SAFE Trial (2004)

Summary by Tarek Elshazly, 11.29.21

https://www.nejm.org/doi/full/10.1056/nejmoa040232

The 2004 Saline versus Albumin Fluid Evaluation (SAFE) trial randomized 6,997 ICU patients requiring IV fluids to either albumin (4%) or saline.

Inclusion criteria: ICU patients, age >/= 18, volume depleted as per physician assessment.

Exclusion criteria: ICU admission post-cardiac surgery, liver transplantation, or burn treatment.

Findings:

- There was no difference in all-cause mortality between the two groups.

- A subgroup analysis demonstrated that albumin was associated with poorer outcomes in TBI (Traumatic Brain Injury) patients --> 28-day mortality in TBI patients was 25% in albumin group vs 15% in NS group (p=0.009).

Take Home:

The use of colloids may be unjustified given their increased cost and lack of benefit --> Although this was specifically studied in ICU patients, it is reasonable to take that into consideration in our daily resuscitative efforts in the operating room. Indeed, there are clinical scenarios (e.g. ascites, or so) where the use of albumin may be favorable in volume replacement, in which cases, as always, clinical judgment is inevitable.

As this initiative continues, I hope that we are mindful of evidence in our daily practice. Below are a couple of additional resources on colloid vs crystalloid.

Additional Evidence:

1) The 2014 Albumin Italian Outcome Sepsis (ALBIOS) trial evaluated daily administration of albumin in 1818 patients with severe sepsis or septic shock at 100 Italian ICUs.

- Daily administration of albumin to maintain serum albumin >/= 3g /dL was NOT ASSOCIATED with a reduction in all-cause mortality at 28 days (and 90 days), when compared to no albumin.

- Secondary outcomes --> albumin group had shorter duration on vasopressors or inotropes. No difference in overall SOFA scores.

REF: Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, Fanizza C, Caspani L, Faenza S, Grasselli G, Iapichino G, Antonelli M, Parrini V, Fiore G, Latini R, Gattinoni L; ALBIOS Study Investigators. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014 Apr 10;370(15):1412-21. doi: 10.1056/NEJMoa1305727. Epub 2014 Mar 18. PMID: 24635772.

2) "There is no evidence from randomized controlled trials that resuscitation with colloids reduces the risk of death, compared to resuscitation with crystalloids, in patients with trauma, burns or following surgery. Furthermore, the use of hydroxyethyl starch might increase mortality. As colloids are not associated with an improvement in survival and are considerably more expensive than crystalloids, it is hard to see how their continued use in clinical practice can be justified."

REF: Perel P, Roberts I, Ker K. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2013 Feb 28;(2):CD000567. doi: 10.1002/14651858.CD000567.pub6. Update in: Cochrane Database Syst Rev. 2018 Aug 03;8:CD000567. PMID: 23450531.