The association of allogeneic blood transfusion and the recurrence of hepatic cancer after surgical resection.

There is conflicting evidence whether allogeneic blood transfusion influences survival or cancer recurrence after resection of hepatocellular cancer. We followed up 1469 patients who had undergone hepatocellular resection for a median (IQR [range]) of 45 (21-78 [0-162]) months, of whom 626 (43%) had had blood transfusion within 7 days of surgery. Both disease-free survival and patient survival were measured using a proportional hazards regression model and inverse probability of treatment weighting. We used restricted cubic splines for the association of the number of packed red blood cell units transfused with cancer recurrence and survival. We found that peri-operative blood transfusion was independently associated with survival and cancer recurrence after resection of hepatocellular carcinoma. Adjusted hazard ratios (95%CI) for the association of blood transfusion with cancer recurrence and all-cause mortality were 1.3 (1.1-1.4) and 1.9 (1.6-2.3), p < 0.001 for both. With more units transfused cancer recurrence was more likely and survival was shorter. The association of the number of transfused units was non-linear for cancer recurrence and linear response for all-cause mortality.

Adaptation of non-linear mixed amount with zero amount response surface model for analysis of concentration-dependent synergism and safety with midazolam, alfentanil, and propofol sedation.

BACKGROUND: The non-linear mixed amount with zero amounts response surface model can be used to describe drug interactions and predict loss of response to noxious stimuli and respiratory depression. We aimed to determine whether this response surface model could be used to model sedation with the triple drug combination of midazolam, alfentanil and propofol. METHODS: Sedation was monitored in 56 patients undergoing gastrointestinal endoscopy (modelling group) using modified alertness/sedation scores. A total of 227 combinations of effect-site concentrations were derived from pharmacokinetic models. Accuracy and the area under the receiver operating characteristic curve were calculated. Accuracy was defined as an absolute difference <0.5 between the binary patient responses and the predicted probability of loss of responsiveness. Validation was performed with a separate group (validation group) of 47 patients. RESULTS: Effect-site concentration ranged from 0 to 108 ng ml-1 for midazolam, 0-156 ng ml-1 for alfentanil, and 0-2.6 µg ml-1 for propofol in both groups. Synergy was strongest with midazolam and alfentanil (24.3% decrease in U50, concentration for half maximal drug effect). Adding propofol, a third drug, offered little additional synergy (25.8% decrease in U50). Two patients (3%) experienced respiratory depression. Model accuracy was 83% and 76%, area under the curve was 0.87 and 0.80 for the modelling and validation group, respectively. CONCLUSION: The non-linear mixed amount with zero amounts triple interaction response surface model predicts patient sedation responses during endoscopy with combinations of midazolam, alfentanil, or propofol that fall within clinical use. Our model also suggests a safety margin of alfentanil fraction <0.12 that avoids respiratory depression after loss of responsiveness.

Social and Financial Outcomes of Living Liver Donation: A Prospective Investigation Within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL-2).

Because results from single-center (mostly kidney) donor studies demonstrate interpersonal relationship and financial strains for some donors, we conducted a liver donor study involving nine centers within the Adult-to-Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL-2) consortium. Among other initiatives, A2ALL-2 examined the nature of these outcomes following donation. Using validated measures, donors were prospectively surveyed before donation and at 3, 6, 12, and 24 mo after donation. Repeated-measures regression models were used to examine social relationship and financial outcomes over time and to identify relevant predictors. Of 297 eligible donors, 271 (91%) consented and were interviewed at least once. Relationship changes were positive overall across postdonation time points, with nearly one-third reporting improved donor family and spousal or partner relationships and >50% reporting improved recipient relationships. The majority of donors, however, reported cumulative out-of-pocket medical and nonmedical expenses, which were judged burdensome by 44% of donors. Lower income predicted burdensome donation costs. Those who anticipated financial concerns and who held nonprofessional positions before donation were more likely to experience adverse financial outcomes. These data support the need for initiatives to reduce financial burden.

Discriminant analysis for anaesthetic decision-making: an intelligent recognition system for epidural needle insertion.

BACKGROUND: Incorrect placement of epidural catheters causes medical complications. We used linear discriminant analysis (LDA) to develop an intelligent recognition system (i-RS) in order to guide epidural placement and reduce physician error. METHODS: We analysed real-time dual-wavelength fibreoptic data recorded from the end of an epidural needle in a live porcine model. Two categories of tissue layers were necessary for correct placement of catheter: epidural space and ligamentum flavum. The data were tested using linear, quadratic and logistic parametric analysis to identify which method could distinguish the two anatomical structures. RESULTS: LDA was the best fit for our model. There was ∼80% sensitivity and specificity for correct anatomical identification. Error rates based on cross-validation were 17.0% for the epidural space and 18.6% for ligamentum flavum. Error rates were greater with the 532 nm compared with 650 nm wavelength. CONCLUSIONS: The sensitivity and specificity of LDA for identifying the correct anatomical structure was similar to a physician who is an expert in epidural placement. Overall performance of an i-RS could be improved by expanding the database for decision-making and adding a category of uncertainty. This would reduce complications caused by incorrect epidural placement.

Clinical controversies surrounding the diagnosis and treatment of hepatopulmonary syndrome.

Hepatopulmonary syndrome (HPS) is a clinical syndrome which complicates liver disease but remains poorly defined. To date there is no consensus on the definition of hypoxemia or the best diagnostic test that provides evidence of intrapulmonary shunting. Furthermore, it is reasonable to question whether the role of intrapulmonary shunting has been overplayed in the etiology of HPS and if echocardiographic intrapulmonary shunts could simply be nonspecific markers of the hyperdynamic circulation of liver disease. These inquiries lend support to theories that HPS is primarily a manifestation of profound pulmonary vascular autoregulatory failure that occurs in predisposed patients. Because there is little experience with clinical interventions for HPS other than liver transplantation, there are few accepted, efficacious therapeutic options for these patients. Because liver transplantation remains the only treatment known to effectively ''treat'' HPS, many medical communities have increased the priority of HPS patients over others who are waiting for life saving organs. Until there is further evidence that effectively identifies patients with HPS and that predicts outcomes, the preferential allocation of organs to patients with suspected HPS may unjustly cause the death of others waiting for transplantation.

Adult living donor liver transplantation using a right hepatic lobe.

BACKGROUND: Living donor liver transplantation has gained wide acceptance as an alternative for children with end-stage liver disease. The standard left lateral segment used in this operation does not provide adequate parenchymal mass to broaden its application to larger children or adults. METHODS: We report two cases of adult to adult living donor liver transplantation using a right hepatic lobe in patients with chronic liver disease. RESULTS: Both recipients experienced excellent initial graft function and have normal liver function 4 and 9 months postoperatively. Both donors are alive and well and returned to normal life 4 weeks postoperatively. CONCLUSIONS: Our initial experience suggests that this technique is a safe and reliable option for adults with chronic end-stage liver disease. A conservative application of this procedure in the adult population could significantly reduce the mortality on the adult waiting list.

Cerebral blood flow velocity in patients with subclinical portal-systemic encephalopathy.

UNLABELLED: Alterations in cerebral blood flow (CBF) are implicated in the etiology of portal-systemic encephalopathy. We hypothesized that CO2 reactivity of the cerebral circulation may be impaired in subjects with chronic liver disease (CLD) who also had subclinical portal-systemic encephalopathy (SPSE). We compared the relationship between PETCO2 and cerebral blood flow velocity in 10 patients with CLD with those of 10 healthy control subjects. Middle cerebral artery mean blood flow velocity (MCAMFV) was measured using transcranial Doppler during rest, hyperventilation, and hypoventilation. The degree of SPSE was quantified by using psychometric testing. Patients with CLD had poorer psychometric test scores compared with control subjects. Patients with CLD had lower PETCO2, MCAMFV, and blood pressure values and higher heart rates, differing from control subjects in all ventilation states. However, CO2 reactivity, the rate of change in MCAMFV to changes in ventilation (expressed as percent change in CBF velocity per mm Hg change in PETCO2) was similar for both groups (4.6% +/- 0.6% vs 4.2% +/- 0.5% for patients with CLD versus control subjects, P = 0.15). IMPLICATIONS: Psychometric test scores in patients with chronic liver disease revealed subclinical impairment compared with control subjects. Transcranial Doppler measurements of middle cerebral artery blood flow with varying PETCO2 were conducted, but the CO2 response of patients with liver disease was within the range of control subjects.

Immediate tracheal extubation after liver transplantation: experience of two transplant centers.

Early tracheal extubation has been safely performed after large operative procedures, questioning the need for routine postoperative ventilation. Because immediate postoperative tracheal extubation of liver transplantation patients has not been previously reported, we performed preliminary studies at two institutions to evaluate potential risk and cost benefit. At the University of Colorado (UC), extubation criteria were derived from the retrospective analysis of patients who were ventilated less than 8 h and experienced an intensive care unit stay less than 48 h in 1994. Preoperative criteria for age, severity of illness, and absence of encephalopathy and coexistent disease were used in a subsequent prospective study in 1995. Donor graft function, blood use, hemodynamic stability, and alveolar-arterial oxygen gradient served as intraoperative criteria. Cost of intensive care services was compared for the 1994 ventilated patients and the 1995 patients whose tracheas were extubated immediately postoperatively. At the second institution, University of California at San Francisco (UCSF), patients were tracheally extubated immediately postoperatively, based on clinical judgment by the anesthesiologist. A retrospective analysis was then completed. Sixteen of 67 patients at UC and 25 of 106 patients at UCSF were tracheally extubated. There were no reintubations at UC, while 2 of 25 patients at UCSF required reintubation. Prior encephalopathy, poor donor liver function, and an increased alveolar-arterial oxygen gradient were present in the patients who suffered perioperative respiratory failure. Seventeen of 25 patients at UCSF did not have all criteria used at UC but did not require reintubation. Wider limits on age and severity of illness did not preclude successful extubation. Cost analysis at UC showed a significant reduction in intensive care unit services and associated cost for extubated patients. We conclude that immediate postoperative tracheal extubation of selected liver transplantation patients is safe and cost effective.

Pulmonary hypertension in chronic liver disease.

Pulmonary hypertension develops in approximately 2% of patients with portal hypertension. Diagnosis is often difficult and requires a high degree of clinical suspicion. Treatment of patients with portal and pulmonary hypertension is limited, and mean survival following diagnosis is approximately 15 months. The effect of liver transplantation on the natural history of disease is discussed.