Prolonged Ischemia Time Research Articles

Complications in Prolonged Intraoperative Ischemia Time in Free Flap Breast Reconstruction: A Systematic Review and Meta-Analysis.

Autologous tissue transfer is an effective option for breast reconstruction post-mastectomy, with microsurgical techniques continually evolving. However, a comprehensive analysis of the relationship between prolonged ischemia time during free flap-based breast reconstruction and increased postoperative complications is still lacking. A systematic review and meta-analysis were conducted following PRISMA guidelines. Methodological quality was evaluated using the MINORS criteria. Studies meeting inclusion criteria were analyzed for total complications, complete and partial flap loss, and secondary outcomes. Data heterogeneity and risk ratios were assessed. Seventeen studies encompassing 5636 patients and 6884 free flaps were included. The mean age of patients was 49.43years (95% CI: 48.27-50.60), with a mean BMI of 26.09 (95% CI: 21.97-30.21), and an average post-harvesting free flap ischemia time of 70.35min (95% CI: 56.71-83.98). These analyses revealed a heightened risk of total complications (RR: 1.99, 95% CI: 1.61-2.46), complete flap loss (RR: 3.15, 95% CI: 1.32-7.52), partial flap loss (RR: 1.91, 95% CI: 0.92-4.00), hematoma (RR: 1.79, 95% CI: 0.96-3.32), and infection (RR: 2.12, 95% CI: 1.32-3.42) in cases with ischemia time exceeding 60min. Venous complications predominated in free flap failure cases. Effectively managing ischemia time could be crucial in free flap breast reconstruction to potentially reduce postoperative complications. Although there is a correlation between managing ischemia time and reducing postoperative complications, further research is needed to investigate the possible causation behind this relationship. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Successful emergency renal auto-transplantation in a child with renovascular disease.

Renal artery occlusion is a rare but potentially catastrophic complication of paediatric endovascular renal artery intervention. Emergency auto-transplantation may be required to salvage the kidney; to date this has only been described in adults. We report our experience of performing emergency kidney auto-transplantation following acute renal artery thrombosis in a child undergoing redo renal artery angioplasty A 20-month-old boy presented with refractory hypertension and hypertensive cardiomyopathy secondary to multifocal fibromuscular dysplasia (FMD) with a single functioning kidney. Acute thrombosis of the renal artery during redo-endovascular balloon angioplasty necessitated emergency renal auto-transplantation. Subsequent acute kidney injury was reversible with benefit to renal function in the medium-term despite prolonged warm ischaemic time of two hours. We recommend that high-risk patients undergoing renal artery intervention do so at centres with on-site renal and vascular surgical backup.

Malignancies After Heart Transplantation.

Heart transplant patients have an increased risk of developing cancer. Patients who underwent HTx between 1985 and 2017 were included. Detection of cancer was obtained by cross-checking the study population with the Swedish Cancer-Registry and the Cause-of-Death-Registry. A total of 664 patients were followed for a median of 7.7years. In all, 231 malignancies were diagnosed in 138 patients. Compared to the general population the excess risk of cancer following HTx was 6.2-fold calculated as the standardized incidence ratio (SIR) and 2.9-fold after exclusion of non-melanoma skin cancer (NMSC). The most common malignancies were NMSC, non-Hodgins lymphoma, and lung cancer. There was no significant difference in overall survival between those with and without a history of cancer before HTx (p = 0.53). During a median follow-up of 7.7years, 19% of HTx recipients developed cancer, 6.2-fold higher relative to the general population, and 2.9-fold higher when excluding NMSC. Risk factors for malignancies (excluding NMSC) included previous smoking, hypertension and prolonged ischemic time; and for NMSC, increasing age, seronegative CMV-donors, and azathioprine. A previous cancer in selected recipients results in similar survival compared to those without cancer prior to HTx.

Donor great vessel free arterial grafts for complex reconstruction during pediatric heart transplantation

ObjectivePrior studies suggest that prolonged donor heart warm ischemia time increases heart transplant mortality. Patients with single-ventricle heart disease requiring transplant with concomitant aortic arch or central pulmonary artery reconstruction present technical challenges that extend donor warm ischemia time using conventional techniques. Studies in larger pediatric and adult patients with single-ventricle anatomy have described the use of prosthetic material for concomitant great vessel reconstruction. We have used donor free arterial grafts to simplify concomitant great vessel reconstructions and reduce warm donor ischemia time in small patients with single-ventricle physiology undergoing heart transplant. The purpose of this study is to review our results in these patients. MethodsChildren with single-ventricle heart disease who underwent free donor arterial graft great vessel reconstruction at heart transplant were identified, divided into aortic arch and central pulmonary artery groups, and retrospectively reviewed. Warm and total ischemia times were recorded contemporaneously at transplant. ResultsFifteen pediatric patients with single-ventricle physiology underwent donor free arterial graft great vessel reconstructions (9 aortic arch, 6 pulmonary artery). Mean donor warm and total ischemia times for the entire cohort were 52.8 ± 10.7 and 341.7 ± 41.2 minutes. Two patients required postoperative extracorporeal membrane oxygenation. Hospital survival was 94% (1 death). There were no late deaths, and 2 patients had late retransplant. There were no early or late aortic or pulmonary artery obstructions, reinterventions, or complications at median follow-up of 14.2 years (interquartile range, 4.2-16.3 years). ConclusionsDonor free arterial grafts for concomitant great vessel reconstruction during heart transplant in small, single-ventricle patients reduces warm ischemia time, simplifies technical demands, and preserves growth potential.

Thoracoabdominal Normothermic Regional Perfusion Using Mobile Closed Extracorporeal Circuit in Circulatory Death Determination Heart Donors.

Thoracoabdominal normothermic regional perfusion (TA-NRP) is increasingly implemented in donation after circulatory determination of death (DCD). Thoracoabdominal normothermic regional perfusion allows thoracic and abdominal organs to be perfused with warm, oxygenated blood after declaration of death, interrupting ischemia. Evidence is accumulating supporting the use of TA-NRP to improve the outcome of grafts from DCD donors. Thoracoabdominal normothermic regional perfusion may restore and maintain a near-physiological environment during procurement. Moreover, during TA-NRP it is feasible to evaluate the heart in situ. Thoracoabdominal normothermic regional perfusion could be performed through different cannulation techniques, central or peripheral, and, with different extracorporeal circuits. The use of conventional cardiopulmonary bypass and extracorporeal life support (ECLS) devices equipped with open circuits has been described. We report the use of a fully mobile, closed ECLS circuit to implement TA-NRP. The procedure was successfully performed in a peripheral center without a cardiac surgery program through a percutaneous cannulation approach. This strategy resulted in combined heart, liver, and kidney recovery despite a significantly prolonged functional warm ischemia time. The feasibility of TA-NRP using modified but still closed fully mobile ECLS circuits could furtherly support the expansion of DCD programs, increasing the availability of heart for transplantation, and the quality of the grafts, improving recipients' outcome.

Evaluation of the suitability of using ArtiSential in various renal surgery: IDEAL stage 1 study

BackgroundArtiSential, a new articulating laparoscopic instruments, addresses the limited movement associated with conventional laparoscopic instruments. This study was conducted to assess the clinical effectiveness of ArtiSential in detailed steps of various renal surgery.MethodsThis study was approved by the Institutional Review Board of our institution and registered on the Clinical Research Information Service site of the Korea Disease Control and Prevention Agency. Participants meeting all inclusion and exclusion criteria were included in the clinical trial and underwent renal surgery. The clinical effectiveness of ArtiSential was assessed in terms of the feasibility and objective and subjective parameters across 9 detailed steps.ResultsOf the 15 potential candidates enrolled from October 2021 to November 2021, 1 patient dropped out due to anaphylaxis from an anesthetic agent, and 14 patients underwent laparoscopic surgery using ArtiSential. Of the 14 patients, 2 patients were converted to laparoscopic surgery using straight-shaped instruments due to the ischemia time exceeding 30 min, and 1 patient due to excessive bleeding. The feasibility for most steps was more than 90%, except the renorrhaphy step. The median total operation time and ischemia time were 161 and 23 min, respectively. The median estimated blood loss was 58.5 mL. Two cases of venous injury occurred during renal pedicle dissection step. The accuracy of the procedure judged by reviewers and usability judged by the operator were acceptable in all steps. The surgeon’s quantitatively measured stress score was the highest during renorrhaphy step.ConclusionsLaparoscopic surgery using ArtiSential is feasible for most steps except the renorrhaphy step. The difficulty of performing renorrhaphy is attributed to prolonged ischemia time, which could be addressed by overcoming the learning curve.Trial registrationClinical Research Information Service site of the Korea Disease Control and Prevention Agency, KCT0006532. Registered 03/09/2021, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24071.

Assessing the degree of hepatic ischemia-reperfusion injury using physiologically based pharmacokinetic modeling of sodium fluorescein disposition in ex vivo machine-perfused livers.

Ischemia-reperfusion injury (IRI) is an intrinsic risk associated with liver transplantation. Ex vivo hepatic machine perfusion (MP) is an emerging organ preservation technique that can mitigate IRI, especially in livers subjected to prolonged warm ischemia time (WIT). However, a method to quantify the biological response to WIT during MP has not been established. Previous studies used physiologically based pharmacokinetic (PBPK) modeling to demonstrate that a decrease in hepatic transport and biliary excretion of the tracer molecule sodium fluorescein (SF) could correlate with increasing WIT in situ. Furthermore, these studies proposed intracellular sequestration of the hepatocyte canalicular membrane transporter multidrug resistance-associated protein 2 (MRP2) leading to decreased MRP2 activity (maximal transport velocity; Vmax) as the potential mechanism for decreased biliary SF excretion. We adapted an extant PBPK model to account for ex vivo hepatic MP and fit a six-parameter version of this model to control time-course measurements of SF in MP perfusate and bile. We then identified parameters whose values were likely insensitive to changes in WIT and fixed them to generate a reduced model with only three unknown parameters. Finally, we fit the reduced model to each individual biological replicate SF time course with differing WIT, found the mean estimated value for each parameter, and compared them using a one-way ANOVA. We demonstrated that there was a significant decrease in the estimated value of Vmax for MRP2 at the 30-min WIT. These studies provide the foundation for future studies investigating real-time assessment of liver viability during ex vivo MP.NEW & NOTEWORTHY We developed a computational model of sodium fluorescein (SF) biliary excretion in ex vivo machine perfusion and used this model to assess changes in model parameters associated with the activity of MRP2, a hepatocyte membrane transporter, in response to increasing warm ischemia time. We found a significant decrease in the parameter value describing MRP2 activity, consistent with a role of decreased MRP2 function in ischemia-reperfusion injury leading to decreased secretion of SF into bile.

A Novel Cooling Device for Kidney Transplant Surgery.

Background: Prolonged warm ischemia time (WIT) in kidney transplantation is associated with numerous adverse outcomes including delayed graft function and decreased patient and graft survival. Circumventing WIT lies in maintaining renal hypothermia and efficiently performing the vascular anastomosis during this portion of the procedure. Although numerous methods of intra-operative renal cooling have been proposed, most suffer from practical limitations, and none have been widely adopted. Herein we describe a novel device specifically designed to maintain renal hypothermia during kidney transplant surgery.Methods: Aluminum tubing was organized in a serpentine pattern to create a malleable, form-fitting cooling jacket to manipulate renal allografts during transplant surgery. Adult porcine kidneys were used to test the device with 4°C saline as coolant. Kidneys were placed at 24°C; surface and core temperatures were monitored using implanted thermocouples. Anastomosis of porcine kidney vessels to GORE-TEX® vascular grafts in an ex-vivo operative field was performed to assess the functionality of the device.Results: The device maintained surface and core graft temperatures of ≤5°C after 60 minutes of WIT. Furthermore, the device provided hands-free retraction and support for the allograft. We found that ex-vivo anastomosis testing was enhanced by the presence of the cooling jacket.Conclusions: This proof-of-concept study demonstrated that our novel device is a practical tool for renal transplantation and can maintain sufficiently cool graft temperatures to mitigate WIT in an ex-vivo setting. This device is the first of its kind and has the potential to improve kidney transplant outcomes by eliminating WIT during graft implantation.

A single center analysis of long-term outcomes and survival related risk factors in liver retransplantation.

Liver retransplant is the only option to save a patient with liver graft failure. However, it is controversial due to its poor survival outcome compared to primary transplantation. Insufficient deceased organ donation in Taiwan leads to high waitlist mortality. Hence, living-donor grafts offer a valuable alternative for retransplantation. This study aims to analyze the single center's outcome in living donor liver retransplantation (re-LDLT) and deceased donor liver retransplantation (re-DDLT) as well as the survival related confounding risk factors. This is a single center retrospective study including 32 adults who underwent liver retransplantation (re-LT) from June 2002 to April 2020. The cohort was divided into a re-LDLT and a re-DDLT group and survival outcomes were analyzed. Patient outcomes over different periods, the effect of timing on survival, and multivariate analysis for risk factors were also demonstrated. Of the 32 retransplantations, the re-LDLT group (n=11) received grafts from younger donors (31.3 vs. 43.75 years, P=0.016), with lower graft weights (688 vs. 1,457.2 g, P<0.001) and shorter cold ischemia time (CIT) (45 vs. 313 min, P<0.001). The 5-year survival was significantly better in the re-LDLT group than in the re-DDLT group (100% vs. 70.8%, P=0.02). This difference was adjusted when only retransplantation after 2010 was analyzed. Further analysis showed that the timing of retransplantation (early vs. late) did not affect patient survival. Multivariate analysis revealed that prolonged warm ischemia time (WIT) and intraoperative blood transfusion were related to poor long-term survival. Retransplantation with living donor graft demonstrated good long-term outcomes with acceptable complications to both recipient and donor. It may serve as a choice in areas lacking deceased donors. The timing of retransplantation did not affect the long-term survival. Further effort should be made to reduce WIT and massive blood transfusion as they contributed to poor survival after retransplantation.

Reduction in pacemaker rates post-heart transplantation with use of organ preservation systems

Abstract Background Approximately 10% of heart transplant recipients require permanent pacemaker (PPM) implantation. (1) Prolonged graft ischaemic time may contribute to conduction system injury and PPM requirement. (2) Ex-vivo preservation of heart allografts at the time of organ retrieval, using either normothermic or hypothermic organ preservation systems (OPS), allows for the reduction of graft ischaemic time which can facilitate long-distance procurements and use of marginal donors including donation after circulatory death (DCD) donors. (3) Purpose We sought to determine if the use of organ preservation systems reduced PPM implantation in heart transplant recipients. Methods This was a single-centre retrospective study of 405 consecutive heart transplant recipients between July 2014 and March 2023. Baseline demographics, utilisation of organ preservation systems, donor ischaemic times, history of graft dysfunction, rejection and chronic allograft vasculopathy were obtained from the medical records. The primary outcome was PPM implantation. Results Of 405 heart transplants performed, an organ preservation system (OPS) was utilised in 118 (29.1%) patients. Normothermic OPS was used in 93/405 (23%) transplants, 90 of which were DCD transplants. Twenty-five of 405 (6.2%) transplants were performed using a hypothermic OPS to facilitate donation after brain death (DBD). The remaining 287 (70.9%) organs underwent cold ischaemic storage (CIS) from retrieval until transplant. Apart from male sex (81% in OPS group versus 69% in the CIS group), there were no significant differences in baseline demographics between the two groups (table 1). Two of 118 (1.7%) patients in the OPS group required PPM implantation, compared to 27/287 (9.4%) in the cold ischaemic storage group (Chi-Square 7.5, p = 0.006). Kaplan-Meier analysis (figure 1) demonstrates a significantly lower rate of PPM implantation in the OPS arm (Log Rank 6.975, p = 0.008). Of the 29 patients who required pacing, 12/29 (41.4%) had AV block and 17/29 (58.6%) had sinus node dysfunction. Thirteen of 29 patients (44.8%) required PPM implantation within 30 days of transplant. Six of 29 patients (20.7%) were pacing dependent at last follow up. Conclusion Heart transplants performed utilising an organ preservation system were associated with lower PPM rates.Table 1.Figure 1.

Impact of Prolonged Cold Ischemia Time on Long-Term Survival in Lung Transplant Recipients

Cold ischemia time (CIT) influences short- and long-term outcomes in lung transplant recipients. Most studies proved that prolonged CIT causes increased mortality. This study aimed to investigate the impact of prolonged CIT on patient survival time after lung transplantation (LTx). The retrospective study group consisted of 139 patients who underwent double LTx in a single center between January 2018 and August 2022. Prolonged ischemic time (PIT) was defined as total ischemic time >6 hours and divided into smaller time intervals according to increasing PIT (6-8, 8-10, 10-12, >12 hours). The assessed outcomes were 1- and 4-year survival. Among the study group, PIT was observed in 98% (n = 137), and its average value was 10.33 hours. The prolonged CIT of 6 to 8 hours occurred in 10% (n = 14), 8 to 10 hours in 34% (n = 47), 10 to 12 hours in 36% (n = 49), and >12 hours in 20% (n = 27). In a comparison of 1-year survival between the PIT 6- to 10-hour group and the >10-hour arm (88% vs 78%), the difference was not statistically significant (P > .05). PIT is a risk factor for reduced long-term survival in LTx recipients. Increasing PIT may be associated with higher mortality at 1 and 4 years. All efforts to reduce the duration of ischemic time can benefit patient survival after LTx.

Salvaging donated kidneys from prolonged warm ischemia during ex vivo hypothermic oxygenated perfusion

Prolonged warm ischemic is the main cause discarding donated organs after cardiac death. Here, we identified that prolonged warm ischemic time induced disseminated intravascular coagulation and severe capillary vasospasm after cardiac death of rat kidneys. Additionally, we found a significant accumulation of fibrinogen in a hypoxic cell culture of human umbilical vein epithelial cells and in isolated kidneys exposed to prolonged warm ischemic following flushing out of blood. However, pre-flushing the kidney with snake venom plasmin in a 90-minute warm ischemic model maximized removal of micro thrombi and facilitated the delivery of oxygen and therapeutic agents. Application of carbon monoxide releasing CORM-401 during ex vivo hypothermic oxygenated perfusion achieved multipath protective effects in prolonged warm ischemic kidneys. This led to significant improvements in perfusion parameters, restoration of the microcirculation, amelioration of mitochondrial injury, oxidative stress, and apoptosis. This benefit resulted in significantly prolonged warm ischemic kidney recipient survival rates of 70%, compared with none in those receiving ex vivo hypothermic oxygenated perfusion alone. Significantly, ex vivo hypothermic oxygenated perfusion combined with cytoprotective carbon monoxide releasing CORM-401 treatment meaningfully protected the donated kidney after cardiac death from ischemia-reperfusion injury by reducing inflammation, oxidative stress, apoptosis, and pathological damage. Thus, our study suggests a new combination treatment strategy to potentially expand the donor pool by increasing use of organs after cardiac death and salvaging prolonged warm ischemic kidneys.

Predictors of early mortality after lung transplantation for idiopathic pulmonary arterial hypertension.

Lung transplantation remains an important therapeutic option for idiopathic pulmonary arterial hypertension (IPAH),yet short-term survival is the poorest among the major diagnostic categories. We sought to develop a prediction model for 90-day mortality using the United Network for Organ Sharing database for adults with IPAH transplanted between 2005 and 2021. Variables with a pvalue ≤ 0.1 on univariate testing were included in multivariable analysis to derive the best subset model. The cohort comprised 693 subjects, of whom 71 died (10.2%) within 90 days of transplant. Significant independent predictors of early mortality were: extracorporeal circulatory support and/or mechanical ventilation at transplant (OR:3; CI: 1.4-5), pulmonary artery diastolic pressure (OR:1.3 per 10 mmHg; CI: 1.07-1.56), forced expiratory volume in the first second percent predicted (OR:0.8 per 10%; CI: 0.7-0.94), recipient total bilirubin >2 mg/dL (OR:3; CI: 1.4-7.2) and ischemic time >6 h (OR: 1.7, CI: 1.01-2.86). The predictive model was able to distinguish 25% of the cohort with a mortality of ≥20% from 49% with a mortality of ≤5%. We conclude that recipient variables associated with increasing severity of pulmonary vascular disease, including pretransplant advanced life support, and prolonged ischemic time are important risk factors for 90-day mortality after lung transplant for IPAH.

O197: Quality Assessment of Human Kidneys by Ex-vivo Normothermic Machine Perfusion prior to Transplantation

Abstract Introduction Ex-vivo normothermic machine perfusion (NMP) is a technique of preservation that can be used to assess the quality and suitability of a kidney for transplantation. This may prevent the unnecessary discard and increase the number of transplanted kidneys. Methods A total of 22 kidneys declined for transplant by all UK transplant centres, were assessed over a three-year period across three centres in the UK. Prior to NMP, most kidneys were declined due to poor quality cold flushing at retrieval. All kidneys were assessed during 1h of NMP. A quality assessment score (QAS) based on the appearance, blood flow and urine output was applied to each kidney. Scores ranged from 1 (best) to 5 (worst). Results Sixteen kidneys (72%) had a QAS of 1 to 3 and were transplanted into matched recipients. One patient died with a non-functioning kidney 12 days post-transplant due to a cardiac arrest. Six recipients (37.5%) had delayed graft function. The mean serum creatinine levels and estimated glomerular filtration rate at 3 months was 154±74µmol/L and 45±15mL/min/1.73m2, respectively. Graft and patient survival at 12 months were 94%. Of the 6 non-transplanted kidneys, 3 were deemed unsuitable after assessment during NMP, 1 was not transplanted due to logistical reasons and a prolonged cold ischaemic time, and the remaining 2 due to chronic degenerative changes assessed by histology scores. Conclusion This clinical research study demonstrated the ability to use NMP technology to successfully increase the number of transplants by assessing kidneys that would otherwise be discarded.

Prolonged warm ischemia time in the recipient is associated with post-transplant biliary stricture following living-donor liver transplantation.

Post-transplant biliary stricture (PBS) is a common and important complication following orthotopic liver transplantation (LT). This study clarified the incidence of PBS and identified its risk factors. We retrospectively reviewed the medical records of 67 patients who underwent living-donor LT (LDLT) at our institute between June 2010 and July 2022 and analyzed their clinical characteristics, prognosis, and risk factors for PBS. Of the 67 patients, 26 (38.8%) developed PBS during the observation period. Multivariate analyses revealed the following independent risk factors for PBS formation: increased red cell transfusion volume per body weight (> 0.2 U/kg; hazard ratio [HR], 3.8; P = 0.002), increased portal vein pressure (PVP) at the end of LT (> 16 mmHg; HR, 2.88; P = 0.032), postoperative biliary leakage (HR, 4.58; P = 0.014), and prolonged warm ischemia time (WIT) (> 48 min; HR, 4.53; P = 0.008). In patients with PBS, the cumulative incidence of becoming stent free was significantly higher in patients with a WIT ≤ 48 min than in those with a WIT > 48 min (P = 0.038). Prolonged WIT is associated with intractable PBS following LDLT.

Sequential Normothermic Regional Perfusion and End-ischemic Ex Situ Machine Perfusion Allow the Safe Use of Very Old DCD Donors in Liver Transplantation.

In Italy, 20 min of continuous, flat-line electrocardiogram are required for death declaration. Despite prolonged warm ischemia time, Italian centers reported good outcomes in controlled donation after circulatory death (cDCD) liver transplantation by combining normothermic regional and end-ischemic machine perfusion (MP). The aim of this study was to evaluate the safety and feasibility of the use of septuagenarian and octogenarian cDCD donors with this approach. All cDCD older than 70 y were evaluated during normothermic regional perfusion and then randomly assigned to dual hypothermic or normothermic MP. In the period from April 2021 to December 2022, 17 cDCD older than 70 y were considered. In 6 cases (35%), the graft was not considered suitable for liver transplantation, whereas 11 (65%) were evaluated and eventually transplanted. The median donor age was 82 y, being 8 (73%) older than 80. Median functional warm ischemia and no-flow time were 36 and 28 min, respectively. Grafts were randomly assigned to ex situ dual hypothermic oxygenated MP in 6 cases (55%) and normothermic MP in 5 (45%). None was discarded during MP. There were no cases of primary nonfunction, 1 case of postreperfusion syndrome (9%) and 2 cases (18%) of early allograft dysfunction. At a median follow-up of 8 mo, no vascular complications or ischemic cholangiopathy were reported. No major differences were found in terms of postoperative hospitalization or complications based on the type of MP. The implementation of sequential normothermic regional and end-ischemic MP allows the safe use of very old donation after circulatory death donors.

Impact of prolonged ischemic time on pediatric heart transplantation outcomes: Improved outcomes in the most recent era

BackgroundImpacts of ischemic time (IT) on pediatric heart transplant outcomes are multifactorial. We aimed to analyze the effect of prolonged IT on graft loss after pediatric heart transplantation. We hypothesized that graft survival with prolonged IT has improved across eras. MethodsPatients <18 years old in the Pediatric Heart Transplant Society database (1993-2019) were included (N=6765) and stratified by diagnosis and era (1993-2004, 2005-2009, and 2010-2019). Severe graft failure (SGF) was defined as death, re-transplant, or need for mechanical circulatory support in the first 7 days post-transplant. Descriptive statistical methods were used to compare differences between patient characteristics and IT. Kaplan-Meier survival analysis compared freedom from graft loss, rejection, and infection. Multivariable analysis was performed for graft loss and SGF (hazard and logistic regression modeling, respectively). ResultsDiagnoses were cardiomyopathy (N=3246) and congenital heart disease (CHD; N=3305). CHD were younger, more likely to have an IT >4.5 hours, and more likely to require extracorporeal membrane oxygenation or mechanical ventilation at transplant (all P<0.001). Median IT was 3.6 hours [IQR 2.98 to 4.31; range 0-10.5]. IT was associated with early graft loss (HR 1.012, 95% CI 1.005-1.019), but not when analyzed only in the most recent era. IT was associated with SGF (OR 1.016 95%CI 1.003 - 1.030). ConclusionsDonor IT was independently associated with increased risk of graft loss, albeit with a small effect relative to other risk factors. Graft survival with prolonged IT has improved in the most recent era but the risk of SGF persists.

Impact of prolonged liver ischemia during intermittent Pringle maneuver on postoperative outcomes following liver resection

BackgroundThe aim of this study was to compare postoperative outcomes following liver resection between patients with prolonged cumulative ischemia time (CIT) which exceeded 60 min and patients with CIT less than 60 min. MethodsBetween March 2020 and October 2022, 164 consecutive patients underwent liver resection at the Unit for hepato-bilio-pancreatic surgery, University Clinic for Digestive Surgery in Belgrade, Serbia. Intermittent Pringle maneuver was routinely applied. Depending on CIT during transection, patients were divided into two groups: group 1 (CIT <60 min) included 101 patients, and group 2 (CIT ≥60 min) included 63 patients. ResultsMedian operative time (210 vs. 400 min) and CIT (30 vs. 76 min) were longer in the Group 2 (p < 0.001). Intraoperative blood loss was higher in the Group 2 (150 vs 500 ml), p < 0.001. The perioperative transfusion rate was similar between the groups (p = 0.107). There was no difference in postoperative overall morbidity (50.5% vs. 58.7%, p = 0.337) and major morbidity (18.8 vs. 19%, p = 0.401). In-hospital mortality, 30-day mortality, and 90-day mortality were similar between the groups (p = 0.408; p = 0.408; p = 0.252, respectively). Non-anatomical liver resection was the only predictive factor of 90-day mortality identified by multivariate analysis (p = 0.047; Relative Risk = 0.179; 95% Confidence Interval 0.033–0.981). ConclusionIntermittent Pringle maneuver with CIT exceeding 60 min is a safe method for bleeding control during liver resection with no impact on postoperative morbidity and mortality. Keywords: intermittent Pringle maneuver, liver ischemia, liver resection.

Donor heart refusal after circulatory death: An analysis of United Network for Organ Sharing refusal codes

ObjectiveDonor hearts procured after circulatory death (DCD) may significantly increase the number of hearts available for transplantation. The purpose of this study was to analyze current DCD and brain-dead donor (DBD) heart transplantation rates and characterize organ refusal using the most up-to-date United Network for Organ Sharing (UNOS) and Organ Procurement and Transplantation Network data. MethodsWe analyzed UNOS and Organ Procurement and Transplantation Network DBD and DCD candidate, transplantation, and demographic data from 2020 through 2022 and 2022 refusal code data to characterize DCD heart use and refusal. Subanalyses were performed to characterize DCD donor demographics and regional transplantation rate variance. ResultsDCD hearts were declined 3.37 times more often than DBD hearts. The most frequently used code for DCD refusal was neurologic function, related to concerns of a prolonged dying process and organ preservation. In 2022, 92% (1329/1452) of all DCD refusals were attributed to neurologic function. When compared with DBD, DCD donor hearts were more frequently declined as the result of prolonged warm ischemic time (odds ratio, 5.65; 95% confidence interval, 4.07-7.86) and other concerns over organ preservation (odds ratio, 4.06; 95% confidence interval, 3.33-4.94). Transplantation rate variation was observed between demographic groups and UNOS regions. DCD transplantation rates are currently experiencing second order polynomial growth. ConclusionsDCD donor hearts are declined more frequently than DBD. DCD heart refusals result from concerns over a prolonged dying process and organ preservation. Heart transplantation rates may be substantially improved by ex situ hemodynamic assessment, adoption of normothermic regional perfusion guidelines, and quality initiatives.

Comparison of different porcine models simulating myocardial cold ischemia of pediatric donor hearts.

Our team previously identified a stem cell-derived cardioprotective additive that can be added to standard cardioplegia to extend myocardial viability during prolonged myocardial cold ischemic time (CIT) in rodent models. The purpose of this study was to utilize a porcine model to compare in-vivo versus ex-vivo porcine simulation of CIT that accompanies cardiac transplantation in humans, in order to determine an optimal method for translation of our studies to larger animals. Eight 39-55kg Yorkshire X pigs were randomly assigned to either in-vivo or ex-vivo simulation. After administration of general anesthesia and endotracheal intubation, baseline measurement of left ventricular performance was obtained via transesophageal echocardiography (TEE). After midline sternotomy and heparin administration, the aorta was cross-clamped and twoliters of HTK-Custodiol were introduced via the aortic root. The in-vivo method utilized cold ischemic heart storage in the chest cavity while supporting the experimental animal with cardiopulmonary bypass (CPB). The ex-vivo method involved standard cardiac procurement, cold ischemic storage outside of the body, and subsequent cardiac reperfusion utilizing cardiac reanimation in a Langendorff heart perfusion mode. After CIT, measurements of post-ischemic left ventricular performance were obtained via echocardiography. Results are presented as: Mean ± Standard Deviation (Median, Minimum-Maximum). Weight (kilograms) was similar in the in-vivo group and the ex-vivo group: 44 ± 1.8 (44, 42-46) versus 44 ± 5.1 (43.5, 39-51), respectively. Cold ischemic time (minutes) was longer in the ex-vivo group: 360 ± 0 (360, 360-360) versus 141 ± 26.7 (149, 102-163). Temperature (degrees Celsius) was colder in the ex-vivo group: 8 ± 0 (8, 8-8) versus 16.5 ± 4.2 (16, 12-16).In the in-vivo group, baseline ejection fraction and ejection fraction after CIT were: 48.25% ± 14.95% (48.5%, 33%-63%) and 41.25% ± 22.32% (41.5%, 20%-62%), respectively. In the ex-vivo group, baseline ejection fraction and ejection fraction after CIT were: 56.4% ± 5.9% (57%, 50%-67%) and 60.4% ± 7.7% (61.5%, 51.9%-67%), respectively. The ex-vivo technique is suitable to evaluate cardioplegia additives that may substantially extend myocardial tolerance to cold ischemia.