 and 2000. Thirty patients were excluded due to heart-lung transplantation or lung transplantation for Eisenmenger's disease, re-transplantation, rejection, or deviation from the standardized triple immunosuppression protocol. The data of remaining 112 patients (control group, 64% single lung, 36% sequential bilateral lung transplants) were compared to the prospectively collected data of 59 lung transplant patients over the last 5 years. All of these 59 patients were managed perioperatively with aprotinin infusion. In addition, Euro-Collins-aprotinin procurement solution (Apt-EC group) was used for 50 donor lungs (58% single lung, 42% sequential bilateral lung transplants). Aprotinin in combination with low-potassium dextran (LPD) flush solution (Apt-LPD group) was used for the procurement of 34 lungs (59% single lung, 41% sequential bilateral lung transplants). The International Society of Heart and Lung Transplantation (ISHLT) grade III injury score was used for the diagnosis of severe PTRI, which is based on a PaO(2)-FIO(2) ratio of less than 200 mmHg. RESULTS: Severe reperfusion injury grade III was observed in 18% of the control group. ECMO support was required in 25% of these patients. The associated mortality rate was 40%. Correlating factors for PTRI were donor age greater than 35 years (45%, p=0.01, mean age 38+/-8) and recipient pulmonary artery systolic pressure greater than 60 mmHg (48%, p<0.05). Lung graft ischemic times (231+/-14 min) and intraoperative techniques (cardiopulmonary bypass in 12%) were not associated with negative outcomes. Despite longer ischemic times (258+/-36 min and 317+/-85 min, respectively) and older donors (42+/-12 years and 46+/-12 years, respectively) in the aprotinin patient groups (Apt-EC and Apt-LPD group), the incidence of PTRI was markedly lower (6% and 9%, respectively). There was no mortality in the Apt-EC group and one patient died in the Apt-LPD group due to PTRI-induced graft failure. CONCLUSIONS: Severe PTRI increased short-term morbidity and mortality. The incidence of reperfusion injury was not dependent upon the duration of donor organ ischemia. The use of aprotinin in the perioperative patient management in lung transplantation had strong beneficial effects on the patient outcomes and decreased the incidence of post-transplant ischemia-reperfusion injury significantly. SN - 1010-7940 UR - https://www.unboundmedicine.com/medline/citation/16386921/Aprotinin_decreases_reperfusion_injury_and_allograft_dysfunction_in_clinical_lung_transplantation_ L2 - https://academic.oup.com/ejcts/article-lookup/doi/10.1016/j.ejcts.2005.12.001 DB - PRIME DP - Unbound Medicine ER -