Phlebotomy resulting in controlled hypovolaemia to prevent blood loss in major hepatic resections (PRICE-1): a pilot randomized clinical trial for feasibility.

BACKGROUND: Major liver resection is associated with blood loss and transfusion. Observational data suggest that hypovolaemic phlebotomy can reduce these risks. This feasibility RCT compared hypovolaemic phlebotomy with the standard of care, to inform a future multicentre trial. METHODS: Patients undergoing major liver resections were enrolled between June 2016 and January 2018. Randomization was done during surgery and the surgeons were blinded to the group allocation. For hypovolaemic phlebotomy, 7-10 ml per kg whole blood was removed, without intravenous fluid replacement. Co-primary outcomes were feasibility and estimated blood loss (EBL). RESULTS: A total of 62 patients were randomized to hypovolaemic phlebotomy (31) or standard care (31), at a rate of 3·1 patients per month, thus meeting the co-primary feasibility endpoint. The median EBL difference was -111 ml (P = 0·456). Among patients at high risk of transfusion, the median EBL difference was -448 ml (P = 0·069). Secondary feasibility endpoints were met: enrolment, blinding and target phlebotomy (mean(s.d.) 7·6(1·9) ml per kg). Blinded surgeons perceived that parenchymal resection was easier with hypovolaemic phlebotomy than standard care (16 of 31 versus 10 of 31 respectively), and guessed that hypovolaemic phlebotomy was being used with an accuracy of 65 per cent (20 of 31). There was no significant difference in overall complications (10 of 31 versus 15 of 31 patients), major complications or transfusion. Among those at high risk, transfusion was required in two of 15 versus three of nine patients (P = 0·326). CONCLUSION: Endpoints were met successfully, but no difference in EBL was found in this feasibility study. A multicentre trial (PRICE-2) powered to identify a difference in perioperative blood transfusion is justified. Registration number: NCT02548910 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La resección hepática mayor se asocia con pérdida de sangre y necesidad de transfusión. Datos observacionales sugieren que la flebotomía hipovolémica (hypovolaemic phlebotomy, HP) puede reducir estos riesgos. Este ensayo clínico aleatorizado (randomised clinical trial, RCT) de factibilidad comparó HP con el tratamiento estándar con el fin de proporcionar información para un futuro ensayo multicéntrico. MÉTODOS: Se reclutaron pacientes sometidos a resecciones hepáticas mayores entre junio 2016 y enero 2018. La aleatorización se realizó durante el intraoperatorio y los cirujanos eran ciegos al resultado de la asignación. Para la HP, se extrajeron 7-10 mL/kg de sangre total, sin reposición de líquidos intravenosos. Los resultados primarios fueron la factibilidad y la pérdida de sangre estimada (estimated blood loss, EBL). RESULTADOS: Un total de 62 pacientes se aleatorizaron a HP (n = 31) y a tratamiento estándar (n = 31), a un ritmo de 3,1 pacientes/mes, cumpliendo el co-objetivo primario de la factibilidad. La mediana de la diferencia de EBL fue 11 mL (P = 0,46). Entre los pacientes con alto riesgo de transfusión, la mediana de la diferencia de EBL fue 448 mL (P = 0,069). Los objetivos secundarios de factibilidad se consiguieron: reclutamiento (89%), cegamiento (98%), y objetivo de la flebotomía (7,6 ± 1,9 mL/kg). Los cirujanos que fueron cegados percibieron que la resección fue más fácil con la HP (52% versus 32%) y acertaron el uso de HP con una exactitud del 65%. No hubo diferencia significativa en las complicaciones globales (32% versus 48%), complicaciones mayores y transfusión. Entre aquellos pacientes de alto riesgo, la trasfusión se realizó en un 13% versus 33% (P = 0,33). CONCLUSIÓN: Se cumplieron los objetivos, pero no se identificó diferencia en EBL en este estudio de factibilidad. Ello justifica un ensayo multicéntrico (PRICE-2) con poder estadístico para identificar una diferencia en la transfusión de sangre perioperatoria.

Validation study of a transcutaneous carbon dioxide monitor in patients in the emergency department.

BACKGROUND: Transcutaneous carbon dioxide tension (TcPco(2)) monitors offer a non-invasive method of continuously measuring arterial carbon dioxide tensions. The concordance between the TcPco(2) measurement and the value obtained from arterial blood gas sampling (Paco(2)) was measured in patients attending the emergency department. METHODS: A prospective observational cohort study was performed in 49 adult patients who were undergoing arterial blood gas sampling as part of their assessment. Blood gas sampling and recording of the TcPco(2) level from the monitor was done simultaneously. Concordance between the two values (Paco(2) and TcPco(2)) was demonstrated using the method described by Bland and Altman. RESULTS: The mean difference was 0.02 kPa (95% CI -0.11 to 0.15). The Pearson's correlation coefficient was 0.94 (p<0.001) and the Bland-Altman limits of agreement were +/-0.9 kPa. CONCLUSIONS: In adult patients, concordance between carbon dioxide measurements by transcutaneous monitor and arterial blood sampling is good. Using the transcutaneous method, patients may be monitored non-invasively which may reduce the need for repeated blood gas sampling.

Predictive value of pretransplant inflammatory markers in renal allograft survival and rejection in children.

Pretransplant (pre-Tx) inflammation has been associated with acute rejection (AR) in adult Tx recipients. Our study was performed to determine whether a single pre-Tx serum C-reactive protein (CRP), Neopterin (Neo), and IL-12 determination could predict outcome in pediatric renal Tx recipients. Pre-Tx sera from 51 children transplanted between 1985 and 2000 were analyzed for serum CRP, Neo, and IL-12 for correlation with Tx-related variables. Endpoints were graft loss and AR. Kaplan-Meier and log-rank statistics were used to compare rejection-free and overall graft survival at different quartiles for each marker. Cox regression analysis was performed to determine the independent effects of various pre-Tx variables on the endpoints. The mean age of the children at Tx was 11 years. The mean CRP, Neo, and IL-12 were 1.3 mg/L, 1.78 ng/mL and 123 pg/mL, respectively. At last-follow-up (mean 4.9 years after Tx), 50% of the children had experienced AR and 29% had lost their grafts. The mean CRP, Neo, and IL-12 were not different between the patients with versus without AR or graft loss (P > .4 for all). Neither rejection-free survival nor graft survival was affected by CRP, Neo, or IL-12 quartiles (log-rank test). Cox regression analysis demonstrated no predictive value of any marker on the outcomes. Unlike adults, a single pre-Tx determination of inflammatory markers was not predictive of AR or graft loss in children. The pathogenesis of AR may be different in children with a lesser contribution of alloantigen-independent factors such as chronic infections.

Increased transplantation of kidneys with multiple renal arteries in the laparoscopic live donor nephrectomy era: surgical technique and surgical and nonsurgical donor and recipient outcomes.

BACKGROUND: For anatomical and technical reasons, many transplant centers restrict laparoscopic live donor nephrectomy (in contrast with open live donor nephrectomy) to left kidneys. HYPOTHESIS: This change in surgical practice increases procurement and transplantation rates of live donor kidneys with multiple renal arteries (RAs), without affecting donor and recipient outcomes. DESIGN AND SETTING: Retrospective review at an academic tertiary care referral center comparing laparoscopically procured single vs multiple-RA kidney grafts (April 1997 to October 2000). PATIENTS: Seventy-nine consecutive left laparoscopic live kidney donors and 78 transplant recipients. MAIN OUTCOME MEASURES: Donor and recipient complications and postoperative length of stay; cold and warm ischemia time; operating time; short-term and long-term graft function; and survival. RESULTS: We noted multiple RAs in 21 (27%) of all kidneys. The proportion of donors with 1 or more perioperative complications was 19% in the single-RA group vs 10% in the multiple-RA group (P was not significant). For the recipients, we noted no significant differences between groups with respect to surgical complications, quality of early and late graft function, rejection rates, graft losses (all immunologic), and graft survival. Cold and warm ischemia time and length of stay were similar for donors and recipients in both groups. Median operating times were significantly longer for the multiple-RA vs single-RA group (difference, 41 minutes for donors and 45 minutes for recipients; P<.02). CONCLUSIONS: While the introduction of laparoscopic live donor nephrectomy has significantly increased the number of grafts with multiple RAs (compared with historical open controls), this change in practice is safe for both donors and recipients from a patient outcome-based perspective. However, from an economic perspective, the longer operating time associated with multiple-RA grafts provides strong added rationale for optimization of surgical instruments and techniques to make right-sided laparoscopic nephrectomy a routine intervention.

Pretransplant systemic inflammation and acute rejection after renal transplantation.

BACKGROUND: There are presently no established pre-transplant tests that consistently identify patients who may be at increased risk for acute rejection episodes after renal transplantation. We studied whether pretransplant serum levels of C-reactive protein (CRP), a marker for the presence of systemic inflammation, would predict the occurrence of acute rejection episodes after renal transplantation. METHODS: Pretransplant serum was tested for CRP level in 97 consecutive renal transplant recipients. Time to acute rejection after transplantation was stratified by CRP level and compared using the Kaplan-Meier method. In addition, Cox regression multivariate analysis was performed to assess whether any pretransplant covariates could independently predict the subsequent occurrence of acute rejection episodes. RESULTS: Pretransplant mean CRP levels were higher in patients who subsequently had a rejection episode versus those who had no rejection (22.2+/-2.9 vs. 11.7+/-1.8 microg/ml, respectively, P=0.003). Patients less than the median CRP value had a significantly longer time to rejection compared to those with higher CRP levels (P=0.002). Similarly, patients within the lowest CRP quartile had longer times to rejection when compared with the highest quartile (P=0.006). Cox proportional hazards regression multivariate analysis identified CRP level as the only independent pretransplant risk factor for rejection identified (P=0.044). CONCLUSIONS: Pretransplant systemic inflammation as manifested by elevated serum CRP level independently predicts the risk of acute rejection after renal transplantation and may be useful in stratifying patients at the time of transplantation according to immunological risk. Thus, assessment of pretransplant systemic inflammatory status may be helpful in prospective individualization of immunosuppression therapy after renal transplantation.

Impact of double helical CT and three-dimensional CT arteriography on surgical planning for hepatic transplantation.

BACKGROUND: To assess the impact of preliver transplant double helical computed tomography (DHCT) and three-dimensional computed tomography arteriography (3D-CTA) on surgical planning for hepatic transplantation. METHODS: Vascular findings detected on DHCT/3D-CTAs of 80 patients were shown to the transplant surgeon in a blinded fashion. These findings included hepatic arterial anatomy, diameters of the major vessels that supplied the liver, celiac axis stenosis, splenic artery (SA) aneurysms, and portal vein thrombosis (PVT). The surgeon was asked to state the "planned" surgical approach for each case based on scan findings. These results were subsequently compared with what "actually" occurred at transplantation by review of surgical records. RESULTS: Fifty-five patients had conventional and 25 patients had nonconventional hepatic arterial anatomy. Three patients had PVT, three patients had celiac axis stenosis, and three patients had SA aneurysms. Correlation between the "actual surgical technique" and the "planned surgical approach" was seen in 50/55 (91%) patients with conventional and in 23/25 (92%) patients with nonconventional anatomy. Five patients requiring aortohepatic interposition grafts for arterial anastomoses had either severe celiac axis stenoses or arterial inflow vessels that were 3 mm or smaller. Three patients with PVT underwent successful surgical resection of the thrombosed segment and standard PV anastomoses as planned. Patients with complete replacement of hepatic arterial supply to the superior mesenteric artery required alteration of the sequence of the vascular anastomoses. Patients with SA aneurysms had surgical ligation of the splenic artery. CONCLUSIONS: DHCT/3D-CTA provides noninvasive means to identify findings that have significant impact on surgical planning for hepatic transplantation including celiac axis stenosis, diameter of inflow arterial vessel

Dissection of an iliac artery conduit to liver allograft: treatment with an endovascular stent.

Hepatic artery thrombosis remains one of the most serious complications after orthotopic liver transplantation. Sepsis, biliary leakage and strictures, and retransplantation are often the result of this devastating complication. Because retransplantation or reoperation is sometimes not possible or advisable, other means of reestablishing hepatic artery continuity are desirable. We describe a liver transplant recipient who developed a dissection of an iliac artery conduit after retransplantation that was treated with fibrinolytic therapy followed by successful placement of an endovascular stent.

Treatment of inferior vena cava anastomotic stenoses with the Wallstent endoprosthesis after orthotopic liver transplantation.

PURPOSE: To evaluate the efficacy of the Wallstent endoprosthesis for treatment of stenotic or occlusive inferior vena cava (IVC) lesions refractory to balloon angioplasty in patients after orthotopic liver transplantation. MATERIALS AND METHODS: Wallstent endoprostheses were implanted in six patients with IVC anastomotic stenoses or occlusions that were refractory to balloon angioplasty. Follow-up included both duplex ultrasound (US) and clinical evaluations. RESULTS: Ten stents were successfully implanted in six patients. Five of six patients (83%) demonstrated primary patency on duplex US for a mean period of 11 months (range, 4-17 months). One patient's symptoms recurred within 3 weeks after intervention. This patient underwent repeated stent placement. Follow-up duplex US in this patient demonstrated primary assisted patency at 7 months. Mean clinical follow-up was 12 months (range, 7-18 months). Other than the previously described case, no patient developed recurrent symptoms of IVC stenosis or occlusion. Two patients who experienced hemorrhagic complications secondary to anticoagulation were treated successfully. CONCLUSIONS: The Wallstent endoprosthesis is a useful adjunct for treatment of IVC stenosis or occlusions in patients who have undergone orthotopic liver transplantation when these lesions are refractory to simple balloon angioplasty.

Endoscopic management of biliary strictures in liver transplant recipients: effect on patient and graft survival.

BACKGROUND: Biliary strictures in liver transplant recipients cause significant morbidity and can lead to reduced patient and graft survival. METHODS: Of 251 liver transplant recipients, 22 patients with biliary strictures were categorized into two groups: donor hepatic duct (n = 12) or anastomotic (n = 10). Strictures were dilated and stented. Endoscopic therapy was considered successful if a patient did not require repeat stenting or dilation for 1 year. RESULTS: Patient and graft survival did not differ significantly in the 22 patients compared with patients without strictures (relative risk of death and graft survival 1.8 and 1.3). Donor hepatic duct strictures required significantly longer therapy than anastomotic strictures (median days 185 versus 67, p = 0.02). Twenty-two months after the first endoscopic treatment, 73% of the donor hepatic duct stricture group were stent free compared with 90% of the anastomotic group (p = 0.02). The former group had significantly more (p < 0.05) hepatic artery thrombosis (58.3% versus 10%), cholangitis (58.3% versus 30%), choledocholithiasis (91% versus 10%), and endoscopic interventions. No patient undergoing endoscopic treatment required retransplantation or biliary reconstruction during a median follow-up of 35.7 months. CONCLUSION: Endoscopic therapy of biliary strictures after liver transplantation is effective and is not accompanied by reduced patient or graft survival.

Predictors of bile leaks after T-tube removal in orthotopic liver transplant recipients.

Bile leaks after T-tube removal are a frequent cause of morbidity in orthotopic liver transplant recipients. The aim of this study was to determine factors that predict the development of these leaks in liver transplant recipients. Records of all patients who had undergone liver transplantation at the University of Washington Medical Center between January 1990 and September 1993 were reviewed. The following were excluded: patients with a Roux-en-Y anastomosis or inadvertent early T-tube removal and patients who died or underwent retransplantation before T-tube removal. All T-tube cholangiograms were reviewed blindly by two authors. Using logistic regression, several variables were assessed for possible association with bile leaks after T-tube removal; these included patient demographics, intraoperative variables, and clinical and cholangiographic variables related to T-tube removal. Of the 166 liver transplants performed in 150 patients, 99 transplants in 97 patients were evaluable for bile leak after T-tube removal. Thirty-three patients developed symptomatic bile leaks, and 21 underwent endoscopic or operative intervention for persistent symptoms. Only duct mural irregularities on the final cholangiogram were strongly associated with the development of a bile leak after T-tube removal (P = 0.001). In conclusion, bile leaks after T-tube removal occurred in one-third of patients undergoing orthotopic liver transplantation; the majority of these patients required some intervention. Duct mural irregularities were associated with bile leaks.

Recombinant human tumor necrosis factor receptor Fc fusion protein therapy in kidney transplant recipients undergoing OKT3 induction therapy.

BACKGROUND: Initial doses of OKT3 are associated with a cytokine-induced acute clinical syndrome (ACS). This study assessed the safety of a recombinant human tumor necrosis factor receptor fusion protein (TNFR:Fc) given to minimize OKT3-ACS symptoms in renal allograft recipients undergoing induction therapy. METHODS: Sixteen patients were randomized into treatment or control groups. Treated patients received TNFR:Fc 1 hr before OKT3 on days 0 and 3. Patients were monitored after transplant for OKT3-ACS symptoms. Levels of cytokines, serum creatinine, and C-reactive protein were followed. RESULTS: Patients receiving TNFR:Fc had lower OKT3-ACS symptoms as measured by a scoring system. There was a higher incidence of infection in treated patients (10/12) compared to controls (1/4) in the 3 months after transplant, but the etiology of this difference was unclear. There were no significant differences in cytokine profiles. CONCLUSIONS: TNFR:Fc is well tolerated by renal transplant patients receiving OKT3 induction therapy and modestly decreases the symptoms associated with OKT3-ACS.

Infection complicating percutaneous liver biopsy in liver transplant recipients.

There is controversy about the frequency of and risk factors for infectious complications of percutaneous liver biopsy in liver transplant recipients. The aim of this study was to identify the incidence and nature of complications associated with liver biopsy after orthotopic liver transplantation (OLT), with particular emphasis on infection. The medical records of all patients undergoing OLT between January 1990 and August 1994 were reviewed retrospectively to identify complications requiring hospitalization within one week of percutaneous liver biopsy. The nature and severity of complications were recorded and possible risk factors for infectious complications were examined. One hundred ninety-eight patients underwent 1,136 percutaneous liver biopsies. There were eleven complications (0.96%), including as follows: 7 infections, 3 bleeding episodes, and 1 vasovagal reaction. Infections after percutaneous liver biopsy included fever and bacteremia (n = 6), and fever without bacteremia (n = 1). All infections developed only in patients with underlying biliary tract abnormalities; the frequency of infection was higher (9.8%) in patients with choledochojejunostomy when compared with those with choledochocholedochostomy (1.4%). Bacteremia was more likely caused by skin flora in patients with choledochocholedochostomy (CDC) and by enteric bacteria in patients with choledochojejunostomy (CDJ). All infections were treated successfully with parenteral antibiotics. We conclude that biliary tract abnormalities are the primary risk factors for infection after percutaneous liver biopsy, although the risk is higher in patients with CDJ than with CDC. These data support the use of antibiotic prophylaxis before percutaneous liver biopsy in OLT recipients with biliary tract abnormalities.