Surgery (Austin & Northern Health) - Research Publications

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    Modern Cardiac Surgical Outcomes in Nonagenarians: A Multicentre Retrospective Observational Study.
    Weinberg, L ; Walpole, D ; Lee, DK ; D'Silva, M ; Chan, JW ; Miles, LF ; Carp, B ; Wells, A ; Ngun, TS ; Seevanayagam, S ; Matalanis, G ; Ansari, Z ; Bellomo, R ; Yii, M (Frontiers Media SA, 2022)
    BACKGROUND: There have been multiple recent advancements in the selection, optimisation and management of patients undergoing cardiac surgery. However, there is limited data regarding the outcomes in nonagenarians, despite this cohort being increasingly referred for these interventions. The objective of this study was to describe the patient characteristics, management and outcomes of a cohort of nonagenarians undergoing cardiac surgery receiving contemporary peri-operative care. METHODS: After receiving ethics approval, we conducted a retrospective observational study of nonagenarians who had undergone cardiac surgery requiring a classic median sternotomy. All operative indications were included. We excluded patients who underwent transcatheter aortic valve implantation (TAVI), and surgery on the thoracic aorta via an endovascular approach (TEVAR). Patients undergoing TEVAR often have the procedure done under sedation and regional blocks with local anesthetic solution. There is no open incision and these patients do not require cardiopulmonary bypass. We also excluded patients undergoing minimally invasive mitral valve surgery via a videoscope assisted approach. These patients do not have a median sternotomy, have the procedure done via erector spinae block, and often are extubated on table. Data were collected from four hospitals in Victoria, Australia, over an 8-year period (January 2012-December 2019). The primary objective was to assess 6-month mortality in nonagenarian patients undergoing cardiac surgery and to provide a detailed overview of postoperative complications. We hypothesized that cardiac surgery in nonagenarian patients would be associated with a 6-month postoperative mortality <10%. As a secondary outcome, we hypothesized that significant postoperative complications (i.e., Clavien Dindo Grade IIIb or greater) would occur in > 30% of patients. RESULTS: A total of 12,358 adult cardiac surgery patients underwent surgery during the study period, of whom 18 nonagenarians (0.15%) fulfilled inclusion criteria. The median (IQR) [min-max] age was 91.0 years (90.0:91.8) [90-94] and the median body mass index was 25.0 (kg/m2) (22.3:27.0). Comorbidities, polypharmacy, and frailty were common. The median predicted mortality as per EuroSCORE-II was 6.1% (4.1:14.5). There were no cases of intra-operative, in-hospital, or 6-month mortality. One (5.6%) patient experienced two Grade IIIa complications. Three (16.7%) patients experienced Grade IIIb complications. Three (16.7%) patients had an unplanned hospital readmission within 30 days of discharge. The median value for postoperative length of stay was 11.6 days (9.8:17.6). One patient was discharged home and all others were discharged to an inpatient rehabilitation facility. CONCLUSION: In this selected, contemporary cohort of nonagenarian patients undergoing cardiac surgery, postoperative 6-month mortality was zero. These findings support carefully selected nonagenarian patients being offered cardiac surgery (Trials Registry: https://www.anzctr.org.au/ACTRN12622000058774.aspx).
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    Intraoperative low tidal volume ventilation and the risk of ICD-10 coded delirium and the use for antipsychotic medications
    Karalapillai, D ; Weinberg, L ; Serpa Neto, A ; Peyton, PJ ; Ellard, L ; Hu, R ; Pearce, B ; Tan, C ; Story, D ; O'Donnell, M ; Hamilton, P ; Oughton, C ; Galtieri, J ; Appu, S ; Wilson, A ; Eastwood, G ; Bellomo, R ; Jones, DA (BMC, 2022-05-16)
    BACKGROUND: Low tidal volume (VT) ventilation and its associated increase in arterial carbon dioxide (PaCO2) may affect postoperative neurologic function. We aimed to test the hypothesis that intraoperative low VT ventilation affect the incidence of postoperative ICD-10 coded delirium and/or the need for antipsychotic medications. METHODS: This is a post-hoc analysis of a large randomized controlled trial evaluating low vs. conventional VT ventilation during major non-cardiothoracic, non-intracranial surgery. The primary outcome was the incidence of ICD-10 delirium and/or the use of antipsychotic medications during hospital stay, and the absolute difference with its 95% confidence interval (CI) was calculated. RESULTS: We studied 1206 patients (median age of 64 [55-72] years, 59.0% males, median ARISCAT of 26 [19-37], and 47.6% of ASA 3). ICD-10 coded delirium and /or antipsychotic medication use was diagnosed in 11.2% with similar incidence between low and conventional VT ventilation (11.1% vs. 11.3%; absolute difference, -0.24 [95%CI, -3.82 to 3.32]; p = 0.894). There was no interaction between allocation group and type of surgery. CONCLUSION: In adult patients undergoing major surgery, low VT ventilation was not associated with increased risk of ICD-10 delirium and/or the use of antipsychotic medications during hospital stay. TRIAL REGISTRATION: ANZCTR Identifier: ACTRN12614000790640 .
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    Serum Creatinine Levels and Nephrocheck® Values With and Without Correction for Urine Dilution-A Multicenter Observational Study
    Hahn, RG ; Yanase, F ; Zdolsek, JH ; Tosif, SH ; Bellomo, R ; Weinberg, L (FRONTIERS MEDIA SA, 2022-02-18)
    BACKGROUND: The Nephrocheck® test is a single-use cartridge designed to measure the concentrations of two novel cell-cycle arrest biomarkers of acute kidney injury, namely tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7). Correlations of serum creatine values and TIMP-2 and IGFBP7 with and without correction for urine dilution have not been previously undertaken in patients undergoing major abdominal surgery. We hypothesized that the Nephrocheck® values would be significantly different with and without correction for urine dilution in patients with elevated creatinine values post major abdominal surgery. METHODS: We performed a post hoc analysis of serum and urine specimens sampled preoperatively and postoperatively in 72 patients undergoing major abdominal surgery. Thirty samples were measured from patients with the greatest decrease and the greatest increase in postoperative serum creatinine values. Urine was analyzed with the Nephrocheck to predict the risk of acute kidney injury (AKIRisk™). We then examined the relationship between serum creatinine and the urinary excretion of TIMP-2 and IGFBP7 as measured by the Nephrocheck test. The AKIRisk between the groups with and without correction for urine dilution was assessed. RESULTS: The median perioperative change in serum creatinine in the two groups was -19% and +57%, respectively. The uncorrected median baseline AKIRisk decreased from 0.70 (25th-75th percentiles, 0.09-1.98) to 0.35 (0.19-0.57) (mg/L)2 in the first group and rose from 0.57 (0.22-1.53) to 0.85 (0.67-2.20) (mg/L)2 in the second group. However, when corrected for the squared urine dilution, the AKIRisk™ in patients with postoperative increases in serum creatinine was not indicative of kidney injury; the corrected AKIRisk was 8.0 (3.2-11.7) μg2/mmol2 before surgery vs.6.9 (5.3-11.0) μg2/mmol2 after the surgery (P = 0.69). CONCLUSION: In the setting of major abdominal surgery, after correction of TIMP-2 and IGFBP7 for urine dilution, the Nephrocheck AKIRisk scores were significantly different from the uncorrected values. These finding imply that the AKIRisk index is a function of urine flow in addition to an increased release of the biomarkers.
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    Intra-operative ventilator mechanical power as a predictor of postoperative pulmonary complications in surgical patients A secondary analysis of a randomised clinical trial
    Karalapillai, D ; Weinberg, L ; Neto A, S ; Peyton, P ; Ellard, L ; Hu, R ; Pearce, B ; Tan, CO ; Story, D ; O'Donnell, M ; Hamilton, P ; Oughton, C ; Galtieri, J ; Wilson, A ; Eastwood, G ; Bellomo, R ; Jones, DA (LIPPINCOTT WILLIAMS & WILKINS, 2022-01)
    BACKGROUND: Studies in critically ill patients suggest a relationship between mechanical power (an index of the energy delivered by the ventilator, which includes driving pressure, respiratory rate, tidal volume and inspiratory pressure) and complications. OBJECTIVE: We aimed to assess the association between intra-operative mechanical power and postoperative pulmonary complications (PPCs). DESIGN: Post hoc analysis of a large randomised clinical trial. SETTING: University-affiliated academic tertiary hospital in Melbourne, Australia, from February 2015 to February 2019. PATIENTS: Adult patients undergoing major noncardiothoracic, nonintracranial surgery. INTERVENTION: Dynamic mechanical power was calculated using the power equation adjusted by the respiratory system compliance (CRS). Multivariable models were used to assess the independent association between mechanical power and outcomes. MAIN OUTCOME MEASURES: The primary outcome was the incidence of PPCs within the first seven postoperative days. The secondary outcome was the incidence of acute respiratory failure. RESULTS: We studied 1156 patients (median age [IQR]: 64 [55 to 72] years, 59.5% men). Median mechanical power adjusted by CRS was 0.32 [0.22 to 0.51] (J min-1)/(ml cmH2O-1). A higher mechanical power was also independently associated with increased risk of PPCs [odds ratio (OR 1.34, 95% CI, 1.17 to 1.52); P < 0.001) and acute respiratory failure (OR 1.40, 95% CI, 1.21 to 1.61; P < 0.001). CONCLUSION: In patients receiving ventilation during major noncardiothoracic, nonintracranial surgery, exposure to a higher mechanical power was independently associated with an increased risk of PPCs and acute respiratory failure. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry no: 12614000790640.
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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)
    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 haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial
    Chiam, E ; Weinberg, L ; Bailey, M ; McNicol, L ; Bellomo, R (WILEY, 2016-04)
    AIM: The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. METHODS: We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. RESULTS: Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP -0.15 mmHg, SBP +1.44 mmHg, DBP --0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). CONCLUSIONS: I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting.
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    A randomized, controlled pilot clinical trial of cryopreserved platelets for perioperative surgical bleeding: the CLIP-I trial
    Reade, MC ; Marks, DC ; Bellomo, R ; Deans, R ; Faulke, DJ ; Fraser, JF ; Gattas, DJ ; Holley, AD ; Irving, DO ; Johnson, L ; Pearse, BL ; Royse, AG ; Wong, J ; Weinberg, L ; Eastwood, G ; Peck, L ; Young, H ; Sidiropoulos, S ; Baulch, S ; Dalyell, A ; Kolar, D ; Martinelli, T ; Reidy, Y ; Caldwell, N ; Royse, A ; Tivendale, L ; Bisignano, M ; Hausler, M ; Williams, Z ; Dong, N ; Buhr, H ; Bannon, P ; Cartwright, B ; Turner, L ; Gibson, J ; Blayney, B ; Beattie, L ; Hutch, D ; Coles, JWJ ; Pearse, B ; Faulke, D ; Zeigenfuss, M ; Tesar, P ; Fraser, J ; Perel, J ; Kahn, C ; Vincent, B ; O'Brien, D ; Holley, A ; Irving, D (WILEY, 2019-09)
    BACKGROUND: Cryopreservation extends platelet (PLT) shelf life from 5 to 7 days to 2 to 4 years. However, only 73 patients have been transfused cryopreserved PLTs in published randomized controlled trials (RCTs), making safety data insufficient for regulatory approval. STUDY DESIGN AND METHODS: The Cryopreserved vs. Liquid Platelet (CLIP) study was a double-blind, pilot, multicenter RCT involving high-risk cardiothoracic surgical patients in four Australian hospitals. The objective was to test, as the primary outcome, the feasibility and safety of the protocol. Patients were allocated to study group by permuted block randomization, with patients and clinicians blinded by use of an opaque shroud placed over each study PLT unit. Up to 3 units of cryopreserved or liquid-stored PLTs were administered per patient. No other aspect of patient care was affected. Adverse events were actively sought. RESULTS: A total of 121 patients were randomized, of whom 23 received cryopreserved PLTs and 18 received liquid-stored PLTs. There were no differences in blood loss (median, 715 mL vs. 805 mL at 24 hr; difference between groups 90 mL [95% CI, -343.8 to 163.8 mL], p = 0.41), but the Bleeding Academic Research Consortium criterion for significant postoperative hemorrhage in cardiac surgery composite bleeding endpoint occurred in nearly twice as many patients in the liquid-stored group (55.6% vs. 30.4%, p = 0.10). Red blood cell transfusion requirements were a median of 3 units in the cryopreserved group versus 4 units with liquid-stored PLTs (difference between groups, 1 unit [95% CI, -3.1 to 1.1 units]; p = 0.23). Patients in the cryopreserved group were more likely to be transfused fresh-frozen plasma (78.3% vs. 27.8%, p = 0.002) and received more study PLT units (median, 2 units vs. 1 unit; difference between groups, 1 unit [95% CI, -0.03 to 2.0 units]; p = 0.012). There were no between-group differences in potential harms including deep venous thrombosis, myocardial infarction, respiratory function, infection, and renal function. No patient had died at 28 days, and postoperative length of stay was similar in each group. CONCLUSION: In this pilot RCT, compared to liquid-stored PLTs, cryopreserved PLTs were associated with no evidence of harm. A definitive study testing safety and hemostatic effectiveness is warranted.
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    Characteristics and outcomes of rapid response team activations for hypotension in orthopaedic patients
    Ramos, JGR ; Zhang, R ; Maher, B ; Hardidge, A ; Weinberg, L ; Robbins, R ; Peyton, PJ ; Bellomo, R ; Jones, D (WILEY, 2020-01)
    BACKGROUND: Hypotension following orthopaedic surgery has been associated with increased morbidity and mortality. Rapid response teams (RRT) review patients on hospital wards with hypotension. AIM: To evaluate the epidemiology of hypotensive RRT activations in adult orthopaedic patients to identify contributing factors and areas for future quality improvement. METHODS: Timing of RRT activations, presumed causes of hypotension and associated treatments were assessed. RESULTS: Among 963 RRT activations in 605 patients over 3 years, the first calls of 226 of 605 patients were due to hypotension, and 213 (94.2%) of 226 had sufficient data for analysis. The median age was 79 (interquartile range 66-87) years; 58 (27.2%) were male, and comorbidities were common. Most (68%) surgery was emergent, and 75.1% received intraoperative vasopressors for hypotension. Most activations occurred within 24 h of surgery, and hypovolaemia, infection and arrhythmias were common presumed causes. Fluid boluses occurred in 173 (81.2%), and the time between surgery and RRT activation was 10 (4.0-26.5) h. in cases where fluid boluses were given, compared with 33 (15.5-61.5) h. where they were not (P < 0.001). Blood transfusion (30, 14.1%) and withholding of medications were also common. Hospital mortality was 8.5% (18), and 13.6% (29) were admitted to critical care at some stage. In-hospital death was associated with older age, functional dependence, arrhythmia and presumed infection. CONCLUSIONS: Hypotension-related RRT calls in orthopaedic patients are common. Future interventional studies might focus on perioperative fluid therapy and vaso-active medications, as well as withholding of anti-hypertensive medications preoperatively.
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    Plasma-Lyte 148: A clinical review.
    Weinberg, L ; Collins, N ; Van Mourik, K ; Tan, C ; Bellomo, R (Baishideng Publishing Group Inc., 2016-11-04)
    AIM: To outline the physiochemical properties and specific clinical uses of Plasma-Lyte 148 as choice of solution for fluid intervention in critical illness, surgery and perioperative medicine. METHODS: We performed an electronic literature search from Medline and PubMed (via Ovid), anesthesia and pharmacology textbooks, and online sources including studies that compared Plasma-Lyte 148 to other crystalloid solutions. The following keywords were used: "surgery", "anaesthesia", "anesthesia", "anesthesiology", "anaesthesiology", "fluids", "fluid therapy", "crystalloid", "saline", "plasma-Lyte", "plasmalyte", "hartmann's", "ringers" "acetate", "gluconate", "malate", "lactate". All relevant articles were accessed in full. We summarized the data and reported the data in tables and text. RESULTS: We retrieved 104 articles relevant to the choice of Plasma-Lyte 148 for fluid intervention in critical illness, surgery and perioperative medicine. We analyzed the data and reported the results in tables and text. CONCLUSION: Plasma-Lyte 148 is an isotonic, buffered intravenous crystalloid solution with a physiochemical composition that closely reflects human plasma. Emerging data supports the use of buffered crystalloid solutions in preference to saline in improving physicochemical outcomes. Further large randomized controlled trials assessing the comparative effectiveness of Plasma-Lyte 148 and other crystalloid solutions in measuring clinically important outcomes such as morbidity and mortality are needed.
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    The hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study
    Chiam, E ; Bellomo, R ; Churilov, L ; Weinberg, L ; Nanayakkara, PWB (PUBLIC LIBRARY SCIENCE, 2018-04-16)
    The hemodynamic effects of intravenous (IV) paracetamol in patients undergoing cardiac surgery are unknown. We performed a prospective single center placebo controlled randomized study with parallel group design in adult patients undergoing elective cardiac surgery. Participants received paracetamol (1 gram) IV or placebo (an equal volume of 0.9% saline) preoperatively followed by two postoperative doses 6 hours apart. The primary endpoint was the absolute change in systolic (SBP) 30 minutes after the preoperative infusion, analysed using an ANCOVA model. Secondary endpoints included absolute changes in mean arterial pressure (MAP) and diastolic blood pressure (DPB), and other key hemodynamic variables after each infusion. All other endpoints were analysed using random-effect generalized least squares regression modelling with individual patients treated as random effects. Fifty participants were randomly assigned to receive paracetamol (n = 25) or placebo (n = 25). Post preoperative infusion, paracetamol decreased SBP by a mean (SD) of 13 (18) mmHg, p = 0.02, compared to a mean (SD) of 1 (11) mmHg with saline. Paracetamol decreased MAP and DBP by a mean (SD) of 9 (12) mmHg and 8 (9) mmHg (p = 0.01 and 0.02), respectively, compared to a mean (SD) of 1 (8) mmHg and 0 (6) mmHg with placebo. Postoperatively, there were no significant differences in pressure or flow based hemodynamic parameters in both groups. This study provides high quality evidence that the administration of IV paracetamol in patients undergoing cardiac surgery causes a transient decrease in preoperative blood pressure when administered before surgery but no adverse hemodynamic effects when administered in the postoperative setting.