A Randomized, Multicenter, Open-Label, Blinded End Point, Phase 2, Feasibility, Efficacy, and Safety Trial of Preoperative Microvascular Protection in Patients Undergoing Major Abdominal Surgery.

BACKGROUND: The endothelial glycocalyx, a carbohydrate-rich layer coating all endothelial surfaces, plays a fundamental role in the function of microcirculation. The primary aim of this study was to evaluate the feasibility of using dexamethasone and albumin to protect the endothelial glycocalyx in patients undergoing abdominal surgery. Secondary and exploratory outcomes included efficacy and safety. METHODS: We conducted a multicenter, open-label, blinded end point, phase 2, randomized trial. Patients undergoing colorectal, pancreas, or liver surgery were recruited and randomized to receive either intravenous dexamethasone (16 mg) and 20% albumin (100 mL) at induction of anesthesia, then 200 mL of 20% albumin with each subsequent 1000 mL of crystalloid administered (dexamethasone and albumin [Dex-Alb] group), or crystalloid fluid only with no dexamethasone (control group). Feasibility end points included patient recruitment and retention, consent rate, and successful study drug administration. The primary efficacy end point was the measurement of plasma syndecan-1 level on postoperative day (POD) 1, and secondary end points were heparan sulfate levels and inflammatory markers measured at 4 perioperative timepoints. Safety end points included errors in administration of the intervention, hyperglycemia, occurrence of postoperative complications, and patient retention. RESULTS: Seventy-two patients were randomized. All feasibility end points were achievable. There were no statistically significant differences observed in median (interquartile range) syndecan-1 levels on POD 1 (39 ng·mL-1 [20-97] in the Dex-Alb group versus 41 ng·mL-1 [19-84] in the control group; difference in medians -2.1, 95% confidence interval [CI], -13 to 8.6; P = .69). The Dex-Alb group had lower POD 1 heparan sulfate levels (319 ng·mL-1 [161-717] in the Dex-Alb group versus 1422 [670-2430] ng·mL-1 in the control group; difference in medians -1085, 95% CI, -1779 to -391) and C-reactive protein (CRP) levels on POD 1 (48 [29-77] mg·L-1 in the Dex-Alb group versus 85 mg·L-1 [49-133] in the control group; difference in medians -48, 95% CI, -75 to -21). Fewer patients had one or more postoperative complication in the Dex-Alb group than in the control group (6 [17%] vs 18 patients [50%]; odds ratio = 0.2, 95% CI, 0.06-0.6). CONCLUSIONS: Intravenous dexamethasone and albumin administration was feasible but did not reduce syndecan-1 on POD 1 in patients undergoing abdominal surgery. Given the clinically important CIs observed between the groups for heparan sulfate, CRP, and postoperative complications, a larger trial assessing the associations between dexamethasone and albumin administration and these outcomes is warranted.

Optimizing patient expectations to improve therapeutic response to medical treatment: A randomized controlled trial of iron infusion therapy.

OBJECTIVES: Patient expectations have the ability to influence health outcomes and have been shown to play an important role as part of the placebo effect to influence the response to medical treatments. Increasing positive expectations have been proposed as an intervention to improve treatment response, although evidence for this to date is limited. We investigated whether a brief 10-min intervention directly targeting patient expectations prior to an iron infusion could enhance expectations and improve treatment response, in terms of patients' reported fatigue. DESIGN: Randomized controlled trial. METHODS: Forty-three patients diagnosed with iron deficiency anaemia were randomized to a brief expectation intervention or active control group prior to an intravenous iron infusion. Chalder Fatigue Scale scores were assessed prior to randomization and at one and four weeks. RESULTS: The expectation intervention significantly improved patients' expectations about the effectiveness of the intravenous iron infusion, t(21) = -3.95, p = .001. While there were no significant differences between groups in fatigue at the one-week follow-up, fatigue was significantly lower in the intervention group at the four-week follow-up compared to the control group, F(1, 25) = 6.25, p = .019. This was largely influenced by a significant reduction in physical, as opposed to mental fatigue scores. CONCLUSIONS: Boosting patients' positive expectations may be an effective way of enhancing patient response to treatment. In particular, targeting patient expectations with a brief intervention prior to medical treatments may result in a greater and longer therapeutic effect.

Recombinant activated factor VII in liver patients: a retrospective cohort study from Australia and New Zealand.

Recombinant factor VIIa (rFVIIa) is used in the treatment of life-threatening haemorrhage that is refractory to conventional treatment. The evidence supporting this practice in patients with liver disease is very limited. It has been used as a salvage therapy in end-stage liver disease (ESLD), in orthotopic liver transplant (OLT), other surgery, and upper gastrointestinal bleeding (UGIB) subpopulations. It has also been used prior to procedures in patients with ESLD. Data were collected by the Australia and New Zealand Haemostasis Registry (ANZHR) to perform a retrospective cohort study on the different subgroups of liver patients. This included 115 cases of use of rFVIIa in liver patients from 20 hospitals. A retrospective cohort study on the different subgroups of liver patients was performed. Main outcome measures were reduction or cessation of bleeding and 28-day mortality. Variables previously shown to predict response to bleeding after administration of rFVIIa were examined to determine whether correlations exist. Salvage therapy with rFVIIa was associated with reduction or cessation in bleeding in 24 of 36 OLT patients, 24 of 36 UGIB patients and 15 of 26 of other surgery patients. Clinical response to rFVIIa in OLT patients and other surgery patients was associated with a significantly lower mortality compared to nonresponders (P = 0.003 and 0.022, respectively). There was no relationship between mortality and bleeding response in patients with UGIB. Variables including acidosis, hypothermia, hypofibrinogenaemia, thrombocytopenia and Model of End-Stage Liver Disease (MELD) score were not associated with clinical response to rFVIIa. Five cases of use prior to procedures are described. Recombinant FVIIa is used as rescue therapy in surgical patients with ESLD and refractory haemorrhage in Australia and New Zealand. Traditional haemostasis variables were not associated with clinical response to rFVIIa in this cohort. Response to rFVIIa is associated with decreased mortality in ESLD patients undergoing OLT and other surgery, but not in UGIB.

Fast track liver resection: the effect of a comprehensive care package and analgesia with single dose intrathecal morphine with gabapentin or continuous epidural analgesia.

BACKGROUND: A comprehensive care package for patients undergoing hepatectomy was developed with the aim of minimal physiological disturbance in the peri-operative period. Peri-operative analgesia with few gastrointestinal effects and reduced requirement for intravenous (IV) fluid therapy was central to this plan. METHODS: Data on 100 consecutive patients managed with continuous epidural infusion (n = 50; bupivicaine 0.125% and fentanyl 2 microg/mL at 0.1 mL/kg/hr) or intrathecal morphine (n = 50; 300 microg in combination with oral gabapentin 1200 mg preoperatively and 400 mg bd postoperatively) was compared. RESULTS: The epidural and intrathecal morphine groups were equivalent in terms of patient demographics, procedures and complications. Patients receiving intrathecal morphine received less intra-operative IV fluids (median 1500 mL versus 2200 mL, P = .06), less postoperative IV fluids (median 1200 mL versus 4300 mL, P = .03) than patients receiving epidural infusion. Patients managed with intrathecal morphine established a normal dietary intake sooner (16 hours versus 20 hours, P = .05) and had shorter hospital stays than those managed with epidural infusions (4.7 +/- 0.9 days versus 6.8 +/- 1.2 days, P = .02). CONCLUSIONS: Single dose intrathecal morphine is a safe and effective means of providing peri-operative analgesia. Patients managed with intrathecal morphine have reduced peri-operative physiological disturbance and return home within a few days of hepatic resection.

Live donor liver transplantation in New Zealand: a report on the first 20 cases.

BACKGROUND: Liver transplantation (LT) is established treatment for adults and children with acute or chronic liver failure, however there are insufficient donor organs to meet demand and 14% of New Zealand patients have died waiting or were de-listed due to deterioration whilst on the waiting list. Live donor liver transplantation (LDLT) offers an alternative graft source that enables timely transplantation, but also carries the risk of morbidity and mortality for the donor. AIM: To report the initial experience with LDLT in New Zealand. METHODS: Review of donor and recipient outcomes for the first 20 cases. RESULTS: 129 potential live liver donors were assessed for 68 recipients. Donors were evaluated according to a multi-step protocol including independent donor advocacy. Twenty LDLT were performed on 7 adults and 13 paediatric recipients using 5 right lobe, 2 extended left lobe, 2 left lobe, and 11 left lateral section grafts. Five donors (25%) experienced postoperative complications, none of which were life-threatening. Four recipients had acute liver failure and 16 had chronic liver disease including one retransplant. There was a high rate of recipient biliary complications (40%) but graft and recipient survival is 100% to date. CONCLUSION: LDLT has been successfully introduced in New Zealand with good donor and recipient outcomes.

Liver transplantation in Jehovah's Witness patients in Australasia.

Until recently, liver transplantation was contraindicated in Jehovah's Witness patients because of recipient-imposed restrictions on use of blood products. However, recent improvements in surgical and anaesthetic techniques and new procoagulant agents challenge this practice. We describe two Jehovah's Witness patients who had successful liver transplantation without blood transfusion. To our knowledge, these are the first such cases in Australasia. The techniques used to minimise blood loss and transfusion requirements could potentially benefit all patients undergoing major surgery.

Liver transplantation in New Zealand: the first four years.

AIM: To summarise the transplant-related activity of the New Zealand Liver Transplant Unit over the first four years. METHODS: The records of all patients assessed for liver transplantation between 1 December 1997 and 30 December 2001 were examined. Listing criteria, demographics, waiting time, transplant-hospitalisation details and long-term outcome for those who underwent liver transplantation were recorded. RESULTS: One hundred and eighty six patients over 14 years of age (acute liver failure 28, chronic liver disease 158) were assessed and 150 were listed for liver transplantation. Fifteen died waiting, 13 were de-listed (6 for cancer progression) and 14 remain listed. One hundred and nine liver transplants (including 1 combined heart-liver, 1 sequential liver-bone marrow and 5 re-transplants) were performed on 104 patients (13 acute liver failure, 96 chronic liver failure or hepatocellular carcinoma). The median waiting time was 2 days (range 0 5) for acute liver failure and 62 days (range 0 320) for other patients. Median age at transplant was 50 years (range 14-70); 73 patients (66%) were male; 71 (65%) were European; 13 (12%) Maori; 12 (11%) Pacific Islander; and 8 (7%) Asian. Median duration of surgery was 480 minutes (range 300 720 minutes); red cell transfusion 5 units (0 32); intensive care and total hospital stays were 2 (range 1 17) and 11 days (range 6 91). One transplanted patient died in hospital, 1- and 3-year patient survival was 94% and 87% and corresponding graft survival was 91% and 83%. Ninety three transplanted patients (89%) are alive. Of the 92 patients at least three months post-transplant, 62 (67%) were employed. CONCLUSION: Liver transplantation is now established in New Zealand as treatment of choice for acute and chronic liver failure and small hepatocellular carcinoma. Excellent outcomes have been attained in those transplanted to date. Reduction in waiting list mortality will require identification of and investment in strategies that will expand the donor organ availability.