Renal perfusion strategy during thoracoabdominal aortic repair-is Custodiol the answer?

Central MessageThis randomized controlled trial documents superior renal protection with Custodiol compared with enriched Ringer's solution in the setting of elective open thoracoabdominal aortic repair.Despite advances in surgical techniques and organ-protection strategies, open repair of thoracoabdominal aneurysms (TAAA) is still associated with substantial morbidity and mortality.1Moulakakis K.C. Karaolanis G. Antonoupoulos C.N. Kakisis J. Klonaris C. Preventza O. et al.Open repair of thoracoabdominal aortic aneurysms in experienced centers.J Vasc Surg. 2018; 68: 634-645Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar,2Khan F.M. Naik A. Hameed I. Robinson N.B. Spadaccio C. Rahouma M. et al.Open repair of descending thoracic and thoracoabdominal aortic aneurysms: a meta-analysis.Ann Thorac Surg. 2020; 110: 1941-1949Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar In a recent systematic review, Moulakakis and colleagues1Moulakakis K.C. Karaolanis G. Antonoupoulos C.N. Kakisis J. Klonaris C. Preventza O. et al.Open repair of thoracoabdominal aortic aneurysms in experienced centers.J Vasc Surg. 2018; 68: 634-645Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar summarized the surgical outcomes of 9963 patients and demonstrated a pooled in-hospital mortality rate of 11.3% (range 2.3%-32.7%) after extent I-IV TAAA repair.1Moulakakis K.C. Karaolanis G. Antonoupoulos C.N. Kakisis J. Klonaris C. Preventza O. et al.Open repair of thoracoabdominal aortic aneurysms in experienced centers.J Vasc Surg. 2018; 68: 634-645Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar Although a decreased mortality is debated for high-volume centers and the modern surgical era, the perioperative rate of major adverse events still remains considerable.1Moulakakis K.C. Karaolanis G. Antonoupoulos C.N. Kakisis J. Klonaris C. Preventza O. et al.Open repair of thoracoabdominal aortic aneurysms in experienced centers.J Vasc Surg. 2018; 68: 634-645Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar, 2Khan F.M. Naik A. Hameed I. Robinson N.B. Spadaccio C. Rahouma M. et al.Open repair of descending thoracic and thoracoabdominal aortic aneurysms: a meta-analysis.Ann Thorac Surg. 2020; 110: 1941-1949Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar, 3Coselli J.S. LeMaire S.A. Preventza O. de la Cruz K.I. Cooley D.A. Price M.D. et al.Outcomes of 3309 thoracoabdominal aortic aneurysm repairs.J Thorac Cardiovasc Surg. 2016; 151: 1323-1327Abstract Full Text Full Text PDF PubMed Scopus (395) Google Scholar, 4Wong D.R. Parenti J.L. Green S.Y. Chowdhary V. Liao J.M. Zarda S. et al.Open repair of thoracoabdominal aortic aneurysm in the modern surgical era: contemporary outcomes in 509 patients.J Am Coll Surg. 2011; 212 (discussion 579-81): 569-579Crossref PubMed Scopus (128) Google Scholar In particular, pre-existing chronic kidney disease (CKD) or acute kidney failure requiring permanent dialysis occurs in approximately 8% of patients after TAAA repair and is associated with poor early and late clinical outcomes.1Moulakakis K.C. Karaolanis G. Antonoupoulos C.N. Kakisis J. Klonaris C. Preventza O. et al.Open repair of thoracoabdominal aortic aneurysms in experienced centers.J Vasc Surg. 2018; 68: 634-645Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar,5Chatterjee S. LeMaire S.A. Amarasekara H.S. Green S.Y. Price M.D. Yanoff M.S. et al.Early-stage acute kidney injury adversely affects thoracoabdominal aortic aneurysm repair outcomes.Ann Thorac Surg. 2019; 107: 1720-1726Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar, 6Coselli J.S. Amarasekara H.S. Zhang Q. Preventza O. de la Cruz K.I. Chatterjee S. et al.The impact of preoperative chronic kidney disease on outcomes after Crawford extent II thoracoabdominal aortic aneurysm repairs.J Thorac Cardiovasc Surg. 2018; 156: 2053-2064Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 7Girardi L.N. Ohmes L.B. Lau C. Di Franco A. Gambardella I. Elsayed M. et al.Open repair of descending thoracic and thoracoabdominal aortic aneurysms in patients with preoperative renal failure.Eur J Cardiothorac Surg. 2017; 51: 971-977Crossref PubMed Scopus (33) Google Scholar Importantly, up to 28% to 40% of patients with TAAA already present with CKD.6Coselli J.S. Amarasekara H.S. Zhang Q. Preventza O. de la Cruz K.I. Chatterjee S. et al.The impact of preoperative chronic kidney disease on outcomes after Crawford extent II thoracoabdominal aortic aneurysm repairs.J Thorac Cardiovasc Surg. 2018; 156: 2053-2064Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar,7Girardi L.N. Ohmes L.B. Lau C. Di Franco A. Gambardella I. Elsayed M. et al.Open repair of descending thoracic and thoracoabdominal aortic aneurysms in patients with preoperative renal failure.Eur J Cardiothorac Surg. 2017; 51: 971-977Crossref PubMed Scopus (33) Google Scholar In a propensity score–matched analysis by Coselli and colleagues,6Coselli J.S. Amarasekara H.S. Zhang Q. Preventza O. de la Cruz K.I. Chatterjee S. et al.The impact of preoperative chronic kidney disease on outcomes after Crawford extent II thoracoabdominal aortic aneurysm repairs.J Thorac Cardiovasc Surg. 2018; 156: 2053-2064Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar patients with CKD had significantly more adverse events rates and worse mid-term survival after TAAA repair compared with those without. In another large observational cohort study, operative mortality was 7 times greater in patients with impaired preoperative renal function and a predictor for operative mortality (odds ratio [OR], 4.91; 95% confidence interval [CI], 2.0-12.0) and major adverse events (OR, 2.0; 95% CI, 1.2-3.5).7Girardi L.N. Ohmes L.B. Lau C. Di Franco A. Gambardella I. Elsayed M. et al.Open repair of descending thoracic and thoracoabdominal aortic aneurysms in patients with preoperative renal failure.Eur J Cardiothorac Surg. 2017; 51: 971-977Crossref PubMed Scopus (33) Google ScholarSee Article page 569. This randomized controlled trial documents superior renal protection with Custodiol compared with enriched Ringer's solution in the setting of elective open thoracoabdominal aortic repair. See Article page 569. Many different renal-protection strategies during TAAA repair have been proposed to reduce acute kidney injury (AKI) and its detrimental sequelae. Beyond optimal perioperative care, the investigators from the Baylor College of Medicine have repeatedly demonstrated the safety and efficacy of selective, intermittent kidney perfusion with cold (4°C) Ringer's lactate solution (enriched with mannitol/methylprednisolone).8Chatterjee S. Casar J.G. LeMaire S.A. Preventza O. Coselli J.S. Perioperative care after thoracoabdominal aortic aneurysm repair: the Baylor College of Medicine experience. Part 2: postoperative management.J Thorac Cardiovasc Surg. 2021; 161: 699-705Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar,9LeMaire S.A. Jones M.M. Conklin L.D. Carter S.A. Criddell M.D. Wang X.L. et al.Randomized comparison of cold blood and cold crystalloid renal perfusion for renal protection during thoracoabdominal aortic aneurysm repair.J Vasc Surg. 2009; 49: 11-19Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar In this issue of the Journal, Kahlberg and colleagues10Kahlberg A. Tshomba Y. Baccellieri D. Bertoglio L. Rinaldi E. Ardita V. et al.Renal perfusion with histidine-tryptophan-ketoglutarate compared with Ringer's solution in patients undergoing thoracoabdominal aortic open repair.J Thorac Cardiovasc Surg. 2023; 165: 569-579.e5Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar present results from the single-center, randomized, double-blind, 2-arm CURITIBA trial (CUstodiol vs RInger: whaT Is the Best Agent? A Randomized Double Blind Trial), which allocated 90 adult patients with TAAA undergoing elective surgical repair in a 1:1 fashion to standardized renal perfusion strategy with Custodiol or methylprednisolone/mannitol-enriched Ringer's lactate solution both provided at 4°C, as suggested by Coselli and colleagues.8Chatterjee S. Casar J.G. LeMaire S.A. Preventza O. Coselli J.S. Perioperative care after thoracoabdominal aortic aneurysm repair: the Baylor College of Medicine experience. Part 2: postoperative management.J Thorac Cardiovasc Surg. 2021; 161: 699-705Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar,9LeMaire S.A. Jones M.M. Conklin L.D. Carter S.A. Criddell M.D. Wang X.L. et al.Randomized comparison of cold blood and cold crystalloid renal perfusion for renal protection during thoracoabdominal aortic aneurysm repair.J Vasc Surg. 2009; 49: 11-19Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar Of note, baseline and operative characteristics, TAAA Crawford extent (type II approximately 37%), rate of pre-existing CKD stage I-III (stage II-III approximately 66%), the amount of the delivered perfusate, and duration of bilateral renal perfusion and ischemia, were comparable between both groups. The primary endpoint of any AKI, defined according to the Kidney Disease Improving Global Outcomes and Acute Kidney Injury Network criteria, was met in 48.9% of in the Custodiol versus 75.6% of the Ringer's group (P = .02). However, the incidence of severe AKI (approximately 30% with Acute Kidney Injury Network stage 2 and 3), need for temporary hemofiltration, or permanent dialysis after surgery was not statistically different between treatment arms. Similarly, operative (6.7% vs 13.3%) and 30-day mortality (8.9% vs 13.3%) were comparable between the Custodiol and Ringer's groups. Multivariable analysis showed that the use of Custodiol solution prevented any AKI (OR, 0.2; 95% CI, 0.1-0-6), but not severe AKI. Based on the results of this study, the authors advocate the safety and superior efficacy of renal perfusion with Custodiol compared with the more commonly used Ringer's solution in TAAA repair. At a first glance, the data derived from this well-controlled trial seem robust enough to support the safe use of Custodiol as an additional renal perfusion solution for open repair of TAAA. Indeed, the histidine–tryptophan–ketoglutarate or Custodiol HTK solution is a well-established, low-potassium solution that has been widely used for organ preservation (for example, kidney transplantation, cardioplegia, etc) for several decades now, with excellent clinical results even when compared with blood-based perfusates.11O'Callaghan J.M. Knight S.R. Morgan R.D. Morris P.J. Preservation solutions for static cold storage of kidney allografts: a systematic review and meta-analysis.Am J Transplant. 2012; 12: 896-906Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar Second, the CURITIBA trial also provides first evidence that Custodiol may offer equal or even superior renal protection in terms of preventing any AKI in TAAA repair compared with Ringer's solution. Nonetheless, the data provided in this study are preliminary and weakened by the single center, small size, and underpowered trial design. However, the CURITIBA investigators have provided us with a robust scientific basis for the initiation of a larger, multi-institutional trial to examine the benefit of AKI prevention with Custodiol and whether its use translates into a reduced morbidity and mortality, especially in higher-risk patients with pre-existing CKD or Crawford extent II TAAA. Renal perfusion with histidine-tryptophan-ketoglutarate compared with Ringer's solution in patients undergoing thoracoabdominal aortic open repairThe Journal of Thoracic and Cardiovascular SurgeryVol. 165Issue 2PreviewThe objective of this study was to compare the efficacy of renal perfusion with Custodiol (Dr Franz-Kohler Chemie GmbH, Bensheim, Germany) versus enriched Ringer's solution for renal protection in patients undergoing open thoracoabdominal aortic aneurysm (TAAA) repair. Full-Text PDF