Albumin resuscitation in burns

Overview

Albumin is the most widely used colloid in burn resuscitation and the colloid with the strongest evidence base in burn care ^[1][2]. It is administered either as a planned component of resuscitation from the outset or as rescue therapy when crystalloid volumes exceed predicted targets ^[2]. The 2024 American Burn Association Clinical Practice Guideline recommends that clinicians consider human albumin solution, especially in patients with larger burns, to lower resuscitation volumes and improve urine output ^[1]. The clinical question is no longer whether to use albumin but when, at what concentration, and in whom. This page covers physiologic rationale, comparative evidence on volume sparing and mortality, timing and dosing strategies, pediatric considerations, and the open controversies that structure current practice.

Physiologic Rationale

Increased capillary permeability and reduced plasma colloid osmotic pressure following burn injury result in hypovolemia and development of edema in burn and nonburn tissues ^[3]. Preclinical work shows that the inflammatory reaction degrades the endothelial glycocalyx layer, accelerating capillary leakage of albumin and fluid ^[17]. Colloids have been used in varying capacities throughout the history of formula-based burn resuscitation, and there is sound experimental evidence that they improve intravascular colloid osmotic pressure, expand intravascular volume, reduce resuscitation requirements, and limit edema in unburned tissue following major burn ^[5].

Animal studies demonstrate that during acute fluid resuscitation, colloids including albumin have no ability to arrest burn wound edema formation but do reduce edema in nonburn soft tissue and help preserve intravascular volume, reducing resuscitation fluid requirements with no apparent increase in extravascular lung water ^[4]. Clinical pharmacokinetic data support meaningful intravascular retention even during burn shock. In burn patients studied between 4 and 14 days after injury (median 7 days), a 20% albumin infusion of 3 mL/kg expanded plasma volume by nearly 15 percent, roughly twice the infused volume, comparable to healthy volunteers, and capillary leakage rates for albumin were not different between groups (3.4 ± 1.5 g/h vs 3.7 ± 1.6 g/h) ^[16]. The median half-life of plasma volume expansion was 5.9 hours in burn patients and 6.9 hours in volunteers ^[16].

Clinical Evidence

The modern evidence base is a mixture of meta-analyses, randomized trials in specific populations, and single-center before-after or matched-cohort studies. No large multicenter randomized trial has yet been published, though one is underway comparing crystalloid with albumin-inclusive resuscitation ^[2].

Meta-analyses

The Cochrane review of albumin for resuscitation and volume expansion in critically ill patients pooled 38 randomized trials with 10,842 participants and found no overall mortality benefit (pooled relative risk of death 1.05, 95% CI 0.95 to 1.16) ^[6]. The burns subgroup analysis reported a relative risk of death of 2.93 (95% CI 1.28 to 6.72) ^[6]. Reviewers concluded that there is no evidence that albumin reduces mortality in critically ill patients with burns and hypoalbuminaemia ^[6]. The Navickis meta-analysis of controlled clinical studies specifically in burn shock resuscitation reached a different conclusion. Pooling four randomized and four nonrandomized studies with 688 adult patients, albumin infusion during the first 24 hours showed no overall mortality effect, but significant heterogeneity was present and could be abolished by excluding two studies at high risk of bias; after exclusion, albumin was associated with reduced mortality (pooled odds ratio 0.34, 95% CI 0.19 to 0.58, P < .001) ^[7]. Albumin administration was also associated with decreased occurrence of compartment syndrome (pooled odds ratio 0.19, 95% CI 0.07 to 0.50, P < .001) ^[7]. The Navickis authors concluded that albumin can improve outcomes of burn shock resuscitation ^[7]. The divergent conclusions of these two syntheses, both anchored to partly overlapping trial sets, drive ongoing disagreement about mortality effects and leave the field without a dispositive answer.

More recent large-database analyses add nuance without resolving the mortality question. A Japanese nationwide inpatient-data analysis of 2,492 severe burn patients matched 530 pairs on propensity score and found no difference in 28-day mortality between patients who received albumin within 2 days of admission and those who did not (21.7% vs 22.8%; risk difference -1.1%, 95% CI -6.1% to +3.9%) ^[19].

Planned early albumin versus rescue albumin

Two scenarios dominate practice. In the first, albumin is folded into the resuscitation protocol from admission or soon after. The Blanco-Schweizer BET formula uses 20% albumin at a 1:1 ratio with lactated Ringer from the start, decreasing the albumin proportion every 8 hours and titrating rate to urine output ^[11]. Patients resuscitated with BET received 2.58 mL/kg/%TBSA in the first 24 hours, significantly less than the 4 mL/kg/%TBSA predicted by the Parkland formula (P < 0.05) ^[11]. Reported complications in that cohort included ARDS 27%, renal dysfunction 53%, wound deepening 20%, and abdominal compartment syndrome 4.5% ^[11]. The authors concluded that the BET formula is capable of resuscitating burn patients successfully while limiting fluid administration ^[11].

In the second scenario, albumin is reserved for rescue when crystalloid volumes run ahead of predicted rates. Lawrence and colleagues demonstrated that addition of 5% albumin to Parkland resuscitation rapidly reduced hourly fluid requirements and restored normal resuscitation ratios ^[9]. In their cohort of 52 patients, those who required albumin supplementation had progressively increasing mean resuscitation ratios up to 1.97, and administration of albumin produced a dramatic and precipitous return of ratios to within predicted ranges throughout the remainder of resuscitation ^[9]. No patient developed abdominal compartment syndrome ^[9]. Comish and colleagues found that rescue 25% albumin administered to patients failing crystalloid-only resuscitation decreased the amount of fluid administered per %TBSA and increased urine output as a marker of end-organ function ^[10]. The rescue group carried larger burns (40.3% vs 34% TBSA; P = 0.047), yet total lactated Ringer volumes were not significantly different between groups, suggesting that albumin offset the higher fluid demand of the larger injury ^[10].

Cochran and colleagues compared patients who received albumin during resuscitation because of increased fluid requirements to age- and TBSA-matched patients who did not ^[8]. Albumin patients had significantly higher mean initial lactate, longer mean time to resuscitation, and higher resuscitation volume (9.4 vs 6.4 mL/kg/%TBSA) ^[8]. Mortality did not differ on unadjusted analysis (OR 1.90, 95% CI 0.85-4.22), and albumin was protective in a multivariate model (OR 0.27, 95% CI 0.07-0.97) ^[8]. Despite more severe systemic dysfunction, patients who received albumin did not suffer increased mortality, and the authors described a decreased likelihood of mortality associated with albumin administration ^[8].

Curry and colleagues showed that a revised institutional guideline optimizing colloid use alongside a lower starting crystalloid rate of 2 mL/kg/%TBSA produced significantly lower 24-hour resuscitation volumes (3.74 vs 2.94 mL/kg/TBSA; P < .01) without an increase in a composite adverse safety outcome ^[12].

Negative and equivocal data

Not every study favors albumin. Cooper and colleagues randomized 42 adults with thermal injury to lactated Ringer alone or 5% albumin plus lactated Ringer, targeted to ABA resuscitation endpoints, and found no significant difference in the lowest multiple-organ-dysfunction score from day 0 to day 14 (P = 0.73) ^[18]. The authors concluded that 5% albumin from day 0 to day 14 does not decrease the burden of MODS in adult burn patients ^[18]. This negative signal, along with the Cochrane burns-subgroup risk estimate ^[6], anchors the ongoing conservative position that mortality benefit has not been definitively demonstrated.

Timing and Dosing

Timing is the most active open question. Traditional teaching delayed colloid until after 24 hours, based on the assumption that early capillary leak renders colloid ineffective. Contemporary evidence supports earlier use in selected patients ^{[1][2][10][11]}. In pediatrics, a randomized trial in 46 children aged 1 to 12 years with burns greater than 15 to 45% TBSA compared early albumin (5% between 8 and 12 hours post-burn) to delayed albumin (at 24 hours post-burn) ^[13]. The intervention group received less crystalloid on each of days 1 through 3 (2.04 vs 3.05 mL/kg/%TBSA on day 1, P = 0.025; 1.2 vs 1.71 on day 2, P = 0.002; 0.82 vs 1.3 on day 3, P = 0.002) ^[13]. Fluid creep was observed in 4.3% of the intervention group versus 56.5% of controls, and hospital length of stay was shorter in the early-albumin group (14 vs 18 days; P = 0.004) ^[13]. A follow-up cohort analysis of the same population reported a shorter hospital stay, less fluid creep (4.3% vs 56.5%; P < 0.001), and less skin grafting and debridement in patients who received early albumin, and fluid creep itself was associated with infection ^[14].

Albumin concentration in clinical use ranges from 5% to 25%. The 2024 ABA CPG recommends considering human albumin solution without specifying a concentration, reflecting the absence of adequately powered head-to-head data ^[1]. Rescue practice in U.S. burn centers typically uses 5% albumin added to crystalloid ^[9] or 25% albumin given as discrete boluses ^[10], and the choice reflects local protocol rather than comparative trial data. Clinical pharmacokinetic data on 20% albumin at 3 mL/kg support intravascular retention consistent with efficient volume expansion ^[16].

Outcomes

The claim most reliably supported by the evidence is that albumin reduces total crystalloid requirements during the first 24 hours ^{[1][2][7][9][10][11][12][13]}. This effect is observed across planned-early, rescue, adult, and pediatric cohorts. The claim most contested is that albumin reduces mortality. The Cochrane burns subgroup reported a harm signal ^[6], the Navickis meta-analysis after sensitivity analysis reported a benefit ^[7], a large Japanese nationwide analysis reported no difference ^[19], and individual matched-cohort studies report either protection or no effect after adjustment ^[8][18]. Intermediate outcomes including abdominal compartment syndrome ^[7][11] and fluid creep ^{[9][10][13][14]} have signaled in favor of albumin-inclusive strategies in multiple studies.

The relationship with acute kidney injury is bidirectional. In a major-burn cohort, TBSA, daily 24-hour fluid balance, and most recent 24-hour albumin transfusion status were all significantly associated with AKI on adjusted analysis, and the authors interpreted this as evidence that intensity of fluid resuscitation may mediate AKI development in major burns rather than as a direct injurious effect of albumin ^[20]. This pattern fits the broader observation that patients who require more fluid and more albumin are sicker to begin with; treatment-indication confounding limits causal inference from observational data.

Special Considerations

Pediatric burn care is where early albumin has the strongest randomized evidence base ^[13][14]. A recent single-center pediatric study substituted albumin for part of the crystalloid volume in patients with greater than 15% TBSA burn who were difficult to resuscitate and found that the albumin group received less total intravenous fluid in 48 hours (7.8 vs 12.4 mL/kg/TBSA; P = 0.037), had lower serum lactate at 48 hours, and had shorter length of stay normalized to TBSA burn ^[15]. The authors concluded that albumin substitution in difficult-to-resuscitate pediatric burn patients reduces total IV volume and length of stay per TBSA while preserving markers of adequate resuscitation ^[15].

Patients with inhalation injury are more likely to receive albumin during resuscitation (OR 4.89, 95% CI 2.58 to 9.30) in matched-cohort data, reflecting higher fluid demand in that group rather than a specific albumin indication ^[8]. Patients with very large burns, full-thickness injuries, or escalating crystalloid rates early in resuscitation are the typical candidates for planned-early or rescue albumin in current protocols ^[1][2][10].

Controversies and Evidence Gaps

Randomized data comparing crystalloid-only resuscitation to albumin-inclusive protocols in adults remain limited. The planned multicenter trial comparing crystalloids with albumin will be the most important new evidence in this space ^[2]. Whether fresh frozen plasma is superior to albumin as a colloid in burns is an emerging question with limited comparative data; the next question identified by burn leaders is whether albumin or plasma is the better colloid ^[2]. Animal work suggests plasma may have specific effects on endothelial glycocalyx preservation that albumin does not replicate, but human comparative trials are lacking.

The optimal timing threshold (within 8 hours, at 8 to 12 hours, at 24 hours) has pediatric randomized support ^[13]. Mortality effects remain contested across the two most cited meta-analyses ^[6][7], and even large modern database analyses have not resolved the question ^[19]. Whether albumin administration is causally protective against acute kidney injury or whether the observed signal reflects reverse-channel confounding (sicker patients receiving more of everything) cannot be determined from currently available data ^[20].

References

[1] Cartotto R, Johnson LS, Savetamal A, et al. "American Burn Association Clinical Practice Guidelines on Burn Shock Resuscitation." J Burn Care Res 2024. PMID: 38051821

[2] Greenhalgh DG. "Current Thoughts on Burn Resuscitation." Adv Surg 2024. PMID: 39089770

[3] Cartotto R. "Fluid resuscitation of the thermally injured patient." Clin Plast Surg 2009. PMID: 19793552

[4] Cartotto R, Callum J. "A review of the use of human albumin in burn patients." J Burn Care Res 2012. PMID: 23143614

[5] Cartotto R, Greenhalgh D. "Colloids in Acute Burn Resuscitation." Crit Care Clin 2016. PMID: 27600123

[6] Roberts I, Blackhall K, Alderson P, et al. "Human albumin solution for resuscitation and volume expansion in critically ill patients." Cochrane Database Syst Rev 2011. PMID: 22071799

[7] Navickis RJ, Greenhalgh DG, Wilkes MM. "Albumin in Burn Shock Resuscitation: A Meta-Analysis of Controlled Clinical Studies." J Burn Care Res 2016. PMID: 25426807

[8] Cochran A, Morris SE, Edelman LS, et al. "Burn patient characteristics and outcomes following resuscitation with albumin." Burns 2007. PMID: 17223485

[9] Lawrence A, Faraklas I, Watkins H, et al. "Colloid administration normalizes resuscitation ratio and ameliorates 'fluid creep'." J Burn Care Res 2010. PMID: 20061836

[10] Comish P, Walsh M, Castillo-Angeles M, et al. "Adoption of rescue colloid during burn resuscitation decreases fluid administered and restores end-organ perfusion." Burns 2021. PMID: 33658146

[11] Blanco-Schweizer P, Sanchez-Ballesteros J, Bendito B, et al. "Resuscitation with albumin using BET formula keeps at bay fluid administration in burned patients." Burns 2020. PMID: 31848084

[12] Curry D, Wray K, Hobbs B, et al. "Revision of an Adult Burn Center's Resuscitation Guideline Leads to Lower Resuscitation Requirements." J Burn Care Res 2024. PMID: 38824401

[13] Muller Dittrich MH, Brunow de Carvalho W, Lopes Lavado E. "Evaluation of the 'Early' Use of Albumin in Children with Extensive Burns: A Randomized Controlled Trial." Pediatr Crit Care Med 2016. PMID: 27077832

[14] Dittrich MHM, Hosni ND, de Carvalho WB. "Association between fluid creep and infection in burned children: A cohort study." Burns 2020. PMID: 32122709

[15] Akpunonu CC, Bergus KC, Rachwal B, et al. "The Impact of Albumin in Pediatric Burn Resuscitation." J Burn Care Res 2026. PMID: 40741975

[16] Zdolsek M, Hahn RG, Sjoberg F, et al. "Plasma volume expansion and capillary leakage of 20% albumin in burned patients and volunteers." Crit Care 2020. PMID: 32366324

[17] Hahn RG, Zdolsek M, Krizhanovskii C, et al. "Elevated Plasma Concentrations of Syndecan-1 Do Not Correlate With Increased Capillary Leakage of 20% Albumin." Anesth Analg 2021. PMID: 33350618

[18] Cooper AB, Cohn SM, Zhang HS, et al. "Five percent albumin for adult burn shock resuscitation: lack of effect on daily multiple organ dysfunction score." Transfusion 2006. PMID: 16398734

[19] Nakamura K, Isogai T, Ohbe H, et al. "Effect of fluid resuscitation with albumin on mortality in patients with severe burns: A nationwide inpatient data analysis." Burns 2024. PMID: 39317540

[20] Kumar AB, Andrews W, Shi Y, et al. "Fluid resuscitation mediates the association between inhalational burn injury and acute kidney injury in the major burn population." J Crit Care 2017. PMID: 27863270