The effect of in vitro recombinant factor VIIA on coagulation parameters for blood taken during liver transplantation.

Recombinant factor VIIa (rFVIIa) has been utilized in pilot studies in orthotopic liver transplantation (OLT) when administered to patients at doses of 68.37 microg/kg and 80 microg/kg. Although some effectiveness in normalizing measurements of coagulation has been demonstrated, the optimal dose for patients undergoing OLT has not been established. This study evaluated the effects of an in vitro equivalent dose of 120 microg/kg of rFVIIa on coagulation parameters when applied to the blood drawn from patients undergoing OLT. Coagulation function was assessed in 10 patients at four points during OLT. These time points were baseline, 5 minutes prior to reperfusion, 10 minutes after reperfusion, and 70 minutes after reperfusion. These patients did not receive rFVIIa perioperatively. At each of these four time points, a native sample was analyzed for prothrombin time (PT) and thromboelastogram. The rFVIIa (6.1 microg/kg or the approximate equivalent dose of 120 microg/kg for a 70 kg patient) was added to a second sample from the same patient. This second sample was also analyzed for PT and thromboelastogram. There was a statistically significant difference in baseline PT between native versus rFVIIa supplemented samples (15.8 +/- 3.21 vs 13.6 +/- 2.36 seconds, P < .02). The maximum amplitude of the thromboelastogram was larger in the native samples at 5 minutes prior to reperfusion (53.5 mm vs 39 mm, P < .02). No significant differences existed in the variables at any of the other sampling times. This study failed to demonstrate a consistent in vitro effect of rFVIIa on the blood taken from patients during OLT.

Aprotinin reduces red blood cell transfusion in orthotopic liver transplantation: a prospective, randomized, double-blind study.

The effect of an aprotinin infusion on blood and blood product transfusion during adult primary orthotopic liver transplantation (OLT) was investigated in a prospective, randomized, double-blind study. Sixty-three patients were enrolled; 33 patients were administered an aprotinin regimen of a 1,000,000-KIU loading dose, followed by a 250,000-KIU/h infusion during surgery, and 30 patients were administered equivalent volumes of normal saline. Red blood cell (RBC) and blood product transfusion intraoperatively and for the first 24 hours postoperatively was by protocol. Intraoperative coagulation testing and thromboelastography (TEG; Hemoscope Corp, Skokie, IL) were performed. Intraoperative RBC transfusion was significantly less in the aprotinin group versus controls: median, 5 units (interquartile range [IQR], 3 to 9 units) versus 7 units (IQR, 5 to 16 units; P =.0016). No significant differences were found for intraoperative blood product transfusion or transfusion of RBCs or blood products in the 24-hour postoperative period. No significant differences were observed in intraoperative coagulation testing or TEG parameters. We conclude that aprotinin infusion reduces RBC transfusion requirements in OLT.

Poor prediction of blood transfusion requirements in adult liver transplantations from preoperative variables.

STUDY OBJECTIVE: To assess the ability of preoperative information to predict intraoperative blood transfusion requirements in adult orthotopic liver transplantation. DESIGN: Retrospective review. SETTING: Liver transplantation program in a referral center. PATIENTS: 583 sequential adult patients undergoing orthotopic liver transplantation. MEASUREMENTS: Preoperative variables with a previously demonstrated relationship to intraoperative transfusion were identified from the literature. These variables were then collected retrospectively from 583 consecutive liver transplantations. Relationships between these and intraoperative blood transfusion requirements were examined by both univariate analyses and multiple linear regression analysis. RESULTS: Univariate analysis revealed significant associations between blood transfused and the following preoperative variables: age, gender, diagnosis, presence of grade 3 or 4 encephalopathy, pseudocholinesterase, creatinine, bilirubin, mean pulmonary artery pressure, activated partial thromboplastin time, and platelet count. Multiple linear regression analysis with correction for diagnosis identified age, creatinine, bilirubin, and pseudocholinesterase as independent predictors; for the final model r(2) = 0.22. CONCLUSION: Preoperative variables are poor predictors of intraoperative transfusion requirements even when significant associations exist, identifying a small proportion of the variability observed. A predictive approach based on this method would be too inaccurate to be of clinical use. The majority of the variability in transfusion requirements during liver transplantation most likely results from intraoperative and donor organ factors.

Accuracy of Doppler echocardiography in the assessment of pulmonary hypertension in liver transplant candidates.

Pulmonary hypertension has been associated with poor outcome after liver transplantation. We assessed the diagnostic accuracy of Doppler echocardiography in detecting significant pulmonary hypertension. Seventy-four potential liver transplant candidates underwent Doppler echocardiography in which the systolic right ventricular pressure (RVsys) was used to estimate the systolic pulmonary artery pressure (PAsys). Group 1 included 39 consecutive patients with RVsys >/=50 mm Hg who underwent elective right heart catheterization. Group 2 consisted of 35 patients with RVsys <50 mm Hg in whom pulmonary artery pressures were measured at the beginning of the transplantation procedure. The accuracy of the estimates by Doppler echocardiography was assessed against measurements made by direct catheterization. Patients in groups 1 and 2 were comparable in their demographic and liver disease characteristics. There was a strong correlation between RVsys by Doppler echocardiography and PAsys by right heart catheterization (r =.78, P <.01). Of the 39 patients in group 1, 29 (72%) had at least moderate pulmonary hypertension (mean pulmonary artery pressure [MPAP] >/=35 mm Hg), including 12 (30%) with severe pulmonary hypertension (MPAP >/=50 mm Hg). Only 1 of the group 2 patients had MPAP >/=35 mm Hg. Thus, in the diagnosis of moderate to severe pulmonary hypertension, the sensitivity of echocardiography was 97% and specificity was 77%. Doppler echocardiography is an accurate screening test to detect moderate to severe pulmonary hypertension. We advise that liver transplant candidates with RVsys >/=50 mm Hg undergo right heart catheterization to fully characterize pulmonary hemodynamics.

Risk of patients with severe aortic stenosis undergoing noncardiac surgery.

Aortic stenosis (AS) is a major risk factor for perioperative cardiac events in patients undergoing noncardiac surgery. We previously showed that selected patients with AS who were not candidates for, or refused, aortic valve replacement could undergo noncardiac surgery with acceptable risk. We extended our previous experience over a subsequent 5-year period by retrospectively analyzing the perioperative course of all patients with severe AS (aortic valve area index < 0.5 cm2/m2 or mean gradient > 50 mm Hg), determined with Doppler echocardiography or cardiac catheterization, who underwent noncardiac surgery. Nineteen patients underwent 28 surgical procedures: 22 elective and 6 emergency. The types of these procedures were 12 orthopedic, 6 intraabdominal, 4 vascular, 4 urologic, 1 otolaryngologic, and 1 thoracic. Mean age was 75 +/- 8 years. Of the 19 patients, 16 (84%) had > or = 1 symptom: dyspnea, angina, syncope, or presyncope. Mean left ventricular ejection fraction was 61 +/- 11%. The type of anesthesia was general in 26 procedures and continuous spinal in 2. Intraarterial monitoring of blood pressure was used in 20 of the 28 surgical procedures. Intraoperative hypotensive events were treated promptly, primarily with phenylephrine. In all cases the anesthesia team was aware of the severity of the AS and integrated this into the anesthetic plan. Two patients (elective operation in 1 and emergency in 1) had complicated postoperative courses and died. There were no other intraoperative or postoperative events in any of the other patients. Although aortic valve replacement remains the primary treatment for patients with severe AS, selected patients with severe AS, who are otherwise not candidates for aortic valve replacement, can undergo noncardiac surgery with acceptable risk when appropriate intraoperative and postoperative management is used.

Post-hospital sub-acute care: an example of a managed care model.

OBJECTIVE: This article describes Transitional Care Centers (TCC), an innovative sub-acute care program developed by a large managed care organization (HealthPartners in Minnesota) in partnership with five area nursing homes. The purpose of the TCC is to promote continuity of care for frail older members covered under a TEFRA risk contract. DESIGN: This is a retrospective study of the experiences and outcomes of enrollees who received TCC compared with a like group of enrollees who received customary continuity care through contract services. SETTING: The TCCs are established contractually in five area nursing homes; these facilities keep at least 15 beds available to the health plan for round-the-clock, 7 days per week admissions for sub-acute care. Designated staff from these facilities and designated geriatric nurse practitioners and geriatricians from HealthPartners follow established targeting, admissions, assessment, care planning, and discharge planning procedures to provide team care for these patients at the facilities. PARTICIPANTS: The TCC program is targeted to patients requiring rehabilitation therapy (post-cardiovascular accident, post-fracture/replacement) who are deconditioned, or those with uncomplicated infections (urinary tract infection, pneumonia). A total of 1144 patients participated in the TCC program in the 1-year program under report, and 253 were surveyed in regard to their experience. One hundred HealthPartners physicians were surveyed about the program. RESULTS: Post-acute length of stay in the TCC was substantially lower than that in customary care settings in contract nursing homes (14.3 versus 20.5 days). Rehospitalization rates from these units were comparable to or better than those from other sub-acute units. Patient and primary care physician satisfaction with the units was high. The program provided economic benefit to both partners. The health plan's negotiated rate for the TCC units was 38% less than that paid in noncontractual facilities. CONCLUSION: The TCC partnership provides rehabilitative and geriatric evaluation services in settings more conducive to and less costly than such care usually, and yields improvements in care and utilization outcomes.

Frequency and clinical implications of increased pulmonary artery pressures in liver transplant patients.

OBJECTIVE: To characterize the pulmonary hemodynamics and identify predictors of pulmonary hypertension in a group of patients before liver transplantation and to determine whether pulmonary hypertension in these patients is related to survival. MATERIAL AND METHODS: In 362 patients before their first liver transplantation (between 1985 and 1993), the clinical history, laboratory data, and results of pulmonary function tests were recorded. Pulmonary artery (PA) catheterization was performed after induction of anesthesia at the time of transplantation. Monthly follow-up was maintained. RESULTS: A hyperdynamic circulation was often present -- an increased mean cardiac output (7.6 L/min), increased mean PA pressure (20.9 mm Hg), correlation of mean PA pressure with cardiac output (r = 0.25; P<0.001), and decreased mean pulmonary vascular resistance (60 dynes times s/cm5). Mean PA pressures were more than 25 mm Hg in 72 patients (20%). Pulmonary hypertension (defined as mean PA pressure of more than 25 mm Hg and pulmonary vascular resistance in excess of 120 dynes times s/cm5) occurred in 15 patients (4%). Pulmonary function tests revealed obstruction in 7%, restriction in 18%, and low diffusing capacity in 46%. By univariate analysis, lower forced expiratory volume in 1 second, forced vital capacity, and total lung capacity were the only preoperative factors associated with pulmonary hypertension (P<0.05). Survival was significantly lower in patients with acute fulminant hepatitis (P<0.001), the group with the highest mean PA pressure, than in those with other diagnoses. Increased PA pressures or mild to moderate pulmonary hypertension was not found to be associated with a worse survival by univariate or multivariate analysis. CONCLUSION: Increased PA pressure is common in liver transplant patients (20%). "True" pulmonary hypertension occurred in only 4% of our patients and was not associated with an adverse outcome.

Risk factors for cytomegalovirus and severe bacterial infections following liver transplantation: a prospective multivariate time-dependent analysis.

Risk factors for cytomegalovirus and severe bacterial infections were studied prospectively by univariate, multivariate and time-dependent Cox model analysis in 79 consecutive liver transplant patients treated with selective bowel decontamination. Cytomegalovirus infection occurred in 39 patients (49%) and was symptomatic in 22 patients. Twenty-six patients (33%) developed at least one of 43 documented severe bacterial infections. In a multivariate analysis of risk factors for all cytomegalovirus infections, the cytomegalovirus seronegative recipient-cytomegalovirus seropositive donor group was the highest risk group (P < 0.001). Using the same analysis for risk factors for symptomatic cytomegalovirus infections, a prolonged prothrombin time (P < 0.005), a diagnosis of acute fulminant hepatitis as the underlying liver disease (P < 0.01) and a cytomegalovirus seronegative patient receiving a liver from a seropositive donor (P < 0.001) were significant. The treatment with OKT3 therapy (P < 0.008) and hepatic artery thrombosis (P < 0.02) were found to be significant risk factors in a time-dependent univariate analysis but were not independent risk factors when multivariate analysis was utilized. Significant risk factors for major bacterial infections (P < 0.03) using univariate analysis included a prolonged anesthesia, anhepatic and surgical times, as well as the transfusion of large amounts of fresh frozen plasma or autologous blood. In a multivariate analysis, only the transfusion of large amounts of fresh frozen plasma (P < 0.04) was a significant independent risk factor. Cytomegalovirus infection was a risk factor for the development of severe bacterial infections (P < 0.03) in a multivariate time-dependent analysis.

Association of coagulation tests with blood use during liver transplantation.

This study is a retrospective review of 263 adult patients who underwent either their first or their second orthotopic liver transplantation between March 1985 and January 1992. Activated partial thromboplastin time (APTT) and prothrombin time (PT) were analyzed for correlation with the amount of blood transfused 70 minutes after reperfusion. The data were analyzed to estimate correlation between variables using Spearman's rank correlation coefficient. A P value less than .05 was considered significant. Data analysis demonstrated a positive association between APTT and blood transfusion in all disease states, with the exception of patients who had retransplantation. A positive association existed between PT and the amount of blood transfused in patients with alcoholic liver disease, primary biliary cirrhosis, and primary sclerosing cholangitis.

Significance of mildly elevated creatine kinase (myocardial band) activity after elective abdominal aortic aneurysmectomy.

The clinical significance of mildly elevated creatine kinase (CK) myocardial band (MB) enzyme levels in patients undergoing elective repair of an abdominal aortic aneurysm was evaluated retrospectively in 348 patients. For each patient, preoperative and postoperative electrocardiograms (ECGs) were interpreted blindly for left ventricular hypertrophy, ST segment abnormality, left bundle branch block, right bundle branch block, left axis deviation, atrial fibrillation, T wave abnormality, and Q waves. A total of 107 patients (31%) had postoperative CK-MB elevations of trace or greater; 37 had trace, 35 had 1% to 4%, and 35 had greater than or equal to 5% elevation. There was no difference in survival between those with trace and no CK-MB elevation. Patients with increased CK-MB (greater than or equal to 1%) values were more likely to have ECG abnormalities. The following ECG (either preoperative or postoperative) abnormalities were univariately related to decreased postoperative survival: left ventricular hypertrophy (P less than 0.001), ST segment abnormalities (P less than 0.001), left bundle branch block (P less than 0.001), the combination of right bundle branch block and left axis deviation (P = 0.006), Q wave infarction (P less than 0.001), and atrial fibrillation (P less than 0.001). There were 15 in-hospital deaths, and 333 patients were discharged and followed-up for a median of 4.6 years. There were 97 posthospitalization deaths, 61% of which were due to cardiac causes. Overall survival was associated with the degree of CK-MB elevation; the higher the CK-MB, the worse the survival.(ABSTRACT TRUNCATED AT 250 WORDS)

UW solution improves duration and quality of clinical liver preservation.

Prolonged liver preservation (up to 17 hours) with UW solution had no adverse effect on perioperative blood loss or results of postoperative serum biochemistry studies. After use of this solution, biliary and vascular complications as well as evidence of histologic damage were less. The advantages of the extended preservation time permit liver transplantation to be done as a semi-elective procedure; more patients can be waiting at home instead of near the transplant center. The availability of UW solution also makes it possible to send grafts long distances throughout the nation. Furthermore, surgeons can arrange for backup patients in case the recipient proves to be inoperable. This capability should reduce organ wastage, even before the time limits of preservation with UW solution have been determined definitely. We feel that UW solution undoubtedly has improved both the duration and quality of liver graft preservation.