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1. Potential Impact of the 2016 Consensus Definitions of Sepsis and Septic Shock on Future Sepsis Research

Author

Peake, Sandra L., Delaney, Anthony, Bailey, Michael, Bellomo, Rinaldo, Bennett, V., Board, J., McCracken, P., McGloughlin, S., Nanjayya, V., Teo, A., Hill, E., Jones, P., O’Brien, E., Sawtell, F., Schimanski, K., Wilson, D., Bellomo, R., Bolch, S., Eastwood, G., Kerr, F., Peak, L., Young, H., Edington, J., Fletcher, J., Smith, J., Ghelani, D., Nand, K., Sara, T., Cross, A., Flemming, D., Grummisch, M., Purdue, A., Fulton, E., Grove, K., Harney, A., Milburn, K., Millar, R., Mitchell, I., Rodgers, H., Scanlon, S., Coles, T., Connor, H., Dennett, J., Van Berkel, A., Barrington-Onslow, S., Henderson, S., Mehrtens, J., Dryburgh, J., Tankel, A., Braitberg, G., O’Bree, B., Shepherd, K., Vij, S., Allsop, S., Haji, D., Haji, K., Vuat, J., Bone, A., Elderkin, T., Orford, N., Ragg, M., Kelly, S., Stewart, D., Woodward, N., Harjola, V.-P., Okkonen, M., Pettilä, V., Sutinen, S., Wilkman, E., Fratzia, J., Halkhoree, J., Treloar, S., Ryan, K., Sandford, T., Walsham, J., Jenkins, C., Williamson, D., Burrows, J., Hawkins, D., Tang, C., Dimakis, A., Holdgate, A., Micallef, S., Parr, M., White, H., Morrison, L., Sosnowski, K., Ramadoss, R., Soar, N., Wood, J., Franks, M., Williams, A., Hogan, C., Song, R., Tilsley, A., Rainsford, D., Wells, R., Dowling, J., Galt, P., Lamac, T., Lightfoot, D., Walker, C., Braid, K., DeVillecourt, T., Tan, H. S., Seppelt, I., Chang, L. F., Cheung, W. S., Fok, S. K., Lam, P. K., Lam, S. M., So, H. M., Yan, W. W., Altea, A., Lancashire, B., Gomersall, C. D., Graham, C. A., Leung, P., Arora, S., Bass, F., Shehabi, Y., Isoardi, J., Isoardi, K., Powrie, D., Lawrence, S., Ankor, A., Chester, L., Davies, M., O’Connor, S., Poole, A., Soulsby, T., Sundararajan, K., Williams, J., Greenslade, J. H., MacIsaac, C., Gorman, K., Jordan, A., Moore, L., Ankers, S., Bird, S., Delaney, A., Fogg, T., Hickson, E., Jewell, T., Kyneur, K., O’Connor, A., Townsend, J., Yarad, E., Brown, S., Chamberlain, J., Cooper, J., Jenkinson, E., McDonald, E., Webb, S., Buhr, H., Coakley, J., Cowell, J., Hutch, D., Gattas, D., Keir, M., Rajbhandari, D., Rees, C., Baker, S., Roberts, B., Farone, E., Holmes, J., Santamaria, J., Winter, C., Finckh, A., Knowles, S., McCabe, J., Nair, P., Reynolds, C., Ahmed, B., Barton, D., Meaney, E., Nichol, A., Harris, R., Shields, L., Thomas, K., Karlsson, S., Kuitunen, A., Kukkurainen, A., Tenhunen, J., Varila, S., Ryan, N., Trethewy, C., Crosdale, J., Smith, J. C., Vellaichamy, M., Furyk, J., Gordon, G., Jones, L., Senthuran, S., Bates, S., Butler, J., French, C., Tippett, A., Kelly, J., Kwans, J., Murphy, M., O’Flynn, D., Kurenda, C., Otto, T., Peake, S., Raniga, V., Williams, P., Ho, H. F., Leung, A., and Wu, H.

Published
2017
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2. Gender differences in mortality and quality of life after septic shock: A post-hoc analysis of the ARISE study

Author

Luethi, N, Bailey, M, Higgins, A, Howe, B, Peake, S, Delaney, A, Bellomo, R, Bennett, V, Board, J, McCracken, P, McGloughlin, S, Nanjayya, V, Teo, A, Hill, E, O'Brien, PJE, Sawtell, F, Schimanski, K, Wilson, D, Bolch, S, Eastwood, G, Kerr, F, Peak, L, Young, H, Edington, J, Fletcher, J, Smith, J, Ghelani, D, Nand, K, Sara, T, Cross, A, Flemming, D, Grummisch, M, Purdue, A, Fulton, E, Grove, K, Harney, A, Milburn, K, Millar, R, Mitchell, I, Rodgers, H, Scanlon, S, Coles, T, Connor, H, Dennett, J, Van Berkel, A, Barrington-Onslow, S, Henderson, S, Mehrtens, J, Dryburgh, J, Tankel, A, Braitberg, G, O'Bree, B, Shepherd, K, Vij, S, Allsop, S, Haji, D, Haji, K, Vuat, J, Bone, A, Elderkin, T, Orford, N, Ragg, M, Kelly, S, Stewart, D, Woodward, N, Harjola, V-P, Pettila, MO, Sutinen, S, Wilkman, E, Fratzia, J, Halkhoree, J, Treloar, S, Ryan, K, Sandford, T, Walsham, J, Jenkins, C, Williamson, D, Burrows, J, Hawkins, D, Tang, C, Dimakis, A, Holdgate, A, Micallef, S, Parr, M, White, H, Morrison, L, Sosnowski, K, Ramadoss, R, Soar, N, Wood, J, Franks, M, Williams, A, Hogan, C, Song, R, Tilsley, A, Rainsford, D, Wells, R, Dowling, J, Galt, P, Lamac, T, Lightfoot, D, Walker, C, Braid, K, DeVillecourt, T, Tan, HS, Seppelt, I, Chang, LF, Cheung, WS, Fok, SK, Lam, PK, Lam, SM, So, HM, Yan, W, Altea, A, Lancashire, B, Gomersall, CD, Graham, CA, Leung, P, Arora, S, Bass, F, Shehabi, Y, Isoardi, J, Isoardi, K, Powrie, D, Lawrence, S, Ankor, A, Chester, L, Davies, M, O'Connor, S, Poole, A, Soulsby, T, Sundararajan, K, Williams, J, Greenslade, JH, MacIsaac, C, Gorman, K, Jordan, A, Moore, L, Ankers, S, Bird, S, Fogg, T, Hickson, E, Jewell, T, Kyneur, K, O'Connor, A, Townsend, J, Yarad, E, Brown, S, Chamberlain, J, Cooper, J, Jenkinson, E, McDonald, E, Webb, S, Buhr, H, Coakley, J, Cowell, J, Hutch, D, Gattas, D, Keir, M, Rajbhandari, D, Rees, C, Baker, S, Roberts, B, Farone, E, Holmes, J, Santamaria, J, Winter, C, Finckh, A, Knowles, S, McCabe, J, Nair, P, Reynolds, C, Ahmed, B, Barton, D, Meaney, E, Nichol, A, Harris, R, Shields, L, Thomas, K, Karlsson, S, Kuitunen, A, Kukkurainen, A, Tenhunen, J, Varila, S, Ryan, N, Trethewy, C, Crosdale, J, Smith, JC, Vellaichamy, M, Furyk, J, Gordon, G, Jones, L, Senthuran, S, Bates, S, Butler, J, French, C, Tippett, A, Kelly, J, Kwans, J, Murphy, M, O'Flynn, D, Kurenda, C, Otto, T, Raniga, V, Williams, P, Ho, HF, Leung, A, Wu, H, Luethi, N, Bailey, M, Higgins, A, Howe, B, Peake, S, Delaney, A, Bellomo, R, Bennett, V, Board, J, McCracken, P, McGloughlin, S, Nanjayya, V, Teo, A, Hill, E, O'Brien, PJE, Sawtell, F, Schimanski, K, Wilson, D, Bolch, S, Eastwood, G, Kerr, F, Peak, L, Young, H, Edington, J, Fletcher, J, Smith, J, Ghelani, D, Nand, K, Sara, T, Cross, A, Flemming, D, Grummisch, M, Purdue, A, Fulton, E, Grove, K, Harney, A, Milburn, K, Millar, R, Mitchell, I, Rodgers, H, Scanlon, S, Coles, T, Connor, H, Dennett, J, Van Berkel, A, Barrington-Onslow, S, Henderson, S, Mehrtens, J, Dryburgh, J, Tankel, A, Braitberg, G, O'Bree, B, Shepherd, K, Vij, S, Allsop, S, Haji, D, Haji, K, Vuat, J, Bone, A, Elderkin, T, Orford, N, Ragg, M, Kelly, S, Stewart, D, Woodward, N, Harjola, V-P, Pettila, MO, Sutinen, S, Wilkman, E, Fratzia, J, Halkhoree, J, Treloar, S, Ryan, K, Sandford, T, Walsham, J, Jenkins, C, Williamson, D, Burrows, J, Hawkins, D, Tang, C, Dimakis, A, Holdgate, A, Micallef, S, Parr, M, White, H, Morrison, L, Sosnowski, K, Ramadoss, R, Soar, N, Wood, J, Franks, M, Williams, A, Hogan, C, Song, R, Tilsley, A, Rainsford, D, Wells, R, Dowling, J, Galt, P, Lamac, T, Lightfoot, D, Walker, C, Braid, K, DeVillecourt, T, Tan, HS, Seppelt, I, Chang, LF, Cheung, WS, Fok, SK, Lam, PK, Lam, SM, So, HM, Yan, W, Altea, A, Lancashire, B, Gomersall, CD, Graham, CA, Leung, P, Arora, S, Bass, F, Shehabi, Y, Isoardi, J, Isoardi, K, Powrie, D, Lawrence, S, Ankor, A, Chester, L, Davies, M, O'Connor, S, Poole, A, Soulsby, T, Sundararajan, K, Williams, J, Greenslade, JH, MacIsaac, C, Gorman, K, Jordan, A, Moore, L, Ankers, S, Bird, S, Fogg, T, Hickson, E, Jewell, T, Kyneur, K, O'Connor, A, Townsend, J, Yarad, E, Brown, S, Chamberlain, J, Cooper, J, Jenkinson, E, McDonald, E, Webb, S, Buhr, H, Coakley, J, Cowell, J, Hutch, D, Gattas, D, Keir, M, Rajbhandari, D, Rees, C, Baker, S, Roberts, B, Farone, E, Holmes, J, Santamaria, J, Winter, C, Finckh, A, Knowles, S, McCabe, J, Nair, P, Reynolds, C, Ahmed, B, Barton, D, Meaney, E, Nichol, A, Harris, R, Shields, L, Thomas, K, Karlsson, S, Kuitunen, A, Kukkurainen, A, Tenhunen, J, Varila, S, Ryan, N, Trethewy, C, Crosdale, J, Smith, JC, Vellaichamy, M, Furyk, J, Gordon, G, Jones, L, Senthuran, S, Bates, S, Butler, J, French, C, Tippett, A, Kelly, J, Kwans, J, Murphy, M, O'Flynn, D, Kurenda, C, Otto, T, Raniga, V, Williams, P, Ho, HF, Leung, A, and Wu, H

Abstract

PURPOSE: To assess the impact of gender and pre-menopausal state on short- and long-term outcomes in patients with septic shock. MATERIAL AND METHODS: Cohort study of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial, an international randomized controlled trial comparing early goal-directed therapy (EGDT) to usual care in patients with early septic shock, conducted between October 2008 and April 2014. The primary exposure in this analysis was legal gender and the secondary exposure was pre-menopausal state defined by chronological age (≤ 50 years). RESULTS: 641 (40.3%) of all 1591 ARISE trial participants in the intention-to-treat population were females and overall, 337 (21.2%) (146 females) patients were 50 years of age or younger. After risk-adjustment, we could not identify any survival benefit for female patients at day 90 in the younger (≤50 years) (adjusted Odds Ratio (aOR): 0.91 (0.46-1.89), p = .85) nor in the older (>50 years) age-group (aOR: 1.10 (0.81-1.49), p = .56). Similarly, there was no gender-difference in ICU, hospital, 1-year mortality nor quality of life measures. CONCLUSIONS: This post-hoc analysis of a large multi-center trial in early septic shock has shown no short- or long-term survival effect for women overall as well as in the pre-menopausal age-group.

Published
2020

3. Can pre-hospital administration reduce time to initial antibiotic therapy in septic patients?.

Author

Lightfoot D., Santamaria J., Winter C., Bates S., Butler J., French C., Tippett A., Shepherd K., Vij S., Cudini D., Smith K., Bernard S., Stephenson M., Andrew E., Cameron P., Lum M., Udy A., Bennett V., Board J., McCracken P., McGloughlin S., Nanjayya V., Teo A., Bellomo R., Bolch S., Eastwood G., Kerr F., Peak L., Young H., Edington J., Fletcher J., Smith J., Cross A., Flemming D., Grummisch M., Purdue A., Coles T., Connor H., Dennett J., Van Berkel A., Braitberg G., O'Bree B., Allsop S., Haji D., Haji K., Vuat J., Bone A., Elderkin T., Orford N., Ragg M., Dowling J., Galt P., Lamac T., Walker C., MacIsaac C., Gorman K., Jordan A., Moore L., Farone E., Holmes J., Lightfoot D., Santamaria J., Winter C., Bates S., Butler J., French C., Tippett A., Shepherd K., Vij S., Cudini D., Smith K., Bernard S., Stephenson M., Andrew E., Cameron P., Lum M., Udy A., Bennett V., Board J., McCracken P., McGloughlin S., Nanjayya V., Teo A., Bellomo R., Bolch S., Eastwood G., Kerr F., Peak L., Young H., Edington J., Fletcher J., Smith J., Cross A., Flemming D., Grummisch M., Purdue A., Coles T., Connor H., Dennett J., Van Berkel A., Braitberg G., O'Bree B., Allsop S., Haji D., Haji K., Vuat J., Bone A., Elderkin T., Orford N., Ragg M., Dowling J., Galt P., Lamac T., Walker C., MacIsaac C., Gorman K., Jordan A., Moore L., Farone E., and Holmes J.

Abstract

Objective: To quantify the potential time saved with pre-hospital antibiotic therapy in sepsis. Method(s): Study data for adult patients transported by Ambulance Victoria (AV), and enrolled into the Australasian Resuscitation In Sepsis Evaluation (ARISE), were linked with pre-hospital electronic records. Result(s): An AV record was identified for 240 of 341 ARISE patients. The pre-hospital case notes referred to potential infection in 165 patients. The median time to first antibiotic administration from loading the patient into the ambulance was 107 (74-160) min. Conclusion(s): ARISE patients in Victoria were frequently identified pre-hospital. An opportunity exists to study the feasibility of pre-hospital antibiotic therapy.Copyright © 2019 Australasian College for Emergency Medicine

Published
2019

4. Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial).

Author

Stub D., Conquest A., Archer J.S., Bernard S., Hart G.K., Bellomo R., Eastwood G.M., Schneider A.G., Suzuki S., Peck L., Young H., Tanaka A., Martensson J., Warrillow S., McGuinness S., Parke R., Gilder E., Mccarthy L., Galt P., Taori G., Eliott S., Lamac T., Bailey M., Harley N., Barge D., Hodgson C.L., Morganti-Kossmann M.C., Pebay A., Stub D., Conquest A., Archer J.S., Bernard S., Hart G.K., Bellomo R., Eastwood G.M., Schneider A.G., Suzuki S., Peck L., Young H., Tanaka A., Martensson J., Warrillow S., McGuinness S., Parke R., Gilder E., Mccarthy L., Galt P., Taori G., Eliott S., Lamac T., Bailey M., Harley N., Barge D., Hodgson C.L., Morganti-Kossmann M.C., and Pebay A.

Abstract

Background: In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested. Method(s): In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24 h of targeted normocapnia (TN) (PaCO2 35-45 mmHg) or TTMH (PaCO2 50-55 mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72 h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients. Result(s): We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment. NSE concentrations increased in the TTMH group (p = 0.02) and TN group (p = 0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p < 0.001) but not in the TN group (p = 0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p = 0.31). Conclusion(s): In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment.Copyright © 2016.

Published
2016

5. Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial).

Author

Eastwood GM, Schneider AG, Suzuki S, Peck L, Young H, Tanaka A, Mårtensson J, Warrillow S, McGuinness S, Parke R, Gilder E, Mccarthy L, Galt P, Taori G, Eliott S, Lamac T, Bailey M, Harley N, Barge D, Hodgson CL, Morganti-Kossmann MC, Pébay A, Conquest A, Archer JS, Bernard S, Stub D, Hart GK, and Bellomo R

Subjects
Analysis of Variance, Biomarkers blood, Female, Glasgow Coma Scale, Heart Arrest mortality, Heart Arrest physiopathology, Humans, Intensive Care Units, Length of Stay, Male, Middle Aged, Heart Arrest therapy, Hypercapnia, Phosphopyruvate Hydratase blood, Respiration, Artificial methods, S100 Calcium Binding Protein beta Subunit blood
Abstract

Background: In intensive care observational studies, hypercapnia after cardiac arrest (CA) is independently associated with improved neurological outcome. However, the safety and feasibility of delivering targeted therapeutic mild hypercapnia (TTMH) for such patients is untested., Methods: In a phase II safety and feasibility multi-centre, randomised controlled trial, we allocated ICU patients after CA to 24h of targeted normocapnia (TN) (PaCO2 35-45mmHg) or TTMH (PaCO2 50-55mmHg). The primary outcome was serum neuron specific enolase (NSE) and S100b protein concentrations over the first 72h assessed in the first 50 patients surviving to day three. Secondary end-points included global measure of function assessment at six months and mortality for all patients., Results: We enrolled 86 patients. Their median age was 61 years (58, 64 years) and 66 (79%) were male. Of these, 50 patients (58%) survived to day three for full biomarker assessment. NSE concentrations increased in the TTMH group (p=0.02) and TN group (p=0.005) over time, with the increase being significantly more pronounced in the TN group (p(interaction)=0.04). S100b concentrations decreased over time in the TTMH group (p<0.001) but not in the TN group (p=0.68). However, the S100b change over time did not differ between the groups (p(interaction)=0.23). At six months, 23 (59%) TTMH patients had good functional recovery compared with 18 (46%) TN patients. Hospital mortality occurred in 11 (26%) TTMH patients and 15 (37%) TN patients (p=0.31)., Conclusions: In CA patients admitted to the ICU, TTMH was feasible, appeared safe and attenuated the release of NSE compared with TN. These findings justify further investigation of this novel treatment., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Published
2016
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