A targeted, non-systematic literature search was conducted using PubMed/PMC and DOI.org to identify studies considered structurally relevant to the research question. The search focused primarily on pivotal randomized controlled trials evaluating albumin use in critical care, notably the SAFE and ALBIOS trials [3][4]. It also included recent meta-analyses and narrative syntheses addressing the role of albumin in sepsis and septic shock, including hyperoncotic formulations [11][12]. International guidelines particularly those from the Surviving Sepsis Campaign 2021 [13] as well as guidelines specifically dedicated to intravenous albumin administration [14], were reviewed. Finally, data from the Cameroonian literature related to critical care and the local hospital context were sought and included when available [9][10].

The search terms used included, but were not limited to, the following: albumin, hypoalbuminemia, critical care, ICU, sepsis, septic shock, traumatic brain injury, Cameroon, and Africa.

Source selection prioritized studies with a high level of evidence, particularly randomized controlled trials, meta-analyses, and guidelines issued by scientific societies. Older studies considered foundational were also included when their role in shaping current understanding of mechanisms, controversies, or therapeutic strategies related to albumin was recognized, including certain pivotal trials and historical conceptual frameworks [1][15][3][4].

This approach was deliberately non-exhaustive, thereby exposing the synthesis to an inherent risk of selection bias typical of narrative reviews. In addition, the transferability of data derived from international studies to the Cameroonian context cannot be assumed to be automatic. Accordingly, the practical propositions advanced in this synthesis should be interpreted as exploratory and hypothesis-generating rather than as normative recommendations, pending prospective validation in local cohorts.

The biological half-life of circulating albumin is approximately 19 - 20 days, supporting the notion that hypoalbuminemia may reflect baseline vulnerability and/or sustained inflammation, in addition to acute care-related variations [16]. This kinetic property does not preclude rapid changes in settings characterized by capillary leak, hemodilution, or fluid redistribution.

In critically ill patients, decreased serum albumin levels are primarily related to: 1) the acute inflammatory response, as albumin is a negative acute-phase protein [6]; 2) increased capillary permeability and leakage into the interstitial space, particularly pronounced in sepsis [8]; 3) iatrogenic effects, including fluid resuscitation, transfusions, and fluid overload, leading to dilutional decreases; and 4) hepatic dysfunction or hypoperfusion, which may impair albumin synthesis.

Albumin contributes to oncotic pressure, serves as a carrier for endogenous and exogenous molecules, and exhibits biological properties including buffering capacity, antioxidant effects, and potential interactions with the endothelial glycocalyx described in mechanistic reviews [8]. However, physiological plausibility does not equate to hard clinical benefit; the persistent gap between observed physiological effects (e.g., blood pressure, fluid balance) and mortality outcomes remains central to the interpretation of clinical trials.

A landmark meta-analysis demonstrated a robust association between hypoalbuminemia and adverse outcomes in acutely ill patients [1]. With respect to renal function, an observational meta-analysis reported an association between hypoalbuminemia and an increased risk of acute kidney injury [2].

Together, these findings support the interpretation of serum albumin as an indicator of disease severity and patient vulnerability rather than as an isolated therapeutic target to be corrected [1][2].

In clinical practice, the question is not only whether albumin is associated with prognosis, but whether it provides useful information beyond clinical assessment and organ dysfunction scores. In this review, the proposed approach is deliberately qualitative: serum albumin is considered a risk modifier integrated into a constellation of indices (e.g., SOFA score, hemodynamic dynamics, and lactate levels when available), rather than as an isolated determinant. The levels of evidence contrasting prognostic use with interventional data are summarized inTable 1.

Table 1.Levels of evidence: prognostic serum albumin versus therapeutic albumin.

Within a pragmatic framework, serum albumin may be viewed as a risk modifier that enriches prognostic information beyond clinical variables alone. A historical example is provided by the SAFE trial analysis, which explored the interaction between baseline serum albumin levels and the effect of fluid type (albumin versus saline) without demonstrating a major interaction on primary outcomes [15]. This suggests that baseline albumin is useful for patient characterization but is insufficient, on its own, to guide universal selection of resuscitation fluids.

In a specific analysis of patients with traumatic brain injury, the use of albumin as a resuscitation fluid was associated with higher mortality [5]. As a pragmatic consequence, traumatic brain injury should be an explicit exclusion criterion in any volume optimization strategy that includes albumin.

The Surviving Sepsis Campaign 2021 guidelines recommend crystalloids as first-line fluids and suggest albumin only after the administration of large volumes of crystalloids, consistent with a targeted rather than systematic approach [13].

Two recent syntheses focusing on hyperoncotic albumin discuss potential effects on fluid balance, shock resolution, and signals of benefit in selected subgroups, while emphasizing limitations in the overall quality of the evidence [11][12]. Finally, a recent guideline based on a systematic review and GRADE assessment proposes a more standardized decision framework across indications and clinical contexts [14]. The main interventional trials and their key messages are summarized inTable 2.

Table 2.Summary of major interventional trials.

Published Cameroonian critical care data, although limited, describe substantial mortality and an activity profile dominated by severe acute conditions, supporting the potential value of simple and transferable prognostic triage tools [9].

Internal medicine data from the Douala General Hospital report frequent hospital undernutrition, with lower serum albumin concentrations among undernourished patients, suggesting that a proportion of ICU admissions may present with “baseline” hypoalbuminemia related to underlying vulnerability [10]. In this context, intermittent availability of laboratory testing, pre-analytical delays, and the cost of certain products—including therapeutic albumin make a systematic correction strategy unrealistic.

In local studies, several sources of bias should be anticipated. First, confounding by severity is expected, as the most critically ill patients tend to have lower serum albumin levels irrespective of any direct causal relationship. Second, dilutional bias is likely, driven by unquantified fluid resuscitation practices, transfusions, and fluid overload. Third, heterogeneity in admission and transfer delays, as well as variability in documented comorbidities, represents an additional source of variability and bias.

Accordingly, any proposed decision thresholds or albumin-based algorithms should be regarded as exploratory and require prospective local validation.

7.3.1. General Principle

Serum albumin may be used as a risk modifier within a comprehensive clinical assessment rather than as a standalone score. At this stage, the proposal is deliberately qualitative, serving as an aid to clinical reasoning rather than as a quantitative adjustment of an existing score. The integrated clinical reasoning process is illustrated in Figure 1, and an illustrative qualitative grid is provided inTable 3.

Table 3.Example of a qualitative grid.

7.3.2. Practical Framework for Interpreting Serum Albumin in Critical Care

First, the clinical context should be clearly defined, for example, by identifying sepsis according to the SEPSIS-3 criteria [17].

Next, situations in which serum albumin cannot be interpreted in isolation should be identified, particularly in the presence of major fluid overload, recent transfusions, severe hepatic failure, or significant protein losses.

Figure 1.Conceptual framework of integrated clinical reasoning.

For therapeutic safety reasons, certain conditions must be explicitly excluded, notably traumatic brain injury, in which the use of albumin as a resuscitation fluid should be avoided [5].

Serum albumin is then integrated into a constellation of clinical and biological indicators. Low serum albumin associated with a high SOFA score, with or without elevated lactate levels when available, constitutes a signal of high overall risk. Low serum albumin in the setting of marked fluid overload instead suggests a dilutional component and requires cautious interpretation. Conversely, moderately low serum albumin combined with a low SOFA score and hemodynamic stability suggests a possibly intermediate risk related to baseline patient vulnerability, warranting recontextualization with consideration of undernutrition or comorbidities.

These different profiles are summarized in an illustrative qualitative grid presented inTable 3.

In the ALBIOS trial, patients randomized to the albumin group received 300 mL of 20% albumin after randomization, followed by daily administration targeting a serum albumin level ≥ 30 g/L [4]. In the Cameroonian context, any transposition of this regimen should be locally protocolized, taking into account availability, cost, respiratory monitoring, and fluid balance, and should be presented as a physiological hypothesis rather than as a recommendation supported by evidence of a mortality benefit. Moreover, in routine practice observed in Cameroon, albumin administration most often corresponds to volumes ranging from 100 to 300 mL of 20% human albumin, while the cost of a single vial of this formulation represents approximately 2.6 times the average monthly income of a Cameroonian, raising a major issue of economic feasibility.

Minimum safety conditions require: 1) exclusion of patients with traumatic brain injury [5]; 2) close monitoring of respiratory tolerance and fluid balance; and 3) positioning albumin use as a targeted, non-systematic strategy, consistent with the Surviving Sepsis Campaign 2021 recommendations, particularly after the administration of large volumes of crystalloids and on a case-by-case basis [13].