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GLYCOCALYX & FLUID THERAPY

MD Anaesthesiology Examination Notes

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PART 1: THE ENDOTHELIAL GLYCOCALYX

1.1 Structure

• Thickness: 0.5–1 μm on continuous capillaries; up to 4–5 μm in some reports
• Protrudes several microns into the vessel lumen
• Covers fenestrations and intercellular clefts

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1.2 The Subglycocalyx Layer (SGL)

• The glycocalyx excludes large proteins (albumin, colloids) from the region immediately below it — the subglycocalyx layer (SGL)
• The SGL is protein-poor fluid in equilibrium with plasma electrolytes
• Volume of SGL ≈ 700–1000 mL — this forms part of the functional intravascular volume
• This explains why the effective intravascular volume is larger than plasma volume alone

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1.3 Functions of the Glycocalyx

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1.4 The Revised Starling Equation — Glycocalyx Model

1. The "no-absorption" rule: At steady state, continuous capillaries do NOT reabsorb fluid at the venous end. The small volume filtered is returned by lymphatics.
2. The relevant oncotic pressure gradient is plasma vs SGL (not plasma vs ISF). Since SGL is protein-poor, this gradient is much larger → opposes filtration more powerfully.
3. Increasing plasma colloid oncotic pressure (e.g., giving albumin) does NOT mobilize oedema from the ISF — because the no-absorption rule applies and oedema cannot re-enter.

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1.5 Glycocalyx Shedding — Causes & Consequences

• Systemic inflammation (sepsis, SIRS, major surgery)
• Hypervolemia → release of cardiac natriuretic peptides (ANP/BNP) → enzymatic digestion of glycocalyx
• Hyperglycaemia
• Ischaemia-reperfusion injury
• Cardiopulmonary bypass
• Inflammatory mediators: TNF-α, bradykinin, C-reactive protein

Key exam point: Atrial natriuretic peptide (ANP), released when preload is excessive, degrades the glycocalyx — this is why aggressive fluid loading is harmful even before frank pulmonary oedema.

• Free heparan sulfate
• Syndecan-1 (↑ = glycocalyx degradation)
• Chondroitin sulfate
• Hyaluronic acid

1. ↑ Capillary permeability → oedema (especially lung, gut, soft tissue)
2. ↑ Large pore number in endothelium
3. Platelet and leukocyte adhesion to endothelium
4. Pro-inflammatory endothelial phenotype
5. Impaired barrier function — protein-rich fluid leaks into ISF

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1.6 Glycocalyx and Fluid Therapy — Clinical Implications

• Crystalloids distribute throughout plasma + SGL
• They do NOT have the exclusion property of colloids
• More fluid is filtered across capillaries per unit of volume expansion

• Avoid hypervolemia (prevents ANP-mediated shedding)
• Maintain normovolaemia with balanced crystalloids or colloids
• Control hyperglycaemia
• Minimize inflammatory insult (gentle surgical technique, limit ischaemia)
• Albumin may help restore glycocalyx integrity (experimental evidence)
• Fresh frozen plasma components (GAG precursors) may be protective in trauma

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PART 2: FLUID THERAPY IN ANAESTHESIOLOGY

2.1 Body Fluid Compartments (Relevant Values)

TBW varies: lean adults 75%, obese 45%; pregnant women have ↑ plasma volume by 50% by term.

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2.2 Classification of IV Fluids

IV Fluids
├── Crystalloids
│   ├── Isotonic
│   │   ├── 0.9% NaCl ("Normal Saline")
│   │   ├── Lactated Ringer's (Hartmann's)
│   │   └── PlasmaLyte / Normosol
│   ├── Hypotonic: 0.45% NaCl, 5% Dextrose
│   └── Hypertonic: 3% NaCl, 7.5% NaCl, Mannitol
└── Colloids
    ├── Human plasma derivatives
    │   ├── Albumin (4.5%, 5%, 20%, 25%)
    │   └── Fresh Frozen Plasma
    ├── Synthetic
    │   ├── Hydroxyethyl Starch (HES) — restricted
    │   ├── Dextrans (Dextran 40, 70)
    │   └── Gelatin (Haemaccel, Gelofusine)

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2.3 Crystalloids

0.9% Normal Saline (NS)

• Hyperchloraemic metabolic acidosis (↑ Cl⁻ → ↓ HCO₃⁻ by strong ion difference)
• Reduced renal perfusion (afferent arteriole vasoconstriction from tubuloglomerular feedback)
• Nausea, abdominal discomfort in healthy volunteers at 50 mL/kg
• More persistent ECF expansion than balanced solutions
• Fluid retention: excess salt/water may take days to excrete

• Hypochloraemic metabolic alkalosis (e.g., pyloric stenosis)
• Hyponatraemia correction
• Head injury (avoids free water; maintains CPP)
• Dilution of blood products

Balanced / Physiological Crystalloids

• Less hyperchloraemia
• Less acute kidney injury
• Smaller persistent ECF expansion
• Preferred for most perioperative fluid administration

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2.4 Colloids

Albumin

• 4.5–5%: isotonic, COP ~20 mmHg → volume expansion
• 20–25%: hyperoncotic → draws fluid from ISF (useful in nephrotic syndrome, SBP)
• SAFE trial: Albumin = saline for general ICU resuscitation; avoid in TBI (↑ mortality); benefit trend in sepsis
• Half-life: 16 hours (intravascular)
• Does NOT improve outcomes in hypoalbuminaemic critically ill patients (no-absorption rule)

Hydroxyethyl Starch (HES)

• Withdrawn/restricted in most countries (FDA, EMA)
• CHEST trial, 6S trial: HES associated with:
  • ↑ acute kidney injury
  • ↑ need for renal replacement therapy
  • ↑ mortality in sepsis
• Mechanism of harm: osmotic nephrosis, accumulation in renal tubules
• Avoid in sepsis, critical illness, renal impairment

Dextrans (Dextran 40, 70)

• Branched polysaccharides from Leuconostoc mesenteroides
• Dextran 40 (40 kDa): ↓ blood viscosity — used in microvascular surgery
• Duration: 6–12 hours
• Side effects:
  • Antithrombotic (↓ factor VIIIc, ↓ vWF, platelet inhibition)
  • Interference with cross-matching (coats RBCs)
  • Anaphylactoid reactions (<0.28%; prevent with Dextran 1 hapten inhibitor)
  • Osmotic nephrosis (low MW dextran)

Gelatins

• Degraded collagen; MW ~30 kDa
• Duration: 2–3 hours (shorter than other colloids)
• Less renal toxicity than HES
• Risk: anaphylaxis (higher than albumin)
• Not available in USA; used in UK and Europe

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2.5 Perioperative Fluid Assessment & Monitoring

Preoperative

• Traditional prolonged fasting → significant pre-existing deficit
• Modern ERAS protocols: allow clear fluids up to 2 hours before surgery → reduce deficit
• Assess: dehydration signs, comorbidities (cardiac, renal), medications (diuretics, ACE-I)

Intraoperative Fluid Losses

1. Altered distribution: Vasodilation from anaesthetics → ↓ preload; negative inotropy
2. Haemorrhage: Direct intravascular loss
3. Insensible losses: Evaporative loss from open body cavities — ~1 mL/kg/h even in major laparotomy
4. Third-spacing: Redistribution to inflamed/infected tissue; peritonitis, burns
5. Renal output: Often ↓ intraoperatively (↑ ADH, ↑ intrathoracic pressure → ↓ ANP → ↓ GFR)

Intraoperative oliguria ≠ hypovolaemia. It is often physiological and should not automatically trigger fluid loading.

Dynamic Haemodynamic Monitoring (Fluid Responsiveness)

• CVP, PCWP — poor predictors of fluid responsiveness

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2.6 Goal-Directed Fluid Therapy (GDFT)

1. IV fluid bolus (250–500 mL)
2. Measure SV response (oesophageal Doppler / FloTrac / LiDCO)
3. If SV ↑ >10% → patient is fluid-responsive → repeat bolus
4. If SV ↑ <10% → on Frank-Starling plateau → stop fluids, consider vasopressors/inotropes

• Effective in perioperative high-risk surgery → ↓ morbidity, ↓ LOS
• NOT effective in established critical illness (sepsis)
• Inconsistent results in laparoscopic/robotic procedures (less physiological trespass)
• Incorporated into ERAS protocols

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2.7 Fluid Strategies: Liberal vs. Restrictive vs. Goal-Directed

Current evidence favours individualised GDFT over fixed liberal or restrictive regimes for major surgery. — Miller's Anesthesia 10e

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2.8 Replacing Blood Loss

• Hb <7 g/dL: generally transfuse
• Hb 7–10 g/dL: transfuse based on clinical context
• Hb >10 g/dL: transfusion rarely indicated

• EBV = estimated blood volume (70 mL/kg ♂, 65 mL/kg ♀)
• Hᵢ = initial haematocrit; H_trig = transfusion trigger haematocrit

• Crystalloid: 3–4× blood loss
• Colloid: 1:1 blood loss (until transfusion trigger)

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2.9 Special Situations

Sepsis / Septic Shock (Surviving Sepsis Campaign 2021)

• 30 mL/kg crystalloid bolus in first 3 hours (initial resuscitation)
• Reassess after each bolus using dynamic parameters
• Prefer balanced crystalloids over NS (↓ AKI)
• Albumin as adjunct in patients requiring large crystalloid volumes
• Avoid HES (↑ mortality, ↑ RRT)
• Target MAP ≥65 mmHg; use vasopressors (noradrenaline first-line)

Traumatic Haemorrhage (Damage Control Resuscitation)

• Permissive hypotension (target SBP 80–90 mmHg) until surgical haemostasis in penetrating trauma
• Balanced blood product ratio: pRBC : FFP : Platelets = 1:1:1
• Minimise crystalloid (↑ dilutional coagulopathy, ↑ hypothermia, ↑ acidosis — "lethal triad")
• Tranexamic acid within 3 hours of injury (CRASH-2 trial)
• Massive transfusion protocol (MTP) activation at >10 units pRBC/24h

Paediatrics

• TBW higher (75–80% in neonates, 60–65% in children)
• Maintenance (Holliday-Segar):
  • 4 mL/kg/h for first 10 kg
  • +2 mL/kg/h for 10–20 kg
  • +1 mL/kg/h for each kg above 20 kg
• Use glucose-containing solutions for neonates and small infants (risk of hypoglycaemia)
• Prefer balanced crystalloids over NS

Cardiopulmonary Bypass (CPB)

• Prime volume: 1–1.5 L balanced crystalloid ± colloid
• Haemodilution: Hct may drop to 20–25%
• Post-CPB: ↑ capillary leak, glycocalyx damage from inflammatory mediators
• Careful post-bypass fluid management; avoid hypervolaemia (ANP release → glycocalyx shedding)

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2.10 Electrolyte Disturbances & Fluid Therapy

Hyponatraemia (Na⁺ <135 mEq/L)

Hypernatraemia (Na⁺ >145 mEq/L)

• Replace free water deficit slowly (≤10–12 mEq/L per 24 hours; risk of cerebral oedema if too rapid)
• Free water deficit = 0.6 × BW × [(Na/140) − 1]
• Central DI: vasopressin (desmopressin)
• Nephrogenic DI: thiazide diuretics, low-salt diet

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PART 3: SUMMARY — HIGH-YIELD EXAM POINTS

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PART 4: IMPORTANT CLINICAL TRIALS

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PART 5: MNEMONICS

• Hyaluronic acid
• Heparan sulfate
• Chondroitin sulfate (glycosaminoglycans)
• Syndecan-1, Glypican (proteoglycans)
• Albumin (bound plasma protein)
• Glycolipids, Glycoproteins

• Hypervolaemia → ANP/BNP
• Anaesthetic stress + surgery
• Sepsis, SIRS
• Hyperglycaemia

• End of 20-min infusion: 70% intravascular
• After 30 min: 50% intravascular
• Long-term: 20–25% intravascular

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