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ItemA double-blind randomised feasibility trial of angiotensin-2 in cardiac surgery.(Wiley, 2022-09)Acute kidney injury is common after cardiac surgery. Vasoplegic hypotension may contribute to kidney injury, and different vasopressors may have variable effects on kidney function. We conducted a double-blind, randomised feasibility trial comparing peri-operative angiotensin-2 with noradrenaline. We randomly allocated 60 patients at two centres to a blinded equipotent angiotensin-2 or noradrenaline infusion intra-operatively and for up to 48 h postoperatively, titrated to mean arterial pressure of 70-80 mmHg. Primary feasibility outcomes included consent rate, protocol adherence, infusion duration, mean arterial pressure maintenance in the target range and major adverse outcomes. Secondary outcomes included kidney injury rate. The consent rate was 47%. Protocol adherence was 100% in the angiotensin-2 group and 94% in the noradrenaline group. Study drug duration was median (IQR [range]) 217 (160-270 [30-315]) vs. 185 (135-301 [0-480]) min (p = 0.78) min intra-operatively, and 5 (0-16 [0-48]) vs. 14.5 (4.8-29 [0-48]) hours (p = 0.075) postoperatively for angiotensin-2 and noradrenaline, respectively. The mean arterial pressure target was achieved postoperatively in 25 of 28 (89%) of the angiotensin-2 group and 27 of 32 (84%) of the noradrenaline group. One participant had a stroke, one required extracorporeal support and three required renal replacement therapy, all in the noradrenaline group (p = 0.99, p = 0.99 and p = 0.1). Acute kidney injury occurred in 7 of 28 in the angiotensin-2 group vs. 12 of 32 patients in the noradrenaline group (p = 0.31). This pilot study suggests that a trial comparing angiotensin-2 with noradrenaline is feasible. Its findings justify further investigations of angiotensin-2 in cardiac surgery.
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ItemModern Cardiac Surgical Outcomes in Nonagenarians: A Multicentre Retrospective Observational Study.(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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ItemIntraoperative low tidal volume ventilation and the risk of ICD-10 coded delirium and the use for antipsychotic medications(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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ItemSerum Creatinine Levels and Nephrocheck® Values With and Without Correction for Urine Dilution-A Multicenter Observational Study(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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ItemIntra-operative ventilator mechanical power as a predictor of postoperative pulmonary complications in surgical patients A secondary analysis of a randomised clinical trial(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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ItemFactors influencing early and long-term survival following hip fracture among nonagenarians(BMC, 2021-10-30)BACKGROUND: The outcomes of nonagenarian patients undergoing orthopaedic surgery are not well understood. We investigated the 30-day mortality after surgical treatment of unilateral hip fracture. The relationship between postoperative complications and mortality was evaluated. METHODS: We performed a single-centre retrospective cohort study of nonagenarian patients undergoing hip fracture surgery over a 6-year period. Postoperative complications were graded according to the Clavien-Dindo classification. Correlation analyses were performed to evaluate the relationship between mortality and pre-specified mortality risk predictors. Survival analyses were assessed using Cox proportional hazards regression modelling. RESULTS: The study included 537 patients. The 30-day mortality rate was 7.4%. The mortality rate over a median follow-up period of 30 months was 18.2%. Postoperative complications were observed in 459 (85.5%) patients. Both the number and severity of complications were related to mortality (p < 0.001). Compared to patients who survived, deceased patients were more frail (p = 0.034), were at higher ASA risk (p = 0.010) and were more likely to have preoperative congestive heart failure (p < 0.001). The adjusted hazard ratio for mortality according to the number of complications was 1.3 (95% CI 1.1, 1.5; p = 0.003). Up to 21 days from admission, any increase in complication severity was associated significantly greater mortality [adjusted hazard ratio: 3.0 (95% CI 2.4, 3.6; p < 0.001)]. CONCLUSION: In a nonagenarian cohort of patients undergoing hip fracture surgery, 30-day mortality was 7.4%, but 30-month mortality rates approached one in five patients. Postoperative complications were independently associated with a higher mortality, particularly when occurring early.
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ItemThe hemodynamic effects of intravenous paracetamol (acetaminophen) in patients with chronic liver disease undergoing liver transplantation: a pilot study(SPRINGERNATURE, 2021-08-24)OBJECTIVE: We performed a single-center double-blinded, randomized trial to investigate the hemodynamic effects of IV paracetamol in patients with chronic liver disease (CLD) undergoing liver transplantation surgery. Patients with CLD are particularly susceptible to hemodynamic derangements given their low systemic vascular resistance state. Accordingly, hypotension is common in this setting. The hemodynamic effects of IV paracetamol in patients undergoing elective liver transplantation are unknown, therefore we evaluated whether the intraoperative administration of IV paracetamol in patients with chronic liver disease undergoing liver transplantation results in adverse hemodynamic effects. The primary end point was a change in systolic blood pressure 30-min after the preoperative infusion. RESULTS: Twenty-four participants undergoing liver transplantation surgery were randomly assigned to receive a single bolus of IV paracetamol (1 g paracetamol + 3.91 g mannitol per 100 mL) (n = 12) or placebo (0.9% Saline 100 mL) (n = 12). All participants completed their study intervention, and there were no breaches or violations of the trial protocol. Baseline characteristics were similar in both groups. There were no significant differences regarding surgical duration, intraoperative use of fluids, and intraoperative noradrenaline use. After the administration of paracetamol there were no significant differences observed in blood pressure or other hemodynamic parameters when compared to placebo.
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ItemThromboelastography in elective total hip arthroplasty(BAISHIDENG PUBLISHING GROUP INC, 2021-08-18)BACKGROUND: Hypercoagulability plays an important role in predisposing patients to venous thromboembolism (VTE) after total hip arthroplasty (THA). We used thromboelastography (TEG) to examine the coagulation status of patients undergoing THA. AIM: To examine coagulation as measured by TEG in patients undergoing THA who received standard VTE chemoprophylaxis with enoxaparin. METHODS: After ethical approval, we performed a retrospective analysis of data collected in patients undergoing primary elective THA. We analyzed TEG data on samples performed before skin incision, intraoperatively and for 5 d postoperatively. Conventional coagulation tests were performed preoperatively and on postoperative day 5. RESULTS: Twenty patients undergoing general anesthesia and 32 patients undergoing spinal anesthesia (SA) were included. TEG demonstrated a progressively hypercoagulable state postoperatively, characterized by elevated maximum amplitude. TEG also demonstrated transient intraoperative hypercoagulability in patients receiving SA. In contrast, conventional coagulation tests were normal in all patients, pre- and postoperatively, except for an increase in plasma fibrinogen day 5 postoperatively. CONCLUSION: Despite VTE prophylaxis, patients following total hip replacement remain in a hypercoagulable state as measured by both TEG and conventional tests. This group may benefit from more optimal anticoagulation and/or additional perioperative hemostatic monitoring, via TEG or otherwise.
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ItemThe 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(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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ItemAssociations between preoperative anaemia and hospital costs following major abdominal surgery: cohort study(OXFORD UNIV PRESS, 2021-03)BACKGROUND: Determining the cost-effectiveness and sustainability of patient blood management programmes relies on quantifying the economic burden of preoperative anaemia. This retrospective cohort study aimed to evaluate the hospital costs attributable to preoperative anaemia in patients undergoing major abdominal surgery. METHODS: Patients who underwent major abdominal surgery between 2010 and 2018 were included. The association between preoperative patient haemoglobin (Hb) concentration and hospital costs was evaluated by curve estimation based on the least-square method. The in-hospital cost of index admission was calculated using an activity-based costing methodology. Multivariable regression analysis and propensity score matching were used to estimate the effects of Hb concentration on variables related directly to hospital costs. RESULTS: A total of 1286 patients were included. The median overall cost was US $18 476 (i.q.r.13 784-27 880), and 568 patients (44.2 per cent) had a Hb level below 13.0 g/dl. Patients with a preoperative Hb level below 9.0 g/dl had total hospital costs that were 50.6 (95 per cent c.i. 14.1 to 98.9) per cent higher than those for patients with a preoperative Hb level of 9.0-13.0 g/dl (P < 0.001), 72.5 (30.6 to 128.0) per cent higher than costs for patients with a Hb concentration of 13.1-15.0 g/dl (P < 0.001), and 62.4 (21.8 to 116.7) per cent higher than those for patients with a Hb level greater than 15.0 g/dl (P < 0.001). Multivariable general linear modelling showed that packed red blood cell (PRBC) transfusions were a principal cost driver in patients with a Hb concentration below 9.0 g/dl. CONCLUSION: Patients with the lowest Hb concentration incurred the highest hospital costs, which were strongly associated with increased PRBC transfusions. Costs and possible complications may be decreased by treating preoperative anaemia, particularly more severe anaemia.