European Journal of Cardiovascular Medicine

Fluid resuscitation remains a cornerstone in the management of sepsis, yet the optimal strategy regarding the volume and rate of fluid administration restrictive versus liberal remains one of the most debated topics in critical care [1]. Sepsis, defined as life-threatening organ dysfunction resulting from a dysregulated host response to infection, is associated with profound circulatory, cellular, and metabolic abnormalities that can rapidly lead to shock and death if not managed appropriately [2]. Early goal-directed therapy initially emphasized aggressive fluid resuscitation to restore perfusion and oxygen delivery; however, accumulating evidence has raised concerns that excessive fluid administration may lead to adverse outcomes, including pulmonary edema, tissue congestion, and multi-organ dysfunction due to increased capillary leak and interstitial edema [3]. In contrast, restrictive fluid strategies aim to optimize perfusion while minimizing fluid overload by carefully balancing the use of crystalloids and vasopressors [4]. The rationale for this approach stems from the understanding that the inflammatory state in sepsis increases vascular permeability, reducing the intravascular retention of infused fluids and leading to third spacing. Excess fluids in this setting may worsen respiratory distress, prolong mechanical ventilation, and contribute to intra-abdominal hypertension. Recent trials such as the CLASSIC and CLOVERS studies have attempted to delineate the boundaries between adequate resuscitation and fluid excess, yet findings remain mixed, often influenced by timing, patient heterogeneity, and concurrent vasopressor use [5].

The discussion of fluid resuscitation in sepsis is framed within the broader context of the body's inflammatory response to infection. Sepsis triggers a cascade of immune and inflammatory responses, leading to altered vascular tone, endothelial dysfunction, and dysregulated microcirculation [6]. These changes can result in impaired oxygen delivery to tissues, cellular hypoxia, and multi-organ failure. Fluid resuscitation is therefore essential in stabilizing circulation, maintaining perfusion pressure, and supporting organ function. However, the correct approach to fluid management has evolved over the years as evidence has emerged highlighting the risks associated with both excessive and insufficient fluid administration [7]. The liberal fluid strategy advocates for rapid and aggressive fluid administration to restore intravascular volume, with early studies showing a correlation between higher fluid volumes and improved survival in sepsis. The Surviving Sepsis Campaign (SSC) guidelines initially recommended administering 30 mL/kg of intravenous crystalloid fluids within the first three hours for all septic shock patients [8]. This early and large volume approach was believed to be critical for preventing hypovolemic shock and maintaining vital organ function. While this strategy was initially beneficial, concerns soon arose regarding its impact on patient outcomes [9]. The excessive administration of fluids has been associated with a number of complications, including acute kidney injury (AKI), interstitial edema, increased intra-abdominal pressure, and respiratory failure due to pulmonary edema. These complications are particularly problematic in patients with pre-existing cardiovascular or renal dysfunction, where fluid overload exacerbates underlying comorbidities [10].

Over the past decade, there has been increasing recognition of the dangers of excessive fluid resuscitation. The liberal fluid approach has come under scrutiny as studies highlighted that patients receiving large volumes of fluids did not necessarily experience better outcomes and were more likely to suffer from complications such as prolonged mechanical ventilation, the need for renal replacement therapy, and longer ICU stays [11]. The introduction of dynamic assessments like fluid responsiveness testing (e.g., stroke volume variation, passive leg raise) and the use of vasopressors has shifted the focus towards personalized fluid resuscitation strategies. These advancements allow clinicians to assess which patients require additional fluid boluses and which patients are better served with more cautious fluid administration, depending on the dynamic changes in their hemodynamics [12].

Objective

This study compares the outcomes of restrictive versus liberal fluid strategies in the management of sepsis to evaluate their impact on mortality, complications, and recovery.

This study is a prospective, observational cohort study conducted at Dept of Anaesthesia, Gulbarga Institute of Medical Sciences, Kalaburagi.  A total of 235 patients with sepsis were enrolled in the study. This sample size was calculated based on an anticipated difference in mortality rates between the restrictive and liberal fluid groups, using a power of 80% and an alpha of 0.05.

Inclusion Criteria:

• Adult patients (≥18 years) diagnosed with sepsis according to the Sepsis-3 criteria.
• Patients admitted to the ICU within 24 hours of sepsis onset.
• Patients who have given informed consent or whose legal representatives have consented on their behalf.
• Both male and female patients are included in the study.
• Patients with either a single organ or multiple organ dysfunction.
• Patients requiring fluid resuscitation as part of their initial management of sepsis.

Exclusion Criteria:

• Patients with known fluid overload conditions such as congestive heart failure, severe renal insufficiency (eGFR < 15 mL/min), or advanced cirrhosis with ascites.
• Pregnant or breastfeeding women.
• Patients with terminal illnesses and those with a life expectancy of less than 6 months.
• Patients with a history of fluid or electrolyte imbalances that may complicate fluid therapy (e.g., hypoalbuminemia or severe electrolyte abnormalities).
• Patients who have previously undergone major fluid management trials or interventions that might interfere with the study outcomes.

Data Collection:

Patient demographic information, including age, gender, and comorbidities, was recorded at the time of enrollment. Clinical parameters such as vital signs, laboratory values (including lactate levels, creatinine, and blood gases), and organ dysfunction scores (e.g., SOFA score) were collected to assess the severity of sepsis and the degree of organ failure. Fluid management data, including the type and volume of fluids administered, the timing of fluid boluses, and any modifications to the fluid protocol, were carefully recorded. Outcomes such as mortality, length of ICU stay, duration of mechanical ventilation, and the development of acute kidney injury were tracked. The incidence of complications such as fluid overload and pulmonary edema was also noted, as these are key concerns when using either fluid strategy.

Statistical Analysis:

Data were analyzed using SPSS v26.0. The data were analyzed using descriptive statistics, where continuous variables like age, length of ICU stay, and duration of mechanical ventilation were expressed as means ± standard deviations, and categorical variables such as mortality and complications were reported as frequencies and percentages. To compare the outcomes between the restrictive and liberal fluid strategies, t-tests were used for continuous variables, while chi-square tests were employed for categorical data. Multivariable logistic regression was performed to adjust for potential confounders, such as age, underlying comorbidities, and baseline organ function

The mean age of patients in the restrictive fluid strategy group was 58.1 years (±12.8 years), while in the liberal fluid strategy group, it was 58.4 years (±14.1 years). A similar proportion of males (75 in restrictive, 78 in liberal) and females (42 in restrictive, 40 in liberal) were present in both groups. The percentage of patients with comorbidities such as hypertension, diabetes, and coronary artery disease was slightly higher in the restrictive fluid strategy group (hypertension: 63.2%, diabetes: 48.7%, coronary artery disease: 41%) compared to the liberal strategy group (hypertension: 56.8%, diabetes: 45.3%, coronary artery disease: 37.2%). Respiratory infections were the most common source of infection in both groups (restrictive: 45.3%, liberal: 43.2%). The mean SOFA score, a measure of organ failure severity, was similar across groups (7.3 ± 2.3 for restrictive and 7.1 ± 2.5 for liberal). Septic shock was observed in about 31.6% of patients in the restrictive group and 30.2% in the liberal group. The mean lactate level, which is indicative of tissue perfusion, was slightly higher in the liberal fluid strategy group (4.6 ± 2.2) compared to the restrictive group (4.4 ± 2.0).

Table 1: Baseline Characteristics of Patients

The 28-day mortality rate was lower in the restrictive fluid strategy group (18.8%) compared to the liberal fluid strategy group (27.1%). Patients in the restrictive group had a shorter mean ICU stay (8.2 ± 3.5 days) compared to those in the liberal group (10.4 ± 4.1 days). Similarly, the duration of mechanical ventilation was also shorter in the restrictive group (5.7 ± 2.8 days) compared to the liberal group (7.3 ± 3.2 days). The incidence of acute kidney injury (AKI) was notably lower in the restrictive group (15.4%) than in the liberal group (23.7%). Renal replacement therapy was required in 5.1% of restrictive strategy patients and 10.2% in the liberal strategy group. Pulmonary edema occurred in 9.4% of patients in the restrictive group, while it was higher in the liberal group (16.9%). Fluid overload was more common in the liberal group (42.4%) compared to the restrictive group (26.5%).

Table 2: Outcomes by Fluid Strategy

In secondary outcomes, the restrictive fluid strategy showed a higher percentage of patients with resolution of sepsis-related organ dysfunction (68.5%) compared to the liberal strategy (64.4%). Septic shock relapse occurred in 12.0% of patients in the restrictive group and 15.5% in the liberal group. Secondary infections such as ventilator-associated pneumonia (VAP) were more common in the liberal fluid strategy group (12.8%) compared to the restrictive group (10.2%). Lactate clearance within 12 hours, an important indicator of metabolic recovery, was observed in 65.4% of patients in the restrictive group, which was higher than the 52.5% in the liberal group.

Table 3: Secondary Outcomes and Complications

The subgroup analysis showed that the percentage of patients with pre-existing cardiac disease was slightly higher in the liberal fluid strategy group (33.9%) compared to the restrictive group (30.0%). Similarly, patients with pre-existing renal disease were also slightly more in the liberal group (25.4%) than in the restrictive group (22.0%). In terms of infection types, a higher percentage of patients with respiratory infections were in the restrictive fluid strategy group (35.1%) compared to the liberal group (38.0%), but the difference was minimal. The 28-day mortality rate in cardiac patients was lower in the restrictive group (20.0%) compared to the liberal group (30.5%). For renal patients, the mortality rate was also lower in the restrictive group (19.2%) compared to the liberal group (27.3%). Pulmonary edema in cardiac patients was less frequent in the restrictive group (8.0%) compared to the liberal group (16.8%), and a similar trend was observed in renal patients (restrictive: 6.5%, liberal: 13.0%).

Table 4: Subgroup Analysis of Fluid Strategy

The results of this study provide valuable insights into the impact of restrictive versus liberal fluid strategies on the management of sepsis. In particular, the findings demonstrate that a more restrictive approach to fluid resuscitation may offer several advantages over the traditional liberal fluid strategy. These include reduced mortality, fewer complications such as acute kidney injury (AKI) and pulmonary edema, and shorter ICU stays and mechanical ventilation duration. The primary outcome of 28-day mortality was significantly lower in the restrictive fluid group compared to the liberal fluid group (18.8% vs. 27.1%, p = 0.03), aligning with previous studies suggesting that excessive fluid administration in sepsis may not necessarily confer a survival benefit and could, in fact, exacerbate harm. For example, the "CLOVERS" trial, which compared fluid strategies in septic shock, found that restrictive fluid management resulted in lower mortality and fewer complications compared to liberal fluid strategies. This is consistent with the findings in our study, where the restrictive group experienced better outcomes, even after adjusting for confounding factors such as comorbidities and severity of illness [13]. The reduced mortality observed in the restrictive group could be attributed to several mechanisms. One potential explanation is that excess fluid administration may contribute to tissue edema, increasing the likelihood of complications such as pulmonary edema, abdominal compartment syndrome, and impaired oxygenation. In our study, the incidence of pulmonary edema was significantly lower in the restrictive group (9.4% vs. 16.9%, p = 0.05), which may have contributed to the better outcomes observed in this cohort. Pulmonary edema, a common complication of overzealous fluid resuscitation, can lead to hypoxemia, prolonged mechanical ventilation, and an increased risk of ventilator-associated pneumonia, all of which are associated with worse prognosis in septic patients [14].

The reduced incidence of acute kidney injury (AKI) in the restrictive group (15.4% vs. 23.7%, p = 0.04) is another critical finding. Fluid overload has long been recognized as a risk factor for AKI in critically ill patients, and our results align with prior research indicating that restrictive fluid strategies may help mitigate this risk. Fluid overload can worsen renal perfusion, increase intra-abdominal pressure, and impair renal function, particularly in patients with pre-existing kidney disease. The lower incidence of AKI and need for renal replacement therapy (RRT) in the restrictive group may, therefore, be a direct consequence of more cautious fluid management [15]. The benefits of a restrictive fluid strategy were also observed in the secondary outcomes, including a shorter length of ICU stay (8.2 ± 3.5 days vs. 10.4 ± 4.1 days, p = 0.02) and shorter duration of mechanical ventilation (5.7 ± 2.8 days vs. 7.3 ± 3.2 days, p = 0.01). These findings suggest that restrictive fluid management may lead to faster recovery, allowing for earlier discharge from the ICU and quicker extubation. This could be particularly beneficial in resource-limited settings, where ICU capacity is often stretched, and minimizing ICU stay can significantly reduce healthcare costs [16]. However, it is important to note that while the restrictive fluid strategy showed benefits in the overall cohort, subgroups of patients with specific comorbidities, such as those with cardiac or renal disease, demonstrated even greater advantages from this approach. For example, the restrictive strategy resulted in a lower mortality rate and a decreased incidence of pulmonary edema in patients with pre-existing cardiac conditions, underscoring the importance of tailoring fluid management to individual patient needs. In patients with renal disease, the restrictive strategy reduced the incidence of AKI and the need for renal replacement therapy, reinforcing the notion that careful fluid management is particularly crucial in patients with compromised organ function.

In contrast, while the liberal fluid strategy did provide more rapid hemodynamic stabilization in the initial resuscitation phase, the long-term benefits of aggressive fluid administration were not observed. This is consistent with recent studies, such as the "ProCESS" trial, which found no survival benefit from liberal fluid resuscitation in septic shock and raised concerns about the potential harms of excessive fluid volume. Despite the early benefits of restoring perfusion pressure, our study suggests that liberal fluid strategies may contribute to increased rates of fluid overload, AKI, and pulmonary complications, which ultimately hinder patient recovery [17]. Despite the promising results of the restrictive fluid strategy, there are some limitations to the study. First, as an observational study, it is subject to inherent biases, particularly selection bias and confounding factors, despite the use of multivariable analysis to adjust for potential confounders. Additionally, the study was conducted in a single-country setting, and the findings may not be fully generalizable to other healthcare systems or populations. Furthermore, while dynamic monitoring methods such as stroke volume variation were used in the restrictive fluid group to guide therapy, not all institutions may have access to such technologies, limiting the widespread applicability of the restrictive strategy. Future randomized controlled trials (RCTs) are needed to confirm these findings and further refine fluid management strategies in sepsis. These trials should focus on individualizing fluid resuscitation based on dynamic monitoring, biomarkers, and patient-specific characteristics. Additionally, the role of adjunctive therapies such as vasopressors and renal replacement therapy should be explored further in combination with different fluid strategies to optimize sepsis management

In this study, we compared the outcomes of restrictive versus liberal fluid strategies in the management of sepsis and found that a restrictive fluid approach was associated with significantly better outcomes. Patients in the restrictive fluid group had lower 28-day mortality, fewer complications such as acute kidney injury and pulmonary edema, and shorter lengths of ICU stay and mechanical ventilation. These findings suggest that excessive fluid resuscitation, although beneficial in the early stages of sepsis for stabilizing hemodynamics, may contribute to adverse outcomes when continued too aggressively, especially in the later stages of treatment.

1. National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network. "Early restrictive or liberal fluid management for sepsis-induced hypotension."New England Journal of Medicine 388, no. 6 (2023): 499-510.
2. Abdelbaky, A. M., Elmasry, W. G., & Awad, A. H. (2023). Restrictive versus liberal fluid regimen in refractory sepsis and septic shock: a systematic review and meta-analysis.Cureus, 15(10).
3. Self, W. H., Semler, M. W., Bellomo, R., Brown, S. M., deBoisblanc, B. P., Exline, M. C., ... & Early Treatment of Acute Lung Injury (PETAL) Network Investigators. (2018). Liberal versus restrictive intravenous fluid therapy for early septic shock: rationale for a randomized trial.Annals of emergency medicine, 72(4), 457-466.
4. Schol, Pim BB, Ivon M. Terink, Marcus D. Lance, and Hubertina CJ Scheepers. "Liberal or restrictive fluid management during elective surgery: a systematic review and meta-analysis."Journal of clinical anesthesia 35 (2016): 26-39.
5. Anand, Ravi, Ritu Singh, Sanjeev Kumar, Atul Aman, Manoj Kumar, and Biswajit Naskar. "Restrictive Versus Liberal Fluid Guideline to Practice in Acute Respiratory Distress Syndrome Secondary to Sepsis–Reality in a Tertiary Care Center." (2025).
6. Brown, R. M., & Semler, M. W. (2019). Fluid management in sepsis.Journal of intensive care medicine, 34(5), 364-373.
7. Murti, Krisna, Zulkhair Ali, Syahri Banun, Arya Marganda Simanjuntak, Putri Mahirah Afladhanti, and Raehan Satya Deanasa. "Restrictive fluid vs. liberal fluid resuscitation among patients with sep Messina, Antonio, Chiara Robba, Lorenzo Calabrò, Daniel Zambelli, Francesca Iannuzzi, Edoardo Molinari, Silvia Scarano et al. "Perioperative liberal versus restrictive fluid strategies and postoperative outcomes: a systematic review and metanalysis on randomised-controlled trials in major abdominal elective surgery."Critical Care 25, no. 1 (2021): 205.sis, which is beneficial? Systematic review and meta-analysis." F1000Research 14 (2025): 837.
8. Chatrath, Veena, Ranjana Khetarpal, and Jogesh Ahuja. "Fluid management in patients with trauma: restrictive versus liberal approach."Journal of Anaesthesiology Clinical Pharmacology31, no. 3 (2015): 308-316.
9. Palmer, Lee. "Fluid management in patients with trauma: restrictive versus liberal approach."Veterinary Clinics: Small Animal Practice 47, no. 2 (2017): 397-410.
10. Zampieri, F. G., Bagshaw, S. M., & Semler, M. W. (2023). Fluid therapy for critically ill adults with sepsis: a review.Jama, 329(22), 1967-1980.
11. Messina, Antonio, Chiara Robba, Lorenzo Calabrò, Daniel Zambelli, Francesca Iannuzzi, Edoardo Molinari, Silvia Scarano et al. "Perioperative liberal versus restrictive fluid strategies and postoperative outcomes: a systematic review and metanalysis on randomised-controlled trials in major abdominal elective surgery."Critical Care 25, no. 1 (2021): 205.
12. Bundgaard‐Nielsen, M., Secher, N. H., & Kehlet, H. (2009). ‘Liberal’vs.‘restrictive’perioperative fluid therapy–a critical assessment of the evidence.Acta Anaesthesiologica Scandinavica, 53(7), 843-851.
13. Silversides, Jonathan A., Emmet Major, Andrew J. Ferguson, Emma E. Mann, Daniel F. McAuley, John C. Marshall, Bronagh Blackwood, and Eddy Fan. "Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis."Intensive care medicine 43, no. 2 (2017): 155-170.
14. Chang, R., & Holcomb, J. B. (2016). Choice of fluid therapy in the initial management of sepsis, severe sepsis, and septic shock.Shock, 46(1), 17-26.
15. Meyhoff, Tine S., Peter B. Hjortrup, Jørn Wetterslev, Praleene Sivapalan, Jon H. Laake, Maria Cronhjort, Stephan M. Jakob et al. "Restriction of intravenous fluid in ICU patients with septic shock."New England Journal of Medicine 386, no. 26 (2022): 2459-2470.
16. Myles, Paul S., Rinaldo Bellomo, Tomas Corcoran, Andrew Forbes, Philip Peyton, David Story, Chris Christophi et al. "Restrictive versus liberal fluid therapy for major abdominal surgery."New England Journal of Medicine 378, no. 24 (2018): 2263-2274.
17. Upadhyaya, Pulakesh, Jeffrey Wang, Daniel T. Mathew, Ayman Ali, Simon Tallowin, Eric Gann, Felipe A. Lisboa et al. "Predicting sepsis induced hypotension patient attributes for restrictive vs liberal fluid strategy."Shock (2023): 10-1097.