Salvage of an Octogenarian Liver Graft Using Normothermic Perfusion: A Case Report.

Liver transplantation with very old donors is safe, but is associated with an increased incidence of ischemic-type biliary lesions and delayed graft function. Normothermic machine perfusion (NMP) is a novel technique for preservation of liver grafts and has the potential to reduce ischemia-reperfusion injury. A case is reported here of a liver transplantation (LT) with a graft from an 83-year-old brain-dead donor. Procurement was with dual perfusion and en bloc, modified fast technique. Donor kidneys were not transplanted due to severe atherosclerosis and poor perfusion. The liver was shipped to the transplantation center and underwent NMP with a blood-based perfusate. During machine perfusion lactates decreased, vascular flow was stable, and bile production restored, and the graft was considered suitable for transplantation. The postoperative course was uneventful and 4 months after surgery the patient is in good clinical condition with normal liver function. To date, few LTs have been performed with NMP in humans, but its preliminary results are promising. NMP allows functional evaluation of the graft and possibly reduction of post-transplantation complications when extended-criteria donor grafts are used.

Solvent detergent vs. fresh frozen plasma in cirrhotic patients undergoing liver transplant surgery: a prospective randomized control study.

BACKGROUND: Although orthotopic liver transplantation (OLT) is nowadays considered standard practice at experienced centres, it can still be affected by a significant risk of massive bleeding and its related complications. Solvent/detergent plasma (S/D Plasma) has been proposed as an alternative to fresh frozen plasma (FFP) to curtail such complications. This study aimed at evaluating the efficacy of S/D Plasma in OLT patients by comparing it to FFP. MATERIALS AND METHODS: Sixty-three OLT patients were randomized into two groups depending on whether they were transfused with FFP or S/D plasma. A thromboelastography-based protocol aimed at achieving and maintaining predetermined coagulation goals was used to guide plasma transfusions. At the beginning and the end of surgery, standard laboratory coagulation tests were performed together with the assessment of the VII, VIII, V, XII factors and S protein blood levels. RESULTS: The two study groups equally achieved the thromboelastography goals but with a reduced amount of transfusions in the S/D plasma group (P < 0.0001). At the end of surgery, factors V and XII and S protein blood levels were lower in the S/D plasma patients who also showed lower INR, aPTT and antithrombin III levels. CONCLUSION: In cirrhotic patients undergoing OLT, the use of S\D plasma associated with thromboelastography allows the same clinical results but with a significant reduction in the amount of plasma transfusions.

Evaluation of an uncalibrated arterial pulse contour cardiac output monitoring system in cirrhotic patients undergoing liver surgery.

BACKGROUND: The pulmonary artery catheter is invasive and may cause serious complications. A safe method of cardiac output (CO) measurement is needed. We have assessed the accuracy and reliability of a recently marketed self-calibrating arterial pulse contour CO monitoring system (FloTrac/Vigileo) in end-stage liver failure patients undergoing liver transplant. The pattern of alterations known as cirrhotic cardiomyopathy, and the transplant procedure itself, provided an evaluation under varying clinical conditions. METHODS: The cardiac index was measured simultaneously by thermodilution (CI(TD): mean of four readings) using a pulmonary artery catheter and pulse contour analysis (CI(V): mean value computed by the FloTrac/Vigileo over the same time period). Readings were made at 10 time-points during liver transplant surgery (T1-T5) and on the intensive care unit (T6-T10). CI(V) was computed using the latest Vigileo software version 01.10. RESULTS: A total of 290 paired readings from 29 patients were collected. Mean (SD) CI(TD) was 5.2 (1.3) and CI(V) was 3.9 (0.9) litre min(-1) m(-2), with a corrected for repeated measures bias between readings of 1.3 (0.2) litre min(-1) m(-2) and 95% limits of agreement of -1.5 (0.2) to 4.1 (0.3) litre min(-1) m(-2). The percentage error (2SD(Bias)/meanCI(TD)) was 54%, which exceeded a 30% limit of acceptance. Low peripheral resistance and increasing bias were related (r=0.69; P<0.001). The Vigileo system failed to reliably trend CI data, with a concordance compared with thermodilution below an acceptable level (at best 68% of sequential readings). CONCLUSIONS: In cirrhotic patients with hyperdynamic circulation, the Vigileo system showed a degree of error and unreliability higher than that considered acceptable for clinical purposes.

Transcranial doppler sonography is useful for the decision-making at the point of care in patients with acute hepatic failure: a single centre's experience.

Acute hepatic failure (ALF) is an uncommon disease characterized by a rapid deterioration of the hepatic function with severe derangements of the mental status in previously healthy subjects due to massive hepatocytes necrosis. Neurological impairment, due to intracranial hypertension and cerebral ischemia, is a key factor because it is a main criterion to decide when to proceed to liver transplantation, which is only treatment for these patients. Therefore, neurological monitoring holds an essential role in the clinical management of ALF patients but it needs to be performed at the point-of-care in the majority of the cases as such critically ill patients cannot be moved away from the ICU because they frequently need continuous hemodynamic, ventilatory and renal support. We herein report and discuss our experience relating to the use of transcranial sonography as a neuro-monitoring tool in ALF patients. In our series this technique allowed a repeatable and reliable non-invasive assessment of cerebral blood flow changes at the bedside thus avoiding the complications associated with the use of an intracranial probe to measure intra-cranial pressure and making it possible to correctly evaluate the timing and feasibility of liver transplantation.

Pancreas transplantation: problems and prospects in intensive care units.

AIM: The aim of this study is to describe personal experience in the intensive management of patients with severe diabetes undergoing pancreas transplantation. METHODS: Clinical records of subjects consecutively undergoing an isolated or combined pancreas transplant have been examinated. RESULTS: During the considered period, 10 patients received an isolated pancreas transplant and 43 a simultaneous kidney-pancreas transplantation (SPKT), including 6 using a kidney from a living donor. The mean stay in the Intensive Care Unit (ICU) was 4.7 days: 52 patients (98.2%) were transferred to the Surgical Department, whereas one (1.8%) belonging to the SPKT group died with a non-functioning graft. Ten patients (18.6%) were re-admitted because of the onset of late complications, including one SPKT who died of sudden cardiac death with functioning grafts. Arterial hypertension appeared in 51% of the recipients, and 5.6% experienced at least one hypotensive episode. Cardiac rhythm alterations were diagnosed in 5 subjects (9.4%), and myocardial ischemia in 9 (17%). CONCLUSIONS: Pancreas transplantation is a therapeutic option that can improve patients' quality of life by also slowing down the evolution of diabetes; however, it is important to bear in mind the associated risks. The best results are obtained in patients in whom the disease has not already seriously impaired the function of the various target organs.

Perioperative anesthetic management for laparoscopic kidney donation.

OBJECTIVES: To report a single-center experience about the perioperative and anesthetic management of laparoscopic living kidney donation. PATIENTS AND INTERVENTIONS: Subjects undergoing laparoscopic (n = 39) (performed between April 2000 and August 2002) and traditional "open" kidney donation (n = 27) received a standard balanced anesthetic technique. However to counterbalance the reported abdominal insufflation-related kidney dysfunction, laparoscopic donors were administered an extra intravascular volume loading with colloid and crystalloid starting on the night before surgery. RESULTS: Laparoscopic donors underwent longer procedures with lower estimated blood losses (P =.0001), were intraoperatively administered higher amounts of intravenous fluids (P <.01), showed less postoperative analgesic requirement (P <.0001), shorter intensive care unit and overall hospitalization (P <.001), quicker resumption of solid oral intake (P <.01), and full return to work (P <.001) with no difference in the postoperative complication rate. Diuresis resumed intraoperatively in all recipients and early graft function did not differ between the two groups, although the serum creatinine declined earlier, but not significantly, in those receiving kidneys procured by the traditional method. No difference was seen in graft rejection rates. DISCUSSION AND CONCLUSIONS: Laparoscopic kidney donation does not require a particularly complex or expensive anesthetic management or approach; as it has been suggested that intra-abdominal hypertension coming from CO(2) insufflation inside the donor's peritoneal cavity may threaten graft function, during laparoscopic kidney donation it is advisable to adopt a strategy for "renal protection." Thus, when a laparoscopic kidney donation is performed at our center, a multidisciplinary approach is commonly adopted based on three key points: perioperative positive volemic balance in donors; intraoperative urinary output of at least 100 mL/h; inflation with an abdominal pressure not exceeding 12 mm Hg.

Cardiac evaluation for simultaneous pancreas-kidney transplantation and incidence of cardiac perioperative complications: preliminary study.

Type I diabetes mellitus (IDDM) is associated with an increased cardiovascular risk, and eligibility protocols for simultaneous pancreas-kidney transplantation (SPKT) are consequently accurate for preoperative cardiovascular assessment. According to our algorithm, coronary angiography in SPKT candidates is indicated for patients not only experiencing previous cardiac events or symptoms, but also those with long-standing diabetes (more than 25 years) and/or age over 45 years. Furthermore, a basal transthoracic echocardiographic exam (TTE) is performed to assess cardiac volumes, left ventricular mass, systolic function, and kinesis. The aims of this study were to evaluate perioperative cardiac morbidity and mortality in 18 SPKT-eligible patients, divided into two groups on the basis of the presence/absence of angiographically evident coronary artery disease (CAD), as well as to assess the impact of left ventricular hypertrophy (LVH) on cardiac complications. Cardiac intraoperative morbidity and mortality and postoperative mortality and major morbidity were absent; minor cardiac morbidity consisted only of silent ischemic ECG alterations, without significant differences between groups, although the incidence seemed to be higher in the CAD-positive population. LVH detected preoperatively by TTE exam also failed to correlate with the incidence of such complications. Selection of SPKT candidates by coronary angiography may have positive effects on perioperative cardiac morbidity and mortality. A larger sample size is needed to give the study statistical power. Medium- and long-term follow-up studies are warranted to evaluate the effects of preoperative selection on survival rates.

Perioperative management for laparoscopic kidney donation.

AIM: To report a single centre's experience in the perioperative management of live kidney laparoscopic donations. METHODS. DESIGN: comparative analysis of all laparoscopic kidney donations performed between April 2000 and August 2002 and a corresponding number of "traditional surgery" donors from a historical series. SETTING: kidney transplant centre of a teaching hospital. INTERVENTIONS: 39 and 27 subjects undergoing respectively laparoscopic and traditional "open" kidney donation were studied. A standard balanced anesthesiological technique was used in both groups but, to counterbalance the reported abdominal insufflation-related kidney dysfunction, laparoscopic donors were administered an extra intravascular volume loading with colloids and crystalloids starting from the night before surgery. RESULTS: Laparoscopic donors underwent a longer procedure with a lower estimated blood loss (p=0.0001) and were intraoperatively administered with a higher amount of intravenous fluids (p<0.01); they showed less postoperative analgesic requirement (p<0.0001), a shorter ICU stay and overall hospitalisation (p<0.001), a quicker resumption of solid oral intakes (p<0.01) and full return to work (p<0.001) with no difference in the rate of postoperative complications. Diuresis resumed intraoperatively in all recipients and early graft function did not differ in the 2 groups although serum creatinine declined earlier, but not significantly, in those receiving kidneys by the traditional method. CONCLUSION: Kidney laparoscopic donation does not require a particularly complex or expensive anaesthetic management or approach; it is advisable to adopt strategies to counterbalance laparoscopy-associated abdominal hypertension.

Control of acute pain after major abdominal surgery in 585 patients given tramadol and ketorolac by intravenous infusion.

The aim of this study was to assess the efficacy and safety of postoperative pain relief using tramadol and ketorolac in continuous intravenous infusion. The 585 patients included in the study underwent major surgery according to a protocol involving the parenteral administration of 100 mg tramadol approximately 40 min before the end of surgery. This was followed by the continuous intravenous infusion of 600 mg tramadol and 180 mg ketorolac diluted with physiological solution to a total volume of 96 ml. Delivery was carried out using an elastomeric pump or a syringe pump and administered over a 48-hour period at a constant rate of 2 ml/h. Any further doses consisted of 100 mg tramadol up to a maximum of 300 mg over a 24-h period. Pain was assessed on a verbal numeric scale (VNS). For each patient the intensity of pain was assessed both at rest and on movement (coughing, deep breathing, movement of lower limbs). At the scheduled times (T0-T72, every 6 h), the following parameters were evaluated: hemodynamic stability; respiratory function; the appearance of any side effects; the level of sedation; and the need for any further doses of analgesic. The analysis of the data obtained showed the good quality of postoperative pain relief achieved: pain intensity at rest was, on average, always below VNS level 3, while during movement it always had an average VNS level of 3-4. The only side effects found with any frequency were nausea (22.6%) and vomiting (8.5%); hemodynamic and respiratory parameters remained stable. The method adopted was of limited cost and was well accepted by both patients and staff. On the basis of the data obtained, it is possible to affirm that the post-operative pain protocol proposed is effective, safe, without significant side effects, and of limited cost. Therefore, it is the first choice protocol for our operating unit after major abdominal surgery.

A new technique for total hepatectomy in the pig for testing liver support devices.

BACKGROUND: A large animal model of total hepatectomy is suitable to test the efficacy of any system designed to support patients in hepatic coma. The models previously described in the pig entail a significant degree of surgical trauma, which might alter the evolution of the ensuring hepatic failure and compromise the reproducibility of the model. METHODS: Twenty-eight pigs underwent a total hepatectomy according to a new technique. A model was considered satisfactory when it required no blood transfusions and when hematologic and hemodynamic parameters determined before, during, and until 4 hours after hepatectomy showed no significant variations. Moreover, to revive the pattern of hepatic coma produced in the anhepatic model, 7 pigs were monitored until brain death occurred. RESULTS: Twenty-five pigs (89%) underwent a smooth total hepatectomy with minimal variations of the selected parameters. They constituted a highly homogeneous group. Survival of the 7 pigs, followed up until brain death occurred, ranged from 625 to 1595 minutes (mean 1013.57 minutes). The animals remained stable until a few hours before brain death, an event heralded by a final sharp increase of the serum ammonia level and by a well-evident decline of both arterial pressure and liver-dependent clotting factors. CONCLUSIONS: This technique of total hepatectomy allows the construction of a reproducible model of anhepaty suitable to test the efficacy of any system conceived to temporarily replace hepatic functions.

Surgical research in orthotopic liver transplantation: experiences in the pig model.

Since the very beginning of liver transplantation in humans, research in animals has had close relationship with clinical practice. Results obtained in animals have been transferred to the clinics and problems borne in the clinics have been addressed again in animals for to be answered clearly. In this review the authors report their experience of transplantation in the pig model and discuss the significance of a team cooperation in the laboratory as a preparatory step for clinical practice.

Phase II study of intensive chemotherapy with carboplatin, ifosfamide and etoposide plus recombinant human granulocyte colony-stimulating factor and sequential radiotherapy in locally advanced, unresectable non-small-cell lung cancer.

From June 1991 to August 1994, 61 patients with stage III unresectable non-small-cell lung cancer (NSCLC; 16 cases of stage IIIA with N2 bulky disease and 45 cases of stage IIIB) were treated with ifosfamide given i.v. at 3 g/m2 on day 1, carboplatin given i.v. at 200 mg/m2 on days 1 and 2, etoposide given i.v. at 120 mg/m2 on days 1-3 (ICE) and recombinant human granulocyte colony-stimulating factor (rhG-CSF) given s.c. at 5 micrograms/kg on days 4-13. Chemotherapy was given every 3 weeks for up to three cycles and, unless the disease progressed, was followed by thoracic radiotherapy on the tumor volume (total dose 60 Gy) and mediastinum (40 Gy). All patients had measurable or evaluable unresectable disease and a performance status (Eastern Cooperative Oncology Group) of 0-1. Only 61% of the enrolled patients received the full program of chemoradiotherapy according to the study design. At the end of sequential chemo-radiotherapeutic treatment, 41% of the patients had an objective response (24 partial responses and 1 complete response), 31% showed no change and 28% had progressive disease. The response rate noted for patients in stage IIIA with N2 bulky disease and that recorded for patients in stage IIIB did not differ significantly. The median time to progression was 5.4 months and the median survival was 8.2 months, with the 1-year survival rate being 31%. Sites of progression were mostly intrathoracic. Haematological toxicity was the main side effect, with grade III-IV thrombocytopenia being reported in 24% of the 165 courses of intensive ICE chemotherapy given. Febrile neutropenia was described in six courses (three patients). Non-haematological toxicities and radiotherapy-related side effects were generally mild and easily manageable. In conclusion, in unresectable stage III NSCLC a short program of moderately intensified ICE chemotherapy with rhG-CSF protection followed by sequential radiotherapy failed to increase the percentage of objective responses and reached a median survival comparable with that previously achieved with standard doses.