Time to antimicrobial therapy in septic shock patients treated with an early goal-directed resuscitation protocol: A post-hoc analysis of the ARISE trial

Esther B Bulle¹, Sandra L Peake^{2

3

4}, Mark Finnis^{3

4

5}, Rinaldo Bellomo^{4

6

7

8}, Anthony Delaney^{4

8}; on behalf of the ARISE Investigators; ARISE Investigators

Collaborators, Affiliations

Collaborators

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

Affiliations

¹ Department of Intensive Care, Amsterdam University Medical Centre, Amsterdam, The Netherlands.
² Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.
³ Discipline of Acute Care Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
⁴ Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
⁵ Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
⁶ Department of Intensive Care, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
⁷ School of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
⁸ Malcolm Fisher Department of Intensive Care Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia.

PMID: 38019012
DOI: 10.1111/1742-6723.13634

Time to antimicrobial therapy in septic shock patients treated with an early goal-directed resuscitation protocol: A post-hoc analysis of the ARISE trial

Esther B Bulle et al. Emerg Med Australas. 2021 Jun.

. 2021 Jun;33(3):409-417.

doi: 10.1111/1742-6723.13634. Epub 2020 Oct 9.

Authors

Esther B Bulle¹, Sandra L Peake^{2

3

4}, Mark Finnis^{3

4

5}, Rinaldo Bellomo^{4

6

7

8}, Anthony Delaney^{4

8}; on behalf of the ARISE Investigators; ARISE Investigators

Collaborators

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

Affiliations

¹ Department of Intensive Care, Amsterdam University Medical Centre, Amsterdam, The Netherlands.
² Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.
³ Discipline of Acute Care Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, South Australia, Australia.
⁴ Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
⁵ Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
⁶ Department of Intensive Care, The Royal Melbourne Hospital, Melbourne, Victoria, Australia.
⁷ School of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
⁸ Malcolm Fisher Department of Intensive Care Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia.

PMID: 38019012
DOI: 10.1111/1742-6723.13634

Abstract

Objective: Intravenous antimicrobial therapy within 1 h of the diagnosis of septic shock is recommended in international sepsis guidelines. We aimed to evaluate the association between antimicrobial timing and mortality in patients presenting to the ED with septic shock.

Methods: Post-hoc analysis of 1587 adult participants enrolled in the Australasian Resuscitation in Sepsis Evaluation (ARISE) multicentre trial of early goal-directed therapy for whom the time of initial antimicrobial therapy was recorded. We compared participants who had initiation of antimicrobials within the first hour (early) or later (delayed) of ED presentation. A propensity score model using inverse probability of treatment weighting was constructed to account for confounding baseline covariates. The primary outcome was 90-day mortality.

Results: The median (interquartile range) time to initiating antimicrobials was 69 (39-112) min with 712 (44.9%) participants receiving the first dose within the first hour of ED presentation. Compared with delayed therapy, early administration was associated with increased baseline illness severity score and greater intensity of resuscitation pre-randomisation (fluid volumes, vasopressors, invasive ventilation). All-cause 90-day mortality was also higher; 22.6% versus 15.5%; unadjusted odds ratio (OR) 1.58 (95% confidence interval [CI] 1.16-2.15), P = 0.004. After inverse probability of treatment weighting, the mortality difference was non-significant; OR 1.30 (95% CI 0.95-1.76), P = 0.1. Live discharge rates from ICU (OR 0.81, 95% CI 0.72-0.91; P = 0.80) and hospital (OR 0.93, 95% CI 0.82-1.06; P = 0.29) were also not different between groups.

Conclusion: In this post-hoc analysis of the ARISE trial, early antimicrobial therapy was associated with increased illness severity, but 90-day adjusted mortality was not reduced.

Keywords: mortality; septic shock; timing anti-microbial agent.

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References

1. Rhodes A, Evans LE, Alhazzani W et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Crit. Care Med. 2017; 45: 486-552.
1. Kumar A, Wood KE, Light B et al. Duration of hypotension before initiation of effective antimicrobial therapy is a critical determinant of survival in human septic shock. Crit. Care Med. 2006; 34: 1589-96.
1. Ferrer R, Martin-Loeches I, Phillips G et al. Empiric antibiotic treatment reduces mortality in severe sepsis and septic shock from the first hour: results from a guideline-based performance improvement program. Crit. Care Med. 2014; 42: 1749-55.
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Time to antimicrobial therapy in septic shock patients treated with an early goal-directed resuscitation protocol: A post-hoc analysis of the ARISE trial

Collaborators

Affiliations

Time to antimicrobial therapy in septic shock patients treated with an early goal-directed resuscitation protocol: A post-hoc analysis of the ARISE trial

Authors

Collaborators

Affiliations

Abstract

References

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