Medicine (Austin & Northern Health) - Research Publications
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ItemThe haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial(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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ItemHealth economic implications of postoperative complications following liver resection surgery: a systematic review(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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ItemPerioperative blood management programme reduces the use of allogenic blood transfusion in patients undergoing total hip and knee arthroplasty(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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ItemThe hemodynamic effects of intravenous paracetamol (acetaminophen) vs normal saline in cardiac surgery patients: A single center placebo controlled randomized study(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.
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ItemAssessment of agreement and interchangeability between the TEG5000 and TEG6S thromboelastography haemostasis analysers: a prospective validation study(BMC, 2019-03-30)BACKGROUND: TEG6S® and TEG5000® (Haemonetics Corp, USA) are haemostasis analysers that measure viscoelasticity properties of whole blood. Both use different mechanisms to assess similar components of the coagulation process. The aim of this study was to assess agreement and interchangeability between the TEG6S and TEG5000 analysers. METHODS: 3.5 mL whole blood was collected from 25 adult patients in a tertiary intensive care unit (ICU). Analysis was performed using TEG6S and TEG5000 haemostatic platforms. Agreement between platforms was measured using Lin's concordance coefficient (Lin's CC), further validated using intraclass correlation coefficients and reduced major axis regression (RMAR). RESULTS: Sixteen (64%) patients were male; mean (range) age: 59yo (23-86). TEG6S and TEG5000 systems were broadly interchangeable. The majority of TEG variables demonstrated almost perfect or substantial agreement and minimal proportional bias (maximum amplitude demonstrated a fixed bias). LY30%, however, demonstrated poor agreement and a proportional bias. Lin's CC coefficients (95% CI, RMAR slope, intercept) between TEG6S and TEG5000 variables were: R time: 0.78 (0.64-0.92, 0.76, 0.92); K time: 0.82 (0.69-0.94, 1.30, - 0.93); alpha angle: 0.79 (0.64-0.95, 1.04, - 1.43); maximum amplitude (MA): 0.90 (0.83-0.96, 0.99, - 5.0); LY30%: 0.34 (0.1-0.58, 0.43, 0.04). CONCLUSIONS: Adult patients with critical illness demonstrate almost perfect agreement in the R time and MA, substantial agreement in K time and alpha angle, but poor agreement in LY30%, as measured by the TEG6S and TEG5000 analysers. With the exception of LY30%, the TEG6S and TEG5000 platforms appear interchangeable. This has important implications for use in clinical practice and multi-site research programs. TRIAL REGISTRATION: ANZCRT number: 12617000062325 , registered 12/Jan17. Retrospectively registered.
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ItemThe financial impact of postoperative complications following liver resection(LIPPINCOTT WILLIAMS & WILKINS, 2019-07)The aim of the study was to determine the financial burden of complications and examine the cost differentials between complicated and uncomplicated hospital stays, including the differences in cost due to extent of resection and operative technique.Liver resection carries a high financial cost. Despite improvements in perioperative care, postoperative morbidity remains high. The contribution of postoperative complications to the cost of liver resection is poorly quantified, and there is little data to help guide cost containment strategies.Complications for 317 consecutive adult patients undergoing liver resection were recorded using the Clavien-Dindo classification. Patients were stratified based on the grade of their worst complication to assess the contribution of morbidity to resource use of specific cost centers. Costs were calculated using an activity-based costing methodology.Complications dramatically increased median hospital cost ($22,954 vs $15,593, P < .001). Major resection cost over $10,000 more than minor resection and carried greater morbidity (82% vs 59%, P < .001). Similarly, open resection cost more than laparoscopic resection ($21,548 vs $15,235, P < .001) and carried higher rates of complications (72% vs 41.5%, P < .001). Hospital cost increased with increasing incidence and severity of complications. Complications increased costs across all cost centers. Minor complications (Clavien-Dindo Grade I and II) were shown to significantly increase costs compared with uncomplicated patients.Liver resection continues to carry a high incidence of complications, and these result in a substantial financial burden. Hospital cost and length of stay increase with greater severity and number of complications. Our findings provide an in-depth analysis by stratifying total costs by cost centers, therefore guiding future economic studies and strategies aimed at cost containment for liver resection.
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ItemGoal directed fluid therapy for major liver resection: A multicentre randomized controlled trial(ELSEVIER SCI LTD, 2019-09)BACKGROUND: The effect a restrictive goal directed therapy (GDT) fluid protocol combined with an enhanced recovery after surgery (ERAS) programme on hospital stay for patients undergoing major liver resection is unknown. METHODS: We conducted a multicentre randomized controlled pilot trial evaluating whether a patient-specific, surgery-specific intraoperative restrictive fluid optimization algorithm would improve duration of hospital stay and reduce perioperative fluid related complications. RESULTS: Forty-eight participants were enrolled. The median (IQR) length of hospital stay was 7.0 days (7.0:8.0) days in the restrictive fluid optimization algorithm group (Restrict group) vs. 8.0 days (6.0:10.0) in the conventional care group (Conventional group) (Incidence rate ratio 0.85; 95% Confidence Interval 0.71:1.1; p = 0.17). No statistically significant difference in expected number of complications per patient between groups was identified (IRR 0.85; 95%CI: 0.45-1.60; p = 0.60). Patients in the Restrict group had lower intraoperative fluid balances: 808 mL (571:1565) vs. 1345 mL (900:1983) (p = 0.04) and received a lower volume of fluid per kg/hour intraoperatively: 4.3 mL/kg/hr (2.6:5.8) vs. 6.0 mL/kg/hr (4.2:7.6); p = 0.03. No significant differences in the proportion of patients who received vasoactive drugs intraoperatively (p = 0.56) was observed. CONCLUSION: In high-volume hepatobiliary surgical units, the addition of a fluid restrictive intraoperative cardiac output-guided algorithm, combined with a standard ERAS protocol did not significantly reduce length of hospital stay or fluid related complications. Our findings are hypothesis-generating and a larger confirmatory study may be justified.
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ItemBereavement practices employed by hospitals and medical practitioners toward attending funeral of patients A systematic review(LIPPINCOTT WILLIAMS & WILKINS, 2019-09)OBJECTIVES: To ascertain bereavement practices offered by hospitals and medical practitioners (MPs), factors that influence the likelihood of MPs' involvement in funeral attendance, the benefits and barriers to attendance to a patient's funeral as perceived by MPs and the rate of attendance to patients' funeral by MPs. DESIGN: MEDLINE (Ovid), Embase, PubMed, and Google Scholar were searched with a systematic search structure for randomized controlled trials, comparative observational studies, case series, cross-sectional studies, editorials, and letters. The search was limited to English only. The study was registered with Prospero (Registration Number: CRD42018095368). RESULTS: A total of 381 articles were identified with 46 articles meeting the inclusion criteria. Of the 46, 16 were editorials and 12 were letters. Eighteen were cross-sectional studies conducted in the United States, Canada, Australia, Israel, and Ireland. Year of publication ranged from 1990 to 2017. Of these, 12 were quantitative, 3 were qualitative, and 3 were mixed-method studies. Two of the cross-sectional studies involved family members of deceased patients while others involved MPs. Bereavement practices offered by hospitals included memorial services, letters, and services provided by bereavement coordinators. Bereavement practices employed by MPs included answering or making phone calls, attending family meetings, and sending condolence letters. MPs' attendance at a patient's funeral was influenced by MPs' gender, age years of experience the medical specialty. Perceived benefits of MPs' attendance at a patient's funeral included providing support to the family, extending the professional relationship, illustrating respect to the patient and the family, resolving guilt and personal growth. Barriers to the attendance included a lack of time, blurring of professional boundaries, personal discomfort with death, emotional arousal, and discouragement by colleagues. General practice had an attendance rate of 71%. Attendance rates for palliative care, oncology, and psychiatrists ranged from 63% to 81%, 7.1% to 67%, and 15% to 67%, respectively. Intensivists had an attendance rate of 22%. CONCLUSION: Several bereavement practices are provided by hospitals and MPs. Funeral attendance is an uncommon bereavement practice. MPs' attitudes toward attending a patient's funeral are understudied in many specialties. Patient factors that influence MPs' participation in bereavement practices are poorly understood.
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ItemRestrictive intraoperative fluid optimisation algorithm improves outcomes in patients undergoing pancreaticoduodenectomy: A prospective multicentre randomized controlled trial(PUBLIC LIBRARY SCIENCE, 2017-09-07)We aimed to evaluate perioperative outcomes in patients undergoing pancreaticoduodenectomy with or without a cardiac output goal directed therapy (GDT) algorithm. We conducted a multicentre randomised controlled trial in four high volume hepatobiliary-pancreatic surgery centres. We evaluated whether the additional impact of a intraoperative fluid optimisation algorithm would influence the amount of fluid delivered, reduce fluid related complications, and improve length of hospital stay. Fifty-two consecutive adult patients were recruited. The median (IQR) duration of surgery was 8.6 hours (7.1:9.6) in the GDT group vs. 7.8 hours (6.8:9.0) in the usual care group (p = 0.2). Intraoperative fluid balance was 1005mL (475:1873) in the GDT group vs. 3300mL (2474:3874) in the usual care group (p<0.0001). Total volume of fluid administered intraoperatively was also lower in the GDT group: 2050mL (1313:2700) vs. 4088mL (3400:4525), p<0.0001 and vasoactive medications were used more frequently. There were no significant differences in proportions of patients experiencing overall complications (p = 0.179); however, fewer complications occurred in the GDT group: 44 vs. 92 (Incidence Rate Ratio: 0.41; 95%CI 0.24 to 0.69, p = 0.001). Median (IQR) length of hospital stay was 9.5 days (IQR: 7.0, 14.3) in the GDT vs. 12.5 days in the usual care group (IQR: 9.0, 22.3) for an Incidence Rate Ratio 0.64 (95% CI 0.48 to 0.85, p = 0.002). In conclusion, using a surgery-specific, patient-specific goal directed restrictive fluid therapy algorithm in this cohort of patients, can justify using enough fluid without causing oedema, yet as little fluid as possible without causing hypovolaemia i.e. "precision" fluid therapy. Our findings support the use of a perioperative haemodynamic optimization plan that prioritizes preservation of cardiac output and organ perfusion pressure by judicious use of fluid therapy, rational use of vasoactive drugs and timely application of inotropic drugs. They also suggest the need for further larger studies to confirm its findings.
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ItemComparative Evaluation of Crystalloid Resuscitation Rate in a Human Model of Compensated Haemorrhagic Shock(LIPPINCOTT WILLIAMS & WILKINS, 2016-08)INTRODUCTION: The most effective rate of fluid resuscitation in haemorrhagic shock is unknown. METHODS: We performed a randomized crossover pilot study in a healthy volunteer model of compensated haemorrhagic shock. Following venesection of 15 mL/kg of blood, participants were randomized to 20 mL/kg of crystalloid over 10 min (FAST treatment) or 30 min (SLOW treatment). The primary end point was oxygen delivery (DO2). Secondary end points included pressure and flow-based haemodynamic variables, blood volume expansion, and clinical biochemistry. RESULTS: Nine normotensive healthy adult volunteers participated. No significant differences were observed in DO2 and biochemical variables between the SLOW and FAST groups. Blood volume was reduced by 16% following venesection, with a corresponding 5% reduction in cardiac index (CI) (P < 0.001). Immediately following resuscitation the increase in blood volume corresponded to 54% of the infused volume under FAST treatment and 69% of the infused volume under SLOW treatment (P = 0.03). This blood volume expansion attenuated with time to 24% and 25% of the infused volume 30 min postinfusion. During fluid resuscitation, blood pressure was higher under FAST treatment. However, CI paradoxically decreased in most participants during the resuscitation phase; a finding not observed under SLOW treatment. CONCLUSION: FAST or SLOW fluid resuscitation had no significant impact on DO2 between treatment groups. In both groups, changes in CI and blood pressure did not reflect the magnitude of intravascular blood volume deficit. Crystalloid resuscitation expanded intravascular blood volume by approximately 25%.