To investigate the impact of hydrocortisone treatment and illness severity on health-related quality of life (HRQoL) at 6 months in septic shock survivors from the ADRENAL trial.
Using the EuroQol questionnaire (EQ-5D-5L) at 6 months after randomization we assessed HRQoL in patient subgroups defined by hydrocortisone or placebo treatment, gender, illness severity (APACHE II < or ≥ 25), and severity of shock (baseline peak catecholamine doses < or ≥ 15 mcg/min). Additionally, in subgroups defined by post-randomisation variables; time to shock reversal (days), treatment with renal replacement therapy (RRT), and presence of bacteremia.
At 6 months, there were 2521 survivors. Of these 2151 patients (85.3%-1080 hydrocortisone and 1071 placebo) completed 6-month follow-up. Overall, at 6 months the mean EQ-5D-5L visual analogue scale (VAS) was 70.8, mean utility score 59.4. Between 15% and 30% of patients reported moderate to severe problems in any given HRQoL domain. There were no differences in any EQ-5D-5L domain in patients who received hydrocortisone vs. placebo, nor in the mean VAS (p = 0.6161), or mean utility score (p = 0.7611). In all patients combined, males experienced lower pain levels compared to females [p = 0.0002). Neither higher severity of illness or shock impacted reported HRQoL. In post-randomisation subgroups, longer time to shock reversal was associated with increased problems with mobility (p = < 0.0001]; self-care (p = 0.0.0142), usual activities (p = <0.0001] and pain (p = 0.0384). Amongst those treated with RRT, more patients reported increased problems with mobility (p = 0.0307) and usual activities (p = 0.0048) compared to those not treated. Bacteraemia was not associated with worse HRQoL in any domains of the EQ-5D-5L.
Approximately one fifth of septic shock survivors report moderate to extreme problems in HRQoL domains at 6 months. Hydrocortisone treatment for septic shock was not associated with improved HRQoL at 6 months. Female gender was associated with worse pain at 6 months.
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Prescott HC, Angus DC (2018) Enhancing recovery from sepsis: a review. JAMA 319(1):62–75
Jawad I, Luksic I, Rafnsson SB (2012) Assessing available information on the burden of sepsis: global estimates of incidence, prevalence and mortality. J Glob Health 2(1):010404
Fleischmann C, Scherag A, Adhikari NK et al (2016) Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations. Am J Respir Crit Care Med 193(3):259–272
Rudd KE, Johnson SC, Agesa KM et al (2020) Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet (London, England). 395(10219):200–211
Desai SV, Law TJ, Needham DM (2011) Long-term complications of critical care. Crit Care Med 39(2):371–379
Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, Sevransky JE (2010) Long-term mortality and quality of life in sepsis: a systematic review. Crit Care Med 38(5):1276–1283
Elliott D, Davidson JE, Harvey MA et al (2014) Exploring the scope of post-intensive care syndrome therapy and care: engagement of non-critical care providers and survivors in a second stakeholders meeting. Crit Care Med 42(12):2518–2526
Prescott HC, Costa DK (2018) Improving long-term outcomes after sepsis. Crit Care Clin 34(1):175–188
Yende S, Austin S, Rhodes A et al (2016) Long-term quality of life among survivors of severe sepsis: analyses of two international trials. Crit Care Med 44(8):1461–1467
Zimmerman JJ, Banks R, Berg RA et al (2020) Critical illness factors associated with long-term mortality and health-related quality of life morbidity following community-acquired pediatric septic shock*. Crit Care Med 48(3):319–328
Venkatesh B, Finfer S, Cohen J et al (2018) Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. The New England journal of medicine. 378(9):797–808
Venkatesh B, Finfer S, Myburgh J, Cohen J, Billot L (2018) Long-term outcomes of the ADRENAL trial. N Engl J Med 378(18):1744–1745
Venkatesh B, Myburgh J, Finfer S et al (2013) The ADRENAL study protocol: adjunctive corticosteroid treatment in critically ill patients with septic shock. Crit Care Resuscit 15(2):83–88
EuroQol Research Foundation https://euroqol.org/. Published 2019. Accessed.
Billot L, Venkatesh B, Myburgh J et al (2017) Statistical analysis plan for the Adjunctive Corticosteroid Treatment in Critically Ill Patients with Septic Shock (ADRENAL) trial. Crit Care Resuscit 19(2):183–191
Janssen MF, Pickard AS, Golicki D et al (2013) Measurement properties of the EQ-5D-5L compared to the EQ-5D-3L across eight patient groups: a multi-country study. Quality Life Res 22(7):1717–1727
Viney R, Norman R, Brazier J et al (2014) An Australian discrete choice experiment to value eq-5d health states. Health Econ 23(6):729–742
Knaus W, Draper E, Wagner D, Zimmerman J (1985) APACHE II: a severity of disease classification system. Crit Care Med 13:818–829
Higgins AM, Peake SL, Bellomo R et al (2019) Quality of life and 1-year survival in patients with early septic shock: long-term follow-up of the australasian resuscitation in sepsis evaluation trial. Crit Care Med 47(6):765–773
Thompson K, Taylor C, Jan S et al (2018) Health-related outcomes of critically ill patients with and without sepsis. Intens Care Med 44(8):1249–1257
Cherepanov D, Palta M, Fryback DG, Robert SA (2010) Gender differences in health-related quality-of-life are partly explained by sociodemographic and socioeconomic variation between adult men and women in the US: evidence from four US nationally representative data sets. Qual Life Res 19(8):1115–1124
Wang AY, Bellomo R, Cass A et al (2015) Health-related quality of life in survivors of acute kidney injury: the prolonged outcomes study of the randomized evaluation of normal versus augmented level replacement therapy study outcomes. Nephrology (Carlton, Vic). 20(7):492–498
Yang T, Li Z, Jiang L, Xi X (2018) Corticosteroid use and intensive care unit-acquired weakness: a systematic review and meta-analysis. Crit Care 22(1):187
Opal SM, Laterre PF, Francois B et al (2013) Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA 309(11):1154–1162
Yealy DM, Kellum JA, Huang DT et al (2014) A randomized trial of protocol-based care for early septic shock. N Engl J Med 370(18):1683–1693
Taylor C, Thompson K, Finfer S et al (2016) Hydroxyethyl starch versus saline for resuscitation of patients in intensive care: long-term outcomes and cost-effectiveness analysis of a cohort from CHEST. Lancet Respir Med 4(10):818–825
Rahmel T, Schmitz S, Nowak H et al (2020) Long-term mortality and outcome in hospital survivors of septic shock, sepsis, and severe infections: The importance of aftercare. PLoS ONE 15(2):e0228952
Payakachat N, Ali MM, Tilford JM (2015) Can the EQ-5D detect meaningful change? A systematic review. Pharmacoeconomics 33(11):1137–1154
Massey MJ, Hou PC, Filbin M et al (2018) Microcirculatory perfusion disturbances in septic shock: results from the ProCESS trial. Crit Care 22(1):308
Linder A, Lee T, Fisher J et al (2016) Short-term organ dysfunction is associated with long-term (10-Yr) mortality of septic shock. Crit Care Med 44(8):e728–736
Brealey D, Brand M, Hargreaves I et al (2002) Association between mitochondrial dysfunction and severity and outcome of septic shock. Lancet (London, England) 360(9328):219–223
The authors would like to thank Sarah Grattan for her assistance with formatting figures and tables. We would also like to thank all the site staff and the patients and their families who contributed to the ADRENAL trial and made this study possible. ADRENAL Trial Investigators Participating sites and investigators (Australia unless stated): Auckland City Hospital CVICU (New Zealand): Keri-Anne Cowdrey, Eileen Gilder, Stephanie Long, Lianne McCarthy, Shay McGuinness and Rachael Parke. Auckland City Hospital DCCM (New Zealand): Kristen Benefield, Yan Chen, Colin McArthur, Rachael McConnochie and Lynette Newby. Austin Hospital: Rinaldo Bellomo, Glenn Eastwood, Daryl Jones, Leah Peck and Helen Young. Bendigo Hospital: Catherine Boschert, John Edington, Jason Fletcher and Julie Smith. Blacktown Hospital: Dhaval Ghelani, Kiran Nand, Graham Reece and Treena Sara. Bristol Royal Infirmary (United Kingdom, England): Jeremy Bewley, Libby Cole, Lisa Grimmer, Lucy Howie, Shanaz James, Marta Kozlowski, Victoria Phillips, Sanjoy Shah, Katie Sweet and Denise Webster. Calvary Mater Hospital Newcastle: Irene Bailey, Katrina Ellem and Toni McKenna. Christchurch Hospital (New Zealand): Seton Henderson, David Knight, Jan Mehrtens, Emmeline Minto and Sascha Noble. Footscray Hospital: Zia Ansari, Samantha Bates, Craig French, Dashiell Gantner, Sathyajith Velandy Koottayi, Forbes McGain, John Mulder, Anna Tippett and Miriam Towns. Freeman Hospital - Newcastle upon Tyne (United Kingdom, England): Christine Boyd, Verity Calder, Kayla Harris, Carmen Scott and Stephen Wright. Fremantle Hospital/Fiona Stanley Hospital: Bart De Keulenaer, Edward Litton, Annamaria Palermo, and Adrian Regli. Geelong Hospital: Alison Bone, Claire Cattigan, Tania Elderkin, Melissa Fraser, Martina Ni Chonghaile, Neil Orford, and Tania Salerno. Gold Coast University Hospital: Maimoonbe Gough, Jody Paxton, Mandy Tallott and James Winearls. Gosford Hospital: Michael Bastick, Robert Cameron, Katrina Ellis, Atul Gaur, Rebecca Gregory, Jessica Naumoff and Mary White. Ipswich General Hospital: Neeraj Bhadange, Nandan Bhende, Umakant Bhutada, Anand Krishnan, Rebecca Nunn, Judith Ochola, Kristine Ryan, Tracey Sandford and Shannon Treay. John Hunter Hospital: Miranda Hardie, Peter Harrigan, Rachael Paton, Emma Pollock and Rachael Whyte. King Abdulaziz Medical City, Riyadh (Kingdom of Saudi Arabia): Fatimah Al Ehnidi, Farhan Al Enizi, Eman Al Qasim, Moudi Al Qahtani, Alawi Al Saeedi, Sami Al Solamy, Shmylan Alharbi, Yaseen Arabi, Maamoun Dbsawy, Samir Hadad, Mohammed Muhaidib, Shihab Mundekkadan, Muath Najjar, Vusala Rzayeva, Musharaf Sadat and Sadaf Saedar. King Fahad Medical City (Kingdom of Saudi Arabia): Husain Abdulmutalib, Mohammed A. AlMaani, Alaa Ashraf B. AlQurashi, Hani Lababidi, and Pendo Ntinika. King Khalid University Hospital, King Saud University (Kingdom of Saudi Arabia): Ahmed Abdulmomen, Mariam Al-Ansari and Mohammad Hussein. King’s College Hospital (United Kingdom, England): Alexander Chan, Clair Harris, Phillip Hopkins, Lucy Johnson, Clare Mellis, Leah Thompson, and Julia Wendon. Lewisham Hospital (United Kingdom, England): Richard Breeze, Michaela Heller, Mick Jennings, Waqas Khaliq, Ingrid Krupe, Ashraf Molokhia, Mathin Mostert, Rosie Reece-Anthony and Bernd Oliver Rose. Liverpool Hospital: Anders Aneman, Kerrie-Ann Bradshaw, Lien Lombardo, Claudia Lopez, Sharon Micallef, William O’Regan and Antony Stewart. Logan Hospital: Lynette Morrison, Kellie Sosnowski, Joanne Sutton and Hayden White. Lyell McEwin Hospital: Natalie Soar, Peter Thomas and Josette Wood. Mackay Hospital: Jacqueline Atkins, Stuart Baker and Neeraj Bhadange. Mater Health Services (Private), Brisbane: Melissa Finney, Kye Gregory, Amod Karnik, Megan Martin, John Morgan, Maria Pietsch, Jeffrey Presneill and David Sturgess. Mater Health Services (Public), Brisbane: Melissa Finney, Kye Gregory, Amod Karnik, Megan Martin and David Sturgess. Middlemore Hospital (New Zealand): Jefferson Aguila, Bernadette Clatworthy, Anisha Dias, Chantal Hogan, Alex Kazemi, Emmanuel Pelayo, Laura Rust, Rima Song, Anna Tilsley and Tony Williams. Monash Medical Centre: Hesham Abdelrahman, Lauren Bulfin, Tim Crozier, Darcy Davey, Jonathan Devine, Dhiraj Dwwivedi, Suzanne Eliott, David Ernest, Michelle Fernando, Kelli Fenech, Pauline Galt, Maja Green, Tammy Lamac, Klaudija Lavrans, Oakleigh Mullan, Paul Ritchie, Stephen Thornhill, Craig Walker, Huichun Wang, Stuart Wilson and Naomi Yarwood. Nambour General Hospital: Jane Brailsford, Anne Buckley, Loretta Forbes, Peter Garrett, John Moore and Lauren Murray. Nepean Hospital: Rebecca Gresham, Julie Lowrey, Kristy Masters, Ian Seppelt, Fiona Symonds, Leonie Weisbrodt and Christina Whitehead. North Shore Hospital (New Zealand): Jeanette Bell, Sheila Caniba, Maud Carpenter, Danielle Hacking, Janet Liang, and Caroline Thomas. Northern Hospital: Olga Burgess, Angaj Ghosh, John Green, Vanessa Leonard-Roberts, Mary Park and Simone Said. Prince Charles Hospital: Amanda Corley, Lizanne Dalgleish, Melannie Edwards, John Fraser, Paul Jarrett, India Lye, David Sellers, Amy Spooner and Marc Ziegenfuss. Prince of Wales Hospital: Maria Albania, Sumesh Arora, Michelle Campbell, Yahya Shehabi, Yi Shi and Nicola Straiton. Princess Alexandra Hospital: Chris Joyce, Jason Meyer, Kelly Perkins, Emma Saylor, Bala Venkatesh, Ellen Venz, James Walsham, and Krista Wetzig. Queen Alexandra Hospital - Portsmouth (United Kingdom, England): David Pogson, Lindsey Roberts and Steve Rose. Queen Elizabeth Hospital - Birmingham (United Kingdom, England): Amy Bamford, Colin Bergin, Ronald Carrera, Lauren Cooper, Liesl Despy, Karen Ellis, Samantha Harkett, Peter Ip, Philip Pemberton, Martin Pope, Emma Reeves, Catherine Snelson, Elaine Spruce, Arlo Whitehouse and Tony Whitehouse. Redcliffe Hospital: Maree Duroux, Hamish Pollock, Megan Ratcliffe and Tim Warhurst. Rigshospitalet (Denmark): Björn Anders Brand, David Lavarett Buck, Vibeke Christiansen, Jette Fredlund Degn, Sofie Riis Jessiman, Maj-Brit Nørregaard Kjær, Vibeke Knudsen, Martin Bruun Madsen, Charlotte Benedikte Mørch Merie, Morten Hylander Møller, Rasmus Müller, Jonas Nielsen, Lizette Helbo Nislev, Anders Perner, Lars Quist, Kis Rønn Uhre, Sofie Louise Rygård, Anne Sofie Svanekier, Hans-Christian Thorsen-Meyer and Jonathan White. Royal Adelaide Hospital: Marianne Chapman, Sarah Doherty, Kathleen Glasby, Sonya Kloeden, Stephanie O’Connor, Alex Poole, Justine Rivett and Krishnaswamy Sundararajan. Royal Brisbane & Women’s Hospital: Jenie Butler, Jeremy Cohen, Rachael Dunlop, Paul Jarrett, Melissa Lassig-Smith, Amelia Livermore, Therese Starr and Janine Stuart. Royal Darwin Hospital: Sidharth Agarwal, Margaret Phillips, Dianne Stephens and Jane Thomas. Royal Gwent Hospital (United Kingdom, Wales): Nicholas Mason and Una Gunter. Royal Hobart Hospital: David Cooper and Rick McAllister. Royal Melbourne Hospital: James Anstey, Deborah Barge, Jai Darvall, Rohit D’Costa, Kieron Gorman, Nerina Harley, Andrea Jordan, Christian Karcher, Christopher MacIsaac, Thomas Rechnitzer and Shyamala Sriram. Royal North Shore Hospital: Frances Bass, Simon Bird, Celia Bradford, Anthony Delaney, Simon Finfer, Naomi Hammond, Roger Harris, Anne O’Connor, Maz Razivian, Sarah Wesley and Elizabeth Yarad. Royal Perth Hospital: Chris Allen, Michelle Barr, Jenny Chamberlain, Janet Ferrier, Elizabeth Jenkinson, Edward Litton, Swapna Mathew, Soumya Ray, Anne Marie Sommers, Louise Wallace, Sharon Waterson and Steve Webb. Royal Prince Alfred Hospital: Heidi Buhr, Jennifer Coakley, Jennifer Coles, Mark Daley, David Gattas, Robert Hislop, Debra Hutch, Megan Keir, Heike Koelzow, Mark Lucey, Margherita Murgo, Michael O’Leary, Paul Phipps, Nudrat Rashid, Máté Rudas, Sanjay Tarvade, Richard Totaro, Clive Woolfe and James Wun. Royal Surrey County Hospital (United Kingdom, England): Ben Creagh-Brown, Nancileigh Doyle, Lui Forni, Christina Hughes, Daniel Hull, Justin Kirk-Bayley, Laura Montague and Eleanor Radford. St George Hospital: Deborah Inskip, Jennene Miller, John Myburgh and Manoj Saxena. St George’s Trust NHS (United Kingdom, England): Hollmann Aya, Maurizio Cecconi, Nora Di Tomasso, Helen Farrah, Fabrizio Iannuccelli, Joao Macedo, Johannes Mellinghoff, Narenduth Poonuth, Sarah Pruden, Andrew Rhodes and Veronica Robinson-Barnes. St John of God Hospital Murdoch: Annamaria Palermo and Adrian Regli. St Peter’s Hospital - Surrey (United Kingdom, England): Catherine Gray, Philomena Mweu, Emily Whisker and Ian White. St Thomas’ Hospital (United Kingdom, England): Ursula Blanco Alonso, Aneta Bociek, Kathryn Chan, Kate Flynn, Anna Hall, Jessica Hall, Naomi Hare, Andrea Kelly, Katie Lei, Marlies Ostermann, Nicola Purchase, John Smith, Samantha Smith and Duncan Wyncoll. St Vincent’s Hospital (Melbourne): Barry Dixon, Espedito Faraone, Jennifer Holmes, John Santamaria, Roger Smith and Antony Tobin. St Vincent’s Hospital (Sydney): Serena Knowles, Serene Leow, Karlee McCann, Priya Nair and Claire Reynolds. Sunshine Hospital: Zia Ansari, Samantha Bates, Craig French, Dashiell Gantner, Sathyajith Velandy Koottayi, Forbes McGain, John Mulder, Anna Tippett and Miriam Towns. Tamworth Rural Hospital: Grant Cave, Tim Constable, Phil Hungerford, Amit Kansal, Peter May, Viji Rao and Chris Trethewy. Tauranga Hospital (New Zealand): Troy Browne, Jennifer Goodson and Shirley Nelson. The Queen Elizabeth Hospital: Catherine Kurenda, Joanne McIntyre, Sandra Peake, Jennie Phillips-Hughes and Tricia Williams. The Tweed Hospital: Rand Butcher, Belinda Foley, Cassandra Lillis, Kerrie Martin, Brunhilde Mulhall, Rebekah Napier, Joe Ogg and Karen Vallance. The Wesley Hospital: Amanda Davie, Alison Leech, Elyse Matsen, Amy Owens, Roslyn Purcell and Bala Venkatesh. Toowoomba Hospital: Vasanth Mariappa and Judy Smith. Townsville Hospital: Kimberly Bury, Shane Finnigan, Elizabeth Heyer, Leonie Jones, Nadine Laffin, Clare Newton and Siva Senthuran. University Hospital Southampton (United Kingdom, England): Clare Bolger, Rebecca Cusack, Max Jonas and Karen Salmon. Waikato Hospital (New Zealand): Jewel Barlow-Armstrong, John Durning, Mary La Pine and Tom O’Rourke. Wellington Hospital (New Zealand): Lynn Andrews, Richard Dinsdale, Caitlin Firkin, Anna Hunt, Sally Hurford, Adelaide Jason-Smith, Eden Lesona, Diane Mackle, Agnes McKay Vucago, Lean Navarra, Raulle Sol Cruz and Paul Young. Wollongong Hospital: Michael Davis, Wenli Geng, Samantha Jakimowicz, Bronwyn Johnson, Clare Merriman and Martin Sterba.
This study was supported by project grants from the National Health and Medical Research Council of Australia (Grant Numbers: 1004108 and 1124926) and the Health Research Council of New Zealand (grant number: 12/306), by indirect funding from the National Institute of Health Research in the United Kingdom, and by Practitioner Fellowships from the National Health and Medical Research Council of Australia (to Drs. Venkatesh, Finfer, Bellomo, and Myburgh).
Conflicts of interest
Dr. Perner reports receiving Grant support from CSL Behring, Ferring Pharmaceuticals, and Fresenius Kabi; and Dr. Rhodes, serving as co-chair of the Surviving Sepsis Campaign. No other potential conflict of interest relevant to this article was reported.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
ADRENAL Trial Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group members are listed the Acknowledgements.
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Hammond, N.E., Finfer, S., Li, Q. et al. Health-related quality of life in survivors of septic shock: 6-month follow-up from the ADRENAL trial. Intensive Care Med 46, 1696–1706 (2020). https://doi.org/10.1007/s00134-020-06169-1