Evaluation of albumin utilization, guideline compliance, and cost in intensive care units: a multicenter point prevalence study

Abstract

Background

Intravenous (IV) albumin is widely used in intensive care units (ICUs), yet its use often deviates from evidence-based recommendations, leading to unnecessary costs. This study evaluates the indications for the use of IV albumin in critically ill patients, compliance with the 2024 “Use of Intravenous Albumin” guidelines, and the associated cost burden.

Methods

A prospective, point prevalence-based observational study was conducted across seven hospitals in Türkiye over one week. Data on IV albumin utilization, guideline compliance, patient demographic and clinical characteristics, and associated costs were collected and analyzed. Statistical analyses included the Kruskal–Wallis test for comparisons of albumin utilization and logistic regression to assess factors influencing its use.

Results

Among 385 ICU patients monitored, 56 (14.5%) received IV albumin therapy. The median age was 68 years (Interquartile range-IQR: 54.2–77.7), and 67.9% were male. The most common physician-reported indications for initiating albumin therapy were low serum albumin levels (41.1%), fluid shifts or intravascular volume support (21.4%), and sepsis or septic shock (14.3%). The desired clinical target was achieved in 73.2% of cases; however, guideline compliance was 0%. Albumin use differed significantly across ICU types (p = 0.049), with a median consumption of 667 (IQR: 250–1,083) vials per 1,000 patient-days and an estimated cost of $70,617.86. Logistic regression identified total hospital stay (p = 0.028) and Acute Physiology and Chronic Health Evaluation (APACHE) II score (p = 0.040) as significant predictors, while mechanical ventilation (MV) duration showed borderline significance (p = 0.070). The model’s classification accuracy was 78.6%.

Conclusion

This study highlights widespread non-compliance with guidelines for IV albumin use in ICUs, resulting in substantial costs. These findings underscore the need to improve compliance with evidence-based guidelines to optimize albumin utilization and reduce economic burden. Future studies should explore the potential impact of targeted interventions, including pharmacist involvement, on improving prescribing practices.

Clinical trial number

Not applicable.

Trial registration

Not applicable.

Background

Human serum albumin is the most abundant protein in plasma, serving as the primary determinant of plasma oncotic pressure and the key regulator of fluid distribution across body compartments [1]. Albumin is widely utilized in various clinical settings for hemodynamic stabilization, enhancement of diuresis, and management of cirrhosis-related complications [2]. Additionally, it plays a crucial role in the management of conditions such as hypovolemia, shock, burns, surgical blood loss, trauma, hemorrhage, acute respiratory distress syndrome (ARDS), acute and chronic liver diseases, nutritional support, resuscitation, and hypoalbuminemia [3].

Low serum albumin levels have been shown to be associated with increased mortality in various studies [4]. Therefore, albumin replacement therapy in critically ill patients with hypoalbuminemia appears to be a rational clinical approach [4]. However, the high prevalence of non-guideline-compliant albumin use, and its associated financial burden have been demonstrated in multiple studies. In a study, the use of albumin in the intensive care unit (ICU) ranged from 5.0% to 32.5% [5]. The most common indications for albumin include end-stage liver disease, high-volume and moderate-volume paracentesis, septic shock, and ARDS [6]. The prevalence of inappropriate albumin utilization differs among research conducted in different countries, ranging from 50% to 70%, with certain studies reporting rates exceeding 90% [7, 8]. In response to the high prevalence of inappropriate albumin utilization, interventions aimed at improving guideline compliance have gained attention.

The prescription of albumin in both general wards and ICUs is frequently associated with non-guideline-compliant use. In some cases, inappropriate albumin administration is linked to contradictory scientific evidence or the absence of established guidelines. In other cases, it is driven by healthcare professionals’ subjective perceptions of potential benefits despite the lack of supporting scientific evidence [9]. Institutional guidelines have been developed to define appropriate indications for albumin use. The implementation of these evidence-based guidelines in hospitals may serve as an effective strategy to reduce inappropriate albumin utilization and to prioritize albumin administration during shortages. The involvement of clinical pharmacists in the development and implementation of such guidelines may play a crucial role in optimizing albumin consumption patterns [10].

Previous studies have shown that clinical pharmacist-led interventions can significantly reduce inappropriate albumin use and generate substantial cost savings; however, these studies were conducted in single-center settings, limiting their generalizability [11, 12]. Similarly, studies evaluating the appropriateness of albumin use based on guideline recommendations have also been restricted to single-center analyses and have not comprehensively addressed the economic burden associated with inappropriate prescribing [13].

In this context, there remains a need for multicenter studies that evaluate real-world prescribing practices using up-to-date international guidelines while also incorporating cost analysis. Therefore, this study aims to provide a comprehensive evaluation of intravenous (IV) albumin use in critically ill ICU patients by assessing indications, utilization rate, and appropriateness based on the recommendations of the 2024 “Use of Intravenous Albumin” guideline, across seven centers, while also analyzing the associated economic burden.

Methods

Study design and participants

This prospective, point prevalence-based observational study focusing on patients receiving IV albumin was conducted to assess its use and compliance with clinical guidelines among critically ill patients. The study was conducted over one week (January 20–24, 2025) on weekdays across seven hospitals in Türkiye. During the study period, all ICU patients were screened daily using hospital information systems, ICU admission records, and electronic medical records, with cross-checking against ICU census data to ensure completeness and avoid missing cases. Among these patients, those receiving IV albumin were identified, and their treatment indications were evaluated for compliance with clinical guidelines. Screening and data evaluation were conducted by a multidisciplinary team of trained clinical pharmacists in collaboration with intensivists. The study population included adult ICU patients hospitalized for at least 24 h, a threshold applied to ensure sufficient clinical stabilization and enable appropriate assessment of albumin use indications.

Inclusion and exclusion criteria

The inclusion criteria for the study were patients aged ≥ 18 years, those admitted to the ICU for at least 24 h, and those who had received IV albumin therapy during the designated study period. Patients who received IV albumin within the first 24 h of ICU admission were not included in the study. Patients with incomplete or missing data were excluded from the analysis.

Sample size calculation

The statistical population of the study consisted of all adult patients admitted to the ICUs of the participating centers during the study period. The total ICU bed capacity of the seven participating centers was 187 and was reported solely to describe institutional capacity rather than the statistical population.

For the sample size calculation, an estimated inappropriate albumin use rate of 95% was adopted from a previous study conducted in Iranian training and research hospitals in 2013 [14]. The required sample size was calculated using a single proportion formula for a finite population, with a margin of error of 5% and a confidence level of 95%, resulting in a minimum sample size of 53 patients.

Data collection

The indication for IV albumin use was determined using a combined approach. Initially, data were extracted from electronic medical records, including physician notes, medication orders, and clinical documentation. When the indication was not clearly documented, the ICU physician responsible was consulted to confirm or clarify the reason for albumin use. This process was conducted by clinical pharmacists in collaboration with intensivists to ensure consistency and accuracy. The collected data encompassed demographic characteristics (age, sex), primary ICU admission diagnosis, comorbidities, start date and duration of IV albumin treatment, serum albumin levels, other laboratory parameters, renal and hepatic function status, estimated glomerular filtration rate in mL/min/1.73m² using Chronic Kidney Disease Epidemiology (CKD-EPI) 2021 equation, mechanical ventilation (MV) status, microbiological culture results, infection site, length of ICU stay, surgical history, and severity scores, including Sequential Organ Failure Assessment (SOFA) score, Glasgow Coma Scale (GCS), and Acute Physiology and Chronic Health Evaluation (APACHE) II score [15–18]. Data collection was conducted in compliance with confidentiality and ethical standards.

Primary outcomes

The primary outcomes of the study were to evaluate the indications for IV albumin use in critically ill ICU patients, assess compliance with established clinical guidelines, determine the overall utilization rate of IV albumin in ICU settings, and analyze the cost implications of IV albumin therapy.

Guideline compliance and definitions

Guideline compliance was assessed by a multidisciplinary team consisting of clinical pharmacists and intensivists at each participating center. The evaluation was conducted using the predefined criteria from the 2024 “Use of Intravenous Albumin” guideline [2]. Each case was reviewed individually, and the appropriateness of IV albumin use was determined through consensus among team members. The indications for IV albumin use were classified according to the following criteria:

1. Critically ill adult patients (excluding those with thermal burns and ARDS): IV albumin is not recommended as first-line volume replacement or for increasing serum albumin levels (Conditional Recommendation, Moderate Certainty of Evidence).

2. Critically ill adults with thermal burns or ARDS: IV albumin is not recommended for volume replacement or increasing serum albumin levels (Conditional Recommendation, Very Low Certainty of Evidence).

3. Critically ill patients: The use of IV albumin with diuretics for extravascular fluid removal is not recommended (Conditional Recommendation, Very Low Certainty of Evidence).

4. Patients undergoing renal replacement therapy: IV albumin is not recommended for preventing intradialytic hypotension or improving ultrafiltration (Conditional Recommendation, Very Low Certainty of Evidence).

5. Patients undergoing cardiovascular surgery: IV albumin is not recommended for priming the cardiopulmonary bypass circuit or for volume replacement (Conditional Recommendation, Moderate Certainty of Evidence).

6. Cirrhotic patients undergoing large-volume paracentesis (> 5 L): IV albumin is recommended to prevent post-paracentesis circulatory dysfunction (Conditional Recommendation, Very Low Certainty of Evidence).

7. Cirrhotic patients with spontaneous bacterial peritonitis (SBP): IV albumin may reduce mortality (Conditional Recommendation, Low Certainty of Evidence).

8. Cirrhotic patients with extraperitoneal infections: IV albumin is not recommended for reducing mortality or renal failure (Conditional Recommendation, Low Certainty of Evidence).

9. Hospitalized patients with decompensated cirrhosis and hypoalbuminemia (< 30 g/L): Repeated IV albumin administration to raise albumin levels > 30 g/L is not recommended to reduce infection, renal dysfunction, or mortality (Conditional Recommendation, Low Certainty of Evidence).

In addition to evaluating the guideline compliance of IV albumin administration, the indications for initiating albumin therapy were assessed by a multidisciplinary team consisting of clinical pharmacists and intensivists. Indications were determined based on electronic medical record review (including physician notes and medication orders) and, when necessary, confirmed with the responsible ICU physician. These indications were recorded to reflect physicians’ real-world clinical reasoning and were categorized into seven main groups. It should be emphasized that these categories were not used to define guideline-appropriate indications but rather to capture clinicians’ perceived reasons for albumin use. Therefore, the assessment of guideline compliance and physician-reported indications were conducted as two distinct frameworks. For each patient, only the primary indication for albumin initiation was recorded and categorized. These indications were classified under seven main headings: (1) Sepsis and Septic Shock, (2) Fluid Shifts or Intravascular Volume Support, (3) Postoperative or Tissue Healing Support, (4) Renal Function Support, (5) Nutrition and Absorption Disorders, (6) Edema Management, and (7) Low Serum Albumin Levels.

The assessment of the physician’s achievement of the intended therapeutic goal was based on whether the expected outcome was achieved according to the initial indication for starting albumin therapy. For example, in patients receiving albumin for hypoalbuminemia, achievement of the clinical goal was defined as reaching the target serum albumin level following administration. These outcomes were evaluated by the treating physicians on the day of data collection, after the course of IV albumin therapy. Each indication was evaluated to determine if the therapy successfully addressed the clinical goal for which it was initiated.

Cost analysis calculation

In this study, albumin utilization was measured and a pharmacoeconomic evaluation was conducted among patients receiving IV albumin. During the selected one-week period, the number of IV albumin vials administered to each patient was recorded daily. Each patient contributed one patient-day per day regardless of the number of vials administered, while the total number of vials was calculated separately. These data were used to calculate total albumin consumption per 1,000 patient-days. The term “patient-days” refers to the total number of ICU hospitalization days and was used as a standard denominator to express albumin utilization per 1,000 patient-days. Patients could receive albumin on multiple days during their ICU stay; therefore, both total albumin use throughout hospitalization and use on the data collection day were recorded. Subsequently, the average albumin usage and associated costs per patient were determined.

All patients received Human Albumin 20%. The cost of each IV albumin vial was calculated as an average of different preparations available during the study period and was set at $90.

Statistical analysis

The study used descriptive statistics to present the central tendency and variability of continuous variables, including mean, median, standard deviation, interquartile range (IQR), or count and percentages, as appropriate. For categorical variables, frequency and percentages were provided. Continuous variables were assessed for normality using the Kolmogorov-Smirnov test. Since the data did not follow a normal distribution, the Mann-Whitney U test was used for analysis. Categorical variables were analyzed using the chi-square test. The median IV albumin vial usage across three different ICU types was analyzed using the Kruskal-Wallis test. Binary logistic regression analysis was performed to identify the risk factors influencing the number of IV albumin vials per patient. For this analysis, factors with a p-value < 0.200 in the univariate analysis were included. Statistical significance was defined as a p-value below 0.05, with a confidence interval (CI) of 95%. Missing data was excluded from the analysis, and the entire dataset was analyzed using IBM Statistical Package for Social Sciences (SPSS) software for Windows, Version 25 (IBM Corp, Armonk, New York).

Results

During the study period, a total of 385 critically ill patients were screened across seven ICUs, and 56 patients (14.5%) were receiving IV albumin therapy. Data was complete for all eligible patients; therefore, no patients were excluded from the study due to missing data. Albumin use was evaluated based on guideline-recommended indications, and appropriateness was classified accordingly. The median age of the patients was 68 years (IQR: 54.2–77.7), and 67.9% were male. Most hospitalizations were medical reasons (75%), while 25% were surgical. Comorbidities were prevalent among the patients, with hypertension (17.3%), diabetes mellitus (12.2%), and ischemic heart disease (5.8%) being the most common. The most frequent admission diagnoses included cardiac arrest (8.3%), pneumonia (7.1%), and breathing problems (6.0%) (Table 1).

Table 1.

Baseline demographic and clinical characteristics of patients

Variable	Total (n = 56)
Age (years), median (IQR)	68 (54.2–77.7)
Sex, n (%)
Male  Female	38 (67.9) 18 (32.1)
Type of hospitalization, n (%)
Medical  Surgical	42 (75) 14 (25)
Comorbidities, n (%)
Hypertension  Diabetes mellitus  Ischemic heart disease  Chronic obstructive pulmonary disease  Atrial fibrillation  Coronary artery disease  Acute kidney disease  Cerebrovascular disease  Congestive heart failure  Chronic kidney disease  Other	24 (17.3) 17 (12.2) 8 (5.8) 6 (4.3) 6 (4.3) 5 (3.6) 5 (3.6) 4 (2.9) 4 (2.9) 4 (2.9) 56 (40.3)
Admission diagnoses, n (%)
Cardiac arrest  Pneumoniae  Breathing problem  Acute respiratory failure  Respiratory arrest  Urosepsis  Aspiration pneumoniae  Femur fracture  General symptoms and signs  Hypernatremia  Other	7 (8.3) 6 (7.1) 5 (6.0) 4 (4.8) 4 (4.8) 3 (3.6) 2 (2.4) 2 (2.4) 2 (2.4) 2 (2.4) 47 (56.0)
APACHE II score (admission), median (IQR)	25.5 (20–29.7)
SOFA score (admission), median (IQR)	9 (6–11)
Total length of stay in the ICU (day), median (IQR)	11.5 (6–54)

APACHE: Acute physiology and chronic health evaluation, ICU: Intensive care unit, IQR: Interquartile range, SOFA: Sequential organ failure assessment

The clinical condition of the patients on the day of albumin administration is summarized in Table 2. Of the 56 patients who received IV albumin, 50 (89.3%) had received albumin on more than one day prior to or during the study period; these patients were already on ongoing albumin therapy. The median serum albumin level was 22.9 g/L (IQR: 20.0–24.0). ARDS was present in 26.8% of the patients. Renal function assessment showed that 55.4% of patients had normal renal functions, while 5.4% were receiving continuous renal replacement therapy. Regarding nutritional status, 76.8% of the patients received enteral nutrition, 5.4% parenteral nutrition, 7.1% oral nutrition, and 10.7% had no nutritional support.

Table 2.

Clinical condition of patients on the day of albumin administration^*

Variable	Total (n = 56)
Serum albumin level (g/L), Median (IQR)	22.9 (20.0–24.0)
SOFA score, Median (IQR)	8 (6–10)
Total MV duration (days), Median (IQR)	8.5 (3–25)
Acute respiratory distress syndrome status, n (%)
Yes  No	15 (26.8) 41 (73.2)
Sepsis and septic shock status, n (%)
Sepsis  Septic Shock  None	13 (23.2) 21 (37.5) 22 (39.3)
Renal status, n (%)
Normal (≥ 60 mL/min/1.73 m2)  Chronic Kidney Failure  Acute Kidney Injury  Continuous Renal Replacement Therapy  eGFR < 60 mL/min/1.73 m²	31 (55.4) 6 (10.7) 7 (12.5) 3 (5.4) 9 (15.1)
Hepatic status, n (%)
Normal  AST - ALT (Three times the upper limit of normal)  Borderline Elevated	49 (87.5) 6 (10.7) 1 (1.8)
MV status, n (%)
Yes  No	49 (87.5) 7 (12.5)
Nutritional status, n (%)
Enteral  Parenteral  Oral  None	43 (76.8) 3 (5.4) 4 (7.1) 6 (10.7)

AST: Aspartate aminotransferase, ALT: Alanine aminotransferase, eGFR: Estimated glomerular filtration rate, IQR: Interquartile range, MV: mechanical ventilation, SOFA: Sequential organ failure assessment

*Although 89.3% of patients had received albumin for more than one day prior to assessment, all variables presented in this table reflect the clinical status on the day of evaluation

Of the seven units included in the study, one was a cardiovascular surgery ICU (3/194; 1.6%), two were general ICUs (17/50; 34.0%), and four were anesthesia and resuscitation ICUs (36/141; 25.5%). The albumin usage rates and the total number of patients evaluated in each center are presented in Fig. 1.

Fig. 1.

Distribution of albumin prescriptions and total patient numbers across centers

According to physician reports, the most common indication for albumin administration was low serum albumin levels, identified in 23 patients (41.1%), of whom 8 did not achieve the target outcome. The second most frequent indication was fluid shifts or intravascular volume support, reported in 12 patients (21.4%), followed by sepsis or septic shock in 8 patients (14.3%). Overall, according to the physicians’ indications for initiating IV albumin therapy, the desired clinical target was achieved in 41 patients (73.2%). Figure 2 illustrates the physicians’ indications for initiating IV albumin therapy and the achievement of target outcomes. The rate of IV albumin prescriptions meeting the indications outlined in international guidelines was 0%. The indications for IV albumin prescriptions were assessed based on physicians’ stated reasons for initiation.

Fig. 2.

Physicians’ indications for initiating intravenous albumin therapy and achievement of target outcomes

The median albumin usage was calculated as 5.5 (IQR: 2–17) vials per patient. The median albumin consumption was 667 (IQR: 250–1,083) vials per 1,000 patient-days. Based on a cost of $90 per vial, the estimated cost of albumin administration was $70,617.86 per 1,000 patient-days. The median number of IV albumin vials used per patient showed a statistically significant difference between the cardiovascular surgery ICU (median: 2, IQR: 2–10), general ICU (median: 1, IQR: 1–5), and anesthesia and reanimation ICU (median: 10, IQR: 2–22) (p = 0.049).

According to the results of the logistic regression analysis, the model was found to be statistically significant (p < 0.001). The explanatory power of the model was determined as 45.3%, based on the Nagelkerke R Square value. Among the variables, the total length of hospital stay (p = 0.028) and APACHE II score (p = 0.040) were found to be significant, while the duration of MV showed a borderline significance (p = 0.070) (Table 3). The overall classification accuracy of the model was calculated as 78.6%.

Table 3.

Binary logistic regression analysis of risk factors influencing the number of intravenous albumin vials per patient

Variables	Univariate analysis		Multivariate analysis
	OR (95% CI)	p	OR (95% CI)	p
Total length of hospital stay	0.949 (0.903–0.996)	0.039	0.809 (0.669–0.978)	0.028
Duration of MV	0.968 (0.932–1.005)	0.092	1.183 (0.986–1.420)	0.070
APACHE II score (at admission)	1.051 (0.977–1.130)	0.185	1.108 (1.004–1.223)	0.040

APACHE: Acute physiology and chronic health evaluation, CI: Confidence interval, MV: mechanical ventilation, OR: Odds ratio

Discussion

This study highlights the widespread non-compliance with international guidelines for IV albumin use in ICUs, emphasizing the urgent need for interventions to optimize clinical practice and reduce associated economic burdens. The inappropriate use of IV albumin remains a significant concern in critical care settings, contributing to unnecessary healthcare costs and potential risks for patients.

Compliance with international guidelines in intravenous albumin use

Consistent with previous literature, our findings indicate a high rate of inappropriate albumin use. Prior studies have reported inappropriate albumin prescription rates ranging from 35% to 50% [19, 20], with some studies indicating rates as high as 90% [10]. Notably, our study identified an inappropriate albumin use rate of 100% based on the guideline criteria, reinforcing the existing concerns regarding its misuse in ICU settings [2]. We believe that the differences in the rates of inappropriate albumin prescriptions may stem from variations in hospital protocols and clinicians’ approaches to treatment. A study conducted in 2022 found that pharmacist-led interventions significantly increased compliance with albumin use guidelines in ICUs, from 16.3% in the retrospective phase to 84.1% after the intervention. Additionally, inappropriate albumin consumption was reduced by 72.9% [21]. In addition to implementing guidelines in patient care, the involvement of pharmacists in direct patient care may reduce the rate of inappropriate prescriptions, thereby decreasing the associated financial burden.

Indications for inappropriate albumin use

One of the key aspects of inappropriate albumin prescribing is its indication. Previous research has demonstrated that hypoalbuminemia, nutritional support, and sepsis are among the most frequently cited reasons for unnecessary albumin administration [20, 22–24]. Similarly, our study found that the most common indications for inappropriate albumin use were low serum albumin levels (41.1%), fluid shifts and intravascular volume support (21.4%), and sepsis/septic shock (14.3%) (Fig. 2). These findings suggest a persistent pattern of guideline deviations despite growing awareness of evidence-based recommendations.

Low serum albumin levels, or hypoalbuminemia, are frequently encountered in ICU patients, particularly those with systemic inflammatory disorders. Since albumin is a negative acute-phase reactant, its serum concentration inversely correlates with inflammation severity. However, albumin replacement has not been shown to improve clinical outcomes in critically ill patients with hypoalbuminemia [25]. Instead, treatment should focus on addressing the underlying disease process, as supported by current evidence [10].

Nutritional disorders are also highly prevalent in ICU patients and represent an important contributor to poor clinical outcomes. Critically ill patients are at increased risk of developing malnutrition due to hypermetabolism, catabolic stress, and inadequate nutrient intake, which has been associated with rapid loss of muscle mass, increased infectious complications, and higher mortality. Recent evidence further highlights that these patients are particularly vulnerable to malnutrition-related adverse outcomes, underscoring the importance of appropriate nutritional strategies in the ICU setting [26]. Although EN or PN is initiated when needed, complications such as aspiration, gastrointestinal bleeding, and severe electrolyte imbalances may lead to temporary interruptions in nutritional support, resulting in low caloric and protein intake [27, 28]. In this context, hypoalbuminemia in ICU patients is often more reflective of underlying inflammation and nutritional derangements rather than true albumin deficiency.

The role of IV albumin in sepsis management remains controversial. A randomized controlled trial (RCT) involving 360 patients with sepsis and cancer found no significant difference between albumin and Ringer’s lactate in terms of mortality, SOFA score improvement, MV duration, vasopressor use, need for renal replacement therapy, or ICU length of stay [29]. Additionally, a systematic review of 23 RCTs found that albumin was not superior to crystalloids in reducing mortality or acute kidney injury in sepsis patients [22]. These findings challenge the routine use of albumin for sepsis management and underscore the need for stricter compliance with guideline recommendations.

Variability in albumin utilization across ICU settings

In this study, albumin use was lowest in cardiovascular surgery ICUs (3/194; 1.6%), followed by anesthesia and resuscitation ICUs (36/141; 25.5%), and highest in general ICUs (17/50; 34.0%). This variability likely reflects differences in patient characteristics, institutional protocols, and prescriber preferences, rather than compliance with clinical guidelines. Similar discrepancies have been documented in previous studies. For example, in an Iranian study, albumin prescription rates were 49.3% in ICUs, 14.5% in cardiac care units, and 8.7% in post-cardiac care units [30]. Likewise, a US-based study found usage rates of 41% in critical care, 28% in nephrology, and 17% in surgical departments [13]. These findings emphasize the need for standardized prescribing protocols to ensure evidence-based decision-making and minimize unnecessary albumin use.

Economic burden of inappropriate albumin use

The financial burden associated with inappropriate albumin use is substantial. In our study, the estimated cost of inappropriate albumin prescriptions among 56 patients was $70,617.86 per 1,000 patient-days. Comparatively, an Egyptian study reported a total cost of $20,449 for 190 ICU patients, where 83.7% of albumin prescriptions were deemed inappropriate [12]. Similarly, an Iranian study found that 78.4% of 1,870 albumin vials prescribed were inappropriate, resulting in a financial burden of $48,900 [11]. Interventions aimed at optimizing albumin use have demonstrated significant cost reductions. A clinical pharmacist-led strategy in a prior study reduced inappropriate albumin use by 86%, leading to cost savings from $397,814.28 to $55,883.77 [21]. In another US-based study, an audit of 150 patient records found that 45% of albumin prescriptions lacked an appropriate indication, highlighting the prevalence of non-compliance with Food and Drug Administration approved guidelines [31]. These findings underscore the urgent need for active pharmacist involvement, drug utilization evaluation programs, and stricter institutional protocols to enhance compliance and mitigate unnecessary healthcare expenditures [12, 21, 32].

Clinical implications and future directions

Despite a 0% compliance rate with guideline recommendations, 73.2% of patients in our study achieved the intended clinical outcomes as assessed by the prescribing physicians. However, the extent to which these outcomes translate into long-term clinical benefits remains unclear. For example, among 23 patients with low serum albumin levels, albumin correction was observed in 15 patients (65.2%). While hypoalbuminemia has been associated with increased mortality risk, with serum albumin levels below 25 g/L linked to a sevenfold increase in mortality risk (Hazard Ratio 7.1, 95% CI 6.7–7.5), studies have failed to demonstrate that albumin supplementation improves survival outcomes [33, 34]. Additionally, a 10 g/L decrease in serum albumin has been correlated with a 137% increase in mortality, an 89% rise in morbidity, a 28% prolongation in ICU stay, and a 71% increase in hospital stay [35].

The role of albumin in intravascular volume expansion and fluid shifts remains controversial [2]. In our study, 91.7% of patients prescribed albumin for volume support achieved the intended fluid stabilization, yet it is unclear whether this provided a clinically meaningful advantage. A systematic review of 55 randomized controlled trials found that while albumin use was associated with increased central venous pressure, mean arterial pressure, and cardiac index, it did not improve mortality rates compared to crystalloids [36]. These findings further support the need for a paradigm shift toward guideline-driven albumin prescribing rather than empirical use.

Factors influencing albumin prescription in critically ill patients

Our study also identified key factors influencing albumin prescription among critically ill patients. Binary logistic regression analysis revealed that longer hospital stays were associated with a 19.1% reduction in the likelihood of albumin prescription, whereas higher APACHE II scores increased the likelihood of albumin use by 10.8%. Notably, no previous studies have systematically evaluated the predictors of IV albumin prescription in critically ill patients, making this a novel contribution to literature. The APACHE II score is recognized as being positively correlated with the severity of illness in ICU patients. As the severity of illness increases, serum albumin levels tend to decline, as albumin is a negative acute-phase reactant influenced by inflammatory processes. The length of hospitalization may also serve as an indicator of illness severity. Based on the results of the logistic regression analysis, it is recommended to exercise heightened caution when managing patients with higher APACHE II scores and prolonged hospitalization durations to avoid the inappropriate use of albumin. Future research should further explore these associations in larger, multicenter cohorts to develop risk-stratified prescribing guidelines.

Policy implications and the need for reimbursement reform

In Türkiye, the Social Security Institution (SGK) covers most healthcare expenses, including IV albumin reimbursement, which is currently limited to patients with serum albumin levels below 25 g/L under the Health Care Implementation/Budget Law regulations. However, using serum albumin levels as the sole criterion for reimbursement increases the tendency for widespread albumin prescriptions, even in cases where its use may not be clinically justified.

Although international guidelines do not support routine albumin therapy for hypoalbuminemia alone, physician prescribing practices often consider multiple clinical factors beyond serum albumin levels, leading to varied indications for IV albumin administration. This raises concerns regarding the clinical applicability of the 25 g/L threshold in real-world ICU practice. There are patients above this threshold who may require IV albumin, just as there are patients below it who may not benefit from its administration.

Consequently, the overall compliance with international guidelines remains low, as reimbursement policies often drive prescription patterns rather than strict compliance with evidence-based recommendations. Therefore, a reassessment of the reimbursement criteria and a shift toward a more comprehensive, clinically justified approach are urgently needed to optimize albumin utilization and align with international best practices.

Limitations and strengths

This study has several strengths. Conducted across seven different hospitals, it provides a broad and representative dataset on albumin usage ICUs, increasing the reliability and generalizability of the findings. By evaluating real-world prescribing patterns, this study highlights the gap between clinical guidelines and actual practice, offering valuable insights for improving guideline compliance. Additionally, the comprehensive cost analysis quantifies albumin consumption per 1,000 patient-days, emphasizing the economic burden of inappropriate use and supporting future cost-effectiveness strategies. The study also identifies key predictors of albumin use, such as total hospital stay and APACHE II score, providing a basis for targeted interventions to optimize prescribing behaviors. Moreover, while these findings may provide indirect insight into factors associated with albumin utilization and healthcare costs, no direct assessment of pharmacist-led interventions or institutional protocols was performed in this study; therefore, future studies are needed to evaluate their potential impact in this setting.

Despite these strengths, the study has several limitations that should be acknowledged. First, as a descriptive observational study, it does not allow causal inferences between albumin use and patient outcomes. Second, the data collection period was limited to one week, which may not reflect seasonal variations or long-term prescribing patterns in ICUs. In addition, reliance on hospital records and physician-reported indications may have introduced information bias due to incomplete documentation. A major methodological limitation of this study is the inclusion of only patients who received albumin, which introduces a potential selection bias and prevents assessment of inappropriate underuse (i.e., patients with an indication for albumin who did not receive it). Therefore, the overall appropriateness of albumin utilization at the population level cannot be fully evaluated. Furthermore, the lack of recorded palliative care limited the ability to assess the appropriateness of albumin use in terminally ill or palliative patients.

Finally, as the study was conducted in a single country, the findings may not be fully generalizable to healthcare systems with different ICU practices, reimbursement policies, or guideline implementations.

Despite these limitations, this study provides critical insights into albumin prescribing patterns and underscores the urgent need for interventions to improve compliance with clinical guidelines and reduce unnecessary healthcare expenditures. Future research should focus on prospective interventional studies, multicenter analyses with longer observation periods, and clinical outcome assessments to further guide evidence-based ICU practices.

Conclusion

This study highlights significant non-compliance with international guidelines for IV albumin use in ICUs, with no prescriptions meeting the recommended criteria. Despite its widespread use, albumin therapy was most frequently initiated for low serum albumin levels, fluid shifts, and sepsis/septic shock—indications that are often unsupported by evidence-based guidelines. While the desired clinical target was achieved in 73.2% of cases, the unnecessary use of albumin poses a substantial economic burden, with an estimated cost of $70,617.86 per 1,000 patient-days. Significant variations in albumin use across ICU types further indicate inconsistencies in prescribing patterns, emphasizing the need for standardized protocols to promote guideline compliance. Logistic regression analysis identified total hospital stay and APACHE II score as significant predictors of albumin use, suggesting that disease severity and length of stay influence prescribing decisions.

Future research should focus on the long-term clinical outcomes of inappropriate albumin use and evaluate the cost-effectiveness of pharmacist-driven interventions. Addressing the discrepancies in prescribing behavior will not only enhance patient care but also reduce healthcare expenditures, ensuring the efficient use of critical ICU resources.

Abbreviations

APACHE

Acute Physiology and Chronic Health Evaluation

ARDS

Acute respiratory distress syndrome

CKD-EPI

Chronic Kidney Disease Epidemiology

CI

Confidence interval

eGFR

Estimated glomerular filtration rate

GCS

Glasgow Coma Scale

ICU

Intensive care unit

IQR

Interquartile range

IV

Intravenous

MV

Mechanical ventilation

OR

Odds ratio

RCT

Randomized controlled trial

SBP

Spontaneous bacterial peritonitis

SOFA

Sequential Organ Failure Assessment

SPSS

Statistical package for social sciences

Author contributions

A. Ç., Y. E. A., M. Y. B. and H. M. designed the study. All authors collected the data for the study. A. Ç., Y. E. A., M. Y. B. and H. M. drafted the manuscript. All the authors have read and approved the final manuscript. A. Ç. and Y. E. A. contributed equally to this work and share first authorship.

Funding

This study was not funded by any organization.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study received ethics committee approval from Non-Interventional Clinical Research Ethics Committee Presidency (Decision No:2025/6994 − 14.01.2025). Informed consent was obtained from the patients or their legal representatives of all participants in this study. All procedures adhered to the ethical standards of the University of Siena and the principles of the 1964 Helsinki Declaration and its later amendments.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.