Survey of public attitudes towards imminent death donation in the United States.

Imminent death donation (IDD) is described as living organ donation prior to a planned withdrawal of life-sustaining care in an imminently dying patient. Although IDD was ethically justified by United Network for Organ Sharing, the concept remains controversial due to presumed lack of public support. The aim of this study was to evaluate the public's attitudes towards IDD. A cross-sectional survey was conducted of US adults age >18 years (n = 2644). The survey included a case scenario of a patient with a devastating brain injury. Responses were assessed on a 5-point Likert scale. Results showed that 68% - 74% of participants agreed or strongly agreed with IDD when posed as a general question and in relation to the case scenario. Participants were concerned about "recovery after a devastating brain injury" (34%), and that "doctors would not try as hard to save a patient's life" (33%). Only 9% of participants would be less likely to trust the organ donation process. In conclusion, our study demonstrates strong public support for IDD in the case of a patient with a devastating brain injury. Notably, participants were not largely concerned with losing trust in the organ donation process. These results justify policy change towards imminent death donation.

Rapid identification of cytomegalovirus in liver allograft biopsies by in situ hybridization.

Identifying the etiology of hepatic dysfunction in liver transplant patients is critical to their clinical management and in maintaining graft survival. While cytomegalovirus (CMV) is a well-known cause of posttransplant hepatitis, the morphologic diagnosis of CMV hepatitis in liver biopsies can be difficult. Because conventional tissue culture for CMV requires days to weeks, the final results often arrive too late to be clinically useful. In this study, 44 liver allograft biopsies from 21 patients with hepatic dysfunction were evaluated for CMV by routine light microscopy, conventional tissue culture, and in situ DNA hybridization (IH) using commercially available biotinylated CMV-specific DNA probes. Whereas 38.6% of the biopsy specimens were positive by IH, 15.9% were culture-positive biopsies and 13.6% were positive by routine light microscopy. Assuming tissue culture to be the standard, IH demonstrated a sensitivity of 100% and a specificity of 73%. In comparison, routine light microscopy showed a sensitivity of 71.4% and specificity of 97.3%. In addition, three biopsy specimens positive only by IH were from three patients who had other liver biopsies positive for CMV by either light microscopy or viral culture. In situ DNA hybridization allows rapid detection (5-6 h) of CMV in paraffin-embedded liver allograft biopsies; it also has a sensitivity that surpasses routine histologic examination and perhaps even tissue culture.

Primary nonfunction. Is there a contribution from the back table bath?

A persistent problem in orthotopic liver transplantation (OLT) is primary nonfunction (PNF) of the hepatic allograft. In most instances the cause of the failure is unknown. In an attempt to minimize these graft failure, modifications in the procurement and operative procedure have been investigated. One change in the procedure at the University of Nebraska Medical Center has been the monitoring of the temperature of the fluid in the back table bath during preparation of the donor liver. Our initial procedure involved creating an ice slurry of lactated Ringer's solution and ice slush in which the donor liver was then prepared. The temperature of this ice slurry was retrospectively found to be from -3 degrees C to -1 degrees C (group I). In this group there was a higher-than-expected incidence of PNF. To investigate whether the temperature of the back table bath influenced the incidence of PNF, beginning with transplant No. 42 the preparation of the back table bath was modified. The bath was created by adding a small amount of PlasmaLyte slush to 2 L of PlasmaLyte (group II). The temperature of the bath was maintained at 2-4 degrees C. Data were collected on 100 consecutive liver transplants. All transplants were performed using standard techniques, the operation for the two groups differing only as described above. Transaminase levels were followed as an index of the allograft function and were expected to begin to normalize within 2-3 days after transplantation. While both groups display this trend, transaminase levels in group II were significantly lower postoperatively than group I levels (P less than 0.05). Preoperative values were similar. There were 7 PNFs in group I; 0 in group II (P less than 0.005). We feel that the change in the back table procedure has positively influenced the function of the hepatic allografts, and we conclude that transplant centers need to monitor the temperature at which all allografts are stored and prepared, and the cognizant that this may influence the postoperative function of the transplanted liver.

The viability of microorganisms in preservation solutions.

In 1988 the University of Wisconsin solution was introduced into clinical transplantation. This solution is unique in that it contains no glucose but rather raffinose, lactobionate, and hydroxyethyl starch. In addition, it contains two antibiotics, penicillin and bactrim. Prior studies have shown that other preservation solutions allow the transmission of bacterial contamination from organ donor to recipient. However, there are no data on whether UW solution, with its unique composition and extended preservation times, allows bacterial transmission. We undertook the present study to establish if bacteria remain viable in UW solution at extended preservation times. Cultures of both aerobic (Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa) and anaerobic (Bacteroides fragilis) bacteria were suspended at 10(5), 10(4), 10(2), and 10(1) org./ml (calibrated from a .5 Macfarland turbidity standard) in both Eurocollins and UW preservation solutions. Samples were then stored in an ice bath to stimulate organ preservation. The organisms were removed and plated on blood and chocolate agar at 0, 6, 12, 18, 24, and 36 hr postsuspension. The samples were then incubated at 37 degrees C and read for growth at 24-48 hr after plating. Our results showed growth of all organisms except S epi in both preservation solutions, at all dilutions and preservation times. S epi grew in the Eurocollins solution at all dilutions and preservation times but did not grow in the UW solution. When the experiment was repeated omitting penicillin from the UW solution, S epi grew at all dilutions and preservation times. These results demonstrate that in spite of the inclusion of two different antibiotics, the majority of the common bacterial contaminants of the organ donor remain viable in UW solution with extended preservation times. It may be possible therefore to omit these antibiotics from the UW solution and obtain similar results. It is also important to note that routine culturing remains an expensive but necessary part of organ procurement and preservation.

Positive pretransplant crossmatches predict early graft loss in liver allograft recipients.

We evaluated the influence of donor-recipient HLA compatibility and recipient pretransplant antidonor sensitization on liver allograft recipient survival. The overall graft survival results for 67 cyclosporine-prednisone treated liver allograft recipients at 3, 6, and 12 months posttransplant were 86%, 83%, and 83%, respectively. No significant differences were observed when comparing the one-year survivals of 81% vs. 85% for men and women or 80% vs. 85% for adult and pediatric patients. Similarly, no differences were observed when comparing one-year graft survivals for well vs. poorly matched recipients of 77% vs. 83% for recipients with < or = 2 HLA A, B vs. > 2 HLA A, B mismatches (MMs) and 82% vs. 82% for recipients with 0-1 HLA-DR MMs vs. 2 HLA-DR MMs, respectively. Pretransplant transfusion history and race also did not influence survival. Standard NIH (long-incubation) and anti-human globulin (AHG) crossmatches were performed. The 12% of recipients (8/67) displaying a positive NIH crossmatch experienced significantly poorer 3-, 6-, and 12-month survivals of 62% vs. 89%, 62% vs. 86%, and 62% vs. 86% (all P < 0.05), respectively, than the 59 NIH-crossmatch negative recipients. Similarly, the 16% (11/67) of recipients displaying a positive AHG crossmatch had significantly poorer 3-, 6-, and 12-month survivals of 63% vs. 91%, 54% vs. 89%, and 54% vs. 89% (all P < 0.05) respectively, than the 56 AHG crossmatch-negative recipients. NIH and AHG crossmatch-positive sera were treated with dithioerythritol (DTE) to establish whether reactivity was due to IgM or IgG immunoglobulin. One-year graft survivals of 65% vs. 30% (P < 0.05) were observed when the crossmatch-positive sera reactivities were due to IgM vs. IgG immunoglobulin. While graft survivals were improved when positive crossmatch serum reactivity was due to IgM, these survivals were still significantly poorer than when the crossmatches were completely negative (86% vs. 60%, P < 0.05 for NIH-negative vs. NIH-positive, but DTE-negative, and 88% vs. 77%, P < 0.05 for AHG-negative vs. AHG-positive, but DTE-negative). Therefore, an NIH- or AHG-positive crossmatch, due either to IgM or IgG reactivity, results in poor early (3- and 6-months) liver allograft survival. Crossmatch-positive recipients experienced significantly (P < 0.05) more rejections and more steroid-resistant rejections (P < 0.05) than crossmatch-negative recipients.(ABSTRACT TRUNCATED AT 400 WORDS)

Hepatic allograft rescue following arterial thrombosis. Role of urgent revascularization.

Hepatic artery thrombosis is a continuing source of morbidity and mortality following orthotopic liver transplantation. The cornerstone of therapy has been urgent retransplantation that is limited by organ availability. For this reason we developed a policy of urgent revascularization for allograft rescue. Hepatic artery thrombosis developed following 15 transplants of which 11 underwent urgent rearterialization. The diagnosis was made a mean of 4.8 days (range 1-10) following transplantation. Duplex ultrasonography was diagnostic in all patients and confirmed by angiography in 4 (36%). Three patients with hepatic artery thrombosis were identified following screening ultrasonography and were clinically unsuspected. Upon reexploration, a specific technical reason for hepatic artery was found in 4 patients (36%). Twelve arterial revascularization procedures were performed in 11 patients including: thrombectomy alone (n = 4); revision of anastomosis with thrombectomy (n = 5); and thrombectomy with placement of vascular conduit (n = 3). Following revascularization, 8 patients maintained hepatic artery patency. Three patients eventually required retransplantation secondary to biliary sepsis. Biliary tract complications developed in 6 patients, at a mean of 23 days following revascularization and included: breakdown of the biliary anastomosis (n = 4); stricture (n = 1); and sludge formation (n = 1). The overall graft and patient survival are 74% and 82% respectively, with a mean follow-up of 6.8 months. Hepatic allograft rescue with the use of urgent revascularization following hepatic artery thrombosis appears to be an effective means of either avoiding retransplantation or providing a bridge until a suitable donor becomes available.

Pontine and extrapontine myelinolysis following liver transplantation. Relationship to serum sodium.

The relationship between central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) and serum sodium changes in the setting of orthotopic liver transplantation (OLT) is examined. Postmortem examination of 14 patients with end-stage liver disease who underwent liver transplantation revealed CPM in four, of which three also had EPM. A retrospective review of clinical and laboratory data was performed on all patients. There were marked perioperative rises (21-32 mEq/L) in the serum sodium concentration in all four patients who developed myelinolysis. In contrast, the largest increase in sodium in patients without demyelination was 16 mEq/L. We conclude that perioperative rises in the serum sodium concentration increase the risk of myelinolysis. CPM and EPM should be considered if the patient develops mental status changes or focal neurological deficits several days after OLT.

The results of reduced-size liver transplantation, including split livers, in patients with end-stage liver disease.

We initiated a policy of using RSLT in critically ill patients in June of 1988. Since that time we have performed 30 RSLTs in 29 patients, including 28 children and 1 adult. The mean age of the children was 27 months (range 1 month to 10 years) with 14 (52%) being 1 year of age or less. The mean weight was 11.3 kg (range 2-50 kg) with 20 being 10 kg or less. A total of 22 patients were in the intensive care unit at the time of RSLT including 9 who were intubated. Of the 30 RSLTs, 23 were performed as a primary transplant while 7 were retransplants. Indications for primary transplantation included biliary atresia (n = 11), fulminant hepatic failure (n = 5), neonatal hepatitis (n = 4) and others (n = 3). The RSLT was used in retransplantation for primary nonfunction (n = 2), hepatic artery thrombosis (n = 2), chronic rejection (n = 2), and herpetic hepatitis (n = 1). The size reductions included 18 left lobes, 7 left lateral segments, and 5 right lobes. This group includes the use of the split-liver technique, which was applied to 10 patients (5 livers). The median donor/recipient weight ratio for left lobe transplants was 2:1; left lateral segments was 7.3:1; and right lobes 1.6:1. One year actuarial patient and graft survivals were 68 and 65%, respectively, with a mean follow-up of 10.6 months. The number of children dying awaiting transplantation has been significantly reduced following the introduction of RSLD (3 of 115, 2.6% vs. 12 of 95, 13%; P less than 0.02).

The impact of extended preservation on clinical liver transplantation.

The introduction of UW solution into clinical transplantation has permitted extended cold storage preservation of the liver. Over a 46-month period, we have performed 308 orthotopic liver transplants (266 primary, 42 retransplants) in 266 recipients. Our experience is divided into cold-storage preservation in Eurocollins (163 transplants in 140 recipients) and UW (145 transplants in 131 recipients) solutions. Donor and recipient factors were comparable between the two groups. The use of UW solution has permitted an increase in the mean preservation time from 5.2 +/- 1.0 [EC] to 12.8 +/- 4.3 [UW] hr (P less than 0.001). The mean total operating time was reduced but intraoperative blood loss was unchanged with UW preservation. The number of transplants performed during the daytime hours has increased dramatically (21.5% [EC] vs. 71% [UW], P less than 0.001). The incidence of primary nonfunction, hepatic artery thrombosis, 1-month graft survival, and early retransplantation were similar in the 2 groups. Initial allograft function as determined by bile production, histology, and clinical assessment were likewise similar. Mean serum bilirubin, transaminase, and prothrombin levels were virtually identical by 5 days posttransplant. The enhanced margin of safety afforded by extended preservation has increased the capability for distant organ procurement and sharing, minimized organ wastage, and improved the efficiency of organ retrieval. With the relaxation of logistical constraints, our rate of liver import has nearly doubled (20.9% [EC] vs. 39.3% [UW], P less than 0.001). Extended preservation has permitted the development of reduced-size liver grafting (n = 12), resulting in a significant reduction in the number of deaths occurring while awaiting transplantation. Therefore, we advocate the use of UW solution with selective extension of preservation based not only on donor and recipient factors but also on manpower, resource, and logistical considerations.

Successful prophylaxis of cytomegalovirus disease after primary CMV exposure in liver transplant recipients.

UNLABELLED: During a 38-month period, we studied 320 liver transplants in 283 recipients (202 adults, 81 children). CMV disease was documented in 85 patients (30.0%) The major risk factor for CMV disease was primary CMV exposure (transplanting a seropositive allograft into a seronegative recipient). A total of 42 patients (14.8%) had primary CMV exposure. Twenty-one patients were historical controls, while the next 21 received prophylaxis for CMV infection in a nonrandomized trial of consecutive study groups. The regimen of prophylaxis consisted of intravenous immune globulin (IgG; 0.5 g/kg) at weekly intervals for 6 weeks and acyclovir for 3 months. CMV prophylaxis resulted in a dramatic reduction in the incidence of CMV disease (71.4% vs. 23.8%, (P less than 0.01). All cases of CMV were treated with intravenous ganciclovir (5 mg/kg b.i.d. for 14 days), with 5 patients in the control group developing recurrent CMV disease (33.3% relapse). In the 16 patients receiving prophylaxis who did not develop CMV disease, all developed positive CMV-IgG titers with the passive administration of IgG. However, none developed any evidence of CMV infection or viral shedding as assessed by IgM titers and surveillance viral cultures. Four deaths occurred (all control patients), but none were related to CMV disease. Overall patient and graft survivals after primary CMV exposure were 90.5% and 82.2%, respectively, after a mean follow-up of 14 months. CONCLUSION: Primary CMV exposure is a major risk factor for CMV disease in liver transplant recipients. Intravenous IgG plus acyclovir is safe and effective in preventing CMV infection and disease in this setting. Because of the scarcity of donor organs, we do not advocate protective matching to avoid primary CMV exposure but rather recommend prophylaxis to prevent CMV disease in this high-risk group.

Disseminated Trichosporon beigelii infection after orthotopic liver transplantation.

A 25-year-old male, who received an orthotopic liver transplant for fulminant hepatic failure resulting from hepatitis B, had disseminated Trichosporon beigelii infection develop. Of the 55 cases of disseminated T. beigelii that have been reported in the English-language medical literature, most have occurred in patients who were both neutropenic and had compromised cell-mediated immunity. Mortality has ranged from 60 to 78%. Outcome appears to depend significantly on leukocyte recovery. Histologically, Trichosporon can be confused with Candida; however, recognition of the arthroconidia and pleomorphic hyphae and pseudohyphae of Trichosporon should allow their differentiation.

The role of intrahepatic cholangiojejunostomy in liver transplant recipients after extensive destruction of the extrahepatic biliary system.

BACKGROUND: Extensive destruction of the extrahepatic biliary system after liver transplantation can be a catastrophic event. We present our experience with the use of intrahepatic cholangiojejunostomy (IHCJ) in this setting. METHODS: From July 1985 through December 1991, 668 liver transplantations were performed in 583 patients. Seven patients required IHCJ. This technique involves creating an anastomosis between the jejunal mucosal and hepatic parenchyma/capsule with the use of a Roux-en-Y limb of bowel. There were four adults and three children. The clinical presentation included bile leak (n = 4), subhepatic abscess (n = 2), and intrahepatic abscess (n = 1). The probable cause of these events included hepatic arterial thrombosis (n = 4), occult bile leak (n = 2), and fungal cholangitis (n = 1). RESULTS: After IHCJ, six of the seven patients are currently alive, with a mean follow-up of 28 months. The current liver function test results include a mean bilirubin of 0.7 mg/dl (range, 0.4 to 1.9 mg/dl), serum glutamic pyruvic transaminase of 69 units/L (range, 32 to 118 units/L), and gamma-glutamyltranspeptidase of 118 IU/L (range, 111 to 265 IU/L). CONCLUSIONS: These results suggest that IHCJ is a safe and effective alternative to retransplantation in liver recipients with extensive destruction of the extrahepatic biliary system.

Diagnosis and treatment of biliary tract complications after orthotopic liver transplantation.

Biliary tract complications are a continuing source of morbidity after liver transplantation. In a 3.5-year period we performed 264 liver transplants in 226 patients (132 adults, 94 children). Biliary tract reconstruction was via Roux limb choledochojejunostomy (n = 144) or choledochocholedochostomy (n = 118). Fifty (19.1%) biliary complications occurred, and 35 (13.4%) necessitated operative repair. The incidence was similar in adults and children and after each method of reconstruction. Risk factors were vascular thrombosis and reduced-sized transplants. Diagnosis was based on the algorithmic use of multiple modalities with early biliary visualization. Roux limb complications usually occurred in the first month after transplant and necessitated operative intervention, whereas duct-to-duct problems appeared later and were more accessible to percutaneous or endoscopic manipulations. Eight (6.8%) patients required conversion to a Roux limb, whereas 8/15 (53.3%) cases of biliary stricture were successfully managed nonoperatively. Three (1.3%) patients and four (1.5%) grafts were lost as a result of biliary complications. One-year actuarial patient survival is 76.4% with a mean follow-up of 13.2 months. Early recognition of biliary complications and prompt interventional therapy can effectively prevent long-term sequelae. Although choledochocholedochostomy is more physiologic and expeditious, Roux-en-Y choledochojejunostomy remains a safe and versatile alternative and is the preferred method of reconstruction in select cases.

Stratifying the causes of death in liver transplant recipients. An approach to improving survival.

The causes of death in 21 adults and 23 children in a consecutive series of 180 liver transplantations were reviewed and classified into four categories. A previously described preoperative risk score was applied prospectively to estimate the relative risk of mortality following liver transplantation in adults. Categorization of the causes of death allowed for a systematic search for errors in management and technique. Comparison of the preoperative risk score with the cause of death category revealed that higher-risk adults were most likely to die of causes related to preoperative morbidity. They also accrued higher hospital costs, regardless of outcome. The data are useful for designing strategies to reduce mortality. However, the inexorable role that preoperative morbidity has on outcome was also emphasized. This has important implications in developing strategies to reduce the costs of liver transplantation and to provide optimal distribution of scarce donor organs.

Clinical spectrum of fungal infections after orthotopic liver transplantation.

During a 50-month period, we identified 91 episodes of fungal infection in 72 liver transplant recipients (23.8%). Candida species accounted for 83.5% of cases. Clinical patterns of fungal infections included disseminated infection (19), peritonitis (17), pneumonitis (15), multiple sites of colonization (13), fungemia (11), and other sites (16). The diagnosis of fungal infection was usually made in the first 2 months (84.7% of cases), at a mean time of 16 days after transplantation. Risk factors for fungal infections included retransplantation, Risk score, intraoperative transfusion requirement, urgent status, Roux limb biliary reconstruction (in adults), steroid dose, bacterial infections and antibiotic therapy, and vascular complications. Fungal infections were successfully treated with amphotericin B in 63 cases (74.1%) but were associated with diminished patient survival (50% vs 83.5%). Fungal infection is a frequent source of early morbidity and can be related to well-defined risk factors, suggesting the need for effective prophylaxis.

Clinical patterns of cytomegalovirus disease after liver transplantation.

During a 43-month period, we performed 248 liver transplantations in 211 patients (127 adults and 84 children). Cytomegalovirus (CMV) disease was documented in 73 recipients (34.6%). Risk factors for CMV disease included donor CMV seropositivity, antilymphocyte therapy, and retransplantation. The mean time of occurrence of CMV disease was 38.3 days after transplantation, and the most frequent site of disease was the hepatic allograft. A total of 69 patients were treated with intravenous ganciclovir, with a prompt and lasting response documented in 51 (73.9%). The remaining 18 (26.1%) developed recurrent CMV disease, which was more common after primary CMV exposure. Cytomegalovirus disease was ultimately controlled by ganciclovir in 94.2% of cases. This disease occurs early after transplantation and can be related to well-defined risk factors. Although ganciclovir therapy is effective, preliminary experience with prophylaxis shows promise in reducing the incidence of CMV disease.

Juvenile nasopharyngeal angiofibroma: management of intracranial extension.

Juvenile nasopharyngeal angiofibroma (JNA) is a histologically benign, locally invasive tumor of the nasopharynx that is found primarily in the pubescent male. While most authors recommend surgical excision for smaller, localized extracranial tumors, opinion varies on the management of more aggressive tumors with intracranial extension. The authors present their experience over the past 15 years with 15 cases of JNA with intracranial extension, and formulate a plan of management. A combined otolaryngologic/neurosurgical approach is recommended in order to assess the extent of the tumor and to isolate feeding vessels. Lateral extension into the middle cranial fossae should be resected in continuity with the nasopharyngeal component, which is approached from below in a separate operative field. Medial extensions are transected, verified angiographically three months after surgery, and irradiated. The results of therapy are presented, and a case of dural penetration by JNA is described.

Prolonged paralysis associated with long-term pancuronium use.

We cared for a 4-year-old patient who had undergone orthotopic liver transplantation and was placed on a ventilator for respiratory distress associated with Pneumocystis carinii pneumonia. The neuromuscular blocking agent pancuronium bromide 1.0-1.2 mg every hour as needed was used to facilitate artificial ventilation for 40 days. On discontinuation of pancuronium, the patient experienced severe, generalized neuromuscular dysfunction. Because no improvement was seen for 2 weeks, the acetylcholinesterase inhibitors edrophonium and pyridostigmine were instituted. Shortly thereafter the patient's condition began to improve. Gradual improvement occurred over 3-4 months and the patient has since returned to baseline neurologic function. We suggest that long-term pancuronium use was the cause of the patient's prolonged paralysis. The improvement experienced after the initiation of antidotal therapy strongly supports our proposal.

Hepatic failure associated with imipramine therapy.

Imipramine, a widely used antidepressant, has rarely been associated with hepatic abnormalities. In the majority of reported cases, hepatic effects have been transient and readily reversible on discontinuation of the drug. We cared for an 11-year-old boy with hepatic failure and massive cell necrosis which followed treatment with imipramine for enuresis. This therapy led to fulminant hepatic failure and subsequent liver transplantation.

Vascular complications after orthotopic liver transplantation.

Over a 57-month period, we performed 430 orthotopic liver transplants in 372 patients. A total of 38 vascular complications were identified including hepatic artery thrombosis (n = 24), portal vein thrombosis (n = 6), combined hepatic artery thrombosis/portal vein thrombosis (n = 3), and hepatic artery rupture (n = 5). A number of potential risk factors for the development of vascular thrombosis were evaluated with only children, weight less than 10 kg, and cold ischemia time found to be significant. The clinical presentation included fulminant hepatic failure, allograft dysfunction, biliary sepsis, and screening ultrasound. Duplex ultrasonography was diagnostic in nearly all cases. Therapeutic modalities included revascularization, revascularization followed by retransplantation, retransplantation alone, and observation. Five cases of hepatic artery rupture occurred in four patients. Infectious arteritis was present in four patients. The 6-month actuarial survival in patients with vascular complications was 70%. Early diagnosis is critical for graft salvage, with surgical intervention the mainstay of therapy.