Washington University Emergency Medicine Journal Club – July 2025
This month’s journal club will look at the use of IV albumin in the management of sepsis and septic shock. As this is the first journal club of the academic year, we will ensure that the PGY-1 presenter gets to watch at least one other class present their article. Remember, this is meant to be stress-free and fun (albeit nerdy) so come prepared but stay relaxed.
The PGY-1, PGY-2, and PGY-4 articles will be assessed using the Therapy Critical Appraisal form. The PGY-3 article will be assessed using the Meta-Analysis form.
Vignette
You are working the weekend shift in TCC when you get a page: triage patient to TCC 3L for low BP. You meet the patient in the room and find a critically ill-appearing 55-year-old female with one week of cough and increased shortness of breath. Her vital signs are:
HR 125 BP 65/30 Sp02 89% on room air RR 28 T 39.2
She is struggling to breathe, getting out 2-to-3-word sentences, and is oriented only to self. You immediately ask the nurses to get two large-bore IVs and begin a bolus of 30 mL/kg of lactated ringers on pressure bags while you prepare to intubate. Following intubation (during which you administer two boluses of phenylephrine, 100 mcg each, for dropping blood pressure), you get a stat portable chest x-ray showing multifocal pneumonia. After your fluid bolus and broad-spectrum antibiotics have been administered, the patient’s blood pressure is still only 80/45.
You place a right-sided internal jugular central line under ultrasound guidance and start a norepinephrine drip. Your deftly placed arterial line begins to demonstrate an improved BP and MAP and you find the patient a bed in the medical ICU. As the patient is being transferred, you wonder whether additional volume in the form of colloid therapy (specifically concentrated albumin) would have been beneficial. You begin to search the literature and realize this has been a controversial topic dating back over 10 years…
PICO Question
Population: Adult patients with sepsis, severe sepsis, or septic shock
Intervention: Routine albumin administration
Comparison: Standard of care without routine albumin administration
Outcome: Mortality, organ failure, kidney failure, need for renal replacement
therapy, need for vasopressors, need for mechanical ventilation, ICU and hospital
length of stay
Search Strategy
Article 1: Annane D, Siami S, Jaber S, Martin C, Elatrous S, Declère AD, Preiser JC, Outin H, Troché G, Charpentier C, Trouillet JL, Kimmoun A, Forceville X, Darmon M, Lesur O, Reignier J, Abroug F, Berger P, Clec’h C, Cousson J, Thibault L, Chevret S; CRISTAL Investigators. Effects of fluid resuscitation with colloids vs crystalloids on mortality in critically ill patients presenting with hypovolemic shock: the CRISTAL randomized trial. JAMA. 2013 Nov 6;310(17):1809-17. doi: 10.1001/jama.2013.280502. Erratum in: JAMA. 2013 Mar 12;311(10):1071. Régnier, Jean [corrected to Reignier, Jean]; Cle’h, Christophe [corrected to Clec’h, Christophe]. PMID: 24108515. [Answer Key]
Article 2: 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. [Answer Key]
Article 3: Bannard-Smith J, Elrakhawy M, Norman G, Owen R, Felton T, Dark P. The efficacy, safety and effectiveness of hyperoncotic albumin solutions in patients with sepsis: A systematic review and meta-analysis. J Intensive Care Soc. 2024 Jun 19;25(3):308-318. doi: 10.1177/17511437241259437. PMID: 39224427; PMCID: PMC11366183. [Answer Key]
Article 4: Williams JM, Greenslade JH, Hills AZ, Ray MT. Intervention With Concentrated Albumin for Undifferentiated Sepsis in the Emergency Department (ICARUS-ED): A Pilot Randomized Controlled Trial. Ann Emerg Med. 2025 Jul;86(1):59-69. doi: 10.1016/j.annemergmed.2024.12.016. Epub 2025 Jan 23. PMID: 39846907. [Answer Key]
Bottom Line
The most recent iteration of the Surviving Sepsis Campaign guidelines continues to
emphasize the importance of fluid resuscitation with crystalloids for patients with
sepsis and septic shock. This guideline does suggest considering albumin
administration for patients who receive large volumes of crystalloids, albeit he
authors admit that this is a weak recommendation based on low quality evidence.
The CRISTAL trial (Annane 2013) randomized 2857 patients with hypovolemic
shock of any etiology to fluid resuscitation with crystalloids or colloids. Among a
subset of 1553 patients whose shock was due to sepsis, there was no significant
difference in 28-day mortality (hazard ratio 0.95, 95% CI 0.78 to 1.10).
In the subsequent ALBIOS trial (Caironi 2014), in which 1818 patients with severe
sepsis or septic shock were randomized to receive 20% albumin plus crystalloid
fluids or crystalloids alone, there was also no significant difference in 28-day
mortality (RR 1.00, 95% CI 0.87 to 1.14) or 90-day mortality (RR 0.94, 95% CI 0.85
to 1.05). Additionally, there was no significant difference in the number of newly
developed organ failures or median SOFA score (6.00 vs. 5.62, p = 0.23), and no
significant differences in other secondary and tertiary outcomes, with the exception
of time to suspension of vasopressors or inotropic agents, which was shorter in the
albumin group (median 3 vs. 4 days, p = 0.007).
The more recent ICARUS-ED trial (Williams 2025) randomized 463 patients with
suspected infection and signs of hypoperfusion to receive albumin, 400 mL of 20%
albumin over 4 hours, or standard of care with albumin use discouraged. This pilot
study found no significant difference in the primary outcome of median SBP at 24
hours (110.5 mmHg vs. 110 mmHg; difference 1 mmHg, 95% CI -2.7 to 4.7) and no
difference in mortality at any time point.
A meta-analysis of 4 studies comparing hyperoncotic albumin administration (≥
20% concentration) with standard fluid resuscitation in patients with sepsis was
published before the release of the ICARUS-ED trial. Pooled results demonstrated no
difference in 28-day mortality (OR 0.95, 95% CI 0.8 to 1.12) with no significant
heterogeneity between studies. Among patients with septic shock, the pooled OR for
28-day mortality was lower among those who received albumin (OR 0.82, 95% CI
0.68 to 0.98). This finding is questionable, however,, as there appear to be a
significant number of patients with septic shock from the CRISTAL trial who were
excluded for unclear reasons.
Given the findings noted from the literature, the Surviving Sepsis Campaign
guidelines weak recommendation to consider albumin administration in those
receiving large volume crystalloid resuscitation seems reasonable. Additionally,
albumin administration may be considered for those with cirrhosis or significant
hypoalbuminemia due to other etiologies. Routine administration of albumin for
patients with sepsis, severe sepsis, or septic shock does not appear to be justified by
the evidence.