Medicine (Austin & Northern Health) - Research Publications

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    Peri-OPerative Pain Management, Education & De-escalation (POPPMED), a novel anaesthesiologist-led program, significantly reduces acute and long-term postoperative opioid requirements: a retrospective cohort study.
    Heldreich, C ; Meyer, I ; Dube, E ; Hu, R ; Howard, W ; Holmes, N ; Maroon, N ; Weinberg, L ; Tan, CO (Ovid Technologies (Wolters Kluwer Health), 2022-09)
    Introduction: The opioid tolerant patient requiring surgery is highly likely to be discharged on high Oral Morphine Equivalent Daily Dosages (OMEDDs), with concomitant risk of increased morbidity and mortality. Objectives: We proposed that a single anaesthesiologist-led POPPMED (Peri-Operative Pain Management, Education & De-escalation) service could reduce both short and long-term postoperative patient OMEDDs. Methods: From April 2017, our anaesthesiologist-led POPPMED service, engaged 102 perioperative patients treated with >50mg preoperative OMEDDs. We utilized behavioural interventions; acute opioid reduction and/ or rotation; and regional, multimodal and ketamine analgesia to achieve lowest possible hospital discharge and long term OMEDDs. Results: Patients' preoperative OMEDDs were [median (IQR): 115mg (114mg)], and were representative of an older [age 62 (15) years], high-risk [89% ASA status 3 or 4] patient population. 46% of patients received an acute opioid rotation; 70% received ketamine infusions; and 44% regional analgesia. OMEDDs on discharge [-25mg (82mg), p=0.003] and at 6-12 months [-55mg (105mg ), p<0.0001] were significantly reduced; 84% and 87% of patients achieved OMEDD reduction on discharge and at 6-12 months. Patients with >90mg preoperative OMEDDs achieved greater reductions [discharge: 71% of patients, -52 mg (118 mg) p<0.0001; 6-12 months: 90% of patients, -90mg (115mg), p<0.0001]. On comparison with a pre-POPPMED surgical cohort, Postoperative Day 1-3 11-point Numerical Rating Scale (NRS-11) area under the curve (AUC) measurements at rest and on movement were not significantly different (largest NRS-11:hours AUC difference [median(IQR)] 22 [13], p= 0.24). Hospital length of stay was variably increased. Conclusions: POPPMED achieved sustained OMEDD reductions safely in an older, high-risk opioid tolerant population, with analgesia comparable to a non-POPPMED cohort, and surgery specific effects on length of stay.
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    A spontaneous retroperitoneal haemorrhage resulting in abdominal compartment syndrome requiring laparotomy: A case report and proposed management algorithm
    Tully, P ; Moshinsky, J ; Spanger, M ; Koshy, AN ; Yii, M ; Weinberg, L (ELSEVIER SCI LTD, 2021-06-15)
    INTRODUCTION AND IMPORTANCE: Spontaneous Retroperitoneal Haemorrhage (SRH) is a rare condition, which in its extreme state can result in Abdominal Compartment Syndrome (ACS). The aim of this case report is to provide an overview of the diagnosis and management of SRH and to present an algorithm to inform and guide clinical decision-making in the context of ACS. CASE PRESENTATION: A 74-year-old woman with multiple risk factors for SRH developed a tense abdomen in ICU post-cardiac graft study. Radiological imaging confirmed multiple bleeding points to the contralateral side of the graft access site. She underwent endovascular treatment for her condition, however, developed ACS necessitating surgical evacuation of the haematoma. CLINICAL DISCUSSION: SRH is a rare condition that may be difficult to diagnose on physical exam. Medical, endovascular and surgical approaches are recognised treatments. ACS is an extreme variant of SRH and although endovascular management can specifically address the acute bleed, surgical evacuation of the haematoma is the only treatment that can effectively reduce abdominal compartment pressures. CONCLUSION: SRH can cause abdominal compartment syndrome with subsequent multiorgan failure. Ultimately, as outlined in this case, surgical evacuation of the haematoma was the only treatment able to reduce abdominal compartment pressures.
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    Relationship between QT interval prolongation and structural abnormalities in cirrhotic cardiomyopathy: A change in the current paradigm
    Koshy, AN ; Gow, PJ ; Testro, A ; Teh, AW ; Ko, J ; Lim, HS ; Han, H-C ; Weinberg, L ; VanWagner, LB ; Farouque, O (WILEY, 2021-02-08)
    It is postulated that cardiac structural abnormalities observed in cirrhotic cardiomyopathy (CCM) contribute to the electrophysiologic abnormality of QT interval (QTc) prolongation. We sought to evaluate whether QTc prolongation is associated with intrinsic abnormalities in cardiac structure and function that characterize CCM. Consecutive patients undergoing liver transplant work-up between 2010 and 2018 were included. Measures of cardiac function on stress testing including cardiac reserve and chronotropic incompetence were collected prospectively and a corrected QTc ≥ 440 ms was considered prolonged. Overall, 439 patients were included and 65.1% had a prolonged QTc. There were no differences in markers of left ventricular and atrial remodeling, or resting systolic and diastolic function across QTc groups. The proportion of patients that met the criteria for a low cardiac reserve (39.2 vs 36.6%, p = .66) or chronotropic incompetence (18.1 vs 21.3%, p = .52) was not different in those with a QTc ≥ 440 vs <440 ms. Further, there was no association between QTc prolongation and CCM by either the 2005 World College of Gastroenterology or modified 2020 Cirrhotic Cardiomyopathy Consortium criteria. QT interval prolongation was not associated with structural or functional cardiac abnormalities that characterize CCM. These findings suggest that CCM and QT interval prolongation in cirrhosis may be two separate entities with distinct pathophysiological origins.
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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, 2016-04-01)
    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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    Health economic implications of postoperative complications following liver resection surgery: a systematic review.
    Cosic, L ; Ma, R ; Churilov, L ; Nikfarjam, M ; Christophi, C ; Weinberg, L (Wiley, 2019-12)
    BACKGROUND: Limited data exists concerning the health economics of liver resection, with even less information on the costs emerging from complications, despite this remaining an important target from a health economic perspective. Our objective was to describe the financial burden of complications following liver resection. METHODS: We conducted a systematic search and included studies reporting resource use of in-hospital complications during the index liver resection admission. All indications for liver resection were considered. All techniques were considered. Data was collected using a data extraction table and a narrative synthesis was performed. RESULTS: We identified 12 eligible articles. There was considerable heterogeneity in study designs, patient populations and outcome definitions. We found weak evidence of increased costs associated with major liver resection compared to minor resections. We found robust evidence supporting the increasing economic burden arising from complications after liver resection. Acceptable evidence for increased cost due to the presence and grade of complication was found. Strong evidence concerning the association of length of stay with costs was demonstrated. CONCLUSIONS: The presence and grade of complications increase hospital cost across diverse settings. The costing methodology should be transparent and complication grading systems should be consistent in future studies.
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    The effects of 0.9% saline versus Plasma-Lyte 148 on renal function as assessed by creatinine concentration in patients undergoing major surgery: A single-centre double-blinded cluster crossover trial
    Weinberg, L ; Li, MH-G ; Churilov, L ; Macgregor, C ; Garrett, K ; Eyles, J ; Bellomo, R ; Dal Pizzol, F (PUBLIC LIBRARY SCIENCE, 2021-05-19)
    OBJECTIVES: Saline and Plasma-Lyte have different physiochemical contents; consequently, they may differently affect patients' renal function. We compared the effects of fluid therapy with 0.9% saline and with Plasma-Lyte 148 on renal function as assessed by creatinine concentration among patients undergoing major surgery. METHODS: We conducted a prospective, double-blinded cluster crossover trial comparing the effects of the two fluids on major surgery patients. The primary aim was to establish the pilot feasibility, safety and preliminary efficacy evidence base for a large interventional trial to establish whether saline or Plasma-Lyte is the preferred crystalloid fluid for managing major surgery patients. The primary efficacy outcome was the proportion of patients with changes in renal function as assessed by creatinine concentration during their index hospital admission. We used changes in creatinine to define acute kidney injury (AKI) according to the RIFLE criteria. RESULTS: The study was feasible with 100% patient and clinician acceptance. There were no deviations from the trial protocol. After screening, we allocated 602 patients to saline and 458 to Plasma-Lyte. The median (IQR) volume of intraoperative fluid received was 2000 mL (1000:2000) in both groups. Forty-nine saline patients (8.1%) and 49 Plasma-Lyte patients (10.7%) developed a postoperative AKI (adjusted incidence rate ratio [aIRR]: 1.34; 95% CI: 0.93-1.95; p = 0.120). No differences were observed in the development of postoperative complications (aIRR: 0.98; 95% CI: 0.89-1.08) or the severity of the worst complication (aIRR: 1.00; 95% CI: 0.78-1.30). The median (IQR) length of hospital stay was six days (3:11) for the saline group and five days (3:10) for the Plasma-Lyte group (aIRR: 0.85; 95% CI: 0.73-0.98). There were no serious adverse events relating to the trial fluids, nor were there fluid crossover or contamination events. CONCLUSIONS: The study design was feasible to support a future follow-up larger clinical trial. Patients treated with saline did not demonstrate an increased incidence of postoperative AKI (defined as changes in creatinine) compared to those treated with Plasma-Lyte. Our findings imply that clinicians can reasonably use either solution intraoperatively for adult patients undergoing major surgery. TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Registry; ACTRN12613001042730; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364988.
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    Effect of QT interval prolongation on cardiac arrest following liver transplantation and derivation of a risk index
    Koshy, AN ; Ko, J ; Farouque, O ; Cooray, SD ; Han, H-C ; Cailes, B ; Gow, PJ ; Weinberg, L ; Testro, A ; Lim, HS ; Teh, AW (WILEY, 2020-07-05)
    Liver transplantation (LT) has a 4-fold higher risk of periprocedural cardiac arrest and ventricular arrhythmias (CA/VAs) compared with other noncardiac surgeries. Prolongation of the corrected QT interval (QTc) is common in patients with liver cirrhosis. Whether it is associated with an increased risk of CA/VAs following LT is unclear. Rates of 30-day CA/VAs post-LT were assessed in consecutive adults undergoing LT between 2010 and 2017. Pretransplant QTc was measured by a cardiologist blinded to clinical outcomes. Among 408 patients included, CA/VAs occurred in 26 patients (6.4%). QTc was significantly longer in CA/VA patients (475 ± 34 vs 450 ± 34 ms, P < .001). Optimal QTc cut-off for prediction of CA/VAs was ≥480 ms. After adjustment, QTc ≥480 ms remained the strongest predictor for the occurrence of CA/VAs (odds ratio [OR] 5.2, 95% confidence interval [CI] 2.2-12.6). A point-based cardiac arrest risk index (CARI) was derived with the bootstrap method for yielding optimism-corrected coefficients (2 points: QTc ≥480, 1 point: Model for End-Stage Liver Disease [MELD] ≥30, 1 point: age ≥65, and 1 point: male). CARI score ≥3 demonstrated moderate discrimination (c-statistic 0.79, optimism-corrected c-statistic 0.77) with appropriate calibration. QTc ≥480 ms was associated with a 5-fold increase in the risk of CA/VAs. The CARI score may identify patients at higher risk of these events. Whether heightened perioperative cardiac surveillance, avoidance of QT prolonging medications, or beta blockers could mitigate the risk of CA/VAs in this population merits further study.
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    Health costs of post-operative complications following rectal resection: a systematic review
    Johnston, S ; Louis, M ; Churilov, L ; Ma, R ; Christophi, C ; Weinberg, L (WILEY, 2020-02-13)
    BACKGROUND: Post-operative complications following rectal resection pose significant health and cost implications for patients and health providers. The objective of this study is to review the associated cost of complications following rectal resection. This included reporting on the proportion and severity of these complications, associated length of stay and surgical technique used. Studies were sourced from Embase OVID, MEDLINE OVID (ALL) and Cochrane Library databases by utilizing a search strategy. METHODS: This search contained studies from 1 January 2010 until 13 February 2019. Studies were included from the year 2010 to account for the implementation of enhanced recovery after surgery protocols. Studies that reported the financial cost associated with complications were included. Any indication for rectal resection was considered. Data was extracted into a formatted table and a narrative synthesis was performed. RESULTS: We identified 13 eligible studies for inclusion. There was strong evidence to suggest that complications are associated with increased costs. There was considerable variation as to the costs attributable to complications ($1443 (P < 0.001) to $17 831 (P < 0.0012), n = 12). The presence of complications was associated with an increased length of stay (5.54 (P-value not given) to 21.04 (P < 0.0001) days, n = 7). There was significant variation in the proportion of complications (6.41 to 64.71%, n = 8). Weak evidence existed around surgical technique used and the associated cost of complications. There was considerable heterogeneity among included studies. CONCLUSIONS: Complications following rectal resection increased health costs. Costs should be standardized and provide a clear methodology for their calculation. Complications should be standardized and include a grading of severity.
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    Perioperative blood management programme reduces the use of allogenic blood transfusion in patients undergoing total hip and knee arthroplasty
    Kopanidis, P ; Hardidge, A ; McNicol, L ; Tay, S ; McCall, P ; Weinberg, L (BMC, 2016-02-29)
    BACKGROUND: Optimisation of blood management in total hip (THA) and knee arthroplasty (TKA) is associated with improved patient outcomes. This study aimed to establish the effectiveness of a perioperative blood management programme in improving postoperative haemoglobin (Hb) and reducing the rate of allogenic blood transfusion. METHODS: This retrospective before and after study involves 200 consecutive patients undergoing elective TKA and THA before (Usual Care group) and after (Intervention group) the introduction of a blood management programme in an Australian teaching hospital. Patients in the Intervention group underwent preoperative treatment for anaemia and received intraoperative tranexamic acid (15 mg/kg). The primary outcomes were to compare postoperative Hb levels and the rate of blood transfusion. Secondary outcomes included measurements of total amount of allogenic blood transfused, transfusion-related complications, postoperative complications, need for inpatient rehabilitation and duration of hospital stay. RESULTS: There were no differences between baseline characteristics between groups. The mean (SD) preoperative Hb was higher in the Intervention group compared to that in the Usual Care group: 138.7 (13.9) vs. 133.4 (13.9) g/L, p = 0.008, respectively. The postoperative day 1 Hb, lowest postoperative Hb and discharge Hb were all higher in the Intervention group (p < 0.001). Blood transfusion requirements were lower in the Intervention group compared to the Usual Care group (6 vs. 20 %, p = 0.003). There were no differences in any of the secondary outcomes measured. Patients who were anaemic preoperatively and who underwent Hb optimisation had higher Hb levels postoperatively (odds ratio 5.7; 95 % CI 1.3 to 26.5; p = 0.024). CONCLUSIONS: The introduction of a perioperative blood optimisation programme improved postoperative Hb levels and reduced the rate of allogenic blood transfusion.
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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.