Monitoring intraoperative coagulation.
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Biomedical subjects
Publications and source records attributed to A De Gasperi.
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Kidney transplantation is now recognized as the treatment of choice for patients with chronic renal failure. Despite the extension of indications to patients suffering severe hypertension, ischemic heart disease, and chronic heart failure, the worldwide results are superb. However, perioperative cardiac complications occur in 6% to 10% of transplanted patients. Aggressive intraoperative volume expansion is still recommended to maximize graft functional recovery (up to 30 mL/kg/h, central venous pressure [CVP] > 15 mm Hg), but patients with preexistent cardiac disease or poor myocardial function are exposed to the risk of fluid overload, acute respiratory failure, and prolonged ventilation. Among the last 90 cases performed at our institution, good functional recovery of the graft was present in 94% of the patients within 2 weeks, despite a much more conservative intraoperative hydration policy (crystalloids 2400 +/- 1000 mL, 15 mL/kg/h, CVP 7-9 mm Hg). Graft failure which occurred in 5 patients was significantly correlated only with donor age, while perioperative cardiovascular complications had been present in 9 cases (10%) who were coronary artery disease patients (55%). Age above 50 years was the only significant risk factor. Supranormal volume loading is probably not always warranted in kidney transplantation.
Recombinant activated factor VII (rFVIIa, Novoseven, Novo Nordisk, Denmark) was introduced as a prohemostatic agent in the early 80s: the only indication approved in USA by Food and Drug Administration (FDA) is the spontaneous bleeding in congenital hemophilia patients who developed inhibitors to FVIII and FIX. Recently, EMEA approved the use of rFVIIa in congenital hemophilia patients with inhibitors undergoing surgery, in subjects with congenital FVII deficiency undergoing surgical or invasive procedures, in patients with acquired hemophilia and in case of Glanzmann's thromboasthenia. Out of these approved indications, the off label use of rFVIIa is rapidly expanding, particularly in surgical patients with acquired coagulation disorders in order to manage severe, uncontrolled bleeding nonresponsive to conventional therapeutic measures or to reduce blood loss and transfusion requirements in potentially bleeding surgical procedures (major liver surgery, liver transplantation, major abdominal or obstetric surgery, trauma surgery). This paper reviews the more recent data coming from retrospective or prospective studies performed in different surgical settings: so far, the major point to be addressed is the place for rFVIIa as an adjunctive but sometimes lifesaving treatment to control haemostasis and critical bleeding in surgery and critically ill patients.
UNLABELLED: Although right hemiliver transplant from living donors (LD) is gaining acceptance as a way to overcome the critical organ shortage, splitting a liver for two adults from cadaveric donor (CD) is still controversial. METHODS: From May 1999 to August 2004 we performed nine right hemiliver transplants using segments 5-6-7-8 from CD and 18 from LD. RESULTS: We compared the two procedures to evaluate both the technical aspects and the patients' outcomes. In the CD group, three recipients died (33%), two of whom were UNOS Status 2A. Patient and graft survivals were 67% (median follow-up: 23 months). Among the LD group, three recipients died (17%) and two were retransplanted; one because of arterial thrombosis and the other as a consequence of small-for-size syndrome. Patient and graft survivals were 83% and 72%, respectively (median follow-up: 8 months). There were five early complications in the CD group (55%) and five (27%) in the LD group. Two patients in the LD group experienced a late stenosis of the biliary anastomosis. DISCUSSION: Data from our early experience show that better results are achieved by right hemiliver transplants from LD; the morbidity and mortality are higher among the CD group. We believe that this finding is probably a consequence of better preoperative donor evaluation, shorter ischemia time, better logistics, and learning curve. Recipient selection is crucial; this kind of graft is at high risk of poor function, technical complications, and infections. Further experience will help to clarify the reliability of right hemiliver transplants from CD.
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The case of a patient who underwent heart transplantation and cholecystectomy in 1993 and admitted for resection of abdominal aortic aneurysm in May 1997, is reported. About 25 minutes after unclamping the abdominal aorta the patient s blood pressure fell suddenly to 70/40 mmHg. In spite of vigorous fluid administration and infusion of Dopamine and Adrenaline the hemodynamic pattern returned to normal only 15 minutes later. The authors discuss the possible explanations of this behaviour (mesenteric traction syndrome, hypovolemia) and conclude that heart transplant patients are particularly affected by hypotension. Of paramount importance remains therefore the correct evaluation of adequate filling pressures which should be maintained slightly above normal range.
In the period 1973-1998, among 2139 allograft recipients treated with standard immunosuppression, posttransplant lymphoproliferative disorders (PTLD) developed in 19 patients (0.9%): one plasmacytic hyperplasia, two polymorphic PTLD, one myeloma, and 15 lymphomas. PTLD developed 1 year after transplantation (tx) in 14 patients. Five patients were diagnosed at autopsy, 2 were lost to follow up, 3 died before therapy could be instituted, and 1 patient has just started chemotherapy. Of the 8 evaluable patients, 2 received acyclovir and are alive in complete remission (CR) and 6 received chemotherapy +/- surgery. Of these 6, 4 died of lymphoma and/or infection, 1 died of unrelated causes in CR, and 1 is alive in CR. PTLD is a severe complication of tx, usually running an aggressive course which may preclude prompt diagnosis and treatment. Nevertheless, therapy is feasible and must be tailored on the histologic subtype. Seventy-four percent of patients were diagnosed with late-onset PTLD stressing the need for long-term follow up.
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Maintenance of adequate immunosuppression and avoidance of side-effects are the goals of long-term management of all organ-transplanted patients. We here report the final results of a prospective, randomized trial comparing early cyclosporine monotherapy versus double-drug therapy (cyclosporine and steroids) in adult liver transplantation patients. One hundred four patients were randomized 3 months after transplantation either to continue (Group I = 50 patients) or to stop steroids (Group II = 54 patients). Patients on a double-drug regimen were maintained long term on methylprednisolone at a dose of 0.1 mg/kg/d. Target cyclosporine trough levels were between 150 and 250 ng/mL in both groups. Our main points of interest were the prevalence of acute and chronic rejections and steroid-related side-effects in the two groups of patients. Mean follow-up was 41 +/- 16 months (range, 4-68 months). Patient actuarial survival 2 and 5 years after randomization was similar in the two groups (82% vs. 83% and 82% vs. 77%). The prevalence of acute rejections after randomization was, respectively, 8% and 4%. A single episode of chronic rejection was observed only in a patient on long-term steroid therapy. Side-effects of steroid therapy were less frequent in patients weaned off steroids, and when considering hypertension and diabetes, the differences between the two groups were statistically significant. Early cyclosporine monotherapy is a safe undertaking in liver transplantation because it allows a significant reduction of steroid-related side-effects without increasing the risk of acute and chronic rejection. After 5 years, patient survival was similar in patients with or without steroids.
Between January 1989 and June 1997, 533 patients (423 male, 110 female, mean age 61 years, range 22-89 years) with hepatocellular carcinoma (HCC) were observed at our center. We report on 419 patients retrospectively compared for different treatments: liver transplantation (LT; 55 patients), resective surgery (RS; 41 patients), transarterial chemoembolization (TACE; 171 patients) and percutaneous ethanol injection (PEI; 152 patients). The 3- and 5-year actuarial survival rates were, respectively, 72% and 68% for LT, 64 and 44% for RS, 54 and 36% for PEI, and 32 and 22% for TACE. Survival curves were compared for sex, age, tumor characteristics, alphafetoprotein level, Child class, and etiology of cirrhosis. All patient-related characteristics examined (sex, age) are not significantly related to patient survival. Tumor-related variables and associated liver disease variables significantly conditioned survival in relation to different treatments. LT seems to be the treatment of choice for monofocal HCC less then 5 cm in diameter and in selected cases of plurifocal HCC.
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To investigate whether early postoperative changes in blood lactate concentration indicate the functional recovery of the newly grafted liver, changes in oxygen supply, oxygen consumption, acid-base equilibrium, and blood lactate concentrations were prospectively studied in a group of 53 postnecrotic cirrhotic patients during the various phases of orthotopic liver transplantation (preanhepatic, anhepatic, neohepatic) and for the first 48 h following reperfusion. The patients were divided into two groups according to the quality of the early graft function, as indicated by alanine aminotransferase, bile flow, and prothrombin activity: group A (49 patients), good immediate graft function and group B (4 patients), immediate graft non-function. Lactate levels rose in the same manner during the preanhepatic and anhepatic stages and peaked after revascularization of the graft. Following reperfusion, however, distinctly different blood lactate profiles were recorded in the two groups of patients. A fall in lactate concentration was recorded in group A patients, whereas a continuous rise occurred in group B patients: the difference becoming significant by the end of surgery (P < or = 0.05). During the first 48 h following revascularization of the graft, opposite trends in lactate concentration, bile flow, alanine aminotransferase, and prothrombin activity were evident in the two groups of patients: 24 h after reperfusion, lactate levels were below 2 mmol/l in 47 of 49 patients from group A, while they plateaued above 4 mmol/l in all patients from group B. Group A patients had lower alanine aminotransferase levels (P < or = 0.001), higher prothrombin activity, (P < or = 0.01), and greater bile flow (P < or = 0.02). If validated in larger series, the blood lactate profile, probably more than the absolute level, appears to be a useful indicator of the early recovery of liver metabolic capacities in the immediate postoperative period of orthotopic liver transplantation.
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Between December 1985 and February 1995, 260 orthotopic liver transplantations (OLTX) were performed on 238 patients at Niguarda Hospital. Sixty-three patients had hepatocellular carcinoma (HCC); in 13 of the patients HCC was incidental. All patients had negative lymph nodes. According to the Child classification, 13 patients were Child A, 30 Child B, and 18 Child C. According to the TNM classification, 11 patients were stage I, 22 stage II, 15 stage III, and 15 stage IVa. Pre-OLTX chemoembolization was performed on 25 patients. The perioperative mortality rate was 27% (17 patients). Overall survival and disease-free actuarial survival rates at 1, 3, and 5 years were 94%, 76%, 76%, and 83%, 75%, 75%, respectively. Survival curves were compared for 16 different variables. No difference was observed for all parameters analyzed except tumor site, TNM stage, pre-OLTX AFP levels and vascular infiltration. These results seem to demonstrate that the OLTX for unresectable HCC can be considered in specifically selected cases as the treatment of choice. An adequate tumor staging is also necessary for a better patient selection in order to increase survival.
Only free magnesium has biological activity: technology for measuring the ionized fraction of magnesium is now available via ion-selective electrodes. We have evaluated an instrument (AVL 988/4) which determines ionized magnesium (cMg2+) with an ion-selective electrode based on the ionophore ETH 7025. The selectivity of the electrode is adequate for the ions normally present in plasma, except for calcium: the interference is automatically corrected by simultaneous measurements of calcium with compensation for the calcium interference to the magnesium signal. We have first verified possible interference caused by sampling procedures: known silicon interference has been avoided by use of glass tubes (BD Vacutainer with no additive, code 7626); heparin interference has been measured and found significant above 20 UI.mL-1 of plasma. Instrument evaluation according to NCCLS protocol gives the following imprecision results on 20 replicated analyses: cMg2+ (mmol.L-1) 1.29, 0.76, 0.23, CVs% (within-run) 0.67, 0.67, 3.00 and CVs% (between-run) 4.06, 3.91, 5.89 respectively. Linearity (in the range 0.23-1.60 mmol.L-1) was: measured cMg2+ = 0.981.(calculated cMg2+) + 0.009 mmol/L; r = 0.999. In healthy adults (n = 103) cMg2+ was in the range 0.46-0.74 mmol.L-1 (with a mean of 0.60 mmol/L and normal distribution). These values represent 57% to 84% of serum total magnesium concentration (TMg) (mean 71%). pH dependence of cMg2+ is present, usually to a lower extent with respect to cCa2+, but it seems different in patients with real or in vitro provoked acidosis and in hemodialyzed patients. Citrate interference on ionized magnesium measurements was found both in vitro and in vivo, whilst that due to lactate was demonstrated only in vitro. On a wide range of cMg2+ (n = 100), a good correlation is obtained both with TMg and ultrafiltrable Mg (UFMg): cMg2+ = 0.723.TMg + 0.008 mmol.L-1, r = 0.978; cMg2+ = 0.912.UFMg + 0.10 mmol.L-1, r = 0.968, respectively. The ionized magnesium in ultrafiltrate was found 25% lower than that in serum. The lifespan of the electrode, evaluated on the basis of both time from installation and on number of measured samples, was estimated longer than 4 months and able to analyze more than 1500 samples, whichever comes first. The four electrodes we used during 18 months behaved all the same way. The correlation between measurements performed in whole blood (WB-cMg2+) and in the corresponding serum (S-cMg2+) was excellent: WB-cMg2+ = 0.954.S-cMg2+ +0.02 mmol.L-1; r = 0.998; n = 60.
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