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Neurotherapeutics : the Journal of the... Apr 2020We review state-of-the-art monitoring techniques for acute, severe traumatic spinal cord injury (TSCI) to facilitate targeted perfusion of the injured cord rather than... (Review)
Review
We review state-of-the-art monitoring techniques for acute, severe traumatic spinal cord injury (TSCI) to facilitate targeted perfusion of the injured cord rather than applying universal mean arterial pressure targets. Key concepts are discussed such as intraspinal pressure and spinal cord perfusion pressure (SCPP) at the injury site, respectively, analogous to intracranial pressure and cerebral perfusion pressure for traumatic brain injury. The concept of spinal cord autoregulation is introduced and quantified using spinal pressure reactivity index (sPRx), which is analogous to pressure reactivity index for traumatic brain injury. The U-shaped relationship between sPRx and SCPP defines the optimum SCPP as the SCPP that minimizes sPRx (i.e., maximizes autoregulation), and suggests that not only ischemia but also hyperemia at the injury site may be detrimental. The observation that optimum SCPP varies between patients and temporally in each patient supports individualized management. We discuss multimodality monitoring, which revealed strong correlations between SCPP and injury site metabolism (tissue glucose, lactate, pyruvate, glutamate, glycerol), monitored by surface microdialysis. Evidence is presented that the dura is a major, but unappreciated, cause of spinal cord compression after TSCI; we thus propose expansion duroplasty as a novel treatment. Monitoring spinal cord blood flow at the injury site has revealed novel phenomena, e.g., 3 distinct blood flow patterns, local steal, and diastolic ischemia. We conclude that monitoring from the injured spinal cord in the intensive care unit is a safe technique that appears to enable optimized and individualized spinal cord perfusion.
Topics: Cerebrospinal Fluid Pressure; Humans; Perfusion; Spinal Cord Injuries
PubMed: 31916236
DOI: 10.1007/s13311-019-00820-6 -
International Journal of Medical... 2021Nowadays, liver transplantation is the most effective treatment for end-stage liver disease. However, the increasing imbalance between growing demand for liver... (Review)
Review
Nowadays, liver transplantation is the most effective treatment for end-stage liver disease. However, the increasing imbalance between growing demand for liver transplantation and the shortage of donor pool restricts the development of liver transplantation. How to expand the donor pool is a significant problem to be solved clinically. Many doctors have devoted themselves to marginal grafting, which introduces livers with barely passable quality but a high risk of transplant failure into the donor pool. However, existing common methods of preserving marginal grafts lead to both high risk of postoperative complications and high mortality. The application of machine perfusion allows surgeons to make marginal livers meet the standard criteria for transplant, which shows promising prospect in preserving and repairing donor livers and improving ischemia reperfusion injury. This review summarizes the progress of recent researches on hepatic machine perfusion.
Topics: Humans; Liver Transplantation; Organ Preservation; Perfusion; Reperfusion Injury; Tissue and Organ Harvesting
PubMed: 33850464
DOI: 10.7150/ijms.56139 -
Journal of Hepatology May 2023Liver graft utilization rates are a hot topic due to the worldwide organ shortage and the increasing number of transplant candidates on waiting lists. Liver perfusion...
BACKGROUND & AIMS
Liver graft utilization rates are a hot topic due to the worldwide organ shortage and the increasing number of transplant candidates on waiting lists. Liver perfusion techniques have been introduced in several countries, and may help to increase the organ supply, as they potentially enable the assessment of livers before use.
METHODS
Liver offers were counted from donation after circulatory death (DCD) donors (Maastricht type III) arising during the past decade in eight countries, including Belgium, France, Italy, the Netherlands, Spain, Switzerland, the UK, and the US. Initial type-III DCD liver offers were correlated with accepted, recovered and implanted livers.
RESULTS
A total number of 34,269 DCD livers were offered, resulting in 9,780 liver transplants (28.5%). The discard rates were highest in the UK and US, ranging between 70 and 80%. In contrast, much lower DCD liver discard rates, e.g. between 30-40%, were found in Belgium, France, Italy, Spain and Switzerland. In addition, we observed large differences in the use of various machine perfusion techniques, as well as in graft and donor risk factors. For example, the median donor age and functional donor warm ischemia time were highest in Italy, e.g. >40 min, followed by Switzerland, France, and the Netherlands. Importantly, such varying risk profiles of accepted DCD livers between countries did not translate into large differences in 5-year graft survival rates, which ranged between 60-82% in this analysis.
CONCLUSIONS
Overall, DCD liver discard rates across the eight countries were high, although this primarily reflects the situation in the Netherlands, the UK and the US. Countries where in situ and ex situ machine perfusion strategies were used routinely had better DCD utilization rates without compromised outcomes.
IMPACT AND IMPLICATIONS
A significant number of Maastricht type III DCD livers are discarded across Europe and North America today. The overall utilization rate among eight Western countries is 28.5% but varies significantly between 18.9% and 74.2%. For example, the median DCD-III liver utilization in five countries, e.g. Belgium, France, Italy, Switzerland, and Spain is 65%, in contrast to 24% in the Netherlands, UK and US. Despite this, and despite different rules and strategies for organ acceptance and preservation, 1- and 5-year graft survival rates remain fairly similar among all participating countries. A highly varying experience with modern machine perfusion technology was observed. In situ and ex situ liver perfusion concepts, and application of assessment tools for type-III DCD livers before transplantation, may be a key explanation for the observed differences in DCD-III utilization.
Topics: Humans; Tissue and Organ Procurement; Liver; Tissue Donors; Liver Transplantation; Cardiovascular System; Graft Survival; Organ Preservation; Perfusion
PubMed: 36740047
DOI: 10.1016/j.jhep.2023.01.025 -
International Journal of Surgery... Oct 2020Dynamic preservation strategies are a promising option to improve graft quality before transplantation, and to extend preservation time for either logistic or treatment... (Review)
Review
Dynamic preservation strategies are a promising option to improve graft quality before transplantation, and to extend preservation time for either logistic or treatment reasons. In contrast to normothermic oxygenated perfusion, which intends to mimic physiological conditions in the human body, with subsequent clinical application for up to 24 hrs, hypothermic perfusion is mainly used for a relatively short period with protection of mitochondria and subsequent reduction of oxidative injury upon implantation. The results from two randomized controlled trials, where recruitment has finished are expected this year. Both ex situ perfusion techniques are increasingly applied in clinical transplantation including recent reports on viability assessment, which could open the door for an increased liver utilization in the future.
Topics: Humans; Hypothermia, Induced; Liver; Liver Transplantation; Organ Preservation; Perfusion; Transplants; Treatment Outcome
PubMed: 32353556
DOI: 10.1016/j.ijsu.2020.04.057 -
International Journal of Molecular... Jun 2023Building the inner layer of our blood vessels, the endothelium forms an important line communicating with deeper parenchymal cells in our organs. Previously considered... (Review)
Review
Building the inner layer of our blood vessels, the endothelium forms an important line communicating with deeper parenchymal cells in our organs. Previously considered passive, endothelial cells are increasingly recognized as key players in intercellular crosstalk, vascular homeostasis, and blood fluidity. Comparable to other cells, their metabolic function strongly depends on mitochondrial health, and the response to flow changes observed in endothelial cells is linked to their mitochondrial metabolism. Despite the direct impact of new dynamic preservation concepts in organ transplantation, the impact of different perfusion conditions on sinusoidal endothelial cells is not yet explored well enough. This article therefore describes the key role of liver sinusoidal endothelial cells (LSECs) together with their mitochondrial function in the context of liver transplantation. The currently available ex situ machine perfusion strategies are described with their effect on LSEC health. Specific perfusion conditions, including perfusion pressure, duration, and perfusate oxygenation are critically discussed considering the metabolic function and integrity of liver endothelial cells and their mitochondria.
Topics: Liver Transplantation; Endothelial Cells; Liver; Hepatocytes; Mitochondria; Perfusion; Organ Preservation
PubMed: 37373238
DOI: 10.3390/ijms241210091 -
The Journal of Thoracic and... Sep 2019
Topics: Cerebrovascular Circulation; Monitoring, Physiologic; Perfusion; Ultrasonography
PubMed: 31130297
DOI: 10.1016/j.jtcvs.2019.04.024 -
Nature Communications Aug 2023Current machine perfusion technology permits livers to be preserved ex situ for short periods to assess viability prior to transplant. Long-term normothermic perfusion...
Current machine perfusion technology permits livers to be preserved ex situ for short periods to assess viability prior to transplant. Long-term normothermic perfusion of livers is an emerging field with tremendous potential for the assessment, recovery, and modification of organs. In this study, we aimed to develop a long-term model of ex situ perfusion including a surgical split and simultaneous perfusion of both partial organs. Human livers declined for transplantation were perfused using a red blood cell-based perfusate under normothermic conditions (36 °C) and then split and simultaneously perfused on separate machines. Ten human livers were split, resulting in 20 partial livers. The median ex situ viability was 125 h, and the median ex situ survival was 165 h. Long-term survival was demonstrated by lactate clearance, bile production, Factor-V production, and storage of adenosine triphosphate. Here, we report the long-term ex situ perfusion of human livers and demonstrate the ability to split and perfuse these organs using a standardised protocol.
Topics: Humans; Liver Transplantation; Liver; Perfusion; Bile; Preservation, Biological
PubMed: 37553343
DOI: 10.1038/s41467-023-40154-8 -
Nature Medicine Jun 2023Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation... (Randomized Controlled Trial)
Randomized Controlled Trial
Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation after circulatory death (DCD) donors have been used to increase transplant rates, but these organs are susceptible to cold ischemic injury in the storage period before transplantation, the clinical consequence of which is high rates of delayed graft function (DGF). Normothermic machine perfusion (NMP) is an emerging technique that circulates a warmed, oxygenated red-cell-based perfusate through the kidney to maintain near-physiological conditions. We conducted a randomized controlled trial to compare the outcome of DCD kidney transplants after conventional static cold storage (SCS) alone or SCS plus 1-h NMP. A total of 338 kidneys were randomly allocated to SCS (n = 168) or NMP (n = 170), and 277 kidneys were included in the final intention-to-treat analysis. The primary endpoint was DGF, defined as the requirement for dialysis in the first 7 d after transplant. The rate of DGF was 82 of 135 (60.7%) in NMP kidneys versus 83 of 142 (58.5%) in SCS kidneys (adjusted odds ratio (95% confidence interval) 1.13 (0.69-1.84); P = 0.624). NMP was not associated with any increase in transplant thrombosis, infectious complications or any other adverse events. A 1-h period of NMP at the end of SCS did not reduce the rate of DGF in DCD kidneys. NMP was demonstrated to be feasible, safe and suitable for clinical application. Trial registration number: ISRCTN15821205 .
Topics: Humans; Kidney Transplantation; Organ Preservation; Kidney; Perfusion; Tissue Donors
PubMed: 37231075
DOI: 10.1038/s41591-023-02376-7 -
General Thoracic and Cardiovascular... Apr 2021Lung transplantation is an established life-saving intervention for patients with end-stage lung diseases. The success of lung transplantation mainly depends on the... (Review)
Review
Lung transplantation is an established life-saving intervention for patients with end-stage lung diseases. The success of lung transplantation mainly depends on the quality and function of the implanted donor lungs, which are frequently subject to brain-death-induced lung injuries and intensive care unit (ICU)-related complications before transplantation. Recent innovations, particularly the development of ex vivo lung perfusion (EVLP), in which donor lungs are ventilated and perfused under normothermic conditions outside the body, have allowed clinicians to more accurately assess the donor lung function prior to transplantation. Therefore, EVLP has been successfully translated into clinical practice with the expansion of the donor lung pool, leading to favorable post-transplant outcomes in a growing number of transplant centers worldwide. The EVLP system and techniques, following the Toronto protocol, have recently been applied for the assessment of extended criteria brain-death donors in clinical lung transplantation in Japan. The advancement of EVLP from organ assessment to organ treatment will be the next challenging stage not only to expand donor lung pool, but also to improve graft survival and long-term outcomes after transplantation.
Topics: Extracorporeal Circulation; Humans; Japan; Lung; Lung Transplantation; Organ Preservation; Perfusion; Tissue Donors
PubMed: 33683575
DOI: 10.1007/s11748-021-01609-1 -
International Angiology : a Journal of... Jun 2023To perform a scoping review analyzing the current evidence reporting on acute kidney injury (AKI) after elective open surgery (OS) of complex abdominal aortic aneurysms... (Review)
Review
INTRODUCTION
To perform a scoping review analyzing the current evidence reporting on acute kidney injury (AKI) after elective open surgery (OS) of complex abdominal aortic aneurysms (c-AAAs) and evaluate the impact of renal perfusion, and the different types of solutions on renal morbidity.
EVIDENCE ACQUISITION
Research questions were defined, and a literature search was performed following the PRISMA guidelines for scoping reviews. Multicenter, single-center observational studies were considered eligible. No abstracts only and unpublished literature were included.
EVIDENCE SYNTHESIS
Two hundred and fifty studies were screened, 20 studies met screening criteria and were included, reporting 1552 patients treated for c-AAAs. The majority did not receive renal perfusion and the others received different types of renal perfusions. Acute kidney injury is a common complication after c-AAAs OS, with an incidence up to 32.5%. Heterogeneity in AKI classifications reduce the ability to compare outcomes after perfusion and nonperfusion strategies. Pre-existing CKD, ischemic injury due to suprarenal aortic clamping are major determinants of AKI after aortic surgery. Most papers reported chronic kidney disease (CKD) at admission. Another debated topic is the indication for renal perfusion during c-AAAs OS. Controversial results for cold renal perfusion have been found.
CONCLUSIONS
In the context of c-AAAs, this review identified the need to standardize the definition of AKI to reduce reporting bias. Besides this, it showed the need to assess the indication for renal perfusion and the type of perfusion solution to be used.
Topics: Humans; Acute Kidney Injury; Aorta, Abdominal; Aortic Aneurysm, Abdominal; Multicenter Studies as Topic; Perfusion; Renal Insufficiency, Chronic
PubMed: 37222507
DOI: 10.23736/S0392-9590.23.05021-6