549 results on '"Myles, PS"'
Search Results
2. A survey of Australian and New Zealand anaesthetists' attitudes towards resuscitation orders in the perioperative setting
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Keon-Cohen, Z, Myles, PS, and Story, DA
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- 2017
Catalog
3. Perioperative management of patients treated with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: A quality improvement audit
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Vijay, A, Grover, A, Coulson, TG, and Myles, PS
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- 2016
4. Postoperative systemic inflammation after major abdominal surgery: patient-centred outcomes.
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Bain, CR, Myles, PS, Martin, C, Wallace, S, Shulman, MA, Corcoran, T, Bellomo, R, Peyton, P, Story, DA, Leslie, K, Forbes, A, RELIEF trial investigators, Bain, CR, Myles, PS, Martin, C, Wallace, S, Shulman, MA, Corcoran, T, Bellomo, R, Peyton, P, Story, DA, Leslie, K, Forbes, A, and RELIEF trial investigators more...
- Abstract
Postoperative systemic inflammation is strongly associated with surgical outcomes, but its relationship with patient-centred outcomes is largely unknown. Detection of excessive inflammation and patient and surgical factors associated with adverse patient-centred outcomes should inform preventative treatment options to be evaluated in clinical trials and current clinical care. This retrospective cohort study analysed prospectively collected data from 3000 high-risk, elective, major abdominal surgery patients in the restrictive vs. liberal fluid therapy for major abdominal surgery (RELIEF) trial from 47 centres in seven countries from May 2013 to September 2016. The co-primary endpoints were persistent disability or death up to 90 days after surgery, and quality of recovery using a 15-item quality of recovery score at days 3 and 30. Secondary endpoints included: 90-day and 1-year all-cause mortality; septic complications; acute kidney injury; unplanned admission to intensive care/high dependency unit; and total intensive care unit and hospital stays. Patients were assigned into quartiles of maximum postoperative C-reactive protein concentration up to day 3, after multiple imputations of missing values. The lowest (reference) group, quartile 1, C-reactive protein ≤ 85 mg.l-1 , was compared with three inflammation groups: quartile 2 > 85 mg.l-1 to 140 mg.l-1 ; quartile 3 > 140 mg.l-1 to 200 mg.l-1 ; and quartile 4 > 200 mg.l-1 to 587 mg.l-1 . Greater postoperative systemic inflammation had a higher adjusted risk ratio (95%CI) of persistent disability or death up to 90 days after surgery, quartile 4 vs. quartile 1 being 1.76 (1.31-2.36), p < 0.001. Increased inflammation was associated with increasing decline in risk-adjusted estimated medians (95%CI) for quality of recovery, the quartile 4 to quartile 1 difference being -14.4 (-17.38 to -10.71), p < 0.001 on day 3, and -5.94 (-8.92 to -2.95), p < 0.001 on day 30. Marked postoperative systemic inflammation was associated more...
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- 2023
5. Universal research index: An inclusive metric to quantify scientific research output
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Keshavarz-Fathi, M, Yazdanpanah, N, Kolahchi, S, Ziaei, H, Darmstadt, GL, Dorigo, T, Dochy, F, Levin, L, Thongboonkerd, V, Ogino, S, Chen, WH, Perc, M, Tremblay, MS, Olusanya, BO, Rao, IM, Hatziargyriou, N, Moradi-Lakeh, M, Bella, F, Rosivall, L, Gandomi, AH, Sorooshian, A, Gupta, M, Gal, C, Lozano, AM, Weaver, C, Tanzer, M, Poggi, A, Sepanlou, SG, Weiskirchen, R, Jambrak, AR, Torres, PJ, Capanoglu, E, Barba, FJ, Ernest, CKJ, Sigman, M, Pluchino, S, Gharehpetian, GB, Fereshtehnejad, SM, Yang, MH, Thomas, S, Cai, W, Comini, E, Scolding, NJ, Myles, PS, Nieto, JJ, Perry, G, Sedikides, C, Rezaei, N, Keshavarz-Fathi, M, Yazdanpanah, N, Kolahchi, S, Ziaei, H, Darmstadt, GL, Dorigo, T, Dochy, F, Levin, L, Thongboonkerd, V, Ogino, S, Chen, WH, Perc, M, Tremblay, MS, Olusanya, BO, Rao, IM, Hatziargyriou, N, Moradi-Lakeh, M, Bella, F, Rosivall, L, Gandomi, AH, Sorooshian, A, Gupta, M, Gal, C, Lozano, AM, Weaver, C, Tanzer, M, Poggi, A, Sepanlou, SG, Weiskirchen, R, Jambrak, AR, Torres, PJ, Capanoglu, E, Barba, FJ, Ernest, CKJ, Sigman, M, Pluchino, S, Gharehpetian, GB, Fereshtehnejad, SM, Yang, MH, Thomas, S, Cai, W, Comini, E, Scolding, NJ, Myles, PS, Nieto, JJ, Perry, G, Sedikides, C, and Rezaei, N more...
- Abstract
Scientometrics and bibliometrics, the subfields of library and information science, deal with the quantity and quality of research outputs. Currently, various scientometric indices are being used to quantify and compare research outputs. The most widely known is the h-index. However, this index and its derivatives suffer from dependence on the mere count of a scholar's highly cited publications. To remedy this deficiency, we developed a novel index, the Universal Research Index (UR-Index) (https://usern2021.github.io/UR-Index/) by which every single publication has its own impact on the total score. We developed this index by surveying international top 1 % cited scientists in various disciplines and included additional component variables such as publication type, leading role of a scholar, co-author count, and source metrics to this scientometric index. We acknowledge that unconscious biases built into the component variables included in the UR-Index might put research from specific groups at a disadvantage, thus continued efforts to improve equitable scholarly impact in science and academia are encouraged. more...
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- 2023
6. Comparison of 6-month outcomes of sepsis versus non-sepsis critically ill patients receiving mechanical ventilation
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Hodgson, CL, Higgins, AM, Bailey, M, Barrett, J, Bellomo, R, Cooper, DJ, Gabbe, BJ, Iwashyna, T, Linke, N, Myles, PS, Paton, M, Philpot, S, Shulman, M, Young, M, Serpa Neto, A, Hodgson, CL, Higgins, AM, Bailey, M, Barrett, J, Bellomo, R, Cooper, DJ, Gabbe, BJ, Iwashyna, T, Linke, N, Myles, PS, Paton, M, Philpot, S, Shulman, M, Young, M, and Serpa Neto, A more...
- Abstract
BACKGROUND: Data on long-term outcomes after sepsis-associated critical illness have mostly come from small cohort studies, with no information about the incidence of new disability. We investigated whether sepsis-associated critical illness was independently associated with new disability at 6 months after ICU admission compared with other types of critical illness. METHODS: We conducted a secondary analysis of a multicenter, prospective cohort study in six metropolitan intensive care units in Australia. Adult patients were eligible if they had been admitted to the ICU and received more than 24 h of mechanical ventilation. There was no intervention. RESULTS: The primary outcome was new disability measured with the WHO Disability Assessment Schedule 2.0 (WHODAS) 12 level score compared between baseline and 6 months. Between enrollment and follow-up at 6 months, 222/888 (25%) patients died, 100 (35.5%) with sepsis and 122 (20.1%) without sepsis (P < 0.001). Among survivors, there was no difference for the incidence of new disability at 6 months with or without sepsis, 42/106 (39.6%) and 106/300 (35.3%) (RD, 0.00 (- 10.29 to 10.40), P = 0.995), respectively. In addition, there was no difference in the severity of disability, health-related quality of life, anxiety and depression, post-traumatic stress, return to work, financial distress or cognitive function. CONCLUSIONS: Compared to mechanically ventilated patients of similar acuity and length of stay without sepsis, patients with sepsis admitted to ICU have an increased risk of death, but survivors have a similar risk of new disability at 6 months. Trial registration NCT03226912, registered July 24, 2017. more...
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- 2022
7. Postoperative anaemia and patient-centred outcomes after major abdominal surgery: a retrospective cohort study.
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Myles, PS, Richards, T, Klein, A, Wood, EM, Wallace, S, Shulman, MA, Martin, C, Bellomo, R, Corcoran, TB, Peyton, PJ, Story, DA, Leslie, K, Forbes, A, RELIEF Trial Investigators, Myles, PS, Richards, T, Klein, A, Wood, EM, Wallace, S, Shulman, MA, Martin, C, Bellomo, R, Corcoran, TB, Peyton, PJ, Story, DA, Leslie, K, Forbes, A, and RELIEF Trial Investigators more...
- Abstract
BACKGROUND: Compared with anaemia before surgery, the underlying pathogenesis and implications of postoperative anaemia are largely unknown. METHODS: This retrospective cohort study analysed prospective data obtained from 2983 adult patients across 47 centres enrolled in a clinical trial evaluating restrictive and liberal intravenous fluids. The primary endpoint was persistent disability or death up to 90 days after surgery. Secondary endpoints included major septic complications, hospital stay, and patient quality of recovery using a 15-item quality of recovery (QoR-15) score, hospital re-admissions, and disability-free survival up to 12 months after surgery. Anaemia and disability were defined according to the WHO definitions. Multivariable regression was used to adjust for baseline risk and surgery. RESULTS: A total of 2983 patients met inclusion criteria for this study, of which 78.5% (95% confidence interval [CI], 76.7-80.1%) had postoperative anaemia. Patients with postoperative anaemia had a higher adjusted risk of death or disability up to 90 days after surgery when compared with those without anaemia: 18.2% vs 9.2% (risk ratio [RR]=1.51; 95% CI, 1.10-2.07, P=0.011); lower QoR-15 scores on Day 3 and Day 30, 105 (95% CI, 87-119) vs 114 (95% CI, 99-128; P<0.001), and 130 (95% CI, 112-140) vs 139 (95% CI, 121-144; P<0.011), respectively; higher adjusted risk of a composite of mortality/septic complications, 2.01 (95% CI, 1.55-42.67; P<0.001); unplanned admission to ICU (RR=2.65; 95% CI, 1.65-4.23; P<0.001); and longer median (inter-quartile range [IQR]) hospital stays, 6.6 (4.4-12.4) vs 3.7 (2.5-6.5) days (P<0.001). CONCLUSIONS: Postoperative anaemia is common and is independently associated with poor outcomes after surgery. Optimal prevention and treatment strategies need to be investigated. CLINICAL TRIAL REGISTRATION: NCT04978285 (ClinicalTrials.gov). more...
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- 2022
8. Current approaches to acute postoperative pain management after major abdominal surgery
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Pirie, K, Traer, E, Finniss, D, Myles, PS, Riedel, BJ, Pirie, K, Traer, E, Finniss, D, Myles, PS, and Riedel, BJ
- Abstract
Poorly controlled postoperative pain is associated with increased morbidity, negatively affects quality of life and functional recovery, and is a risk factor for persistent pain and longer-term opioid use. Up to 10% of opioid-naïve patients have persistent opioid use after many types of surgeries. Opioid-related side-effects and the opioid abuse epidemic emphasise the need for alternative, opioid-minimising, multimodal analgesic strategies, including neuraxial (epidural/intrathecal) techniques, truncal nerve blocks, and lidocaine infusions. The preference for minimally invasive surgical techniques has changed anaesthetic and analgesic requirements in abdominal surgery compared with open laparotomy, leading to a decline in popularity of epidural anaesthesia and an increasing interest in intrathecal morphine and truncal nerve blocks. Limited research exists on patient quality of recovery using specific analgesic techniques after intra-abdominal surgery. Poorly controlled postoperative pain after major abdominal surgery should be a research priority as it affects patient-centred short-term and long-term outcomes (including quality of life scores, return to function measurements, disability-free survival) and has broad community health and economic implications. more...
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- 2022
9. Professor Michael Paech - editor of anaesthesia and intensive care: 2007 to 2016
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Myles, PS
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- 2016
10. Transition from acute to chronic pain after surgery
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ANZCA Clinical Trials Network, Glare, PA, Myles, PS, Glare P, Aubrey K, Myles PS, ANZCA Clinical Trials Network, Glare, PA, Myles, PS, Glare P, Aubrey K, and Myles PS
- Abstract
Over the past decade there has been an increasing reliance on strong opioids to treat acute and chronic pain, which has been associated with a rising epidemic of prescription opioid misuse, abuse, and overdose-related deaths. Deaths from prescription opioids have more than quadrupled in the USA since 1999, and this pattern is now occurring globally. Inappropriate opioid prescribing after surgery, particularly after discharge, is a major cause of this problem. Chronic postsurgical pain, occurring in approximately 10% of patients who have surgery, typically begins as acute postoperative pain that is difficult to control, but soon transitions into a persistent pain condition with neuropathic features that are unresponsive to opioids. Research into how and why this transition occurs has led to a stronger appreciation of opioid-induced hyperalgesia, use of more effective and safer opioid-sparing analgesic regimens, and non-pharmacological interventions for pain management. This Series provides an overview of the epidemiology and societal effect, basic science, and current recommendations for managing persistent postsurgical pain. We discuss the advances in the prevention of this transitional pain state, with the aim to promote safer analgesic regimens to better manage patients with acute and chronic pain. more...
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- 2019
11. Integration of the Duke Activity Status Index into preoperative risk evaluation: a multicentre prospective cohort study
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Wijeysundera, DN, Beattie, WS, Hillis, GS, Abbott, TEF, Shulman, MA, Ackland, GL, Mazer, CD, Myles, PS, Pearse, RM, Cuthbertson, BH, Measurement of Exercise Tolerance before Surgery Study Investiga, Wallace, S, Farrington, C, Thompson, B, Ellis, M, Borg, B, Kerridge, RK, Douglas, J, Brannan, J, Pretto, J, Godsall, MG, Beauchamp, N, Allen, S, Kennedy, A, Wright, E, Malherbe, J, Ismail, H, Riedel, B, Melville, A, Sivakumar, H, Murmane, A, Kenchington, K, Kirabiyik, Y, Gurunathan, U, Stonell, C, Brunello, K, Steele, K, Tronstad, O, Masel, P, Dent, A, Smith, E, Bodger, A, Abolfathi, M, Sivalingam, P, Hall, A, Painter, TW, Macklin, S, Elliott, A, Carrera, AM, Terblanche, NCS, Pitt, S, Samuels, J, Wilde, C, Leslie, K, MacCormick, A, Bramley, D, Southcott, AM, Grant, J, Taylor, H, Bates, S, Towns, M, Tippett, A, Marshall, F, Kunasingam, J, Yagnik, A, Crescini, C, Yagnik, S, McCartney, CJL, Choi, S, Somascanthan, P, Flores, K, Karkouti, K, Clarke, HA, Jerath, A, McCluskey, SA, Wasowicz, M, Granton, JT, Day, L, Pazmino-Canizares, J, Oh, P, Belliard, R, Lee, L, Dobson, K, Chan, V, Brull, R, Ami, N, Stanbrook, M, Hagen, K, Campbell, D, Short, T, Van Der Westhuizen, J, Higgie, K, Lindsay, H, Jang, R, Wong, C, Mcallister, D, Ali, M, Kumar, J, Waymouth, E, Kim, C, Dimech, J, Lorimer, M, Tai, J, Miller, R, Sara, R, Collingwood, A, Olliff, S, Gabriel, S, Houston, H, Dalley, P, Hurford, S, Hunt, A, Andrews, L, Navarra, L, Jason-Smith, A, Thompson, H, McMillan, N, Back, G, Croal, BL, Lum, M, Martin, D, James, S, Filipe, H, Pinto, M, Kynaston, S, Phull, M, Beilstein, C, Bodger, P, Everingham, K, Hu, Y, Niebrzegowska, E, Corriea, C, Creary, T, Januszewska, M, Ahmad, T, Whalley, J, Haslop, R, McNeil, J, Brown, A, MacDonald, N, Pakats, M, Greaves, K, Jhanji, S, Raobaikady, R, Black, E, Rooms, M, Lawrence, H, Koutra, M, Pirie, K, Gertsman, M, Jack, S, Celinski, M, Levett, D, Edwards, M, Salmon, K, Bolger, C, Loughney, L, Seaward, L, Collins, H, Tyrell, B, Tantony, N, Golder, K, Stephens, RCM, Gallego-Paredes, L, Reyes, A, Gutierrez Del Arroyo, A, Raj, A, Lifford, R, International and National Coordinators, Central Project Office Operations Committee, CPET Methods Committee, Outcome Adjudication Committee, and International Steering Committee more...
- Abstract
BACKGROUND: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications. METHODS: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes. RESULTS: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05). CONCLUSIONS: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability. more...
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- 2020
12. Association between pre-hospital chest pain severity and myocardial injury in ST elevation myocardial infarction: A post-hoc analysis of the AVOID study
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Fernando, H, Nehme, Z, Peter, K, Bernard, S, Stephenson, M, Bray, JE, Myles, PS, Stub, R, Cameron, P, Ellims, AH, Taylor, AJ, Kaye, DM, Smith, K, Stub, D, Fernando, H, Nehme, Z, Peter, K, Bernard, S, Stephenson, M, Bray, JE, Myles, PS, Stub, R, Cameron, P, Ellims, AH, Taylor, AJ, Kaye, DM, Smith, K, and Stub, D more...
- Abstract
BACKGROUND: We sought to determine if an association exists between prehospital chest pain severity and markers of myocardial injury. METHODS AND RESULTS: Patients with confirmed ST elevation myocardial infarction (STEMI) treated by emergency medical services were included in this retrospective cohort analysis of the AVOID study. The primary endpoint was the association of pre-hospital initial chest pain severity, cardiac biomarkers and infarct size based on cardiac magnetic resonance imaging. Groups were categorized based on moderate to severe chest pain (numerical rating scale pain ≥ 5/10) or less than moderate severity to compare procedural and clinical outcomes. 414 patients were included in the analysis. There was a weak correlation between initial pre-hospital chest pain severity and peak creatine kinase (r = 0.16, p = 0.001) and peak cardiac troponin I (r = 0.14, p = 0.005). Both were no longer significant after adjusting for known confounders. There was no association between moderate to severe chest pain on arrival and major adverse cardiac events at 6 months (20% vs. 14%, p=0.12). There was a weak correlation between history of ischemic heart disease (r = 0.16, p = 0.001), percutaneous coronary intervention (r = 0.16, p = 0.001), left anterior descending artery (r = 0.12, p = 0.012) as the culprit vessel and a weak negative correlation between age (r = -0.14, p = 0.039) and chest pain. CONCLUSION: Only a weak association between pre-hospital chest pain severity and markers of myocardial injury was identified, supporting more judicious use of opioid analgesia with a focus on patient comfort. more...
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- 2021
13. A Dual-Antigen Enzyme-Linked Immunosorbent Assay Allows the Assessment of Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Seroprevalence in a Low-Transmission Setting
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Hicks, SM, Pohl, K, Neeman, T, McNamara, HA, Parsons, KM, He, J-S, Ali, SA, Nazir, S, Rowntree, LC, Nguyen, THO, Kedzierska, K, Doolan, DL, Vinuesa, CG, Cook, MC, Coatsworth, N, Myles, PS, Kurth, F, Sander, LE, Mann, GJ, Gruen, RL, George, AJ, Gardiner, EE, Cockburn, IA, Hicks, SM, Pohl, K, Neeman, T, McNamara, HA, Parsons, KM, He, J-S, Ali, SA, Nazir, S, Rowntree, LC, Nguyen, THO, Kedzierska, K, Doolan, DL, Vinuesa, CG, Cook, MC, Coatsworth, N, Myles, PS, Kurth, F, Sander, LE, Mann, GJ, Gruen, RL, George, AJ, Gardiner, EE, and Cockburn, IA more...
- Abstract
Estimates of seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies have been hampered by inadequate assay sensitivity and specificity. Using an enzyme-linked immunosorbent assay-based approach that combines data about immunoglobulin G responses to both the nucleocapsid and spike receptor binding domain antigens, we show that excellent sensitivity and specificity can be achieved. We used this assay to assess the frequency of virus-specific antibodies in a cohort of elective surgery patients in Australia and estimated seroprevalence in Australia to be 0.28% (95% Confidence Interval, 0-1.15%). These data confirm the low level of transmission of SARS-CoV-2 in Australia before July 2020 and validate the specificity of our assay. more...
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- 2021
14. The impact of COVID-19 critical illness on new disability, functional outcomes and return to work at 6 months: a prospective cohort study
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Hodgson, CL, Higgins, AM, Bailey, MJ, Mather, AM, Beach, L, Bellomo, R, Bissett, B, Boden, IJ, Bradley, S, Burrell, A, Cooper, DJ, Fulcher, BJ, Haines, KJ, Hopkins, J, Jones, AYM, Lane, S, Lawrence, D, van der Lee, L, Liacos, J, Linke, NJ, Gomes, LM, Nickels, M, Ntoumenopoulos, G, Myles, PS, Patman, S, Paton, M, Pound, G, Rai, S, Rix, A, Rollinson, TC, Sivasuthan, J, Tipping, CJ, Thomas, P, Trapani, T, Udy, AA, Whitehead, C, Hodgson, IT, Anderson, S, Neto, AS, Hodgson, CL, Higgins, AM, Bailey, MJ, Mather, AM, Beach, L, Bellomo, R, Bissett, B, Boden, IJ, Bradley, S, Burrell, A, Cooper, DJ, Fulcher, BJ, Haines, KJ, Hopkins, J, Jones, AYM, Lane, S, Lawrence, D, van der Lee, L, Liacos, J, Linke, NJ, Gomes, LM, Nickels, M, Ntoumenopoulos, G, Myles, PS, Patman, S, Paton, M, Pound, G, Rai, S, Rix, A, Rollinson, TC, Sivasuthan, J, Tipping, CJ, Thomas, P, Trapani, T, Udy, AA, Whitehead, C, Hodgson, IT, Anderson, S, and Neto, AS more...
- Abstract
BACKGROUND: There are few reports of new functional impairment following critical illness from COVID-19. We aimed to describe the incidence of death or new disability, functional impairment and changes in health-related quality of life of patients after COVID-19 critical illness at 6 months. METHODS: In a nationally representative, multicenter, prospective cohort study of COVID-19 critical illness, we determined the prevalence of death or new disability at 6 months, the primary outcome. We measured mortality, new disability and return to work with changes in the World Health Organization Disability Assessment Schedule 2.0 12L (WHODAS) and health status with the EQ5D-5LTM. RESULTS: Of 274 eligible patients, 212 were enrolled from 30 hospitals. The median age was 61 (51-70) years, and 124 (58.5%) patients were male. At 6 months, 43/160 (26.9%) patients died and 42/108 (38.9%) responding survivors reported new disability. Compared to pre-illness, the WHODAS percentage score worsened (mean difference (MD), 10.40% [95% CI 7.06-13.77]; p < 0.001). Thirteen (11.4%) survivors had not returned to work due to poor health. There was a decrease in the EQ-5D-5LTM utility score (MD, - 0.19 [- 0.28 to - 0.10]; p < 0.001). At 6 months, 82 of 115 (71.3%) patients reported persistent symptoms. The independent predictors of death or new disability were higher severity of illness and increased frailty. CONCLUSIONS: At six months after COVID-19 critical illness, death and new disability was substantial. Over a third of survivors had new disability, which was widespread across all areas of functioning. Clinical trial registration NCT04401254 May 26, 2020. more...
- Published
- 2021
15. COVID-19 risk in elective surgery during a second wave: a prospective cohort study
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Myles, PS, Wallace, S, Story, DA, Brown, W, Cheng, AC, Forbes, A, Sidiropoulos, S, Davidson, A, Tan, N, Jeffreys, A, Hodgson, R, Scott, DA, Radnor, J, Myles, PS, Wallace, S, Story, DA, Brown, W, Cheng, AC, Forbes, A, Sidiropoulos, S, Davidson, A, Tan, N, Jeffreys, A, Hodgson, R, Scott, DA, and Radnor, J more...
- Abstract
BACKGROUND: The COVID-19 pandemic has greatly affected access to elective surgery, largely because of concerns for patients and healthcare workers. A return to normal surgery workflow depends on the prevalence and transmission of coronavirus in elective surgical patients. The aim of this study was to determine the prevalence of active SARS-coronavirus-2 infection during a second wave among patients admitted to hospital for elective surgery in Victoria. METHODS: Prospective cohort study across eight hospitals in Victoria during July-August 2020 was conducted enrolling adults and children admitted to hospital for elective surgery or interventional procedure requiring general anaesthesia. Study outcomes included a positive polymerase chain reaction (PCR) test for SARS-CoV-2 in the preoperative period (primary outcome), and for those with a negative test preoperatively, the incidence of a positive PCR test for SARS-CoV-2 in the post-operative period. RESULTS: We enrolled 4965 elective adult and paediatric surgical patients from 15 July to 31 August 2020. Four patients screened negative on questionnaire but had a positive PCR test for coronavirus, resulting in a Bayesian estimated prevalence of 0.12% (95% probability interval 0-0.26%). There were no reports of healthcare worker infections linked to elective surgery during and up to 2 weeks after the study period. CONCLUSION: The prevalence of SARS-CoV-2 in asymptomatic elective surgical patients during a second wave was approximately 1 in 833. Given the very low likelihood of coronavirus transmission, and with existing current hospital capacity, recommencement of elective surgery should be considered. A coronavirus screening checklist should be mandated for surgical patients. more...
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- 2021
16. Dexamethasone and Surgical-Site Infection
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ANZCA Clinical Trials Network, Chan, MTV, Corcoran, T, Ho, KM, Leslie, K, Myles, PS, O'Loughlin, E, Short, TG, Story, DA, PADDI Investigators, Australasian Society for Infectious Diseases Clinical Research Network, Corcoran Tomas B, Myles Paul S, Forbes Andrew B, Cheng Allen C, Bach Leon A, O'Loughlin Edmond, Leslie Kate, Chan Matthew TV, Story David, Short Timothy G, Martin Catherine, Coutts Pauline, Ho Kowk M, Australian and New Zealand College of Anaesthetists Clinical Trials Network, ANZCA Clinical Trials Network, Chan, MTV, Corcoran, T, Ho, KM, Leslie, K, Myles, PS, O'Loughlin, E, Short, TG, Story, DA, PADDI Investigators, Australasian Society for Infectious Diseases Clinical Research Network, Corcoran Tomas B, Myles Paul S, Forbes Andrew B, Cheng Allen C, Bach Leon A, O'Loughlin Edmond, Leslie Kate, Chan Matthew TV, Story David, Short Timothy G, Martin Catherine, Coutts Pauline, Ho Kowk M, and Australian and New Zealand College of Anaesthetists Clinical Trials Network more...
- Abstract
Background: The glucocorticoid dexamethasone prevents nausea and vomiting after surgery, but there is concern that it may increase the risk of surgical-site infection. less... Methods: In this pragmatic, international, noninferiority trial, we randomly assigned 8880 adult patients who were undergoing nonurgent, noncardiac surgery of at least 2 hours' duration, with a skin incision length longer than 5 cm and a postoperative overnight hospital stay, to receive 8 mg of intravenous dexamethasone or matching placebo while under anesthesia. Randomization was stratified according to diabetes status and trial center. The primary outcome was surgical-site infection within 30 days after surgery. The prespecified noninferiority margin was 2.0 percentage points. Results: A total of 8725 participants were included in the modified intention-to-treat population (4372 in the dexamethasone group and 4353 in the placebo group), of whom 13.2% (576 in the dexamethasone group and 572 in the placebo group) had diabetes mellitus. Of the 8678 patients included in the primary analysis, surgical-site infection occurred in 8.1% (354 of 4350 patients) assigned to dexamethasone and in 9.1% (394 of 4328) assigned to placebo (risk difference adjusted for diabetes status, -0.9 percentage points; 95.6% confidence interval [CI], -2.1 to 0.3; P<0.001 for noninferiority). The results for superficial, deep, and organ-space surgical-site infections and in patients with diabetes were similar to those of the primary analysis. Postoperative nausea and vomiting in the first 24 hours after surgery occurred in 42.2% of patients in the dexamethasone group and in 53.9% in the placebo group (risk ratio, 0.78; 95% CI, 0.75 to 0.82). Hyperglycemic events in patients without diabetes occurred in 22 of 3787 (0.6%) in the dexamethasone group and in 6 of 3776 (0.2%) in the placebo group. Conclusions: Dexamethasone was noninferior to placebo with respect to the incidence of surgical-site infection within 30 days after more...
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- 2021
17. Monitoring
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Myles, PS, primary
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- 2013
- Full Text
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18. Bispectral index monitoring to prevent awareness during anaesthesia: the B-Aware randomised controlled trial
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Myles, PS, Leslie, K., McNeil, J., Forbes, A., and Chan, Mtv
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- 2004
19. Auditory Evoked Potential Anaesthesia Monitoring Design Constraints
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Burton, D, Myles, PS, Brown, I, Xu, M, and Zilberg, M
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- 2006
20. Data on the modulatory effects of a single bolus dexamethasone on the surface marker expression of various leucocyte subsets
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Draxler, DF, Bain, CR, Taylor, R, Wallace, S, Gouldthorpe, O, Corcoran, TB, Myles, PS, Bozaoglu, K, Medcalf, RL, Draxler, DF, Bain, CR, Taylor, R, Wallace, S, Gouldthorpe, O, Corcoran, TB, Myles, PS, Bozaoglu, K, and Medcalf, RL more...
- Abstract
Dexamethasone is frequently administered to surgical patients for anti-emetic prophylaxis. We have examined the immunomodulatory effects of a single bolus of dexamethasone on circulating peripheral blood mononuclear cells (PBMCs) in the same 10 healthy male volunteers, previously used in our investigation on early in vivo effects of a single anti-emetic dose of dexamethasone on innate immune cell gene expression and activation [1]. Blood samples were drawn at baseline, 2 h, 4 h and 24 h. Immune cell phenotypes were examined with flow cytometry. In this data article the expression strength of markers involved in immune activation and immunosuppression as well as maturation, migration, cell death and responsiveness to signalling on monocyte and cDC subsets, as well as NK cells, CD4+ and CD8+ T cells and regulatory T cells (Treg) are presented. These data improve our understanding of the immunomodulatory effects of the glucocorticoid dexamethasone in-vivo, which may be important for the optimisation of treatment regimens as well as the evaluation of new indications for glucocorticoid treatment. more...
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- 2020
21. DNA methylation patterns from peripheral blood separate coronary artery disease patients with and without heart failure
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Bain, CR, Ziemann, M, Kaspi, A, Khan, AW, Taylor, R, Trahair, H, Khurana, I, Kaipananickal, H, Wallace, S, El-Osta, A, Myles, PS, Bozaoglu, K, Bain, CR, Ziemann, M, Kaspi, A, Khan, AW, Taylor, R, Trahair, H, Khurana, I, Kaipananickal, H, Wallace, S, El-Osta, A, Myles, PS, and Bozaoglu, K more...
- Abstract
AIMS: Natriuretic peptides are useful for diagnosis and prognostication of heart failure of any cause. Now, research aims to discover novel biomarkers that will more specifically define the heart failure phenotype. DNA methylation plays a critical role in the development of cardiovascular disease with the potential to predict fundamental pathogenic processes. There is a lack of data relating DNA methylation in heart failure that specifically focuses on patients with severe multi-vessel coronary artery disease. To begin to address this, we conducted a pilot study uniquely exploring the utility of powerful whole-genome methyl-binding domain-capture sequencing in a cohort of cardiac surgery patients, matched for the severity of their coronary artery disease, aiming to identify candidate peripheral blood DNA methylation markers of ischaemic cardiomyopathy and heart failure. METHODS AND RESULTS: We recruited a cohort of 20 male patients presenting for coronary artery bypass graft surgery with phenotypic extremes of heart failure but who otherwise share a similar coronary ischaemic burden, age, sex, and ethnicity. Methylation profiling in patient blood samples was performed using methyl-binding domain-capture sequencing. Differentially methylated regions were validated using targeted bisulfite sequencing. Gene set enrichment analysis was performed to identify differences in methylation at or near gene promoters in certain known Reactome pathways. We detected 567 188 methylation peaks of which our general linear model identified 68 significantly differentially methylated regions in heart failure with a false discovery rate <0.05. Of these regions, 48 occurred within gene bodies and 25 were located near enhancer elements, some within coding genes and some in non-coding genes. Gene set enrichment analyses identified 103 significantly enriched gene sets (false discovery rate <0.05) in heart failure. Validation analysis of regions with the strongest differential methylation da more...
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- 2020
22. Stopping vs. Continuing Aspirin before Coronary Artery Surgery
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Myles PS, Smith JA, Forbes A, Silbert B, Jayarajah M, Painter T, Cooper DJ, Marasco S, McNeil J, Bussières JS, Wallace S, ATACAS Investigators of the ANZCA Clinical Trials Network, Landoni G, Myles, P, Smith, Ja, Forbes, A, Silbert, B, Jayarajah, M, Painter, T, Cooper, Dj, Marasco, S, Mcneil, J, Bussières, J, Wallace, S, ATACAS Investigators of the ANZCA Clinical Trials, Network, and Landoni, G more...
- Subjects
Male ,medicine.medical_specialty ,Postoperative Hemorrhage ,030204 cardiovascular system & hematology ,Placebo ,Coronary artery disease ,03 medical and health sciences ,Postoperative Complications ,0302 clinical medicine ,Double-Blind Method ,Preoperative Care ,medicine ,Humans ,Blood Transfusion ,030212 general & internal medicine ,Myocardial infarction ,Coronary Artery Bypass ,Stroke ,Aged ,Aspirin ,business.industry ,Platelet Aggregation Inhibitor ,Coronary Artery Bypa ,Medicine (all) ,Thrombosis ,General Medicine ,Perioperative ,Length of Stay ,Middle Aged ,medicine.disease ,Surgery ,Bypass surgery ,Thrombosi ,Commentary ,Female ,Postoperative Complication ,business ,Platelet Aggregation Inhibitors ,Human ,medicine.drug - Abstract
BACKGROUND Most patients with coronary artery disease receive aspirin for primary or secondary prevention of myocardial infarction, stroke, and death. Aspirin poses a risk of bleeding in patients undergoing surgery, but it is unclear whether aspirin should be stopped before coronary artery surgery. METHODS We used a 2-by-2 factorial trial design to randomly assign patients who were scheduled to undergo coronary artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the aspirin trial are reported here. Patients were randomly assigned to receive 100 mg of aspirin or matched placebo preoperatively. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. RESULTS Among 5784 eligible patients, 2100 were enrolled; 1047 were randomly assigned to receive aspirin and 1053 to receive placebo. A primary outcome event occurred in 202 patients in the aspirin group (19.3%) and in 215 patients in the placebo group (20.4%) (relative risk, 0.94; 95% confidence interval, 0.80 to 1.12; P = 0.55). Major hemorrhage leading to reoperation occurred in 1.8% of patients in the aspirin group and in 2.1% of patients in the placebo group (P = 0.75), and cardiac tamponade occurred at rates of 1.1% and 0.4%, respectively (P = 0.08). CONCLUSIONS Among patients undergoing coronary artery surgery, the administration of preoperative aspirin resulted in neither a lower risk of death or thrombotic complications nor a higher risk of bleeding than that with placebo. (Funded by the Australian National Health and Medical Research Council and others; Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639.). more...
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- 2016
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23. Heart rate recovery and morbidity after noncardiac surgery: Planned secondary analysis of two prospective, multi-centre, blinded observational studies
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Bianchi, C, Ackland, GL, Abbott, TEF, Minto, G, Clark, M, Owen, T, Prabhu, P, May, SM, Reynolds, JA, Cuthbertson, BH, Wijesundera, D, Pearse, RM, Myles, PS, Shulman, MA, Wallace, S, Farrington, C, Thompson, B, Ellis, M, Borg, B, Kerridge, RK, Douglas, J, Brannan, J, Pretto, J, Godsall, MG, Beauchamp, N, Allen, S, Kennedy, A, Wright, E, Malherbe, J, Ismail, H, Riedel, B, Melville, A, Sivakumar, H, Murmane, A, Kenchington, K, Kirabiyik, Y, Gurunathan, U, Stonell, C, Brunello, K, Steele, K, Tronstad, O, Masel, P, Dent, A, Smith, E, Bodger, A, Abolfathi, M, Sivalingam, P, Hall, A, Painter, TW, Macklin, S, Elliott, A, Carrera, AM, Terblanche, NCS, Pitt, S, Samuels, J, Wilde, C, Leslie, K, MacCormick, A, Bramley, D, Southcott, AM, Grant, J, Taylor, H, Bates, S, Towns, M, Tippett, A, Marshall, F, Mazer, CD, Kunasingam, J, Yagnik, A, Crescini, C, Yagnik, S, McCartney, CJL, Choi, S, Somascanthan, P, Flores, K, Wijeysundera, DN, Beattie, WS, Karkouti, K, Clarke, HA, Jerath, A, McCluskey, SA, Wasowicz, M, Granton, JT, Day, L, Pazmino-Canizares, J, Oh, P, Belliard, R, Lee, L, Dobson, K, Chan, V, Brull, R, Ami, N, Stanbrook, M, Hagen, K, Campbell, D, Short, T, Van Der Westhuizen, J, Higgie, K, Lindsay, H, Jang, R, Wong, C, Mcallister, D, Ali, M, Kumar, J, Waymouth, E, Kim, C, Dimech, J, Lorimer, M, Tai, J, Miller, R, Sara, R, Collingwood, A, Olliff, S, Gabriel, S, Houston, H, Dalley, P, Hurford, S, Hunt, A, Andrews, L, Navarra, L, Jason-Smith, A, Thompson, H, McMillan, N, Back, G, Croal, BL, Lum, M, Martin, D, James, S, Filipe, H, Pinto, M, Kynaston, S, Phull, M, Beilstein, C, Bodger, P, Everingham, K, Hu, Y, Niebrzegowska, E, Corriea, C, Creary, T, Januszewska, M, Ahmad, T, Whalley, J, Haslop, R, McNeil, J, Brown, A, MacDonald, N, Pakats, M, Greaves, K, Jhanji, S, Raobaikady, R, Black, E, Rooms, M, Lawrence, H, Koutra, M, Pirie, K, Gertsman, M, Jack, S, Celinski, M, Levett, D, Edwards, M, Salmon, K, Bolger, C, Loughney, L, Seaward, L, Collins, H, Tyrell, B, Tantony, N, Golder, K, Stephens, RCM, Gallego-Paredes, L, Reyes, A, del Arroyo, AG, Raj, A, Lifford, R, King, A, Pollak, C, Williams, C, Patrick, A, West, C, Vickers, E, Green, R, Jones, A, Otto, J, Lach, A, Whittle, J, Paredes, LG, Toner, A, Williams, A, Pradhu, P, Hull, D, Montague, L, Bianchi, C, Ackland, GL, Abbott, TEF, Minto, G, Clark, M, Owen, T, Prabhu, P, May, SM, Reynolds, JA, Cuthbertson, BH, Wijesundera, D, Pearse, RM, Myles, PS, Shulman, MA, Wallace, S, Farrington, C, Thompson, B, Ellis, M, Borg, B, Kerridge, RK, Douglas, J, Brannan, J, Pretto, J, Godsall, MG, Beauchamp, N, Allen, S, Kennedy, A, Wright, E, Malherbe, J, Ismail, H, Riedel, B, Melville, A, Sivakumar, H, Murmane, A, Kenchington, K, Kirabiyik, Y, Gurunathan, U, Stonell, C, Brunello, K, Steele, K, Tronstad, O, Masel, P, Dent, A, Smith, E, Bodger, A, Abolfathi, M, Sivalingam, P, Hall, A, Painter, TW, Macklin, S, Elliott, A, Carrera, AM, Terblanche, NCS, Pitt, S, Samuels, J, Wilde, C, Leslie, K, MacCormick, A, Bramley, D, Southcott, AM, Grant, J, Taylor, H, Bates, S, Towns, M, Tippett, A, Marshall, F, Mazer, CD, Kunasingam, J, Yagnik, A, Crescini, C, Yagnik, S, McCartney, CJL, Choi, S, Somascanthan, P, Flores, K, Wijeysundera, DN, Beattie, WS, Karkouti, K, Clarke, HA, Jerath, A, McCluskey, SA, Wasowicz, M, Granton, JT, Day, L, Pazmino-Canizares, J, Oh, P, Belliard, R, Lee, L, Dobson, K, Chan, V, Brull, R, Ami, N, Stanbrook, M, Hagen, K, Campbell, D, Short, T, Van Der Westhuizen, J, Higgie, K, Lindsay, H, Jang, R, Wong, C, Mcallister, D, Ali, M, Kumar, J, Waymouth, E, Kim, C, Dimech, J, Lorimer, M, Tai, J, Miller, R, Sara, R, Collingwood, A, Olliff, S, Gabriel, S, Houston, H, Dalley, P, Hurford, S, Hunt, A, Andrews, L, Navarra, L, Jason-Smith, A, Thompson, H, McMillan, N, Back, G, Croal, BL, Lum, M, Martin, D, James, S, Filipe, H, Pinto, M, Kynaston, S, Phull, M, Beilstein, C, Bodger, P, Everingham, K, Hu, Y, Niebrzegowska, E, Corriea, C, Creary, T, Januszewska, M, Ahmad, T, Whalley, J, Haslop, R, McNeil, J, Brown, A, MacDonald, N, Pakats, M, Greaves, K, Jhanji, S, Raobaikady, R, Black, E, Rooms, M, Lawrence, H, Koutra, M, Pirie, K, Gertsman, M, Jack, S, Celinski, M, Levett, D, Edwards, M, Salmon, K, Bolger, C, Loughney, L, Seaward, L, Collins, H, Tyrell, B, Tantony, N, Golder, K, Stephens, RCM, Gallego-Paredes, L, Reyes, A, del Arroyo, AG, Raj, A, Lifford, R, King, A, Pollak, C, Williams, C, Patrick, A, West, C, Vickers, E, Green, R, Jones, A, Otto, J, Lach, A, Whittle, J, Paredes, LG, Toner, A, Williams, A, Pradhu, P, Hull, D, and Montague, L more...
- Abstract
BACKGROUND: Impaired cardiac vagal function, quantified preoperatively as slower heart rate recovery (HRR) after exercise, is independently associated with perioperative myocardial injury. Parasympathetic (vagal) dysfunction may also promote (extra-cardiac) multi-organ dysfunction, although perioperative data are lacking. Assuming that cardiac vagal activity, and therefore heart rate recovery response, is a marker of brainstem parasympathetic dysfunction, we hypothesized that impaired HRR would be associated with a higher incidence of morbidity after noncardiac surgery. METHODS: In two prospective, blinded, observational cohort studies, we established the definition of impaired vagal function in terms of the HRR threshold that is associated with perioperative myocardial injury (HRR ≤ 12 beats min-1 (bpm), 60 seconds after cessation of cardiopulmonary exercise testing. The primary outcome of this secondary analysis was all-cause morbidity three and five days after surgery, defined using the Post-Operative Morbidity Survey. Secondary outcomes of this analysis were type of morbidity and time to become morbidity-free. Logistic regression and Cox regression tested for the association between HRR and morbidity. Results are presented as odds/hazard ratios [OR or HR; (95% confidence intervals). RESULTS: 882/1941 (45.4%) patients had HRR≤12bpm. All-cause morbidity within 5 days of surgery was more common in 585/822 (71.2%) patients with HRR≤12bpm, compared to 718/1119 (64.2%) patients with HRR>12bpm (OR:1.38 (1.14-1.67); p = 0.001). HRR≤12bpm was associated with more frequent episodes of pulmonary (OR:1.31 (1.05-1.62);p = 0.02)), infective (OR:1.38 (1.10-1.72); p = 0.006), renal (OR:1.91 (1.30-2.79); p = 0.02)), cardiovascular (OR:1.39 (1.15-1.69); p<0.001)), neurological (OR:1.73 (1.11-2.70); p = 0.02)) and pain morbidity (OR:1.38 (1.14-1.68); p = 0.001) within 5 days of surgery. CONCLUSIONS: Multi-organ dysfunction is more common in surgical patients with cardiac vagal dys more...
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- 2019
24. The perioperative administration of dexamethasone and infection (PADDI) trial protocol: rationale and design of a pragmatic multicentre non-inferiority study
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Corcoran, TB, Myles, PS, Forbes, AB, O'Loughlin, E, Leslie, K, Story, D, Short, TG, Chan, MTV, Coutts, P, Sidhu, J, Cheng, AC, Bach, LA, Ho, KM, Corcoran, TB, Myles, PS, Forbes, AB, O'Loughlin, E, Leslie, K, Story, D, Short, TG, Chan, MTV, Coutts, P, Sidhu, J, Cheng, AC, Bach, LA, and Ho, KM more...
- Abstract
INTRODUCTION: The intraoperative administration of dexamethasone for prophylaxis against postoperative nausea and vomiting is a common and recommended practice. The safety of the administration of this immunosuppressive agent at a time of significant immunological disruption has not been rigorously evaluated in terms of infective complications. METHODS/ANALYSIS: This is a pragmatic, multicentre, randomised, controlled, non-inferiority trial. A total of 8880 patients undergoing elective major surgery will be enrolled. Participants will be randomly allocated to receive either dexamethasone 8 mg or placebo intravenously following the induction of anaesthesia in a 1:1 ratio, stratified by centre and diabetes status. Patient enrolment into the trial is ongoing. The primary outcome is surgical site infection at 30 days following surgery, defined according to the Centre for Disease Control criteria. ETHICS/DISSEMINATION: The PADDI trial has been approved by the ethics committees of over 45 participating sites in Australia, New Zealand, Hong Kong, South Africa and the Netherlands. The trial has been endorsed by the Australia and New Zealand College of Anaesthetists Clinical Trials Network and the Australian Society for Infectious Diseases Clinical Research Network. Participant recruitment began in March 2016 and is expected to be complete in mid-2019. Publication of the results of the PADDI trial is anticipated to occur in early 2020. TRIAL REGISTRATION NUMBER: ACTRN12614001226695. more...
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- 2019
25. Measurement of exercise tolerance before surgery (METS) study: A protocol for an international multicentre prospective cohort study of cardiopulmonary exercise testing prior to major non-cardiac surgery
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Myles, PS, Shulman, MA, Wijeysundera DN, Pearse RM, Shulman MA, Abbott TE, Torres E, Croal BL, Granton JT, Thorpe KE, Grocott MP, Farrington C, Myles PS, Cuthbertson BH, METS Study Investigators, Myles, PS, Shulman, MA, Wijeysundera DN, Pearse RM, Shulman MA, Abbott TE, Torres E, Croal BL, Granton JT, Thorpe KE, Grocott MP, Farrington C, Myles PS, Cuthbertson BH, and METS Study Investigators more...
- Abstract
Preoperative functional capacity is considered an important risk factor for cardiovascular and other complications of major non-cardiac surgery. Nonetheless, the usual approach for estimating preoperative functional capacity, namely doctors' subjective assessment, may not accurately predict postoperative morbidity or mortality. 3 possible alternatives are cardiopulmonary exercise testing; the Duke Activity Status Index, a standardised questionnaire for estimating functional capacity; and the serum concentration of N-terminal pro-B-type natriuretic peptide (NT pro-BNP), a biomarker for heart failure and cardiac ischaemia. METHODS AND ANALYSIS: The Measurement of Exercise Tolerance before Surgery (METS) Study is a multicentre prospective cohort study of patients undergoing major elective non-cardiac surgery at 25 participating study sites in Australia, Canada, New Zealand and the UK. We aim to recruit 1723 participants. Prior to surgery, participants undergo symptom-limited cardiopulmonary exercise testing on a cycle ergometer, complete the Duke Activity Status Index questionnaire, undergo blood sampling to measure serum NT pro-BNP concentration and have their functional capacity subjectively assessed by their responsible doctors. Participants are followed for 1 year after surgery to assess vital status, postoperative complications and general health utilities. The primary outcome is all-cause death or non-fatal myocardial infarction within 30 days after surgery, and the secondary outcome is all-cause death within 1 year after surgery. Both receiver-operating-characteristic curve methods and risk reclassification table methods will be used to compare the prognostic accuracy of preoperative subjective assessment, peak oxygen consumption during cardiopulmonary exercise testing, Duke Activity Status Index scores and serum NT pro-BNP concentration. ETHICS AND DISSEMINATION: The METS Study has received research ethics board approval at all sites. Participant recruitment be more...
- Published
- 2016
26. Severe Nausea and Vomiting in the Evaluation of Nitrous Oxide in the Gas Mixture for Anesthesia II Trial
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Myles, PS, Myles PS, Chan MT, Kasza J, Paech MJ, Leslie K, Peyton PJ, Sessler DI, Haller G, Beattie WS, Osborne C, Sneyd JR, Forbes A, Myles, PS, Myles PS, Chan MT, Kasza J, Paech MJ, Leslie K, Peyton PJ, Sessler DI, Haller G, Beattie WS, Osborne C, Sneyd JR, and Forbes A more...
- Abstract
BACKGROUND: The Evaluation of Nitrous oxide in the Gas Mixture for Anesthesia II trial randomly assigned 7,112 noncardiac surgery patients to a nitrous oxide or nitrous oxide-free anesthetic; severe postoperative nausea and vomiting (PONV) was a prespecified secondary end point. Thus, the authors evaluated the association between nitrous oxide, severe PONV, and effectiveness of PONV prophylaxis in this setting. METHODS: Univariate and multivariate analyses of patient, surgical, and other perioperative characteristics were used to identify the risk factors for severe PONV and to measure the impact of severe PONV on patient outcomes. RESULTS: Avoiding nitrous oxide reduced the risk of severe PONV (11 vs. 15%; risk ratio [RR], 0.74 [95% CI, 0.63 to 0.84]; P < 0.001), with a stronger effect in Asian patients (RR, 0.55 [95% CI, 0.43 to 0.69]; interaction P = 0.004) but lower effect in those who received PONV prophylaxis (RR, 0.89 [95% CI, 0.76 to 1.05]; P = 0.18). Gastrointestinal surgery was associated with an increased risk of severe PONV when compared with most other types of surgery (P < 0.001). Patients with severe PONV had lower quality of recovery scores (10.4 [95% CI, 10.2 to 10.7] vs. 13.1 [95% CI, 13.0 to 13.2], P < 0.0005); severe PONV was associated with postoperative fever (15 vs. 20%, P = 0.001). Patients with severe PONV had a longer hospital stay (adjusted hazard ratio, 1.14 [95% CI, 1.05 to 1.23], P = 0.002). CONCLUSIONS: The increased risk of PONV with nitrous oxide is near eliminated by antiemetic prophylaxis. Severe PONV, which is seen in more than 10% of patients, is associated with postoperative fever, poor quality of recovery, and prolonged hospitalization. more...
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- 2016
27. Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial.
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Chan, MTV, Leslie, K, Myles, PS, O'Loughlin, E, Paech, MJ, Peyton, PJ, Halliwell, R, McMillan, H, Beattie, WS, Wijeysundera, DN, Sessler, DI, Wallace, S, Galagher, W, Farrington, C, Ditoro, A, Baulch, S, Sidiropoulos, S, Bulach, R, Bryant, D, Mitteregger, V, Bolsin, S, Osborne, C, McRae, R, Backstrom, M, Cotter, R, March, S, Said, S, Cope, J, Fahlbusch, D, Crump, D, Thompson, G, Jefferies, A, Reeves, M, Buckley, N, Tidy, T, Schricker, T, Lattermann, R, Iannuzzi, D, Carroll, J, Jacka, M, Bryden, C, Badner, N, Tsang, MWY, Cheng, BCP, Fong, ACM, Chu, LCY, Ko, EGY, Mohd, N, Ming, LE, Campbell, D, McAllister, D, Walker, S, Olliff, S, Kennedy, R, Eldawlatly, A, Alzahrani, T, Chua, N, Sneyd, R, Parkinson, I, Brennan, A, Balaji, P, NIghtingale, J, Kunst, G, Dickinson, M, Subramaniam, B, Banner-Godspeed, V, Liu, J, Kurz, A, Hesler, B, Fu, AY, Egan, C, Fiffick, AN, Hutcherson, MT, Turan, A, Naylor, A, Obal, D, Cooke, E, ANZCA Clinical Trials Network for the ENIGMA-II Investigators, X, Chan, MTV, Leslie, K, Myles, PS, O'Loughlin, E, Paech, MJ, Peyton, PJ, Halliwell, R, McMillan, H, Beattie, WS, Wijeysundera, DN, Sessler, DI, Wallace, S, Galagher, W, Farrington, C, Ditoro, A, Baulch, S, Sidiropoulos, S, Bulach, R, Bryant, D, Mitteregger, V, Bolsin, S, Osborne, C, McRae, R, Backstrom, M, Cotter, R, March, S, Said, S, Cope, J, Fahlbusch, D, Crump, D, Thompson, G, Jefferies, A, Reeves, M, Buckley, N, Tidy, T, Schricker, T, Lattermann, R, Iannuzzi, D, Carroll, J, Jacka, M, Bryden, C, Badner, N, Tsang, MWY, Cheng, BCP, Fong, ACM, Chu, LCY, Ko, EGY, Mohd, N, Ming, LE, Campbell, D, McAllister, D, Walker, S, Olliff, S, Kennedy, R, Eldawlatly, A, Alzahrani, T, Chua, N, Sneyd, R, Parkinson, I, Brennan, A, Balaji, P, NIghtingale, J, Kunst, G, Dickinson, M, Subramaniam, B, Banner-Godspeed, V, Liu, J, Kurz, A, Hesler, B, Fu, AY, Egan, C, Fiffick, AN, Hutcherson, MT, Turan, A, Naylor, A, Obal, D, Cooke, E, ANZCA Clinical Trials Network for the ENIGMA-II Investigators, and X more...
- Abstract
BACKGROUND: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery. METHODS: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs). RESULTS: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55-4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26-3.92]). Patients who suffered a MAPE with troponin elevation but withou more...
- Published
- 2018
28. The early in-vivo effects of a single anti-emetic dose of dexamethasone on innate immune cell gene expression and activation in healthy volunteers
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Bain, CR, Draxler, DF, Taylor, R, Wallace, S, Gouldthorpe, O, Corcoran, TB, Myles, PS, Medcalf, RL, Bozaoglu, K, Bain, CR, Draxler, DF, Taylor, R, Wallace, S, Gouldthorpe, O, Corcoran, TB, Myles, PS, Medcalf, RL, and Bozaoglu, K more...
- Abstract
Dexamethasone is often administered to surgical patients for anti-emetic prophylaxis. This study examined the early (up to 24 h) in-vivo effects of dexamethasone (8 mg) to demonstrate the magnitude and temporal nature of changes on circulating peripheral blood mononuclear cell gene expression and activation in 10 healthy male volunteers. Blood samples were drawn at baseline, 2 h, 4 h and 24 h. Gene expression was measured using quantitative real-time polymerase chain reaction. Cytokine expression was measured using multiplex immuno-assays. Innate immune cell phenotypes were examined with flow cytometry. Dexamethasone resulted in rapid transient changes in immunophilin (p = 0.0247), plasminogen activator inhibitor-1 (p = 0.0004), forkhead box P3 (p = 0.0068) and dual specific phosphatase-1 (p = 0.0157) gene expression at 4 h compared with pre-dexamethasone. Plasma interleukin-10 levels increased within 2 h (p = 0.0071) and returned to baseline at 24 h. Reductions in classical (p = 0.0009) and intermediate monocytes (p = 0.0178) and dendritic cells (p = 0.0012) were followed by increases in the level of these populations at 24 h compared with pre-dexamethasone (classical monocytes p = 0.0073, intermediate monocytes p = 0.0271, dendritic cells p = 0.0142). There was a profound reduction in the mean fluorescence intensity of the maturation marker, human histocompatibility leucocyte antigen, at 24 h in all monocyte subsets (p = 0.0002 for classical and non-classical monocytes, p = 0.0001 for intermediate monocytes) and dendritic cells (p = 0.0001). This study confirms rapid transient effects of 8 mg dexamethasone on innate immune cells with the potential to alter the inflammatory response to surgery and provides support for the hypothesis that intra-operative administration may be both immunosuppressive and immune-activating in the immediate peri-operative period. more...
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- 2018
29. Restrictive versus liberal fluid therapy for major abdominal surgery
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ANZCA Clinical Trials Network, Chan, MTV, Leslie, K, McGuinness, S, Myles, PS, Painter, TW, Peyton, PJ, Story, D, Bellomo, R, Corcoran, T, Forbes, A, Peyton, P, Christophi, C, Parke, R, Serpell, J, Painter, T, McCluskey, S, Minto, G, Wallace, S, NZ Intensive Care Society Clinical Trials Group, ANZCA Clinical Trials Network, Chan, MTV, Leslie, K, McGuinness, S, Myles, PS, Painter, TW, Peyton, PJ, Story, D, Bellomo, R, Corcoran, T, Forbes, A, Peyton, P, Christophi, C, Parke, R, Serpell, J, Painter, T, McCluskey, S, Minto, G, Wallace, S, and NZ Intensive Care Society Clinical Trials Group more...
- Abstract
BACKGROUND Guidelines to promote the early recovery of patients undergoing major surgery recommend a restrictive intravenous-fluid strategy for abdominal surgery. However, the supporting evidence is limited, and there is concern about impaired organ perfusion. METHODS In a pragmatic, international trial, we randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery. The primary outcome was disability-free survival at 1 year. Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death. RESULTS During and up to 24 hours after surgery, 1490 patients in the restrictive fluid group had a median intravenous-fluid intake of 3.7 liters (interquartile range, 2.9 to 4.9), as compared with 6.1 liters (interquartile range, 5.0 to 7.4) in 1493 patients in the liberal fluid group (P<0.001). The rate of disability-free survival at 1 year was 81.9% in the restrictive fluid group and 82.3% in the liberal fluid group (hazard ratio for death or disability, 1.05; 95% confidence interval, 0.88 to 1.24; P=0.61). The rate of acute kidney injury was 8.6% in the restrictive fluid group and 5.0% in the liberal fluid group (P<0.001). The rate of septic complications or death was 21.8% in the restrictive fluid group and 19.8% in the liberal fluid group (P=0.19); rates of surgical-site infection (16.5% vs. 13.6%, P=0.02) and renal-replacement therapy (0.9% vs. 0.3%, P=0.048) were higher in the restrictive fluid group, but the between-group difference was not significant after adjustment for multiple testing. CONCLUSIONS Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen and w more...
- Published
- 2018
30. Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: patient comfort.
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Myles, PS, Peyton, PJ, Cyna, AM, Boney, O, Botti, M, Gan, TJ, Jensen, MP, Kehlet, H, Kurz, A, De Oliveira, GS Jr, Peyton, P, Sessler, DI, Tramèr, MR, Wu, CL, StEP–COMPAC Group, Myles, P, Grocott, M, Biccard, B, Blazeby, J, Chan, M, Diouf, E, Fleisher, L, Kalkman, C, Moonesinghe, R, Wijeysundera, D, Myles, PS, Peyton, PJ, Cyna, AM, Boney, O, Botti, M, Gan, TJ, Jensen, MP, Kehlet, H, Kurz, A, De Oliveira, GS Jr, Peyton, P, Sessler, DI, Tramèr, MR, Wu, CL, StEP–COMPAC Group, Myles, P, Grocott, M, Biccard, B, Blazeby, J, Chan, M, Diouf, E, Fleisher, L, Kalkman, C, Moonesinghe, R, and Wijeysundera, D more...
- Abstract
BACKGROUND: Maximising patient comfort during and after surgery is a primary concern of anaesthetists and other perioperative clinicians, but objective measures of what constitutes patient comfort in the perioperative period remain poorly defined. The Standardised Endpoints in Perioperative Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. METHODS: We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus process that included up to 89 clinician researchers was then used to refine a recommended list of outcome measures. RESULTS: We identified 122 studies in a literature search, which were the basis for a preliminary list of 24 outcome measures and their definitions. The response rates for Delphi Rounds 1, 2, and 3 were 100% (n=22), 90% (n=79), and 100% (n=13), respectively. A final list of six defined endpoints was identified: pain intensity (at rest and during movement) at 24 h postoperatively, nausea and vomiting (0-6 h, 6-24 h, and overall), one of two quality-of-recovery (QoR) scales (QoR score or QoR-15), time to gastrointestinal recovery, time to mobilisation, and sleep quality. CONCLUSIONS: As standardised outcomes will support benchmarking and pooling (meta-analysis) of trials, one or more of these recommended endpoints should be considered for inclusion in clinical trials assessing patient comfort and pain after surgery more...
- Published
- 2018
31. Restrictive versus liberal fluid therapy for major abdominal surgery
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Myles, PS, Bellomo, R, Corcoran, T, Forbes, A, Peyton, P, Story, D, Christophi, C, Leslie, K, McGuinness, S, Parke, R, Serpell, J, Chan, MTV, Painter, T, McCluskey, S, Minto, G, Wallace, S, ANZCA Clinical Trials Network, NZ Intensive Care Society Clinical Trials Group, Myles, PS, Bellomo, R, Corcoran, T, Forbes, A, Peyton, P, Story, D, Christophi, C, Leslie, K, McGuinness, S, Parke, R, Serpell, J, Chan, MTV, Painter, T, McCluskey, S, Minto, G, Wallace, S, ANZCA Clinical Trials Network, and NZ Intensive Care Society Clinical Trials Group more...
- Abstract
BACKGROUND Guidelines to promote the early recovery of patients undergoing major surgery recommend a restrictive intravenous-fluid strategy for abdominal surgery. However, the supporting evidence is limited, and there is concern about impaired organ perfusion. METHODS In a pragmatic, international trial, we randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery. The primary outcome was disability-free survival at 1 year. Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death. RESULTS During and up to 24 hours after surgery, 1490 patients in the restrictive fluid group had a median intravenous-fluid intake of 3.7 liters (interquartile range, 2.9 to 4.9), as compared with 6.1 liters (interquartile range, 5.0 to 7.4) in 1493 patients in the liberal fluid group (P<0.001). The rate of disability-free survival at 1 year was 81.9% in the restrictive fluid group and 82.3% in the liberal fluid group (hazard ratio for death or disability, 1.05; 95% confidence interval, 0.88 to 1.24; P=0.61). The rate of acute kidney injury was 8.6% in the restrictive fluid group and 5.0% in the liberal fluid group (P<0.001). The rate of septic complications or death was 21.8% in the restrictive fluid group and 19.8% in the liberal fluid group (P=0.19); rates of surgical-site infection (16.5% vs. 13.6%, P=0.02) and renal-replacement therapy (0.9% vs. 0.3%, P=0.048) were higher in the restrictive fluid group, but the between-group difference was not significant after adjustment for multiple testing. CONCLUSIONS Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen and w more...
- Published
- 2018
32. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery.
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Myles, PS, Painter, T, Silbert, BS, McGuinness, S, Byrne, K, Chan, MTV, Smith, Julian A, Forbes, Andrew, Jayarajah, Mohandas, Cooper, D James, Marasco, Silvana, McNeil, John, Bussières, Jean S, Landoni, Giovanni, Wallace, Sophie, Myles, PS, Painter, T, Silbert, BS, McGuinness, S, Byrne, K, Chan, MTV, Smith, Julian A, Forbes, Andrew, Jayarajah, Mohandas, Cooper, D James, Marasco, Silvana, McNeil, John, Bussières, Jean S, Landoni, Giovanni, and Wallace, Sophie more...
- Abstract
Tranexamic acid reduces the risk of bleeding among patients undergoing cardiac surgery, but it is unclear whether this leads to improved outcomes. Furthermore, there are concerns that tranexamic acid may have prothrombotic and proconvulsant effects. In a trial with a 2-by-2 factorial design, we randomly assigned patients who were scheduled to undergo coronary-artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. Of the 4662 patients who were enrolled and provided consent, 4631 underwent surgery and had available outcomes data; 2311 were assigned to the tranexamic acid group and 2320 to the placebo group. A primary outcome event occurred in 386 patients (16.7%) in the tranexamic acid group and in 420 patients (18.1%) in the placebo group (relative risk, 0.92; 95% confidence interval, 0.81 to 1.05; P=0.22). The total number of units of blood products that were transfused during hospitalization was 4331 in the tranexamic acid group and 7994 in the placebo group (P<0.001). Major hemorrhage or cardiac tamponade leading to reoperation occurred in 1.4% of the patients in the tranexamic acid group and in 2.8% of the patients in the placebo group (P=0.001), and seizures occurred in 0.7% and 0.1%, respectively (P=0.002 by Fisher's exact test). Among patients undergoing coronary-artery surgery, tranexamic acid was associated with a lower risk of bleeding than was placebo, without a higher risk of death or thrombotic complications within 30 days after surgery. Tranexamic acid was associated with a higher risk of postoperative seizures. (Funded by the Australian National Health and Medical Research Council and others; ATACAS Australia New Zealand more...
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- 2017
33. Restrictive versus liberal fluid therapy in major abdominal surgery (RELIEF): rationale and design for a multicentre randomised trial
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Myles, PS, Peyton, P, Story, D, Leslie, K, McGuinness, S, Bellomo, R, Corcoran, T, Forbes, A, Wallace, S, Christophi, C, Story, DA, Serpell, J, Parke, R, Myles, PS, Peyton, P, Story, D, Leslie, K, McGuinness, S, Bellomo, R, Corcoran, T, Forbes, A, Wallace, S, Christophi, C, Story, DA, Serpell, J, and Parke, R more...
- Abstract
Introduction The optimal intravenous fluid regimen for patients undergoing major abdominal surgery is unclear. However, results from many small studies suggest a restrictive regimen may lead to better outcomes. A large, definitive clinical trial evaluating perioperative fluid replacement in major abdominal surgery, therefore, is required. Methods/analysis We designed a pragmatic, multicentre, randomised, controlled trial (the RELIEF trial). A total of 3000 patients were enrolled in this study and randomly allocated to a restrictive or liberal fluid regimen in a 1:1 ratio, stratified by centre and planned critical care admission. The expected fluid volumes in the first 24 hour from the start of surgery in restrictive and liberal groups were ≤3.0 L and ≥5.4 L, respectively. Patient enrolment is complete, and follow-up for the primary end point is ongoing. The primary outcome is disability-free survival at 1 year after surgery, with disability defined as a persistent (at least 6 months) reduction in functional status using the 12-item version of the World Health Organisation Disability Assessment Schedule. Ethics/dissemination The RELIEF trial has been approved by the responsible ethics committees of all participating sites. Participant recruitment began in March 2013 and was completed in August 2016, and 1-year follow-up will conclude in August 2017. Publication of the results of the RELIEF trial is anticipated in early 2018. more...
- Published
- 2017
34. Measurement of Exercise Tolerance before Surgery (METS) study: a protocol for an international multicentre prospective cohort study of cardiopulmonary exercise testing prior to major non-cardiac surgery
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Wijeysundera, DN, Pearse, RM, Shulman, MA, Abbott, TEF, Torres, E, Croal, BL, Granton, JT, Thorpe, KE, Grocott, MPW, Farrington, C, Myles, PS, Cuthbertson, BH, Wijeysundera, DN, Pearse, RM, Shulman, MA, Abbott, TEF, Torres, E, Croal, BL, Granton, JT, Thorpe, KE, Grocott, MPW, Farrington, C, Myles, PS, and Cuthbertson, BH more...
- Abstract
INTRODUCTION: Preoperative functional capacity is considered an important risk factor for cardiovascular and other complications of major non-cardiac surgery. Nonetheless, the usual approach for estimating preoperative functional capacity, namely doctors' subjective assessment, may not accurately predict postoperative morbidity or mortality. 3 possible alternatives are cardiopulmonary exercise testing; the Duke Activity Status Index, a standardised questionnaire for estimating functional capacity; and the serum concentration of N-terminal pro-B-type natriuretic peptide (NT pro-BNP), a biomarker for heart failure and cardiac ischaemia. METHODS AND ANALYSIS: The Measurement of Exercise Tolerance before Surgery (METS) Study is a multicentre prospective cohort study of patients undergoing major elective non-cardiac surgery at 25 participating study sites in Australia, Canada, New Zealand and the UK. We aim to recruit 1723 participants. Prior to surgery, participants undergo symptom-limited cardiopulmonary exercise testing on a cycle ergometer, complete the Duke Activity Status Index questionnaire, undergo blood sampling to measure serum NT pro-BNP concentration and have their functional capacity subjectively assessed by their responsible doctors. Participants are followed for 1 year after surgery to assess vital status, postoperative complications and general health utilities. The primary outcome is all-cause death or non-fatal myocardial infarction within 30 days after surgery, and the secondary outcome is all-cause death within 1 year after surgery. Both receiver-operating-characteristic curve methods and risk reclassification table methods will be used to compare the prognostic accuracy of preoperative subjective assessment, peak oxygen consumption during cardiopulmonary exercise testing, Duke Activity Status Index scores and serum NT pro-BNP concentration. ETHICS AND DISSEMINATION: The METS Study has received research ethics board approval at all sites. Participant more...
- Published
- 2016
35. Stopping vs. Continuing Aspirin before Coronary Artery Surgery
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ANZCA Clinical Trials Network, Myles, PS, Painter, TW, Silbert, BS, Smith, JA, Forbes, A, Silbert, B, Jayarajah, M, Painter, T, Cooper, DJ, Marasco, S, McNeil, J, Bussières, JS, Wallace, S, ATACAS Investigators of the ANZCA Clinical Trials Network, ANZCA Clinical Trials Network, Myles, PS, Painter, TW, Silbert, BS, Smith, JA, Forbes, A, Silbert, B, Jayarajah, M, Painter, T, Cooper, DJ, Marasco, S, McNeil, J, Bussières, JS, Wallace, S, and ATACAS Investigators of the ANZCA Clinical Trials Network more...
- Abstract
BACKGROUND: Most patients with coronary artery disease receive aspirin for primary or secondary prevention of myocardial infarction, stroke, and death. Aspirin poses a risk of bleeding in patients undergoing surgery, but it is unclear whether aspirin should be stopped before coronary artery surgery. METHODS: We used a 2-by-2 factorial trial design to randomly assign patients who were scheduled to undergo coronary artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. The results of the aspirin trial are reported here. Patients were randomly assigned to receive 100 mg of aspirin or matched placebo preoperatively. The primary outcome was a composite of death and thrombotic complications (nonfatal myocardial infarction, stroke, pulmonary embolism, renal failure, or bowel infarction) within 30 days after surgery. RESULTS: Among 5784 eligible patients, 2100 were enrolled; 1047 were randomly assigned to receive aspirin and 1053 to receive placebo. A primary outcome event occurred in 202 patients in the aspirin group (19.3%) and in 215 patients in the placebo group (20.4%) (relative risk, 0.94; 95% confidence interval, 0.80 to 1.12; P=0.55). Major hemorrhage leading to reoperation occurred in 1.8% of patients in the aspirin group and in 2.1% of patients in the placebo group (P=0.75), and cardiac tamponade occurred at rates of 1.1% and 0.4%, respectively (P=0.08). CONCLUSIONS: Among patients undergoing coronary artery surgery, the administration of preoperative aspirin resulted in neither a lower risk of death or thrombotic complications nor a higher risk of bleeding than that with placebo. (Funded by the Australian National Health and Medical Research Council and others; Australia New Zealand Clinical Trials Registry number, ACTRN12605000557639.). more...
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- 2016
36. Aspirin in Patients Undergoing Noncardiac Surgery
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Devereaux, Pj, Mrkobrada, M, Sessler, Di, Leslie, K, Alonso Coello, P, Kurz, A, Villar, Jc, Sigamani, A, Biccard, Bm, Meyhoff, Cs, Parlow, Jl, Guyatt, G, Robinson, A, Garg, Ax, Rodseth, Rn, Botto, F, Lurati Buse, G, Xavier, D, Chan, Mt, Tiboni, M, Cook, D, Kumar, Pa, Forget, P, Malaga, G, Fleischmann, E, Amir, M, Eikelboom, J, Mizera, R, Torres, D, Wang, Cy, Vanhelder, T, Paniagua, P, Berwanger, O, Srinathan, S, Graham, M, Pasin, L, Le Manach, Y, Gao, P, Pogue, J, Whitlock, R, Lamy, A, Kearon, C, Baigent, C, Chow, C, Pettit, S, Chrolavicius, S, Yusuf, S, DeBeer J, POISE 2 I. n. v. e. s. t. i. g. a. t. o. r. s., Patel, A, Dechert, W, Jackson, P, Allard, R, Dumerton Shore, D, Mccourt, J, Jones, Pm, Lavi, R, Lavi, S, Moor, R, Dresser, Gk, Gros, Ml, Schumann, Vc, Baur, M, Macdonald, C, Wirzba, B, Regalado, O, Srinathan, Sk, Ong, Dd, Todd, A, Abbas, S, Beattie, Ws, Chan, Vw, Chin, Kj, Wijeysundera, Dn, Graham, Mm, Irwin, M, Jacka, M, El Beheiry, H, Mcmullen, Sm, Macdonald, P, Akhtar, Z, Ayad, S, Buttar, M, Deroee, A, Eshraghi, Y, Fergany, A, Finnigan, P, Fu, A, Grady, M, Helper, S, Hesler, B, Honar, H, Hutcherson, M, Krebs, V, Lee, J, Malik, M, Podolyak, A, Salmasi, V, Arora, H, Coombs, Rf, Martinelli, Sm, Bergese, Sd, Melibary, Sb, Uribe, Aa, Jordan, M, Miller, Sa, Cata, Jp, Nemergut, Ec, Candiotti, Ka, Memtsoudis, Sg, Mckay, Re, Montes, Fr, Parra, Ga, Rojas, Mf, Plata, R, Vásquez, Sm, Sarquis, T, Haider, Z, Jane, Nb, Lanjewar, Pp, Rahate, Pv, Mehra, Br, Premendaran, B, Abraham, V, George, P, Kumar, P, Gaikwad, Sb, Mohan, Nv, Sidhu, G, Alvarez, J, Gonzalez, R, Maestre, M, Popova, E, Urrutia, G, de Nadal, M, González Suárez, S, González Tallada, A, Plou, P, Mena, E, Riveira, C, del Valle, S, Tena, B, Lang, Sa, Ludbrook, Gl, Painter, Tw, Terblanche, Nc, Osborne, C, Mahood, Jr, Myles, Ps, Sivalingam, P, Riedel, B, Elhalawani, I, Drummond, L, Mugabi, A, Naidoo, P, Myburgh, Al, Porrill, Os, Diedericks, Bj, Turton, Ew, Bøgeskov, M, Dahl, Rm, Madsen, Mv, Søndergaard, Es, Bauer, Ne, Martinsen, Kr, Choi, Gy, Gin, T, Ng, Ss, Bidgoli, Sj, Van der Linden PJ, De Kock, M, Kabon, B, Luf, F, Radonic, M, Ishtiaq, O, Safdar, J, Acuna Villaorduna, A, Barrionuevo, P, Castaneda Guarderas, A, Caballero, Ja, Lau, Ve, Aphang Lam MR, Lembo, R, Gossetti, Bruno, Jara, X, Leon, P, Ong, Gs, Lee, Hs, Seeberger, Ee, Seeberger, Md, Alfonsi, P, Coriat, P, Piriou, V, Vizcaychipi, Mp, Rech, Rl, Bergo, Rr, Walker, S, Rodseth, R, Lemanach, Y, Díaz, R, Cortés, Ol, Wetterslev, J, Hoeft, A, Wittmann, M, Chan, M, Landoni, G, Conen, D, Balaji, P, Sovereign, T, Blake, L, Sephton, J, Serra, A, Agrippa, C, Lawrence, M, Biccard, B, Gluud, C, Karthikeyan, G, Auerbach, A, Beattie, S, Buckley, N, Douketis, J, Gerstein, H, Ghali, W, Hart, R, Hill, M, Mcalister, F, Mcauley, D, Miller, S, O'Donnell, M, Pais, P, Parlow, J, Schricker, T, Sessler, D, Simunovic, M, Teoh, K, Walsh, M, Wijeysundera, D, Yang, H, Alshalash, S, Bessissow, A, Duceppe, E, Khalid, Z, Khan, J, Lauw, M, Martinsen, K, Neary, J, Oczkowski, W, Papina, M, Seeberger, M, Tandon, V, Thomas, S, Friedman, L, Cheng, D, Johnstone, D, Lowenstein, E, Roberts, R., Devereaux, Pj, Mrkobrada, M, Sessler, Di, Leslie, K, Alonso Coello, P, Kurz, A, Villar, Jc, Sigamani, A, Biccard, Bm, Meyhoff, C, Parlow, Jl, Guyatt, G, Robinson, A, Garg, Ax, Rodseth, Rn, Botto, F, Lurati Buse, G, Xavier, D, Chan, Mt, Tiboni, M, Cook, D, Kumar, Pa, Forget, P, Malaga, G, Fleischmann, E, Amir M, Eikelboom J, Mizera, R, Torres, D, Wang, Cy, Vanhelder, T, Paniagua, P, Berwanger, O, Srinathan, S, Graham, M, Pasin, L, Le Manach, Y, Gao, P, Pogue, J, Whitlock, R, Lamy, A, Kearon, C, Baigent, C, Chow, C, Pettit, S, Chrolavicius, S, Yusuf, S, and Landoni, Giovanni more...
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Male ,Myocardial Infarction ,Kaplan-Meier Estimate ,noncardiac surgery ,postoperative period ,law.invention ,low drug dose ,hazard ratio ,Postoperative Complications ,Randomized controlled trial ,law ,Myocardial infarction ,Treatment Failure ,Aspirin ,Medicine (all) ,Hazard ratio ,drug effect ,article ,risk assessment ,General Medicine ,Middle Aged ,female ,priority journal ,Anesthesia ,drug withdrawal ,factorial design ,Surgical Procedures, Operative ,Platelet aggregation inhibitor ,Female ,medicine.drug ,hospitalization ,heart infarction ,perioperative period ,preoperative treatment ,Postoperative Hemorrhage ,Perioperative Care ,length of stay ,death ,medicine ,Humans ,follow up ,controlled study ,human ,clonidine ,outcome assessment ,Aged ,treatment duration ,Vascular disease ,business.industry ,Platelet Aggregation Inhibitor ,patient care ,acetylsalicylic acid ,medicine.disease ,bleeding ,major clinical study ,Confidence interval ,purl.org/pe-repo/ocde/ford#3.02.00 [https] ,Clinical research ,multicenter study ,randomized controlled trial ,placebo ,Postoperative Complication ,business ,Platelet Aggregation Inhibitors - Abstract
BACKGROUND: There is substantial variability in the perioperative administration of aspirin in patients undergoing noncardiac surgery, both among patients who are already on an aspirin regimen and among those who are not. METHODS: Using a 2-by-2 factorial trial design, we randomly assigned 10,010 patients who were preparing to undergo noncardiac surgery and were at risk for vascular complications to receive aspirin or placebo and clonidine or placebo. The results of the aspirin trial are reported here. The patients were stratified according to whether they had not been taking aspirin before the study (initiation stratum, with 5628 patients) or they were already on an aspirin regimen (continuation stratum, with 4382 patients). Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. RESULTS: The primary outcome occurred in 351 of 4998 patients (7.0%) in the aspirin group and in 355 of 5012 patients (7.1%) in the placebo group (hazard ratio in the aspirin group, 0.99; 95% confidence interval [CI], 0.86 to 1.15; P = 0.92). Major bleeding was more common in the aspirin group than in the placebo group (230 patients [4.6%] vs. 188 patients [3.8%]; hazard ratio, 1.23; 95% CI, 1.01, to 1.49; P = 0.04). The primary and secondary outcome results were similar in the two aspirin strata. CONCLUSIONS: Administration of aspirin before surgery and throughout the early postsurgical period had no significant effect on the rate of a composite of death or nonfatal myocardial infarction but increased the risk of major bleeding. (Funded by the Canadian Institutes of Health Research and others; POISE-2 ClinicalTrials.gov number, NCT01082874.) Copyright © 2014 Massachusetts Medical Society. more...
- Published
- 2014
37. Clonidine in patients undergoing noncardiac surgery
- Author
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Devereaux, Pj, Sessler, Di, Leslie, K, Kurz, A, Mrkobrada, M, Alonso Coello, P, Villar, Jc, Sigamani, A, Biccard, Bm, Meyhoff, Cs, Parlow, Jl, Guyatt, G, Robinson, A, Garg, Ax, Rodseth, Rn, Botto, F, Lurati Buse, G, Xavier, D, Chan, Mt, Tiboni, M, Cook, D, Kumar, Pa, Forget, P, Malaga, G, Fleischmann, E, Amir, M, Eikelboom, J, Mizera, R, Torres, D, Wang, Cy, Vanhelder, T, Paniagua, P, Berwanger, O, Srinathan, S, Graham, M, Pasin, L, Le Manach, Y, Gao, P, Pogue, J, Whitlock, R, Lamy, A, Kearon, C, Chow, C, Pettit, S, Chrolavicius, S, Yusuf, S, Debeer, J, Patel, A, Dechert, W, Jackson, P, Allard, R, Dumerton Shore, D, Mccourt, J, Jones, Pm, Lavi, R, Lavi, S, Moor, R, Dresser, Gk, Gros, Ml, Schumann, Vc, Baur, M, Macdonald, C, Wirzba, B, Regalado, O, Srinathan, Sk, Ong, Dd, Todd, A, Abbas, S, Beattie, Ws, Chan, Vw, Chin, Kj, Wijeysundera, Dn, Graham, Mm, Irwin, M, Jacka, M, El Beheiry, H, Mcmullen, Sm, Macdonald, P, Akhtar, Z, Ayad, S, Buttar, M, Deroee, A, Eshraghi, Y, Fergany, A, Finnigan, P, Fu, A, Grady, M, Helper, S, Hesler, B, Honar, H, Hutcherson, M, Krebs, V, Lee, J, Malik, M, Podolyak, A, Salmasi, V, Arora, H, Coombs, Rf, Martinelli, Sm, Bergese, Sd, Melibary, Sb, Uribe, Aa, Jordan, M, Miller, Sa, Cata, Jp, Nemergut, Ec, Candiotti, Ka, Memtsoudis, Sg, Mckay, Re, Montes, Fr, Parra, Ga, Rojas, Mf, Plata, R, Vásquez, Sm, Sarquis, T, Haider, Z, Jane, Nb, Lanjewar, Pp, Rahate, Pv, Mehra, Br, Premendaran, B, Abraham, V, George, P, Kumar, P, Gaikwad, Sb, Mohan, Nv, Sidhu, G, Alvarez, J, Gonzalez, R, Maestre, M, Popova, E, Urrutia, G, de Nadal, M, González Suárez, S, González Tallada, A, Plou, P, Mena, E, Riveira, C, del Valle, S, Tena, B, Lang, Sa, Ludbrook, Gl, Painter, Tw, Terblanche, Nc, Osborne, C, Mahood, Jr, Myles, Ps, Sivalingam, P, Riedel, B, Elhalawani, I, Drummond, L, Mugabi, A, Naidoo, P, Myburgh, Al, Porrill, Os, Diedericks, Bj, Turton, Ew, Bøgeskov, M, Dahl, Rm, Madsen, Mv, Søndergaard, Es, Bauer, Ne, Martinsen, Kr, Choi, Gy, Gin, T, Ng, Ss, Bidgoli, Sj, Van der Linden PJ, De Kock, M, Kabon, B, Luf, F, Radonic, M, Ishtiaq, O, Safdar, J, Acuna Villaorduna, A, Barrionuevo, P, Castaneda Guarderas, A, Caballero, Ja, Lau, Ve, Aphang Lam MR, Lembo, R, Gossetti, Bruno, Jara, X, Leon, P, Ong, G, Lee, Hs, Seeberger, Ee, Seeberger, Md, Alfonsi, P, Coriat, P, Piriou, V, Vizcaychipi, Mp, Rech, Rl, Bergo, Rr, Walker, S, Rodseth, R, Lemanach, Y, Díaz, R, Cortés, Ol, Wetterslev, J, Hoeft, A, Wittmann, M, Chan, M, Landoni, G, Conen, D, Balaji, P, Sovereign, T, Blake, L, Sephton, J, Serra, A, Agrippa, C, Lawrence, M, Biccard, B, Gluud, C, Baigent, C, Karthikeyan, G, Auerbach, A, Beattie, S, Buckley, N, Douketis, J, Gerstein, H, Ghali, W, Hart, R, Hill, M, Mcalister, F, Mcauley, D, Miller, S, O'Donnell, M, Pais, P, Parlow, J, Schricker, T, Sessler, D, Simunovic, M, Teoh, K, Walsh, M, Wijeysundera, D, Yang, H, Alshalash, S, Bessissow, A, Duceppe, E, Khalid, Z, Khan, J, Lauw, M, Martinsen, K, Neary, J, Oczkowski, W, Papina, M, Seeberger, M, Tandon, V, Thomas, S, Friedman, L, Cheng, D, Johnstone, D, Lowenstein, E, and Roberts, R. more...
- Subjects
Male ,hypotension ,drug safety ,Heart disease ,Myocardial Infarction ,Kaplan-Meier Estimate ,high risk patient ,noncardiac surgery ,surgery ,low drug dose ,hazard ratio ,Postoperative Complications ,dose response ,Adrenergic alpha-2 Receptor Agonists ,Myocardial infarction ,Treatment Failure ,risk reduction ,Aspirin ,Hazard ratio ,drug effect ,article ,risk assessment ,General Medicine ,Middle Aged ,Clonidine ,aged ,female ,priority journal ,Anesthesia ,factorial design ,Surgical Procedures, Operative ,Female ,Hypotension ,medicine.drug ,medicine.medical_specialty ,heart infarction ,perioperative period ,preoperative treatment ,Placebo ,bradycardia ,Perioperative Care ,length of stay ,death ,medicine ,Humans ,controlled study ,human ,Aged ,treatment duration ,business.industry ,Perioperative ,Vascular surgery ,acetylsalicylic acid ,medicine.disease ,major clinical study ,purl.org/pe-repo/ocde/ford#3.02.00 [https] ,drug efficacy ,multicenter study ,randomized controlled trial ,incidence ,treatment outcome ,placebo ,business ,heart arrest - Abstract
Background: Marked activation of the sympathetic nervous system occurs during and after noncardiac surgery. Low-dose clonidine, which blunts central sympathetic outflow, may prevent perioperative myocardial infarction and death without inducing hemodynamic instability. Methods: We performed a blinded, randomized trial with a 2-by-2 factorial design to allow separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery. A total of 10,010 patients at 135 centers in 23 countries were enrolled. For the comparison of clonidine with placebo, patients were randomly assigned to receive clonidine (0.2 mg per day) or placebo just before surgery, with the study drug continued until 72 hours after surgery. The primary outcome was a composite of death or nonfatal myocardial infarction at 30 days. Results: Clonidine, as compared with placebo, did not reduce the number of primary-outcome events (367 and 339, respectively; hazard ratio with clonidine, 1.08; 95% confidence interval [CI], 0.93 to 1.26; P=0.29). Myocardial infarction occurred in 329 patients (6.6%) assigned to clonidine and in 295 patients (5.9%) assigned to placebo (hazard ratio, 1.11; 95% CI, 0.95 to 1.30; P=0.18). Significantly more patients in the clonidine group than in the placebo group had clinically important hypotension (2385 patients [47.6%] vs. 1854 patients [37.1%]; hazard ratio 1.32; 95% CI, 1.24 to 1.40; P more...
- Published
- 2014
38. Nitrous Oxide and Serious Long-term Morbidity and Mortality in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA)-II Trial.
- Author
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Leslie, K, Myles, PS, Chan, MTV, Peyton, P, Paech, MJ, Kasza, Jessica, Forbes, Andrew, Sessler, Daniel I, Beattie, W Scott, Devereaux, P J, Wallace, Sophie, x1, x2, x3, x4, x5, x6, Leslie, K, Myles, PS, Chan, MTV, Peyton, P, Paech, MJ, Kasza, Jessica, Forbes, Andrew, Sessler, Daniel I, Beattie, W Scott, Devereaux, P J, Wallace, Sophie, x1, x2, x3, x4, x5, and x6 more...
- Abstract
The Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia (ENIGMA)-II trial randomly assigned 7,112 noncardiac surgery patients at risk of perioperative cardiovascular events to 70% N2O or 70% N2 groups. The aim of this follow-up study was to determine the effect of nitrous oxide on a composite primary outcome of death and major cardiovascular events at 1 yr after surgery. One-year follow-up was conducted via a medical record review and telephone interview. Disability was defined as a Katz index of independence in activities of daily living score less than 8. Adjusted odds ratios and hazard ratios were calculated as appropriate for primary and secondary outcomes. Among 5,844 patients evaluated at 1 yr, 435 (7.4%) had died, 206 (3.5%) had disability, 514 (8.8%) had a fatal or nonfatal myocardial infarction, and 111 (1.9%) had a fatal or nonfatal stroke during the 1-yr follow-up period. Exposure to nitrous oxide did not increase the risk of the primary outcome (odds ratio, 1.08; 95% CI, 0.94 to 1.25; P = 0.27), disability or death (odds ratio, 1.07; 95% CI, 0.90 to 1.27; P = 0.44), death (hazard ratio, 1.17; 95% CI, 0.97 to 1.43; P = 0.10), myocardial infarction (odds ratio, 0.97; 95% CI, 0.81 to 1.17; P = 0.78), or stroke (odds ratio, 1.08; 95% CI, 0.74 to 1.58; P = 0.70). These results support the long-term safety of nitrous oxide administration in noncardiac surgical patients with known or suspected cardiovascular disease. more...
- Published
- 2015
39. The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomised, single-blind trial.
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ANZCA Clinical Trials Network, Chan, MTV, Myles, PS, Paech, MJ, Silbert, BS, Leslie, K, Forbes, A, Peyton, PJ, Beattie, S, Sessler, DI, Devereaux, PJ, Schricker, T, Wallace, S, ANZCA Trials Group for the ENIGMA-II investigators, ANZCA Clinical Trials Network, Chan, MTV, Myles, PS, Paech, MJ, Silbert, BS, Leslie, K, Forbes, A, Peyton, PJ, Beattie, S, Sessler, DI, Devereaux, PJ, Schricker, T, Wallace, S, and ANZCA Trials Group for the ENIGMA-II investigators more...
- Abstract
BACKGROUND: Nitrous oxide is commonly used in general anaesthesia but concerns exist that it might increase perioperative cardiovascular risk. We aimed to gather evidence to establish whether nitrous oxide affects perioperative cardiovascular risk. METHODS: We did an international, randomised, assessor-blinded trial in patients aged at least 45 years with known or suspected coronary artery disease having major non-cardiac surgery. Patients were randomly assigned via automated telephone service, stratified by site, to receive a general anaesthetic with or without nitrous oxide. Attending anaesthetists were aware of patients' group assignments, but patients and assessors were not. The primary outcome measure was a composite of death and cardiovascular complications (non-fatal myocardial infarction, stroke, pulmonary embolism, or cardiac arrest) within 30 days of surgery. Our modified intention-to-treat population included all patients randomly assigned to groups and undergoing induction of general anaesthesia for surgery. This trial is registered at ClinicalTrials.gov, number NCT00430989. FINDINGS: Of 10,102 eligible patients, we enrolled 7112 patients between May 30, 2008, and Sept 28, 2013. 3543 were assigned to receive nitrous oxide and 3569 were assigned not to receive nitrous oxide. 3483 patients receiving nitrous oxide and 3509 not receiving nitrous oxide were assessed for the primary outcome. The primary outcome occurred in 283 (8%) patients receiving nitrous oxide and in 296 (8%) patients not receiving nitrous oxide (relative risk 0·96, 95% CI 0·83–1·12; p=0·64). Surgical site infection occurred in 321 (9%) patients assigned to nitrous oxide, and in 311 (9%) patients in the no-nitrous oxide group (p=0·61), and severe nausea and vomiting occurred in 506 patients (15%) assigned to nitrous oxide and 378 patients (11%) not assigned to nitrous oxide (p<0·0001). INTERPRETATION: Our findings support the safety profile of nitrous oxide use in major non-cardiac surgery more...
- Published
- 2014
40. The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomised, single-blind trial.
- Author
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Myles, PS, Leslie, K, Chan, MTV, Peyton, P, Paech, MJ, Silbert, B, Forbes, Andrew, Beattie, W Scott, Sessler, Daniel I, Devereaux, P J, Schricker, Thomas, Wallace, Sophie, Myles, PS, Leslie, K, Chan, MTV, Peyton, P, Paech, MJ, Silbert, B, Forbes, Andrew, Beattie, W Scott, Sessler, Daniel I, Devereaux, P J, Schricker, Thomas, and Wallace, Sophie more...
- Abstract
Nitrous oxide is commonly used in general anaesthesia but concerns exist that it might increase perioperative cardiovascular risk. We aimed to gather evidence to establish whether nitrous oxide affects perioperative cardiovascular risk. We did an international, randomised, assessor-blinded trial in patients aged at least 45 years with known or suspected coronary artery disease having major non-cardiac surgery. Patients were randomly assigned via automated telephone service, stratified by site, to receive a general anaesthetic with or without nitrous oxide. Attending anaesthetists were aware of patients' group assignments, but patients and assessors were not. The primary outcome measure was a composite of death and cardiovascular complications (non-fatal myocardial infarction, stroke, pulmonary embolism, or cardiac arrest) within 30 days of surgery. Our modified intention-to-treat population included all patients randomly assigned to groups and undergoing induction of general anaesthesia for surgery. This trial is registered at ClinicalTrials.gov, number NCT00430989. Of 10,102 eligible patients, we enrolled 7112 patients between May 30, 2008, and Sept 28, 2013. 3543 were assigned to receive nitrous oxide and 3569 were assigned not to receive nitrous oxide. 3483 patients receiving nitrous oxide and 3509 not receiving nitrous oxide were assessed for the primary outcome. The primary outcome occurred in 283 (8%) patients receiving nitrous oxide and in 296 (8%) patients not receiving nitrous oxide (relative risk 0·96, 95% CI 0·83–1·12; p=0·64). Surgical site infection occurred in 321 (9%) patients assigned to nitrous oxide, and in 311 (9%) patients in the no-nitrous oxide group (p=0·61), and severe nausea and vomiting occurred in 506 patients (15%) assigned to nitrous oxide and 378 patients (11%) not assigned to nitrous oxide (p<0·0001). Our findings support the safety profile of nitrous oxide use in major non-cardiac surgery. Nitrous oxide did not increase the risk of de more...
- Published
- 2014
41. Safety, feasibility, and effect of remote ischemic conditioning in patients undergoing lung transplantation.
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Lin, E, Buckland, MR, Myles, PS, Snell, Gregory I, Levvey, Bronwyn J, Mifsud, Nicole, Paul, Moumita, Gooi, Julian, Marasco, Silvana, Sharland, Alexandra F, Lin, E, Buckland, MR, Myles, PS, Snell, Gregory I, Levvey, Bronwyn J, Mifsud, Nicole, Paul, Moumita, Gooi, Julian, Marasco, Silvana, and Sharland, Alexandra F more...
- Abstract
Primary graft dysfunction (PGD) remains a significant problem after lung transplantation. Data from animal and clinical studies suggest that remote ischemic conditioning (RIC) may reduce ischemia-reperfusion injury in solid organ transplantation. A pilot randomized controlled trial of 60 patients undergoing bilateral sequential lung transplantation assessed the utility of RIC in attenuating PGD. Treated recipients underwent 3 cycles of lower limb ischemic conditioning before allograft reperfusion. The primary outcome measure was a comparison of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P/F ratio) between treatment groups. No adverse effects of tourniquet application were observed. The mean lowest P/F ratio during the first 24 hours after transplantation was 271.3 mm Hg in the treatment arm vs 256.1 mm Hg in the control arm (p = 0.46). PGD grade and severity and the rate of acute rejection also showed a tendency to favor the treatment arm. Sub-group analysis demonstrated a significant benefit of treatment in patients with a primary diagnosis of restrictive lung disease, a group at high risk for the development of PGD. RIC was not accompanied by systemic release of high-molecular-weight group box 1. Levels of cytokines, high-molecular-weight group box 1, and endogenous secretory receptor for advanced glycation end products peaked within 2 hours after reperfusion and likely reflected donor organ quality rather than an effect of RIC. RIC did not significantly improve P/F ratios or PGD in this randomized controlled trial. However, encouraging results in this small study warrant a large multicenter trial of RIC in lung transplantation. more...
- Published
- 2014
42. [Video recorded at ANZCA ASM 2014 for ENIGMA-II launch]
- Author
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Myles, PS and Myles, PS
- Published
- 2014
43. Leukocyte DNA damage and wound infection after nitrous oxide administration: a randomized controlled trial.
- Author
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Gin, T, Leslie, K, Myles, P, Chan, MTV, Chen, Yan, Liu, Xiaodong, Cheng, Christopher H K, Myles, PS, Gin, T, Leslie, K, Myles, P, Chan, MTV, Chen, Yan, Liu, Xiaodong, Cheng, Christopher H K, and Myles, PS more...
- Abstract
Nitrous oxide inactivates methionine synthase and may lead to DNA damage and wound infection. By using single-cell gel electrophoresis (comet assay), the authors determined the effect of nitrous oxide on DNA damage in circulating leukocytes. In this double-blind, randomized controlled trial, 91 patients undergoing major colorectal surgery were randomized to receive 70% nitrous oxide (n = 31) or nitrous oxide-free anesthesia using 30 (n = 30) or 80% (n = 30) oxygen. Venous blood was collected before and 24 h after surgery. The primary outcome was extent of DNA damage, quantified as the percentage of DNA staining intensity in the comet tail using digital fluorescence microscopy. Incidence of postoperative wound infection was also recorded. Nitrous oxide exposure was associated with a two-fold increase in the percentage of DNA intensity in tail (P = 0.0003), but not in the 30 (P = 0.181) or 80% oxygen groups (P = 0.419). There was a positive correlation between the duration of nitrous oxide exposure and extent of DNA damage, r = 0.33, P = 0.029. However, no correlation was observed in nitrous oxide-free patients. The proportions of postoperative wound infection, using the Centers for Disease Control and Prevention criteria, were 19.4% (6 of 31) in the 70% nitrous oxide group and 6.7% (2 of 30) in both the 30 and 80% oxygen groups, P = 0.21. An increase in DNA damage was associated with a higher risk of wound infection, adjusted odds ratio (95% CIs): 1.19 (1.07-1.34), P = 0.003. Nitrous oxide increased DNA damage compared with nitrous oxide-free anesthesia and was associated with postoperative wound infection. more...
- Published
- 2013
44. The Australian approach to peri-operative fluid balance
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Myles, PS, Glasford, NJ, Bellomo, R, Myles, PS, Glasford, NJ, and Bellomo, R
- Abstract
PURPOSE OF REVIEW: The role of fluid balance as an important contributor to patient morbidity and mortality in the peri-operative period is only now being understood. Numerous studies in disparate populations undergoing different surgeries suggest that. RECENT FINDINGS: There is wide disparity in fluid administration regimen between speciality, country, and clinician. Recent meta-analyses of published studies have shown that restrictive fluid administration strategies may improve patient-centred outcomes when compared to liberal regimens. Current evidence suggests a significant role for fluid accumulation in the development of peri-operative complications. Fluid balance is best achieved using goal-directed techniques. The evidence base is, at present, sub-optimal, with a paucity of level 1 evidence for clinical decision-making. SUMMARY: In the absence of level 1 evidence it is difficult to make firm recommendations about practice, though observational and single-centre data suggest a significant survival advantage may be conferred by the peri-operative administration of fluids to monitored physiological targets only. The Australian approach to peri-operative fluid management is to create level 1 evidence. To this end, the development of a large multicentre randomized controlled trial of peri-operative fluid administration is underway. more...
- Published
- 2012
45. Nitrous oxide and long-term morbidity and mortality in the ENIGMA trial.
- Author
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Chan, MTV, Leslie, K, Myles, PS, Paech, MJ, Peyton, PJ, Silbert, BS, Forbes, A, Williamson, E, Chan, MTV, Leslie, K, Myles, PS, Paech, MJ, Peyton, PJ, Silbert, BS, Forbes, A, and Williamson, E
- Abstract
BACKGROUND: There is a plausible pathophysiologic rationale for increased long-term cardiovascular morbidity and mortality in patients receiving significant exposure to nitrous oxide. However, this relationship has not been established clinically. The ENIGMA trial randomized 2050 patients having noncardiac surgery lasting more than 2 hours to nitrous oxide-based or nitrous oxide-free anesthesia. We conducted a follow-up study of the ENIGMA patients to evaluate the risk of cardiovascular events in the longer term. METHODS: The trial case report forms and medical records of all study patients were reviewed. The date and cause of death and occurrence of myocardial infarction or stroke were recorded. A telephone interview was then conducted with all surviving patients. The primary endpoint of the study was survival. RESULTS: The median follow-up time was 3.5 (range: 0 to 5.7) years. Three hundred eighty patients (19%) had died since the index surgery, 91 (4.5%) were recorded as having myocardial infarction, and 44 (2.2%) had a stroke during the entire follow-up period. Nitrous oxide did not significantly increase the risk of death [hazard ratio = 0.98 (95% confidence interval, CI: 0.80 to 1.20; P = 0.82)]. The adjusted odds ratio for myocardial infarction in patients administered nitrous oxide was 1.59 (95% CI: 1.01 to 2.51; P = 0.04) and for stroke was 1.01 (95% CI: 0.55 to 1.87; P = 0.97). CONCLUSIONS: The administration of nitrous oxide was associated with increased long-term risk of myocardial infarction, but not of death or stroke in patients enrolled in the ENIGMA trial. The exact relationship between nitrous oxide administration and serious long-term adverse outcomes will require confirmation by an appropriately designed large randomized controlled trial. more...
- Published
- 2011
46. Perioperative epidural analgesia for major abdominal surgery for cancer and recurrence-free survival: randomised trial.
- Author
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ANZCA Clinical Trials Network, Myles, PS, Peyton, PJ, Silbert, BS, Rigg, J, Hunt, J, Rigg, JR, Sessler, DI, ANZCA Clinical Trials Network, Myles, PS, Peyton, PJ, Silbert, BS, Rigg, J, Hunt, J, Rigg, JR, and Sessler, DI more...
- Abstract
Objective To compare long term recurrence of cancer and survival of patients having major abdominal surgery for cancer. Design Long term follow-up of prospective randomised controlled clinical trial in which patients were randomly assigned to receive general anaesthesia with or without epidural block for at least three postoperative days. Setting 23 hospitals in Australia, New Zealand, and Asia. Participants 503 adult patients who had potentially curative surgery for cancer. Main outcome measure Cancer-free survival (analysis was by intention to treat). Results Long term follow-up data were available for 94% (n=446) of eligible participants. The median time to recurrence of cancer or death was 2.8 (95% confidence interval 0.7 to 8.7) years in the control group and 2.6 (0.7 to 8.7) years in the epidural group (P=0.61). Recurrence-free survival was similar in both epidural and control groups (hazard ratio 0.95, 95% confidence interval 0.76 to 1.17; P=0.61). Conclusion Use of epidural block in abdominal surgery for cancer is not associated with improved cancer-free survival. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12607000637448 more...
- Published
- 2011
47. Nitrous oxide and long-term morbidity and mortality in the ENIGMA trial.
- Author
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Leslie, K, Myles, PS, Chan, MTV, Paech, MJ, Peyton, P, Silbert, BS, Forbes, Andrew, Williamson, Elizabeth, Leslie, K, Myles, PS, Chan, MTV, Paech, MJ, Peyton, P, Silbert, BS, Forbes, Andrew, and Williamson, Elizabeth more...
- Abstract
There is a plausible pathophysiologic rationale for increased long-term cardiovascular morbidity and mortality in patients receiving significant exposure to nitrous oxide. However, this relationship has not been established clinically. The ENIGMA trial randomized 2050 patients having noncardiac surgery lasting more than 2 hours to nitrous oxide-based or nitrous oxide-free anesthesia. We conducted a follow-up study of the ENIGMA patients to evaluate the risk of cardiovascular events in the longer term. The trial case report forms and medical records of all study patients were reviewed. The date and cause of death and occurrence of myocardial infarction or stroke were recorded. A telephone interview was then conducted with all surviving patients. The primary endpoint of the study was survival. The median follow-up time was 3.5 (range: 0 to 5.7) years. Three hundred eighty patients (19%) had died since the index surgery, 91 (4.5%) were recorded as having myocardial infarction, and 44 (2.2%) had a stroke during the entire follow-up period. Nitrous oxide did not significantly increase the risk of death [hazard ratio = 0.98 (95% confidence interval, CI: 0.80 to 1.20; P = 0.82)]. The adjusted odds ratio for myocardial infarction in patients administered nitrous oxide was 1.59 (95% CI: 1.01 to 2.51; P = 0.04) and for stroke was 1.01 (95% CI: 0.55 to 1.87; P = 0.97). The administration of nitrous oxide was associated with increased long-term risk of myocardial infarction, but not of death or stroke in patients enrolled in the ENIGMA trial. The exact relationship between nitrous oxide administration and serious long-term adverse outcomes will require confirmation by an appropriately designed large randomized controlled trial. more...
- Published
- 2011
48. A cost-benefit analysis of the ENIGMA trial
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Chan, MTV, Leslie, K, Myles, PS, Paech, MJ, Peyton, PJ, Graham, AM, Chan, MT, El Dawlatly, AA, Chan, MTV, Leslie, K, Myles, PS, Paech, MJ, Peyton, PJ, Graham, AM, Chan, MT, and El Dawlatly, AA
- Abstract
BACKGROUND: The ENIGMA trial was a prospective, randomized, multicenter study that evaluated the clinical consequences of including N₂O in general anesthesia. Patients who were given a N₂O-free anesthetic when undergoing major surgery for which the expected hospital stay was at least 3 days had lower rates of some postoperative complications. This suggests that, despite a higher consumption of potent inhalational agent, there could be a financial benefit when N₂O is avoided in such settings. METHODS: A retrospective cost analysis of the 2,050 patients recruited to the ENIGMA trial was performed. We measured costs from the perspective of an implementing hospital. Direct health care costs include the costs for maintaining anesthesia, daily medications, hospitalization, and complications. The primary outcome was the net financial savings from avoiding N₂O in major noncardiac surgery. Comparisons between groups were analyzed using Student t test and bootstrap methods. Sensitivity analyses were also performed. RESULTS: Rates of some serious complications were higher in the N₂O group. Total costs in the N₂O group were $16,203 and in the N₂O-free group $13,837, mean difference of $2,366 (95% CI: 841-3,891); P = 0.002. All sensitivity analyses retained a significant difference in favor of the N₂O-free group (all P ≤ 0.005). CONCLUSIONS: Despite N₂O reducing the consumption of more expensive potent inhalational agent, there were marked additional costs associated with its use in adult patients undergoing major surgery because of an increased rate of complications. There is no cogent argument to continue using N₂O on the basis that it is an inexpensive drug. more...
- Published
- 2011
49. Complications and mortality in older surgical patients in Australia and New Zealand (the REASON study): a multicentre, prospective, observational study.
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ANZCA Clinical Trials Network, Beavis, V, Kerridge, R, Leslie, K, Myles, PS, Story, D, Story, DA, Fink, M, Poustie, SJ, Forbes, A, Yap, S, REASON Investigators, ANZCA Clinical Trials Network, Beavis, V, Kerridge, R, Leslie, K, Myles, PS, Story, D, Story, DA, Fink, M, Poustie, SJ, Forbes, A, Yap, S, and REASON Investigators more...
- Abstract
We conducted a prospective study of non-cardiac surgical patients aged 70 years or more in 23 hospitals in Australia and New Zealand. We studied 4158 consecutive patients of whom 2845 (68%) had pre-existing comorbidities. By day 30, 216 (5%) patients had died, and 835 (20%) suffered complications; 390 (9.4%) patients were admitted to the Intensive Care Unit. Pre-operative factors associated with mortality included: increasing age (80-89 years: OR 2.1 (95% CI 1.6-2.8), p < 0.001; 90+ years: OR 4.0 (95% CI 2.6-6.2), p < 0.001); worsening ASA physical status (ASA 3: OR 3.1 (95% CI 1.8-5.5), p < 0.001; ASA 4: OR 12.4 (95% CI 6.9-22.2), p < 0.001); a pre-operative plasma albumin < 30 g.l⁻¹ (OR: 2.5 (95% CI 1.8-3.5), p < 0.001); and non-scheduled surgery (OR 1.8 (95% CI 1.3-2.5), p < 0.001). Complications associated with mortality included: acute renal impairment (OR 3.3 (95% CI 2.1-5.0), p < 0.001); unplanned Intensive Care Unit admission (OR 3.1 (95% CI 1.9-4.9), p < 0.001); and systemic inflammation (OR 2.5 (95% CI 1.7-3.7), p < 0.001). Patient factors often had a stronger association with mortality than the type of surgery. Strategies are needed to reduce complications and mortality in older surgical patients. more...
- Published
- 2010
50. Complications and mortality in older surgical patients in Australia and New Zealand (the REASON study): a multicentre, prospective, observational study.
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Story, DA, Leslie, K, Myles, PS, Yap, S, Beavis, V, Kerridge, R, Fink, M, Poustie, S J, Forbes, A, REASON Investigators, Australian and New Zealand College of Anaesthetists Trials Group, Story, DA, Leslie, K, Myles, PS, Yap, S, Beavis, V, Kerridge, R, Fink, M, Poustie, S J, Forbes, A, REASON Investigators, and Australian and New Zealand College of Anaesthetists Trials Group more...
- Abstract
We conducted a prospective study of non-cardiac surgical patients aged 70 years or more in 23 hospitals in Australia and New Zealand. We studied 4158 consecutive patients of whom 2845 (68%) had pre-existing comorbidities. By day 30, 216 (5%) patients had died, and 835 (20%) suffered complications; 390 (9.4%) patients were admitted to the Intensive Care Unit. Pre-operative factors associated with mortality included: increasing age (80-89 years: OR 2.1 (95% CI 1.6-2.8), p < 0.001; 90+ years: OR 4.0 (95% CI 2.6-6.2), p < 0.001); worsening ASA physical status (ASA 3: OR 3.1 (95% CI 1.8-5.5), p < 0.001; ASA 4: OR 12.4 (95% CI 6.9-22.2), p < 0.001); a pre-operative plasma albumin < 30 g.l⁻¹ (OR: 2.5 (95% CI 1.8-3.5), p < 0.001); and non-scheduled surgery (OR 1.8 (95% CI 1.3-2.5), p < 0.001). Complications associated with mortality included: acute renal impairment (OR 3.3 (95% CI 2.1-5.0), p < 0.001); unplanned Intensive Care Unit admission (OR 3.1 (95% CI 1.9-4.9), p < 0.001); and systemic inflammation (OR 2.5 (95% CI 1.7-3.7), p < 0.001). Patient factors often had a stronger association with mortality than the type of surgery. Strategies are needed to reduce complications and mortality in older surgical patients. more...
- Published
- 2010
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