Fluid Resuscitation in Sepsis

 

Fluid Resuscitation in Sepsis: Nuances and Evidence-Based Approaches

Dr Neeraj Manikath ,claude.ai

Abstract

Sepsis remains a significant cause of morbidity and mortality worldwide despite advances in critical care medicine. Fluid resuscitation continues to be a cornerstone of early sepsis management, yet controversies persist regarding optimal fluid selection, timing, volume, and assessment of fluid responsiveness. This review provides a comprehensive analysis of current evidence and clinical practices in fluid resuscitation for sepsis. We examine the pathophysiological basis of fluid therapy, evaluate different types of resuscitation fluids, discuss monitoring strategies, and explore evolving paradigms that challenge traditional approaches. Special attention is given to patient-specific considerations and potential pitfalls in fluid management. Contemporary evidence suggests a more individualized approach to fluid resuscitation is warranted, moving beyond the "one-size-fits-all" strategy toward precision medicine in sepsis care.

Keywords: Sepsis, Fluid resuscitation, Crystalloids, Colloids, Fluid responsiveness, Microcirculation, Hemodynamic monitoring

Introduction

Sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, represents a major global health challenge with approximately 48.9 million cases and 11 million sepsis-related deaths worldwide annually.^1^ Despite significant advances in our understanding of the pathophysiology and management of sepsis, mortality rates remain unacceptably high, ranging from 25-30% for sepsis and 40-60% for septic shock in high-income countries, with even higher rates in resource-limited settings.^2^

Early and appropriate fluid resuscitation remains a cornerstone of initial sepsis management, being the first step in hemodynamic stabilization before vasopressor initiation and source control. The Surviving Sepsis Campaign (SSC) guidelines have consistently emphasized the importance of early fluid administration, with the most recent 2021 guidelines continuing to recommend an initial fluid challenge of 30 mL/kg of intravenous crystalloid fluid within the first 3 hours of recognition.^3^ However, this seemingly straightforward intervention involves complex physiological principles and clinical nuances that require careful consideration.

This review aims to provide a comprehensive analysis of the current evidence and clinical practice in fluid resuscitation for sepsis, with a particular focus on the nuances that can significantly impact patient outcomes. We examine the pathophysiological basis of fluid therapy, evaluate different types of resuscitation fluids, discuss monitoring strategies to guide fluid administration, and explore evolving paradigms that challenge traditional approaches. Furthermore, we address special considerations in specific patient populations and potential pitfalls in fluid management.

Pathophysiology of Sepsis Relevant to Fluid Resuscitation

Hemodynamic Alterations in Sepsis

Sepsis induces profound alterations in the cardiovascular system, characterized by a hyperdynamic state with decreased systemic vascular resistance, increased cardiac output, and distributive shock.^4^ At the microcirculatory level, sepsis causes endothelial dysfunction, glycocalyx degradation, and impaired autoregulation, leading to heterogeneous microcirculatory flow, arteriovenous shunting, and tissue hypoxia despite seemingly adequate macrocirculatory parameters.^5^

The endothelial glycocalyx, a glycoprotein-polysaccharide layer lining the luminal surface of the endothelium, plays a critical role in vascular permeability, coagulation, and leukocyte adhesion.^6^ In sepsis, inflammatory mediators, reactive oxygen species, and endotoxins induce glycocalyx shedding, contributing to increased capillary permeability, interstitial edema, and organ dysfunction.^7^ This pathophysiological process has significant implications for fluid resuscitation, as excessive fluid administration may exacerbate glycocalyx damage and worsen endothelial dysfunction.

Four Phases of Fluid Therapy in Sepsis

The dynamic nature of sepsis necessitates a time-sensitive approach to fluid management. Four distinct phases have been described:^8,9^

1. Rescue phase (minutes to hours): Immediate fluid resuscitation to correct life-threatening hypoperfusion and shock.
2. Optimization phase (hours): Continued fluid administration guided by hemodynamic monitoring to optimize tissue perfusion.
3. Stabilization phase (days): Cautious fluid management with the goal of achieving zero or negative fluid balance.
4. De-escalation phase (days to weeks): Active fluid removal to mobilize accumulated fluid and restore physiological function.

This conceptual framework emphasizes that fluid requirements change dramatically throughout the course of sepsis and that strategies appropriate in one phase may be detrimental in another.

Types of Resuscitation Fluids

Crystalloids

Crystalloid solutions remain the first-line fluid choice for sepsis resuscitation.^3^ The two main categories are:

Balanced Crystalloids

These solutions (e.g., Lactated Ringer's, Plasma-Lyte) have electrolyte compositions closer to plasma, with lower chloride content than normal saline. Growing evidence suggests their superiority over 0.9% saline in critically ill patients.

The SMART trial, a cluster-randomized, multiple-crossover trial involving 15,802 critically ill adults, demonstrated that the use of balanced crystalloids resulted in a lower rate of the composite outcome of death, new renal replacement therapy, or persistent renal dysfunction compared to normal saline (14.3% vs. 15.4%, p=0.04).^10^ Similarly, the SALT-ED trial showed fewer major adverse kidney events with balanced crystalloids in non-critically ill patients.^11^

For sepsis specifically, a secondary analysis of the SMART trial found that among patients with sepsis, balanced crystalloids resulted in lower 30-day mortality compared to saline (25.2% vs. 29.4%, p=0.01).^12^

0.9% Saline

Normal saline (0.9% NaCl) has been traditionally used for resuscitation but has significant drawbacks. Its high chloride content (154 mmol/L compared to plasma chloride of approximately 100 mmol/L) can induce hyperchloremic metabolic acidosis, renal vasoconstriction, and decreased glomerular filtration rate.^13^ Multiple observational studies have associated chloride-rich solutions with increased risk of acute kidney injury and mortality in critically ill patients.^14,15^

Based on current evidence, balanced crystalloids should be preferred over normal saline for fluid resuscitation in sepsis, although normal saline remains appropriate in specific situations such as hypochloremic metabolic alkalosis or traumatic brain injury with risk of cerebral edema.

Colloids

Colloid solutions contain macromolecules that theoretically remain within the intravascular space longer than crystalloids, potentially requiring smaller volumes for equivalent hemodynamic effects.

Albumin

Human albumin (4-5% or 20-25%) has been extensively studied in sepsis. The SAFE trial found no significant difference in 28-day mortality between 4% albumin and normal saline in critically ill patients overall, but a subgroup analysis suggested a potential benefit in patients with sepsis (relative risk 0.87, 95% CI 0.74-1.02).^16^ The subsequent ALBIOS trial specifically evaluated 20% albumin in patients with severe sepsis or septic shock, demonstrating no difference in 28-day or 90-day mortality compared to crystalloids alone, although post-hoc analysis showed a potential benefit in patients with septic shock.^17^

Based on these findings, the SSC guidelines suggest that albumin may be considered in patients with sepsis who require substantial amounts of crystalloids.^3^ Albumin may be particularly beneficial in patients with hypoalbuminemia (serum albumin <3 g/dL) or those who develop significant tissue edema despite careful fluid management.

Synthetic Colloids

Hydroxyethyl starch (HES) solutions have been associated with increased risk of acute kidney injury and mortality in sepsis. The 6S trial demonstrated that patients with severe sepsis randomized to HES 130/0.42 had significantly higher mortality and increased need for renal replacement therapy compared to those receiving Ringer's acetate.^18^ Similarly, the CHEST trial found increased use of renal replacement therapy with HES 130/0.4 compared to normal saline in critically ill patients.^19^

Based on this evidence, the use of HES solutions is generally contraindicated in patients with sepsis. Other synthetic colloids, including gelatins and dextrans, have limited evidence supporting their use and have been associated with significant adverse effects, including coagulopathy and anaphylactoid reactions.

Nuances of Fluid Administration

Initial Resuscitation: The 30 mL/kg Paradigm

The SSC guidelines recommend administering at least 30 mL/kg of intravenous crystalloid fluid within the first 3 hours of sepsis recognition.^3^ This recommendation is based primarily on expert opinion and observational data suggesting improved outcomes with early fluid administration. However, this "one-size-fits-all" approach has been increasingly questioned.

Several important nuances deserve consideration:

1. Patient heterogeneity: The ideal resuscitation volume likely varies based on individual patient characteristics, including age, body composition, comorbidities, and sepsis etiology.^20^

2. Risk of fluid overload: Excessive fluid administration is associated with increased mortality, prolonged mechanical ventilation, and organ dysfunction.^21,22^ A meta-analysis by Marik et al. found that a positive fluid balance was consistently associated with increased mortality in sepsis.^23^

3. Timing of presentation: Patients presenting later in their sepsis course may have already transitioned to the stabilization or de-escalation phase, where aggressive fluid administration may be harmful.

4. Pre-existing fluid status: Patients with pre-existing volume depletion (e.g., due to gastrointestinal losses or poor oral intake) may benefit from larger fluid volumes, while those with pre-existing fluid overload (e.g., heart failure, end-stage renal disease) may require more conservative fluid strategies.

A recent observational study by Leisman et al. found that approximately 25% of septic patients did not receive the recommended 30 mL/kg within 3 hours, often due to concerns about fluid overload.^24^ Interestingly, after adjustment for illness severity and comorbidities, there was no significant association between compliance with the 30 mL/kg recommendation and mortality.

These findings highlight the need for more personalized approaches to initial fluid resuscitation, potentially incorporating dynamic assessments of fluid responsiveness rather than relying solely on weight-based formulas.

Rate of Fluid Administration

The optimal rate of fluid administration in sepsis remains debated. While the SSC guidelines emphasize the importance of early resuscitation (within 3 hours), they do not specify exact infusion rates.^3^

The FEAST trial, conducted in African children with severe febrile illness and impaired perfusion, raised concerns about rapid fluid boluses after demonstrating increased mortality with bolus fluid administration compared to no bolus.^25^ Although this study was conducted in a unique population with different resource availability and a high prevalence of malaria, it highlighted potential risks of rapid fluid administration.

More recently, the RIFLEX trial compared restricted vs. liberal fluid bolus therapy in septic shock and found no difference in time to shock reversal but lower cumulative fluid balance in the restricted group.^26^ Similarly, the CLASSIC trial compared restrictive versus standard fluid therapy after initial resuscitation in septic shock and showed that a restrictive strategy resulted in lower cumulative fluid balance without affecting mortality or serious adverse events.^27^

Based on current evidence, an individualized approach is warranted:

1. For patients in frank shock with clear evidence of hypoperfusion, rapid administration of initial fluids (e.g., 500 mL over 15-30 minutes) with frequent reassessment is appropriate.

2. For less severe presentations, slower infusion rates with careful monitoring for signs of fluid responsiveness and overload may be preferable.

3. After initial stabilization, maintenance fluids should be administered cautiously, with the goal of achieving neutral or negative fluid balance as soon as clinically appropriate.

Assessing Fluid Responsiveness

Determining which patients will benefit from additional fluid administration—termed "fluid responsiveness"—is a critical aspect of sepsis management. Fluid responsiveness is typically defined as an increase in cardiac output (CO) or stroke volume (SV) by at least 10-15% in response to a fluid challenge.^28^

Several methods are available to assess fluid responsiveness:

Static Pressure Measurements

Traditional static measures such as central venous pressure (CVP) have been shown to be poor predictors of fluid responsiveness.^29^ A systematic review by Marik et al. found that CVP failed to predict fluid responsiveness consistently, with a pooled area under the receiver operating characteristic curve of only 0.56.^30^ Therefore, CVP should not be used in isolation to guide fluid therapy decisions.

Dynamic Parameters

Dynamic parameters, which assess variations in preload induced by heart-lung interactions or postural changes, have shown superior performance in predicting fluid responsiveness.

1. Pulse Pressure Variation (PPV) and Stroke Volume Variation (SVV): These metrics assess changes in pulse pressure or stroke volume during the respiratory cycle. A PPV >12-13% or SVV >10-12% predicts fluid responsiveness with good sensitivity and specificity in mechanically ventilated patients with regular rhythms and no spontaneous breathing efforts.^31^ However, their utility is limited in spontaneously breathing patients, those with cardiac arrhythmias, or with low tidal volumes.

2. Passive Leg Raising (PLR): PLR provides a reversible "autotransfusion" of approximately 300 mL of blood from the lower extremities to the central circulation.^32^ A meta-analysis found that PLR-induced changes in cardiac output predicted fluid responsiveness with a pooled sensitivity of 85% and specificity of 91%.^33^ Importantly, PLR remains valid in spontaneously breathing patients and those with cardiac arrhythmias, making it particularly useful in the emergency department and early phases of sepsis management.

3. End-Expiratory Occlusion Test: This test involves a brief (15-30 second) interruption of mechanical ventilation at end-expiration, eliminating the cyclic impediment to venous return.^34^ An increase in cardiac output or SV >5% during this maneuver predicts fluid responsiveness with good accuracy.

4. Mini-Fluid Challenge: Administration of a small volume (100-250 mL) of fluid over a short period (5-10 minutes) with assessment of hemodynamic response can predict the effect of larger fluid volumes while minimizing the risk of fluid overload.^35^

5. Inferior Vena Cava (IVC) Assessment: Ultrasonographic measurement of IVC diameter and respiratory variation can be used to predict fluid responsiveness non-invasively.^36^ However, performance varies based on patient populations and respirator settings, with more reliable results in mechanically ventilated patients.

A practical approach combines these methods based on available monitoring and patient characteristics. For instance, in a mechanically ventilated patient with invasive arterial monitoring, PPV/SVV might be the first choice. In a spontaneously breathing patient without invasive monitoring, PLR combined with non-invasive cardiac output measurement or IVC assessment provides valuable information.

Targeting Endpoints of Resuscitation

The ultimate goal of fluid resuscitation is to correct tissue hypoperfusion and improve oxygen delivery to vital organs. However, the optimal endpoints to target remain controversial.

Traditional Endpoints

1. Mean Arterial Pressure (MAP): The SSC guidelines recommend targeting MAP ≥65 mmHg during initial resuscitation.^3^ However, optimal MAP targets may vary based on age, pre-existing hypertension, and specific organ vulnerabilities.^37^ For instance, patients with pre-existing hypertension may require higher MAP targets to maintain adequate organ perfusion.

2. Central Venous Oxygen Saturation (ScvO2): Previously emphasized in early goal-directed therapy, targeting ScvO2 >70% has shown no mortality benefit in more recent trials (ProCESS, ARISE, ProMISe).^38-40^ However, persistently low ScvO2 values should prompt investigation for ongoing hypoperfusion or increased oxygen consumption.

3. Urine Output: While targeting urine output ≥0.5 mL/kg/hour is common, interpretation requires consideration of renal function, diuretic use, and other factors affecting urine production.

Advanced Endpoints

1. Lactate Clearance: Lactate normalization or clearance >10-20% over 2-6 hours has been associated with improved outcomes.^41^ The SSC guidelines suggest targeting lactate normalization as a guide to resuscitation.^3^

2. Capillary Refill Time (CRT): The ANDROMEDA-SHOCK trial found that targeting normalization of CRT was non-inferior to targeting lactate clearance for 28-day mortality, with potential benefits in the CRT group.^42^ CRT provides a simple, non-invasive assessment of peripheral perfusion.

3. Microcirculatory Assessment: Techniques such as sublingual dark field microscopy can directly visualize microcirculatory flow.^43^ Persistence of microcirculatory abnormalities despite normalized macrocirculatory parameters is associated with organ dysfunction and mortality.^44^ However, these techniques remain primarily research tools.

4. Integrated Parameters: Indices such as the Capillary Refill Time/Central-to-peripheral temperature gradient/Peripheral Perfusion Index (CRT/ΔT/PPI) provide composite assessments of peripheral perfusion and may guide resuscitation more effectively than single parameters.^45^

A multimodal approach to monitoring is recommended, integrating clinical assessment, basic hemodynamic parameters, and when available, advanced monitoring techniques. The trend of these parameters over time, rather than absolute values at a single timepoint, often provides more valuable information regarding response to therapy.

Special Clinical Scenarios

Sepsis in Patients with Heart Failure

Fluid management in septic patients with pre-existing heart failure presents unique challenges. These patients have limited cardiac reserve and are at high risk for pulmonary edema with excessive fluid administration.^46^ However, inadequate resuscitation may exacerbate sepsis-induced organ dysfunction.

Key considerations include:

1. Smaller initial fluid boluses: Consider 250-500 mL increments with frequent reassessment rather than standard 30 mL/kg.

2. Earlier vasopressor initiation: Norepinephrine may be started earlier to maintain perfusion pressure while limiting fluid administration.

3. Advanced hemodynamic monitoring: Patients with heart failure particularly benefit from dynamic assessments of fluid responsiveness and cardiac function (e.g., echocardiography, pulse contour analysis).

4. Careful monitoring for signs of volume overload: B-lines on lung ultrasound provide early detection of pulmonary congestion before clinical deterioration.^47^

Sepsis in Chronic Kidney Disease and End-Stage Renal Disease

Patients with renal dysfunction represent another challenging population. While these patients may have expanded extracellular fluid volume at baseline, they can still develop intravascular depletion during sepsis.

Specific considerations include:

1. Assessment of pre-sepsis volume status: Clinical examination, bioimpedance analysis, and IVC assessment can help determine baseline volume status.

2. Type of fluid: Balanced crystalloids with lower potassium content (e.g., Plasma-Lyte) may be preferred in hyperkalemic patients.

3. Integration with renal replacement therapy (RRT): For patients on chronic dialysis, coordinating fluid resuscitation with the dialysis schedule is essential. In some cases, earlier initiation of continuous RRT may facilitate both fluid management and solute clearance.

Sepsis in Cirrhosis

Patients with cirrhosis often have baseline hemodynamic derangements resembling those in sepsis, including splanchnic vasodilation, hyperdynamic circulation, and relative central hypovolemia.^48^ Sepsis can exacerbate these abnormalities, leading to rapid decompensation.

Management pearls include:

1. Cautious albumin use: Albumin may be particularly beneficial in cirrhotic patients with sepsis, as demonstrated in studies of spontaneous bacterial peritonitis.^49^

2. Higher MAP targets: Patients with cirrhosis often require higher MAP goals (70-75 mmHg) to maintain adequate organ perfusion due to chronic arterial vasodilation.

3. Early vasopressor support: Terlipressin or norepinephrine may be initiated earlier to support MAP and renal perfusion while limiting fluid accumulation.

4. Monitoring for hepatorenal syndrome (HRS): Sepsis can precipitate HRS, which requires specific management approaches.

Sepsis in Pregnancy

Physiological adaptations of pregnancy, including increased plasma volume, cardiac output, and reduced systemic vascular resistance, influence fluid management during sepsis.^50^ Pregnant patients are generally more vulnerable to both hypovolemia and volume overload.

Important considerations include:

1. Left lateral positioning during resuscitation to minimize inferior vena cava compression by the gravid uterus.

2. Higher MAP targets (usually 65-70 mmHg) to ensure adequate uteroplacental perfusion.

3. More aggressive initial fluid resuscitation due to increased baseline fluid requirements and greater intravascular capacity.

4. Fetal monitoring during fluid resuscitation, as fetal heart rate patterns provide valuable information about maternal hemodynamic status and uteroplacental perfusion.

5. Multidisciplinary approach involving critical care, infectious disease, and obstetric specialists.

Emerging Concepts and Future Directions

Restrictive Fluid Strategies

Recent trials have challenged the traditional paradigm of aggressive fluid administration in sepsis. The CLASSIC trial, which randomized 1,554 patients with septic shock to restrictive vs. standard fluid therapy after initial resuscitation, found no difference in 90-day mortality but significantly lower cumulative fluid balance with the restrictive approach.^27^ Similarly, the RIFLEX trial comparing restricted vs. liberal fluid bolus therapy in septic shock showed no difference in shock reversal but lower fluid accumulation in the restricted group.^26^

These findings have led to increased interest in more conservative fluid approaches, particularly after the initial resuscitation phase. The concept of "permissive hypoperfusion"—tolerating slightly suboptimal hemodynamic parameters to avoid fluid overload—has gained traction, although definitive evidence supporting this approach is lacking.

Personalized Fluid Resuscitation

Advances in monitoring technologies and understanding of individual variability in sepsis physiology are driving movement toward personalized fluid strategies. Several approaches show promise:

1. Phenotyping septic patients based on hemodynamic profiles, inflammatory biomarkers, or genetic factors may allow tailored fluid approaches.^51^

2. Artificial intelligence algorithms integrating multiple clinical variables to predict fluid responsiveness and optimal resuscitation strategies are being developed and validated.^52^

3. Point-of-care ultrasound protocols combining cardiac, lung, and vascular assessments provide comprehensive evaluation of volume status and fluid tolerance.^53^

Novel Resuscitation Fluids

Research into optimized resuscitation fluids continues:

1. Albumin-crystalloid combinations in specific ratios may provide optimal balance between intravascular efficacy and tissue edema.

2. Plasma-derived products beyond albumin, including plasma protein fraction and fresh frozen plasma, are being investigated for their effects on endothelial function and glycocalyx preservation.

3. Crystalloids with specific electrolyte compositions tailored to different clinical scenarios (e.g., high sodium for traumatic brain injury, low potassium for hyperkalemic states) may improve outcomes.

Targeting the Glycocalyx

Emerging evidence suggests that the endothelial glycocalyx plays a central role in vascular barrier function and fluid homeostasis during sepsis.^54^ Strategies targeting glycocalyx preservation or restoration include:

1. Hydroxyl radical scavengers such as N-acetylcysteine to reduce oxidative stress-induced glycocalyx damage.

2. Sulodexide and other glycosaminoglycan precursors to facilitate glycocalyx regeneration.

3. Low-dose hydrocortisone, beyond its hemodynamic effects, may help preserve glycocalyx integrity.

4. Fluid management strategies that minimize glycocalyx shedding, including avoiding rapid large-volume infusions and hyperchloremia.

Clinical trials specifically targeting glycocalyx protection in sepsis are underway and may provide novel therapeutic approaches in the future.

Clinical Pearls and Practice Recommendations

1. Individualize initial resuscitation: While the 30 mL/kg guideline provides a starting point, consider patient-specific factors such as age, comorbidities, and timing of presentation. In high-risk patients (severe heart failure, end-stage renal disease), consider starting with smaller boluses (250-500 mL) with frequent reassessment.

2. Choose fluids wisely: Balanced crystalloids should be first-line for most patients. Consider albumin for patients requiring large volumes of crystalloids or those with hypoalbuminemia. Avoid synthetic colloids.

3. Incorporate dynamic assessments: Whenever possible, use dynamic parameters (PLR, PPV/SVV, mini-fluid challenge) rather than static measures to guide fluid decisions.

4. Monitor for fluid overload early: Signs of fluid overload (peripheral edema, pulmonary congestion) often develop before overt clinical deterioration. Consider serial lung ultrasound to detect early pulmonary congestion.

5. Transition from resuscitation to maintenance phase: Once the patient is hemodynamically stable with improving signs of perfusion, transition to a conservative fluid strategy aiming for neutral or negative fluid balance.

6. Consider early vasopressor support: In patients with high risk of fluid overload or those not responding to initial fluid challenges, early initiation of vasopressors may reduce unnecessary fluid administration.

7. Integration with overall sepsis management: Fluid resuscitation is just one component of sepsis care. Timely antimicrobial therapy, source control, and supportive care remain essential.

8. Avoid hypotonic fluids: Solutions such as 5% dextrose in water or 0.45% saline should be avoided during acute resuscitation as they rapidly distribute into the interstitial space and can exacerbate tissue edema.

9. Reassess and adjust: Fluid requirements change rapidly throughout the course of sepsis. Regular reassessment of hemodynamic status, perfusion parameters, and fluid tolerance is essential.

10. Balance macrocirculation and microcirculation: Normalizing traditional hemodynamic parameters (MAP, heart rate) does not guarantee adequate microcirculatory perfusion. Incorporate clinical signs of peripheral perfusion (capillary refill, mottling score) into assessment.

Conclusion

Fluid resuscitation remains a cornerstone of sepsis management, but its application requires nuanced understanding of complex pathophysiology and individual patient factors. The traditional paradigm of aggressive, protocol-driven fluid administration is evolving toward more personalized approaches guided by sophisticated monitoring and emerging concepts in vascular biology.

Current evidence supports the use of balanced crystalloids as first-line therapy, with potential roles for albumin in specific scenarios. Dynamic assessments of fluid responsiveness should guide ongoing fluid decisions, with early transition to conservative fluid strategies once initial stabilization is achieved. Special attention is needed for challenging patient populations, including those with heart failure, renal dysfunction, cirrhosis, and pregnancy.

Future directions in sepsis fluid management will likely include further refinement of restrictive strategies, development of novel resuscitation fluids, and targeted interventions to preserve endothelial function and glycocalyx integrity. The ultimate goal remains optimizing tissue perfusion while minimizing iatrogenic harm from excessive fluid administration.

By integrating evidence-based principles with careful clinical assessment and individualized decision-making, clinicians can navigate the complexities of fluid resuscitation in sepsis and improve outcomes for this challenging patient population.

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