Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock

Holst LB, Haase N, Wetterslev J, et al.; TRISS Trial Group

N Engl J Med. 2014 Oct 9;371(15):1381-91. doi: 10.1056/NEJMoa1406617. [Full text]

Today in 2021, restrictive transfusion is generally accepted in almost all of adult practice. So review of the 2014 Transfusion Requirements in Septic Shock (TRISS) trial is almost a history lesson more than it is a scrutiny of evidence.

In critical care there actually already existed evidence of equivalence between a liberal and restrictive transfusion strategy going back to 1999: the Transfusion Requirements in Critical Care or TRICC trial (see related 52in52 post) [1]. Yet because of the early goal directed therapy (EGDT) and surviving sepsis guidelines (the 4th surviving sepsis campaign guidelines now recommend a restrictive approach [2]), a high transfusion threshold remained a part of the management of septic shock well past 1999.

So while other fields (i.e., TRACS for cardiac surgery [3], FOCUS for hip fracture repair [4]) were moving towards a restrictive strategy, it was not 2014 that the ICU saw a major shift in practice via TRISS. Interestingly, 2014 was a also a landmark year in that it saw the “end” of EGDT (see ProCESS, ARISE, and the following year ProMISe), though it has been argued that by then many of the elements of EGDT had become routine practice .

Patient Population

TRISS enrolled adults≥ 18 yo with septic shock (based on the Sepsis-2 definition) and Hgb ≤ 9 g/dL. It involved 32 general Scandinavian ICUs with roughly equal number of medical and surgical patients. Key exclusion criteria were those with a history of an adverse transfusion reaction, had already received a transfusion during their ICU stay, had a life threatening bleed, had ACS, acute burn injury, or declined transfusion.

A total of 998 patients were enrolled with 502 in the restrictive Hgb ≤7 g/dL transfusion threshold and 496 in the liberal Hgb ≤9 g/dL threshold. The patients groups were equivalent at baseline with an average age of 67 yrs, 53% were male, 70% were on mechanical ventilation with had a median SOFA score of 10.


Effectively the restrictive group maintained an average Hgb in the 7-8 range during the study period, while the liberal group averaged 9-10 g/dL. The restrictive group only received a median 1 transfusion compared to 4 for the liberal group (P<0.001) and 36% received no transfusion compared to only 1.2% with no transfusion in the liberal group (P<0.001).

The primary outcome was death by 90 days and there were 216 (43%) in the restrictive group versus 223 (45%) deaths in the liberal group (RR 0.94, 95% CI 0.78-1.09, P=0.44). Power estimates had a assumed a 45% mortality rate – the estimate was spot on. There were no differences in secondary outcomes including ischemic events, myocardial infarction (MI, via post hoc analysis), or need for “life support at multiple time point. There were no differences in adverse events either.


A restrictive strategy is now standard for septic shock and EGDT no longer exists as it did at its inception thanks to TRISS and other trials as noted from 2014-15. Perhaps the only “knock” on the trial is how myocardial infarction was only analyzed after the fact. Acute coronary syndrome (ACS) remains an area where high quality evidence for a restrictive strategy has not been published. Currently a threshold of ≤8 g/dL is generally accepted based on meta-analysis and multiple observational or pilot trials. The REALITY trial was presented at the European Society of Cardiology in 2020 in abstract form but we will need to await full results from that to change practice in ACS. But for now a ≤7 g/dL threshold has support for most other conditions, even gastrointestinal bleeding [5-7] (though exact timing and threshold is still debated), and including septic shock.

PS – Asymptomatic patients that are clinically compensated may not need transfusion even with a Hgb ≤7 g/dL – but this would be based on clinical judgement.

  1. Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999 Feb 11;340(6):409-17. doi: 10.1056/NEJM199902113400601. Erratum in: N Engl J Med 1999 Apr 1;340(13):1056. PMID: 9971864.
  2. 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 Mar;45(3):486-552. doi: 10.1097/CCM.0000000000002255.
  3. Hajjar LA, Vincent JL, Galas FR, et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010 Oct 13;304(14):1559-67. doi: 10.1001/jama.2010.1446.
  4. Carson JL, Terrin ML, Magaziner J, Chaitman BR, Apple FS, Heck DA, Sanders D; FOCUS Investigators. Transfusion trigger trial for functional outcomes in cardiovascular patients undergoing surgical hip fracture repair (FOCUS). Transfusion. 2006 Dec;46(12):2192-206. doi: 10.1111/j.1537-2995.2006.01056.x.
  5. Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013 Jan 3;368(1):11-21. doi: 10.1056/NEJMoa1211801. Erratum in: N Engl J Med. 2013 Jun 13;368(24):2341.
  6. Jairath V, Kahan BC, Gray A, et al. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet. 2015 Jul 11;386(9989):137-44. doi: 10.1016/S0140-6736(14)61999-1. Epub 2015 May 5.
  7. Chen YC, Hsiao CT, Lin LC, Hsiao KY, Hung MS. The association between red blood cell transfusion and outcomes in patients with upper gastrointestinal bleeding. Clin Transl Gastroenterol. 2018 Mar 29;9(3):138. doi: 10.1038/s41424-018-0004-9.