# Fluid Resuscitation: Crystalloids, Colloids, and Albumin

## Introduction

Intravenous fluid therapy is one of the most common interventions in hospital medicine, yet the choice of fluid type, volume, and rate remains a source of considerable debate. Recent landmark trials have clarified the superiority of balanced crystalloids over normal saline in many clinical contexts and defined the limited role of colloids. A nuanced understanding of fluid physiology and the evidence base is essential for internal medicine residents.

## Fluid Physiology

- **Total body water**: approximately 60% of body weight (42 L in a 70 kg male)
- Distribution: **intracellular** (2/3) and **extracellular** (1/3); extracellular divided into **interstitial** (3/4) and **intravascular** (1/4)
- IV crystalloids distribute primarily into the extracellular space; approximately 25% remains intravascular after 1 hour
- The **revised Starling model** and the **endothelial glycocalyx** govern transvascular fluid movement; the glycocalyx is degraded by sepsis, surgery, and hypervolemia, increasing capillary leak
- **Effective circulating volume**, not total body water, determines organ perfusion

## Crystalloids

### Normal Saline (0.9% NaCl)

- **Composition**: Na 154 mEq/L, Cl 154 mEq/L; pH 5.5; osmolality 308 mOsm/L
- **Supraphysiologic chloride load**: leads to hyperchloremic non-anion gap metabolic acidosis
- High chloride causes renal afferent arteriolar vasoconstriction, reducing GFR and urine output
- Appropriate use: **hypochloremic metabolic alkalosis**, **hyponatremia**, **hyperkalemia** (no potassium content), and as a **diluent for certain medications**

### Balanced Crystalloids

| Component | Normal Saline | Lactated Ringer's | Plasma-Lyte | Plasma |
|-----------|:------------:|:-----------------:|:-----------:|:------:|
| Na (mEq/L) | 154 | 130 | 140 | 135-145 |
| K (mEq/L) | 0 | 4 | 5 | 3.5-5.0 |
| Cl (mEq/L) | 154 | 109 | 98 | 95-105 |
| Ca (mEq/L) | 0 | 3 | 0 | 4.5-5.5 |
| Buffer | None | Lactate 28 | Acetate 27, Gluconate 23 | HCO3 24 |
| Osmolality | 308 | 273 | 294 | 275-295 |
| pH | 5.5 | 6.5 | 7.4 | 7.35-7.45 |

- More closely approximate plasma electrolyte composition
- Lactate in LR is rapidly metabolized by the liver; does NOT worsen lactic acidosis

### Key Trials: Balanced vs. Normal Saline

- **SMART trial** (2018, single-center): balanced crystalloids reduced the composite of death, new renal replacement therapy, and persistent renal dysfunction vs. saline in critically ill patients (absolute risk reduction 1.1%)
- **SALT-ED trial** (2018): similar findings in non-critically ill ED patients
- **BaSICS trial** (2021, multi-center): no significant difference between balanced solutions and saline in ICU patients (mortality or AKI); however, trend favoring balanced solutions in sepsis subgroup
- **PLUS trial** (2022): no significant difference between Plasma-Lyte and saline in ICU patients
- **Current consensus**: balanced crystalloids are preferred as the default resuscitation fluid; normal saline reserved for specific indications (hyponatremia, metabolic alkalosis, hyperkalemia, brain injury)

![Composition comparison of common IV crystalloids](images/crystalloid-comparison.png)

## Colloids

### Albumin

- **5% albumin**: iso-oncotic; expands intravascular volume approximately 1:1 (500 mL infused yields approximately 500 mL intravascular expansion)
- **25% albumin** (hyperoncotic): draws fluid from interstitial space; 100 mL expands intravascular volume by approximately 400-500 mL
- **SAFE trial** (2004): 4% albumin equivalent to normal saline for resuscitation in general ICU patients; HARM in traumatic brain injury subgroup (increased mortality)
- **ALBIOS trial** (2014): albumin + crystalloid vs. crystalloid alone in sepsis; maintained higher MAP but no mortality difference; post-hoc subgroup analysis suggested benefit in septic shock
- **Indications for albumin**:
  - **Spontaneous bacterial peritonitis**: albumin 1.5 g/kg day 1, 1 g/kg day 3 (reduces renal failure and mortality)
  - **Large-volume paracentesis**: 6-8 g albumin per liter removed after > 5 L
  - **Hepatorenal syndrome**: albumin with terlipressin or norepinephrine
  - **Septic shock** refractory to crystalloids (reasonable adjunct)
  - **ARDS with hypoproteinemia**: albumin + furosemide may improve fluid balance

### Hydroxyethyl Starch (HES)

- **SHOULD NOT BE USED** for fluid resuscitation
- **6S trial** and **CHEST trial**: HES increased mortality and acute kidney injury requiring renal replacement therapy in sepsis and critically ill patients
- FDA black box warning against use in critically ill patients
- Removed from formularies in many countries

### Other Colloids

- **Dextrans**: rarely used; risk of anaphylaxis, coagulopathy, AKI
- **Gelatin-based solutions** (Gelofusine): used in some countries; associated with anaphylaxis and AKI; insufficient evidence for routine use

![Evidence summary for crystalloid and colloid choices](images/fluid-evidence-summary.png)

## Assessing Fluid Responsiveness

- Only approximately 50% of hemodynamically unstable patients are fluid responsive
- **Static markers** (CVP, PCWP) are **poor predictors** of fluid responsiveness; CVP should NOT guide fluid administration
- **Dynamic assessments**:
  - **Passive leg raise (PLR)**: elevate legs to 45 degrees; if cardiac output or pulse pressure increases by >= 10%, the patient is fluid responsive; works in spontaneous breathing and arrhythmias
  - **Pulse pressure variation (PPV)**: > 13% variation during positive pressure ventilation predicts fluid responsiveness (requires sinus rhythm and controlled ventilation with Vt >= 8 mL/kg)
  - **Stroke volume variation (SVV)**: similar utility to PPV
  - **IVC ultrasound**: IVC diameter < 2.1 cm with > 50% collapse suggests low CVP but does NOT reliably predict fluid responsiveness; best used to identify volume overload (plethoric IVC)
  - **Mini-fluid challenge**: 100-200 mL crystalloid over 1 minute; assess cardiac output response

## Volume of Resuscitation

- **Initial sepsis resuscitation**: 30 mL/kg crystalloid within the first 3 hours (SSC 2021 guideline); however, this is a weak recommendation and should be individualized
- **CLOVERS trial** (2023): restrictive fluid strategy (vasopressors first) vs. liberal fluids in sepsis-induced hypotension showed no difference in mortality; supports individualized approach
- **CLASSIC trial** (2022): restrictive IV fluids in ICU patients with septic shock did not differ from standard care in 90-day mortality
- **Conservative fluid management** after initial resuscitation reduces ventilator days and ICU stay (FACTT trial in ARDS)
- General principle: **resuscitate early, de-escalate quickly**; transition from "rescue" to "maintenance" to "de-resuscitation" phases

## Special Populations

- **Traumatic hemorrhage**: damage control resuscitation with balanced blood products (1:1:1 ratio of PRBC:FFP:platelets); limit crystalloid; permissive hypotension (target SBP 80-90 mmHg) until surgical control
- **Diabetic ketoacidosis**: initial bolus of normal saline (or balanced crystalloid), then transition based on corrected sodium
- **Burns**: Parkland formula (4 mL/kg/% TBSA over 24 hours); titrate to urine output 0.5-1 mL/kg/hr
- **Traumatic brain injury**: avoid hypotonic solutions (LR is mildly hypotonic); normal saline or hypertonic saline preferred

![Fluid resuscitation strategy by clinical phase](images/fluid-resuscitation-phases.png)

## Key Clinical Pearls

- Balanced crystalloids (LR or Plasma-Lyte) should be the default resuscitation fluid; normal saline is appropriate for specific indications (hyponatremia, hyperkalemia, brain injury)
- Hydroxyethyl starch is harmful and should never be used for resuscitation
- CVP is a poor predictor of fluid responsiveness; use dynamic assessments (passive leg raise, pulse pressure variation) instead
- After initial resuscitation, shift to a conservative fluid strategy; every liter of unnecessary fluid contributes to organ edema and worsened outcomes

## References

1. Semler MW, Self WH, Wanderer JP, et al. Balanced Crystalloids versus Saline in Critically Ill Adults (SMART). *N Engl J Med*. 2018;378(9):829-839.
2. Finfer S, Bellomo R, Boyce N, et al. A Comparison of Albumin and Saline for Fluid Resuscitation in the ICU (SAFE). *N Engl J Med*. 2004;350(22):2247-2256.
3. National Heart, Lung, and Blood Institute. Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension (CLOVERS). *N Engl J Med*. 2023;388(6):499-510.
4. Myburgh JA, Finfer S, Bellomo R, et al. Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care (CHEST). *N Engl J Med*. 2012;367(20):1901-1911.