Clinical School (Austin Health) - Research Publications

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    Sodium bicarbonate infusion in patients undergoing orthotopic liver transplantation: a single center randomized controlled pilot trial
    Weinberg, L ; Broad, J ; Pillai, P ; Chen, G ; Nguyen, M ; Eastwood, GM ; Scurrah, N ; Nikfarjam, M ; Story, D ; McNicol, L ; Bellomo, R (WILEY-BLACKWELL, 2016-05-01)
    BACKGROUND: Liver transplantation-associated acute kidney injury (AKI) carries significant morbidity and mortality. We hypothesized that sodium bicarbonate would reduce the incidence and/or severity of liver transplantation-associated AKI. METHODS: In this double-blinded pilot RCT, adult patients undergoing orthotopic liver transplantation were randomized to an infusion of either 8.4% sodium bicarbonate (0.5 mEq/kg/h for the first hour; 0.15 mEq/kg/h until completion of surgery); (n = 30) or 0.9% sodium chloride (n = 30). PRIMARY OUTCOME: AKI within the first 48 h post-operatively. RESULTS: There were no significant differences between the two treatment groups with regard to baseline characteristics, model for end-stage liver disease and acute physiology and chronic health evaluation (APACHE) II scores, and pre-transplantation renal function. Intra-operative factors were similar for duration of surgery, blood product requirements, crystalloid and colloid volumes infused and requirements for vasoactive therapy. Eleven patients (37%) in the bicarbonate group and 10 patients (33%) in the sodium chloride group developed a post-operative AKI (p = 0.79). Bicarbonate infusion attenuated the degree of immediate post-operative metabolic acidosis; however, this effect dissipated by 48 h. There were no significant differences in ventilation hours, ICU or hospital length of stay, or mortality. CONCLUSIONS: The intra-operative infusion of sodium bicarbonate did not decrease the incidence of AKI in patients following orthotopic liver transplantation.
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    The impact of fluid intervention on complications and length of hospital stay after pancreaticoduodenectomy (Whipple's procedure)
    Weinberg, L ; Wong, D ; Karalapillai, D ; Pearce, B ; Tan, CO ; Tay, S ; Christophi, C ; McNicol, L ; Nikfarjam, M (BIOMED CENTRAL LTD, 2014-05-14)
    BACKGROUND: There is limited information on the impact on perioperative fluid intervention on complications and length of hospital stay following pancreaticoduodenectomy. Therefore, we conducted a detailed analysis of fluid intervention in patients undergoing pancreaticoduodenectomy at a university teaching hospital to test the hypothesis that a restrictive intravenous fluid regime and/or a neutral or negative cumulative fluid balance, would impact on perioperative complications and length of hospital stay. METHODS: We retrospectively obtained demographic, operative details, detailed fluid prescription, complications and outcomes data for 150 consecutive patients undergoing pancreaticoduodenectomy in a university teaching hospital. Prognostic predictors for length of hospital stay and complications were determined. RESULTS: One hundred and fifty consecutive patients undergoing pancreaticoduodenectomy were evaluated between 2006 and 2012. The majority of patients were, middle-aged, overweight and ASA class III. Postoperative complications were frequent and occurred in 86 patients (57%). The majority of complications were graded as Clavien-Dindo Class 2 and 3. Postoperative pancreatic fistula occurred in 13 patients (9%), and delayed gastric emptying occurred in 25 patients (17%). Other postoperative surgical complications included sepsis (22%), bile leak (4%), and postoperative bleeding (2%). Serious medical complications included pulmonary edema (6%), myocardial infarction (8%), cardiac arrhythmias (13%), respiratory failure (8%), and renal failure (7%). Patients with complications received a higher median volume of intravenous therapy and had higher cumulative positive fluid balances. Postoperative length of stay was significantly longer in patients with complications (median 25 days vs. 10 days; p < 0.001). After adjustment for covariates, a fluid balance of less than 1 litre on postoperative day 1 and surgeon caseloads were associated with the development of complications. CONCLUSIONS: In the context of pancreaticoduodenectomy, restrictive perioperative fluid intervention and negative cumulative fluid balance were associated with fewer complications and shorter length of hospital stay. These findings provide good opportunities to evaluate strategies aimed at improving perioperative care.
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    Assessment of Liver Remnant Using ICG Clearance Intraoperatively during Vascular Exclusion: Early Experience with the ALIIVE Technique.
    Lau, L ; Christophi, C ; Nikfarjam, M ; Starkey, G ; Goodwin, M ; Weinberg, L ; Ho, L ; Muralidharan, V (Hindawi Limited, 2015)
    Background. The most significant risk following major hepatectomy is postoperative liver insufficiency. Current preoperative assessment of the future liver remnant relies upon assumptions which may not be valid in the setting of advanced resection strategies. This paper reports the feasibility of the ALIIVE technique which assesses the liver remnant with ICG clearance intraoperatively during vascular exclusion. Methods. 10 patients undergoing planned major liver resection (hemihepatectomy or greater) were recruited. Routine preoperative assessment included CT and standardized volumetry. ICG clearance was measured noninvasively using a finger spectrophotometer at various time points including following parenchymal transection during inflow and outflow occlusion before vascular division, the ALIIVE step. Results. There were one case of mortality and three cases of posthepatectomy liver failure. The patient who died had the lowest ALIIVE ICG clearance (7.1%/min versus 14.4 ± 4.9). Routine preoperative CT and standardized volumetry did not predict outcome. Discussion/Conclusion. The novel ALIIVE technique is feasible and assesses actual future liver remnant function before the point of no return during major hepatectomy. This technique may be useful as a check step to offer a margin of safety to prevent posthepatectomy liver failure and death. Further confirmatory studies are required to determine a safety cutoff level.
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    Glucagon-like peptide 1 and peptide YY are in separate storage organelles in enteroendocrine cells
    Cho, H-J ; Robinson, ES ; Rivera, LR ; McMillan, PJ ; Testro, A ; Nikfarjam, M ; Bravo, DM ; Furness, JB (SPRINGER, 2014-07-01)
    A sub-group of enteroendocrine cells (L cells) release gastrointestinal hormones, GLP-1 and PYY, which have different but overlapping physiological effects, in response to intraluminal nutrients. Whilst their release profiles are not identical, how the plasma levels of these two hormones are differentially regulated is not well understood. We investigate the possibility that GLP-1 and PYY are in separate storage vesicles. In this study, the subcellular location of GLP-1 and PYY storage organelles is investigated using double-labelling immunohistochemistry, super resolution microscopy and high-resolution confocal microscopy. In all species tested, human, pig, rat and mouse, most cytoplasmic stores that exhibited GLP-1 or PYY immunofluorescence were distinct from each other. The volume occupancy, determined by 3D analysis, overlapped by only about 10∼20 %. At the lower resolution achieved by conventional confocal microscopy, there was also evidence of GLP-1 and PYY being in separate storage compartments but, in subcellular regions where there were many storage vesicles, separate storage could not be resolved. The results indicate that different storage vesicles in L cells contain predominantly GLP-1 or predominantly PYY. Whether GLP-1 and PYY storage vesicles are selectively mobilised and their products are selectively released needs to be determined.