Liver transplant with controlled donors after circulatory death with normothermic regional perfusion and brain dead donors: A multicenter cohort study of transfusion, one-year graft survival and mortality.

BACKGROUND: Controlled donation after circulatory death (cDCD) has expanded the donor pool for liver transplantation (LT). However, transfusion requirements and perioperative outcomes should be elucidated. The aim of this multicenter study was to assess red blood cell (RBC) transfusions, one-year graft and patient survival after LT after cDCD with normothermic regional perfusion (NRP) compared with donors after brain death (DBD). METHODS: 591 LT carried out in ten centers during 2019 were reviewed. Thromboelastometry was used to manage coagulation and blood product transfusion in all centers. Normothermic regional perfusion was the standard technique for organ recovery. RESULTS: 447 patients received DBD and 144 cDCD with NRP. Baseline MCF Extem was lower in the cDCD group There were no differences in the percentage of patients (63% vs. 61% p = 0.69), nor in the number of RBC units transfused (4.7 (0.2) vs 5.5 (0.4) in DBD vs cDCD, p = 0.11. Twenty-six patients (6%) died during admission for LT in the DBD group compared with 3 patients (2%) in the cDCD group (p = 0.15). To overcome the bias due to a worse coagulation profile in cDCD recipients, matched samples were compared. No differences in baseline laboratory data, or in intraoperative use of RBC or one-year outcome data were observed between DBD and cDCD recipients. CONCLUSIONS: cDCD with NRP is not associated with increased RBC transfusion. No differences in graft and patient survival between cDCD and DBD were found. Donors after controlled circulatory death with NRP can increasingly be utilized with safety, improving the imbalance between organ donors and the ever-growing demand.

Recomendaciones prácticas para el manejo perioperatorio del paciente con sospecha o infección grave por coronavirus SARS-CoV-2 / Practical recommendations for the perioperative management of the patient with suspection or serious infection by coronavirus SARS-CoV

En diciembre del 2019, la Comisión Municipal de Salud y Sanidad de Wuhan (provincia de Hubei, China) informó de una serie de casos de neumonía de etiología desconocida. El 7 de enero del 2020, las autoridades chinas identificaron como agente causante del brote un nuevo tipo de virus de la familia Coronaviridae, denominado SARS-CoV-2. Desde entonces, se han notificado miles de casos con una diseminación global. Las infecciones en humanos provocan un amplio espectro clínico que va desde infección leve del tracto respiratorio superior, hasta síndrome de distrés respiratorio agudo grave y sepsis. No existe un tratamiento específico para SARS-CoV-2, motivo por lo que los aspectos fundamentales son establecer medidas adecuadas de prevención y el tratamiento de soporte y manejo de las complicaciones

In December 2019, the Wuhan Municipal Health and health Commission (Hubei Province, China) reported a series of cases of pneumonia of unknown etiology. On January 7, 2020, the Chinese authorities identified as a causative agent of the outbreak a new type of virus of the Coronaviridiae family, called SARS-CoV-2. Since then, thounsands of cases have been reported with global dissemination. Infections in humans cause a broad clinical spectrum ranging from mild upper respiratory tract infection, to severe acute respiratory distress syndrome and sepsis. There is not specific treatment for SARS-CoV-2, which is why the fundamental aspects are to establish adequate prevention measures and support treatment and management of complications

Practical recommendations for the perioperative management of the patient with suspection or serious infection by coronavirus SARS-CoV. / Recomendaciones prácticas para el manejo perioperatorio del paciente con sospecha o infección grave por coronavirus SARS-CoV-2.

In December 2019, the Wuhan Municipal Health and health Commission (Hubei Province, China) reported a series of cases of pneumonia of unknown etiology. On January 7, 2020, the Chinese authorities identified as a causative agent of the outbreak a new type of virus of the Coronaviridiae family, called SARS-CoV-2. Since then, thounsands of cases have been reported with global dissemination. Infections in humans cause a broad clinical spectrum ranging from mild upper respiratory tract infection, to severe acute respiratory distress syndrome and sepsis. There is not specific treatment for SARS-CoV-2, which is why the fundamental aspects are to establish adequate prevention measures and support treatment and management of complications.

Anestesia en el paciente con alteración de la función hepática / Anesthesia in the patient with impaired liver function

Se ha analizado la información relevante relacionada con la alteración de la función hepática y el acto anestésico y la reanimación postoperatoria. Se ha analizado de manera sistemática la afectación hepática por sistemas y las complicaciones del paciente cirrótico según el tipo de cirugía. La corrección de la coagulopatía en el paciente cirrótico es especialmente controvertida, ya que la expansión de volumen puede ser un factor de sangrado al incrementar la presión portal y producir un desequilibrio entre los factores pro y anticoagulantes. La morbilidad y mortalidad perioperatorias se correlacionan bien con la clasificación de Child-Pugh y el MELD, de forma que los pacientes con Child A tienen un riesgo moderado y por ello no se contraindica la cirugía. Por el contrario, los pacientes en la clase C o con un valor de MELD superior a 20, no deben ser intervenidos de forma electiva por el elevado riesgo que tienen. En general se considera que la cirugía abdominal es de alto riesgo, ya que altera el flujo sanguíneo hepático y facilita la hemorragia quirúrgica debida a la hipertensión portal(AU)

We review information on impaired liver function, focusing on concepts relevant to anesthesia and postoperative recovery. The effects of impaired function are analyzed by systems of the body, with attention to the complications the patient with liver cirrhosis may develop according to type of surgery. Approaches to correcting coagulation disorders in the cirrhotic patient are particularly controversial because an increase in volume may be a factor in bleeding owing to increased portal venous pressure and imbalances in the factors that favor or inhibit coagulation. Perioperative morbidity and mortality correlate closely to Child-Pugh class and the score derived from the model for end-stage liver disease (MELD). Patients in Child class A are at moderate risk and surgery is therefore not contraindicated. Patients in Child class C or with a MELD score over 20, on the other hand, are at high risk and should not undergo elective surgical procedures. Abdominal surgery is generally considered to put patients with impaired liver function at high risk because it causes changes in hepatic blood flow and increases intraoperative bleeding because of high portal venous pressures(AU)

[Anesthesia in the patient with impaired liver function]. / Anestesia en el paciente con alteración de la función hepática.

We review information on impaired liver function, focusing on concepts relevant to anesthesia and postoperative recovery. The effects of impaired function are analyzed by systems of the body, with attention to the complications the patient with liver cirrhosis may develop according to type of surgery. Approaches to correcting coagulation disorders in the cirrhotic patient are particularly controversial because an increase in volume may be a factor in bleeding owing to increased portal venous pressure and imbalances in the factors that favor or inhibit coagulation. Perioperative morbidity and mortality correlate closely to Child-Pugh class and the score derived from the model for end-stage liver disease (MELD). Patients in Child class A are at moderate risk and surgery is therefore not contraindicated. Patients in Child class C or with a MELD score over 20, on the other hand, are at high risk and should not undergo elective surgical procedures. Abdominal surgery is generally considered to put patients with impaired liver function at high risk because it causes changes in hepatic blood flow and increases intraoperative bleeding because of high portal venous pressures.

Hemodynamic changes during reperfusion of the graft in an animal model of liver xenotransplantation.

UNLABELLED: Our goal was to determine the hemodynamic changes that are witnessed during the initial minutes of reperfusion of the graft in liver xenotransplantation from pig to baboon. METHOD: We studied a group of 12 baboons undergoing transplantation of a pig liver via the classic technique with arterial anastomosis to the aorta. The anesthesia technique was similar to that used in humans. Hemodynamic monitoring, due to the size of the recipient, consisted of heart rate (HR), mean arterial pressure (MAP), and central venous pressure (CVP) recorded at the beginning and end of each of the three phases: preanhepatic (A1, A2), anhepatic (B1, B2), and neohepatic (C1 and C2). We aimed to maintain the following values by means of crystalloids, colloids, and blood derivates: HR >50 beats/minute; MAP >60 mm Hg; and CVP >10 mm Hg. RESULTS: Both HR and CVP remained unchanged throughout the procedure. MAP droped briefly after vascular clamping (B1) but not on reperfusion (C1). CONCLUSION: In cirrhotic patients there is an autonomic dysfunction, demonstrated as cardiovascular instability at times like the clamping of major vessels and reperfusion of the graft. On the other hand, the intact baboon has an intact nervous system. After vascular clamping, the sharp decrease in venous return lead to an adequate vasopressor response. Likewise, the extreme vasodilatation involved with reperfusion managed to maintain MAP above 70 mm Hg.

Hemodynamic assessment during auxiliary heterotopic liver transplantation with portal vein arterialization in a Swine model: preliminary report of 10 transplants.

UNLABELLED: Portal vein arterialization (PVA) is a technical variation of auxiliary heterotopic liver transplantation (AHLT) that is rarely studied but that simplifies the AHLT surgical technique because it does not act on the portal area. The objective of this study was to analyze the hemodynamic consequences of this auxiliary transplant in an experimental model. MATERIALS AND METHODS: Ten AHLT-PVA were analyzed in a pig model. A PiCCO (Pulsion) monitor was used for the hemodynamic study of the recipient. The following were measured: cardiac index, (CI), systemic vascular resistance index, (SVRI), mean arterial pressure (MAP), global end-diastolic volume, central venous pressure, and intrathoracic blood volume. The measurements were taken at four times during transplant: at baseline, after inferior vena cava clamping, after graft reperfusion, and at closure. RESULTS: After graft reperfusion there was a reduction in SVRI (968 +/- 168.03 vs 1686.25 +/- 290.66; P < .05) and in MAP, and there was an increase in CI. At the end of the transplant MAP and SVRI recovered (1254.2 +/- 225.79 vs 968 +/- 168.03; P < .05) but CI remained slightly high. The end-diastolic volume showed greater variation than central venous pressure, although this was only statistically significant at the inferior vena cava clamping phase (244.75 +/- 52.05 vs 333.37 +/- 170.13; P < .05). DISCUSSION: Heterotopic liver transplantation with portal arterialization is well-tolerated hemodynamically. Graft reperfusion decreases SVRI and increases CI to compensate for this. This behavior, which in healthy recipients like ours is not a problem, could imply a contraindication in patients with a prior hyperdynamic state.

Doppler ultrasonographic and scintigraphic assessment of an auxiliary heterotopic liver transplantation with portal vein arterialization in pigs.

OBJECTIVE: Our aim was to evaluate liver graft integrity and function using scintigraphy and ultrasonography in a porcine model of auxiliary heterotopic liver transplantation with portal vein arterialization (AHLT-PVA). MATERIALS AND METHODS: Using Doppler ultrasonography we evaluated eight AHLT-PVA by parenchymal echogenicity, portal and arterial anatomy, and portal and biliary system flow. Two types of scintigraphy were performed: microaggregated human albumin colloid scintigraphy and diisopropyl iminodiacetic acid (DISIDA) scintigraphy, both labeled with 99mTc. RESULTS: The animals were distributed into two groups. The first group consisted of three animals with clinical suspicion of graft dysfunction, in which the ultrasonographic study revealed areas of parenchymal destructuring. In the scintigraphic study, heterogenous uptake was observed; there was no uptake in one animal. Necropsy of these three animals revealed areas of graft necrosis. The second group consisted of five animals with good clinical evolutions, in which the ultrasonographic study showed portal dilation, portal flow with arterial spiculations, and homogenous echogenicity of the hepatic parenchyma. The scintigraphic study revealed homogenous uptake by the graft and an elimination speed of the hepatobiliary agent similar to that of the native liver. CONCLUSIONS: An heterogenous echostructure of the graft provided a sign of poor prognosis indicating necrosis in the same way as heterogenous uptake or nonuptake of radioisotope upon scintigraphy. Scintigraphy is a good method to evaluate biliary function and bile elimination. In an AHLT-PVA, the main ultrasound findings derived from arterialization were dilation of the portal system and portal flow with arterial spiculations.

Portopulmonary hypertension and liver transplantation: hemodynamic consequences at reperfusion.

BACKGROUND: The absence of portopulmonary hypertension (PH) upon preoperative evaluation for liver transplantation (OLT) does not exclude the occasional occurrence of an acquired PH while awaiting a graft. We sought to estimate hemodynamic changes and right ventriculoarterial coupling during reperfusion. METHODS: We studied 11 cirrhotic patients diagnosed with mild PH, according to the current classification: mean pulmonary artery pressure (MPAP)-25 to 34 mm Hg. These patients underwent OLT, using the piggyback technique (group PH). None of them had exhibited criteria for PH on preoperative echocardiography. This cohort was compared with 20 consecutive cirrhotic patients with normal MPAP at OLT. We performed a complete hemodynamic profile using a pulmonary artery catheter (RVEF, Baxter-Edwards, Calif, USA) before and 5 minutes after reperfusion. The variables were MPAP and right ventricular (RV) end-diastolic volume index (RVEDVI). Using standard formulas we calculated RV stroke work index (RVSWI), RV end-systolic elastance (Ees), pulmonary effective elastance (Ea), and RV-arterial coupling efficiency as the Ees/Ea ratio. Systolic ventricular function was expressed as RVSWI versus RVEDVI. RESULTS: During the anhepatic phase, MPAP, Ees, Ea, and RVSWI were higher in the PH group; but RVEDVI was lower. After reperfusion the pressure (MPAP), contractility (RVSWI) and preload (RVEDVI) increased in both groups. However, afterload (Ea) decreased in the non-PH group; accordingly, Es/Ea increased only in these patients. DISCUSSION: At reperfusion, the expansion in preload and cardiac output, without a similar afterload decrease, is responsible for the steady increase in pressure. Our results have shown that in the PH patient group, systolic ventricular function improves during reperfusion by a Frank-Starling mechanism; however, ventricular-arterial uncoupling is maintained (Ees/Ea < 1) because ventricular contractility is not appropriately balanced by simultaneous declines in afterload.

Effects of rapid paracentesis on right ventricular-arterial coupling in liver transplantation.

BACKGROUND: In cirrhotic patients intra-abdominal pressure (IAP) changes markedly modify splanchnic and systemic hemodynamics. Previous studies have evaluated the effects of increased IAP on steady-state cardiac performance, showing that right ventricular (RV) function becomes more depressed than that of the left ventricular. We sought to evaluate the effects of paracentesis on RV function and ventricular-arterial coupling among cirrhotics undergoing liver transplantation (OLT). METHODS: Twelve cirrhotic patients undergoing OLT underwent hemodynamic profiles before and 5 minutes after paracentesis, employing a right ventricular ejection fraction catheter in the pulmonary artery. We studied heart rate, systolic pulmonary artery pressure, central venous pressure (CVP), stroke volume index (SVI), RV end-diastolic volume index (RVEDI), and RV ejection fraction. In addition RV stroke work index (RVSWI), RV end-diastolic compliance (RVEDC), RV end-systolic elastance (Ees), pulmonary artery effective elastance (Ea), and RV coupling efficiency (Ees/Ea ratio) were calculated employing standard formulas. RESULTS: After removal of mean ascites volume of 5.6 +/- 2.2 L (range 4.0 to 8.04 L), SVI, RVEDI, RVSWI, and RVEDC were significantly increased and conversely CVP, Ees, and Ea were decreased with an ea/ea ratio unchanged. CONCLUSIONS: Before paracentesis Ees/Ea is preserved by increased of RV contractility; after paracentesis the coupling was maintained.

Effects of dobutamine on right ventricular function and pulmonary circulation in pulmonary hypertension during liver transplantation.

INTRODUCTION: In the setting of orthotopic liver transplantation (OLT), pulmonary hypertension (PH) affects right ventricular (RV) function. When RV failure occurs, reducing RV afterload, optimizing RV preload, and preserving coronary perfusion through maintenance of systemic blood pressure are the primary goals of intraoperative treatment. PATIENTS AND METHODS: To verify the effect of dobutamine on RV function and RV-arterial coupling, we compared a group of 9 cirrhotic patients with mild PH treated with OLT to a group of 20 patients with normal mean pulmonary artery pressure (MPAP). All patients received dobutamine (5-10 microg/kg/min) to maintain a cardiac index (CI) >3 L/min/m(2), during the anhepatic phase. Hemodynamic profile, using a pulmonary artery catheter, was performed before and during dobutamine infusion, studying MPAP, CI, and RV end-diastolic volume index (RVEDVI). RV stroke work index (RVSWI), RV end-systolic elastance (Ees), pulmonary effective elastance (Ea), and RV-arterial coupling efficiency as the Ees/Ea ratio were also calculated. RESULTS: RV contractility (Ees and RVSWI) and afterload (Ea) were significantly higher among the PH group. In both groups, all the studied variables improved with dobutamine: RV contractility increased, afterload decreased, and thus Ees/Ea coupling markedly increased. CONCLUSION: Cirrhotic patients with mild PH who were undergoing OLT still have a reserve of RV contractile performance and pulmonary vasodilation.

Differential response of the systemic and pulmonary circulation related to disease severity of cirrhosis.

BACKGROUND: In cirrhotic patients, the degree of hepatic insufficiency has been related to a physiological landmark: arterial vasodilatation. We sought to assess how the severity of disease, which was stratified according to the Child-Pugh criteria, influences the pulmonary and systemic circulation among patients undergoing liver transplantation. METHODS: We studied 86 cirrhotic patients in three groups: grade A (n = 10), grade B (n = 54), and grade C (n = 22). The outurnes were classified based upon a complete hemodynamic profile obtained using a pulmonary artery catheter (RVEF, Baxter-Edwards, Calif, USA) after induction of anesthesia. The variables were mean arterial and pulmonary artery pressures and cardiac index (CI). Using standard formulae, afterload was calculated as elastance of systemic (Es) and pulmonary (Ep) arterial beds, expressed by the ratio of end-systolic pressure to stroke volume. The relation between pulmonary and systemic circulation was also evaluated by the ratio (Ep/Es). RESULTS: Es was significantly lower in each class than in previous one. Also, Ep was smaller in class B than in class C patients. In addition, CI was significantly higher with disease severity. CONCLUSION: We observed that the hyperdynamic circulation in cirrhosis is directly related to severity of disease. Nevertheless Ep/Es was progressively higher among each group; these data suggest that the hyperdynamic circulation is mainly due to circulatory alterations in the splanchnic area. We conclude that pulmonary vasodilatation is directly related to the severity of cirrhosis, although its evolution is independent of other vascular areas.

Pathology findings in a model of auxiliary liver transplantation with portal vein arterialization in pigs.

OBJECTIVE: To determine the histological findings and temporal evolution that occur in auxiliary liver grafts as a consequence of arterialization of the portal vein (PVA). MATERIALS AND METHODS: We evaluated 10 auxiliary heterotopic liver transplants with arterialization of the PVA. The histological study was performed using an optical microscope to process liver samples with staining using hematoxylin and eosin. A biopsy of native liver tissue was used as a control. RESULTS: Two animals were excluded from the study, one due to ischemic necrosis of the graft and one that died 4 hours after transplant. All of the remaining eight animals underwent a histological study at 1 day, 7 days, and 14 days. The most significant histological findings were: (1) dilation of portal areas and sinusoids, which were detected at 24 hours and persisted; (2) thickening of the interlobular septum, which was observed after day 7 and progressively increased to day 14; (3) bile duct hyperplasia detected at the seventh day. CONCLUSIONS: The consistent, early findings in a pig liver with PVA included vascular dilation of the portal area and the sinusoids, with bile duct hyperplasia extending progressively and the thickening of interlobular connective tissue septa with a generalized perilobular connective tissue reaction, which did not seem to alter the internal structure of the lobule, which showed histologically normal hepatocytes. The fibrous reaction may be the first stage in chronic hepatopathy. Further long-term studies are required in this model.

Prevention of hyperacute rejection in a model of orthotopic liver xenotransplantation from pig to baboon using polytransgenic pig livers (CD55, CD59, and H-transferase).

INTRODUCTION: The search for alternative sources for transplant organs leads us to the search for animals as an inexhaustible source of organs. The objective of this study was to analyze whether livers from polytransgenic pigs expressing the human complement regulatory proteins CD55 (hDAF), CD59, and alfa alpha1,2-fucosyltransferase (H-transferase), protected against hyperacute rejection after orthotopic liver xenotransplantation to a baboon and also to study pig liver function in a nonhuman primate. MATERIALS AND METHODS: Nine liver transplants from pig to baboon were divided into two groups: a control group (n = 4) of genetically unmodified pigs and an experimental group (n = 5) of pigs transgenic for CD55, CD59, and H-transferase as donors. All the donating piglets obtained through hysterectomy were maintained in specific pathogen-free conditions. The selection of transgenic pig donors followed demonstration of transgene expression using monoclonal antibodies (antiCD55, antiCD59) and immunohistological studies on liver biopsies. RESULTS: All animals in the control group developed hyperacute rejection with survival rates less than 16 hours without function of transplanted livers. In the experimental group none of the animals suffered hyperacute rejection. Survival in this group was between 13 and 24 hours. The livers were functional, producing bile and maintaining above 35% prothrombin activity. Only in one case was there primary dysfunction of the xenograft. CONCLUSION: Polytransgenic livers for complement regulatory proteins prevent hyperacute rejection when xenotransplanted into a baboon.

Immunopathology of an hDAF transgenic pig model liver xenotransplant into a primate.

BACKGROUND: hDAF transgenic pigs do not display the inherent hyperacute rejection reactions of pig-to-primate xenotransplants. The purpose of this study was to determine the immunopathologic phenomena following an hDAF transgenic pig hepatic orthotopic xenotransplant into a baboon. METHODS: Donor animals were unmodified pigs (n=4) and hDAF transgenic pigs (n=2). Recipient animals were baboons (Papio anubis). Liver biopsies were immunostained using monoclonal antibodies to C3, C5b-9, IgG, IgM, CD2, CD4, CD8, CD68, CD20, Bric 216, CD31, and fibrin, and polyclonal antibody to C4. RESULTS: hDAF transgenic grafts showed IgG, IgM, and C4 endothelial deposits. However, no fibrin, C3, or C5b9 deposits were observed after reperfusion. hDAF xenografts displayed CD31 staining in the portal spaces, perilobular areas, and at hepatic sinuisoidal levels. The baboon that lived for 4 days displayed either CD4 or CD8 T-cells periportal infiltrate. CONCLUSIONS: Future studies will seek to determine the physiologic role of CD31 hepatic sinusoidal expression in transgenic xenotransplants, and will also study the role of T-cell infiltrates in xenograft rejection.

Description of a new auxiliary heterotopic partial liver transplantation technique with portal vein arteriolization of applicability in heterotopic liver xenotransplantation.

OBJECTIVE: The aim of this study was to describe a new model of auxiliary heterotopic partial liver transplantation with portal vein arterialization. MATERIALS AND METHODS: Three standard hepatectomies were performed in pigs. The left lateral lobe was surgically resected and portal vein arteriolization constructed by an end-to-side "Y" anastomoses between the distal to the celiac axis aorta and the portal vein. RESULTS: The graft was placed in the left iliaca fossa using anastomoses of the donor infrahepatic inferior cava vein end-to-side to the host infrarenal inferior vein and the donor aortic stump with portal vein arteriolization end-to-side to the left iliac artery. After graft reperfusion, the 3 recipients showed intraoperative hypotension, which was treated with fluid administration and vasoactive drugs. At the end of the operation, the graft displayed normal arterial blood flow and good venous drainage. The donor liver graft appeared more red than the host liver, which was due to the increased arterial blood flow. One pig of 3 died at 24 hours after surgery, probably due to hypothermia. However, the other 2 pigs survived the procedure and remained stable. Echographic monitoring showed intrahepatic arterial expansion, which may be the result of high blood pressure due to the arteriolization procedure. CONCLUSIONS: We have developed a novel and easy to perform technique that diminishes the number of anastomoses and does not involve vessels from other organs.