Crush Syndrome

Definition

• Crush injury = the local mechanical damage (lacerations, fractures, degloving, bleeding)
• Crush syndrome = the downstream systemic toxidrome that follows

"Crush syndrome is the systemic manifestation of muscle cell damage resulting from pressure or crushing with or without subsequent compartment syndrome." - Tintinalli's Emergency Medicine, p. 75

History

Epidemiology

• Occurs in 3-20% of earthquake victims; up to 40% of survivors of multi-story building collapses
• Incidence of crush syndrome with subsequent renal failure ranges from 1-25% in various reports, depending on disaster type, rescue timing, and quality of early care
• Most common in the extremities (trunk/head-neck crush is usually quickly lethal)
• Associated injuries: fractures, lacerations, degloving injury

Pathophysiology

Step 1 - Muscle Cell Destruction

Step 2 - Reperfusion Injury

• Oxidant production and complement activation
• Neutrophil and platelet interaction with endothelium
• Systemic inflammatory response

Step 3 - Fluid Third-Spacing & Hypovolemia

Step 4 - Renal Failure (Most Serious Complication)

1. Systemic hypoperfusion from hypovolemia
2. Renal vasoconstriction (reflex + mediator-driven)
3. Direct myoglobin nephrotoxicity: myoglobin forms ferriheme, which generates free hydroxyl radicals → lipid peroxidation → tubular damage
4. Tubular obstruction by precipitation of myoglobin, uric acid, and phosphate (worsened by low urine pH)

Compartment Pressure Dynamics

• Pressures > 30 mmHg → muscle ischemia
• Irreversible nerve and muscle damage after 4-6 hours at these pressures

Clinical Features

"Appears Stable, Then Deteriorates"

Timeline

• Can develop within 1 hour in severe cases
• Typically takes 4-6 hours to manifest
• All patients trapped ≥ 4 hours should be treated as having crush injury

Compartment Syndrome: The 5 Ps

1. Pain - diffuse, intense, out of proportion, worsened by passive stretch
2. Paresthesias - numbness/tingling from nerve compression
3. Passive stretch pain - hallmark of compartment syndrome
4. Pressure - compartment feels tense and tight
5. Pulselessness - late and unreliable sign (macrovasculature often spared)

Systemic Manifestations

• Hypovolemic shock (third-spacing + capillary leak)
• Hyperkalemia + hypocalcemia → arrhythmias, cardiac arrest
• Metabolic acidosis → worsens arrhythmogenicity
• Myoglobinuria - urine appears dark brown/"cola-colored"
• Acute kidney injury / renal failure
• ARDS, sepsis, ischemic organ injury, DIC (delayed causes of death)

Early vs. Late Death

Diagnosis

Laboratory Tests (every 2-4 hours)

• Serum CK - marker and monitoring tool (not perfectly predictive of AKI severity)
• Serum potassium - critical; fatal hyperkalemia can occur without renal failure
• Serum calcium, phosphorus
• ABG/pH - metabolic acidosis severity
• Serum creatinine - AKI monitoring
• Coagulation indices - DIC surveillance
• Urine myoglobin, pH, electrolytes
• Creatinine clearance calculations may be considered

Compartment Pressure Measurement

• Dedicated device (e.g., Stryker STIC) or saline-filled needle manometry
• Positive: pressure > 30 mmHg
• Delta pressure (diastolic BP - compartment pressure) < 30 mmHg is also an indication for fasciotomy

Treatment

1. Pre-Extrication (BEFORE releasing the patient)

"Treatment of crush syndrome should start before extrication." - Bailey & Love's Surgery, 28th Ed., p. 480

• Start IV fluids immediately - aggressive volume loading before, during, and after extrication is the single most important intervention
• Start cardiac monitoring (can be done in confined spaces)
• Begin hyperkalemia management: insulin + glucose, calcium, ion exchange resins, β-agonists

2. Fluid Resuscitation

• Two large-bore IV lines
• Fluid of choice: Normal saline (0.9% NaCl)
• AVOID Ringer's lactate and other potassium-containing fluids - can precipitate fatal hyperkalemia
• Initial bolus: 1-2 L, then:
  • 1000 mL/h for first 2 hours → reduce to 500 mL/h
  • Target urine output: 200-300 mL/h (~5-7 L/24 hours) in adults
  • Bailey & Love recommends 1000-1500 mL/h saline initially in adults
  • May require up to 12 L/day total

3. Forced Alkaline Diuresis

• Mannitol - osmotic diuretic; reduces reperfusion injury component, increases tubular flow
• Urine alkalinization - keep urinary pH > 6.5 to prevent myoglobin/uric acid precipitation
• Target: alkaline diuresis of up to 8 L/day
• Continue until myoglobin is no longer detectable in urine

4. Fasciotomy - Controversial Timing

• Absent distal pulses
• Need for debridement of necrotic muscle
• Compartment pressure > 30 mmHg (measured within 6 hours)
• Delta pressure < 30 mmHg

"A late fasciotomy, when it is obvious that the muscles of that compartment must be dead, is only likely to cause a massive release of myoglobin, as well as potentially introducing infection into dead tissue. It is therefore best not to perform a fasciotomy in cases where entrapment has been for over 12 hours." - Bailey & Love, 28th Ed.

5. ICU Monitoring & Renal Support

• Catheterize for accurate urine output monitoring
• Serial labs every 2-4 hours
• Renal dialysis if AKI progresses
• Monitor fluid balance closely

6. Adjunct: Hyperbaric Oxygen Therapy

• Supplements oxygen to hypoxic tissues in early post-injury period
• At 2 atm: blood oxygen content increased by ~125% (via plasma oxygen)
• Also reduces edema through oxygen-induced vasoconstriction (reduces blood flow 10-20% while maintaining oxygen delivery)
• Useful adjunct for both crush injury and compartment syndrome

Summary of Key Points

• [Tintinalli's Emergency Medicine, 9th Ed.](p. 75-76) - Pathophysiology, diagnosis, treatment
• [Rosen's Emergency Medicine, 9th Ed.](p. 3777) - Epidemiology, pre-extrication management
• [Bailey & Love's Surgery, 28th Ed.](p. 479-480) - Clinical management, fasciotomy guidance
• Recent reviews: Fernandez & Smith, J Am Acad Orthop Surg 2024 and Luo et al., Diagnostics 2023 confirm the above management principles remain current

Hyperkalemia Management

Definition & Severity Classification

First Step: ECG

1. Peaked (tall, narrow, symmetric) T waves - earliest change
2. Prolonged PR interval
3. Widened QRS complex
4. Sine wave pattern (merging of QRS and T wave)
5. Ventricular fibrillation / asystole

Treatment Framework

"The treatment of hyperkalemia is generally divided into three categories: (1) antagonism of the cardiac effects of hyperkalemia; (2) rapid reduction in K⁺ by redistribution into cells; and (3) removal of K⁺ from the body." - Brenner & Rector's The Kidney

Step 1 - Stabilize the Myocardium (Membrane Antagonism)

Calcium (First-Line for ECG Changes)

• Onset: 1-3 minutes; Duration: 30-60 minutes
• Repeat if no ECG improvement or if changes recur
• CAUTION in digoxin toxicity: hypercalcemia potentiates digitalis cardiac toxicity - give 10 mL Ca gluconate diluted in 100 mL D5W over 20-30 minutes instead
• Never mix calcium with bicarbonate (precipitates calcium carbonate)

Step 2 - Redistribute K⁺ into Cells (Temporizing)

A. Insulin + Glucose (Most Reliable)

• Dose: 10 U regular insulin IV bolus + 50 mL of 50% dextrose (D50W, 1 ampule) IV
• Follow with continuous 5% dextrose at 100 mL/h to prevent late hypoglycemia
• Onset: within 15 minutes; peak effect ~60 min
• If blood glucose > 300 mg/dL (in diabetes): insulin can be given without concurrent dextrose
• Never give dextrose alone without insulin in patients with inadequate endogenous insulin - the resulting hyperglycemia can paradoxically raise K⁺
• Monitor blood glucose closely - hypoglycemia is common, especially in renal failure (prolonged insulin half-life)

B. Beta-2 Agonists (Additive to Insulin)

• Dose: Albuterol (salbutamol) 20 mg nebulized over 10 minutes
  • Note: This is far higher than the asthma dose - only a small fraction of nebulized albuterol is absorbed systemically
  • IV albuterol 0.5 mg (available in Europe) produces equivalent effect
• Onset: ~30 minutes
• Some patients (~20-40%) are non-responders (particularly dialysis patients)

C. Sodium Bicarbonate (Controversial)

• Useful in patients with severe metabolic acidosis (HCO₃⁻ < 10 mmol/L)
• Lowers K⁺ by enhancing renal K⁺ excretion in patients with residual kidney function
• Not effective in anuric patients / ESKD - does not enhance effects of insulin or albuterol
• Use isotonic sodium bicarbonate
• Caution: can cause hypernatremia, volume overload, and reduce ionized calcium

Step 3 - Remove K⁺ from the Body (Definitive)

A. Diuretics (for patients with residual renal function)

• Loop diuretics (furosemide, torsemide, bumetanide) preferred
• In CKD: prefer torsemide (highest bioavailability, least renal metabolism) or furosemide (least hepatic metabolism for IV use)
• Combine loop + thiazide-like diuretics for greater efficacy (ceiling dose strategy)
• Ensure adequate Na⁺ delivery to distal tubule to augment K⁺ excretion (saline hydration)
• Not effective in oliguria or ESKD

B. Hemodialysis (Most Effective - for ESKD / Severe AKI)

• Most effective method to remove K⁺
• Can rarely be initiated quickly enough to preclude the emergency measures above
• Indicated when: anuric/oliguric ESKD, severe AKI, K⁺ unresponsive to other measures

C. Potassium Binders (Adjunct / Chronic Prevention)

• Patiromer and SZC are not approved for emergency monotherapy but can be adjuncts
• A 2025 systematic review and network meta-analysis (Huang et al., Drugs) confirmed both novel binders (patiromer, SZC) effectively lower K⁺ by ~1 mEq/L and allow continuation of RAASi in CKD/heart failure

Non-Emergent / Chronic Management

1. Exclude pseudohyperkalemia (hemolysis, thrombocytosis, prolonged tourniquet time)
2. Dietary K⁺ restriction (~60 mEq/day); avoid salt substitutes (contain KCl)
3. Discontinue offending drugs: ACE inhibitors, ARBs, K⁺-sparing diuretics (spironolactone, amiloride), NSAIDs, heparin, TMP-SMX
4. Loop diuretics if adequate renal function
5. Oral NaHCO₃ if metabolic acidosis present
6. K⁺ binders (patiromer or SZC) to enable continued RAASi therapy in CKD/HF

Special Situations

Digoxin Toxicity

• If hyperkalemia is driven by digoxin, treat the digoxin toxicity first with anti-digoxin Fab fragments
• Give calcium slowly and with caution (hypercalcemia worsens digoxin toxicity)

Renal Failure / ESKD

• Bicarbonate less effective (no renal excretion)
• Insulin half-life prolonged → higher hypoglycemia risk; consider lispro/aspart (not renally metabolized)
• Dialysis is the cornerstone of definitive management
• Fludrocortisone (0.1-0.3 mg/day) may be considered in hypoaldosteronism but evidence for interdialytic hyperkalemia is modest

Mineralocorticoid Deficiency (Hypoaldosteronism)

• Fludrocortisone 0.1-0.3 mg/day is the treatment of choice

Summary: Rapid Action Table

• [Brenner & Rector's The Kidney](p. 774-780) - Detailed mechanisms and dosing
• [NKF Primer on Kidney Diseases, 8e](p. 128-129) - Practical clinical approach
• Huang et al., Drugs 2025 - PMID 40542996 - Novel K⁺ binders meta-analysis (recent evidence)

Hyponatremia

Definition & Severity

Step 1: Classify by Plasma Osmolality

Step 2: Urine Osmolality (for true hypo-osmolar hyponatremia)

Step 3: ECF Volume Status + Urine Na⁺

Hypovolemic Hyponatremia (↓ ECF volume)

Euvolemic Hyponatremia (normal ECF volume, urine Na⁺ > 20 mEq/L)

• SIADH (most common euvolemic cause)
• Hypothyroidism
• Cortisol/glucocorticoid deficiency (Addison's disease)
• Reset osmostat

Hypervolemic Hyponatremia (↑ ECF volume, edematous states)

Clinical Features

Acute Hyponatremia (< 24-48 hours)

• Headache, nausea, vomiting
• Confusion, disorientation
• Seizures, respiratory arrest
• Brain herniation (most feared - almost exclusively acute)
• Noncardiogenic pulmonary edema can exacerbate brain swelling via hypoxia

Chronic Hyponatremia (> 48 hours)

• Often labelled "asymptomatic" but subtle deficits are common
• Headache, nausea, mood disturbances
• Cognitive slowing, difficulty concentrating
• Gait instability, falls (markedly increased fracture risk)
• Increased osteoporosis and bone fractures in older patients
• Seizures (can still occur)

"Many such patients very often do have neurologic symptoms, even if milder and more subtle in nature... The major clinical significance of chronic hyponatremia may lie in the increased morbidity and mortality associated with falls and fractures in older populations." - NKF Primer on Kidney Diseases, 8e

Treatment

The Cardinal Rule: Rate of Correction

• Caused by overly rapid correction of chronic hyponatremia
• Risk threshold: correction > 10-12 mEq/L in 24 hours
• Clinical features: flaccid paralysis (locked-in syndrome), dysarthria, dysphagia
• Diagnosis: CT/MRI of brain (demyelination in pons)
• Risk factors: hypokalemia, malnutrition, alcohol use disorder, chronic liver disease
• In acute hyponatremia (< 24-48 h): rapid correction is safe and needed - ODS risk is from correcting chronic hyponatremia too fast

Treatment by Type

1. Symptomatic / Severe Hyponatremia (neurologic symptoms, seizures, herniation)

• Bolus method (preferred for emergencies): 100 mL of 3% NaCl IV bolus; repeat once after 30 min if no improvement
  • Raises serum Na⁺ by ~2-4 mEq/L per bolus
  • Sufficient to reduce brain swelling and lower intracranial pressure in acute hyponatremia
• Continuous infusion (stable severe hyponatremia): 0.25-0.3 mL/kg/h as a safer starting rate (titrate based on labs)
• Simple formula to estimate infusion rate:

  Patient's weight (kg) × desired correction rate (mEq/L/h) = infusion rate of 3% NaCl (mL/h)

• CRITICAL: No equation reliably predicts dynamic water balance; recheck serum Na⁺ frequently (every 2-4 hours) and adjust
• Can be given peripherally (low rate of minor complications); central line not always required
• DDAVP can be given prophylactically to clamp aquaporins and prevent overcorrection, especially in patients with a reversible ADH cause (e.g., pain, hypovolemia) where Na⁺ may correct too rapidly once the stimulus resolves

2. Hypovolemic Hyponatremia (asymptomatic)

• Supplement with K⁺ (30-40 mmol/L) if diuretic-induced, even if serum K⁺ is not low
• Avoid isotonic saline in SIADH - it will worsen hyponatremia in euvolemic patients by providing a Na⁺ load that is excreted while free water is retained

3. SIADH - Euvolemic Hyponatremia

• Restrict to 500-1000 mL/24 hours
• Guide degree of restriction using the electrolyte-to-Na⁺ ratio formula:

• Loop diuretics - impair urine concentrating ability, enhance free water excretion
• Salt tablets / oral urea - increase solute excretion; each gram of urea excreted obligates water co-excretion
• Vasopressin receptor antagonists (Vaptans):
  • Conivaptan (IV, V1a/V2 antagonist) - inpatient only
  • Tolvaptan (oral, selective V2 antagonist) - inpatient and outpatient
  • Mechanism: block ADH at V2 receptors in collecting duct → aquaresis (free water excretion without significant Na⁺ or K⁺ loss)
  • Approved for euvolemic and hypervolemic hyponatremia (SIADH, heart failure, cirrhosis - though EMA restricts tolvaptan to SIADH only)
  • Contraindicated in hypovolemic hyponatremia (can worsen hypotension)
  • Tolvaptan FDA warning: potential for irreversible/fatal liver injury (based on TEMPO ADPKD trial at higher doses); limit to ≤ 30 days; avoid in underlying liver disease/cirrhosis
  • Ineffective if serum creatinine > 3.0 mg/dL
  • Risk: overly rapid Na⁺ correction - requires close monitoring; start only in hospital
  • Generic tolvaptan available since 2020 (cost barrier reduced)

• Demeclocycline - works too slowly; nephrotoxic; not recommended for acute management
• Fludrocortisone/mineralocorticoids - adjunct in specific salt-wasting conditions

4. Hypervolemic Hyponatremia (CHF, cirrhosis, nephrotic syndrome)

• Definitive treatment: manage the underlying condition
• Fluid restriction to attenuate hyponatremia
• Loop diuretics (furosemide) to remove free water and Na⁺ together
• Vaptans (conivaptan/tolvaptan): approved but tolvaptan now restricted in cirrhosis (FDA warning); EMA does not approve for HF or cirrhosis
• Avoid isotonic saline (worsens volume overload)
• A 2025 AGA Clinical Practice Update (Orman et al., Gastroenterology) addresses hyponatremia specifically in cirrhosis

SIADH Diagnosis (Criteria)

1. Hypo-osmolality (serum osm < 275 mOsm/L)
2. Urine osmolality > 100 mOsm/L (inappropriately concentrated for the hypo-osmolar state)
3. Urine Na⁺ > 20 mEq/L (on normal salt intake)
4. Euvolemia (no hypovolemia, no edema)
5. Normal thyroid and adrenal function
6. Not on diuretics

Treatment Summary Table

Key Safety Rules

1. Never correct chronic hyponatremia faster than 8 mEq/L/24 h - risk of osmotic demyelination
2. Never use isotonic saline for SIADH - will worsen hyponatremia
3. Never use hypertonic saline for hypovolemic hyponatremia as primary therapy - isotonic saline corrects the ADH stimulus
4. Monitor Na⁺ every 2-4 hours when using 3% NaCl - no formula fully predicts water balance
5. DDAVP as rescue if correction is going too fast - clamps the aquaresis

• [Brenner & Rector's The Kidney](p. 674-677) - Pathophysiology, hypertonic saline, vaptans
• [NKF Primer on Kidney Diseases, 8e](p. 127-129) - Clinical algorithm, rates of correction, CPM
• [Washington Manual of Medical Therapeutics](p. 446-448) - Diagnostic algorithm and fluid restriction formula
• Ayus et al., JAMA Intern Med 2025 - PMID 39556338 - Meta-analysis on correction rates and outcomes