Hyperkalemia - Nephrology Lectures 2025

🚰 FIRST CATHETER = FOLEY CATHETER (Not Central Line!)

🔑 Clinical Decision Point

If NO EKG changes AND able to establish urine output → May avoid hemodialysis

Therefore: Foley catheter is the FIRST catheter to place in hyperkalemia, not a central line for dialysis access.

✅ Foley First When:

No EKG changes present
Hyperkalemia unexplained
Clinical suspicion of obstruction
Trying to avoid dialysis
ANY bladder scan >300mL

⚡ Central Line When:

EKG changes present
K+ >7.5 mEq/L
Symptomatic hyperkalemia
Failed medical management
Anuric or dialysis-dependent

🚨 Emergency Protocol: STABILIZE → FOLEY → SHIFT → REMOVE

1 STABILIZE MEMBRANE: Calcium Gluconate 30mL IV (or CaCl₂ 10mL if central line)
• Onset: 1-3 minutes • Duration: 30-60 minutes • NO effect on K+ levels • ONLY if EKG changes present

2 FOLEY CATHETER: Especially if no EKG changes - may prevent need for dialysis
• May reduce K+ 0.8-1.1 mEq/L in 4-6 hrs • Can prevent need for dialysis • Check bladder scan • Post-void residual >100mL

3 SHIFT INTRACELLULAR: Insulin (most reliable) + Albuterol (variable response)
• Insulin 10U IV + D50 25g IV (90% response rate, K+ ↓ 0.6-1.2 mEq/L)
• Albuterol 10-20mg neb (60-80% respond, K+ ↓ 0.5-1.0 mEq/L)
• Synergistic effects when combined • Monitor glucose hourly × 6hrs
• If respiratory acidosis: Improve ventilation (each 0.1 pH ↑ = 0.6 mEq/L K+ ↓)

4 REMOVE POTASSIUM: Lokelma 10g PO IMMEDIATELY (don't wait!)
• Give ASAP, don't wait 1-2 hours • Onset: 1 hour, K+ ↓ 0.4 mEq/L @ 1hr, 0.7 mEq/L @ 4hrs • Works in small intestine

💊 LOKELMA: Give IMMEDIATELY, Don't Wait!

⏰ Timing is Critical

Common Mistake: Waiting 1-2 hours after insulin/albuterol to give Lokelma

Correct Approach: Give Lokelma IMMEDIATELY with other treatments

✅ Why Give ASAP:

1-hour onset means earlier benefit
Synergistic with shifting agents
Prevents K+ rebound after insulin wears off
Provides sustained K+ removal
May prevent need for dialysis

🚫 Lokelma Won't Work If:

Bowel obstruction (works in small intestine)
Severe gastroparesis
Recent bowel surgery
Inability to take PO medications
Ileus or severe constipation

🧠 Mechanism: Small Intestine Action

Lokelma (sodium zirconium cyclosilicate) works primarily in the small intestine by exchanging sodium and hydrogen for potassium. This is why it won't work in bowel obstruction - the medication must reach the small intestine to be effective.

🔍 Comprehensive Etiology: Why Is K+ High?

📋 Systematic Approach to Hyperkalemia Causes

💀 Cellular Death/Lysis

Massive K+ Release from Cells

Rhabdomyolysis: Muscle cell breakdown
• CPK >1000, myoglobin in urine • Check for dark/coca-cola urine
Tumor Lysis Syndrome: Oncology emergency
• Chemotherapy initiation • High LDH, uric acid, phosphate
Gut Ischemia: Intestinal cell death
• Mesenteric ischemia • Often with severe acidosis
Massive Hemolysis: RBC destruction
• Check LDH, haptoglobin, indirect bilirubin
Compartment Syndrome: Muscle necrosis
• Trauma, prolonged immobilization
Massive Burns: Tissue destruction
• >20% body surface area • Peak K+ at 24-48 hours
Malignant Hyperthermia: Anesthesia emergency
• Succinylcholine trigger • Hyperthermia + rigidity

🫘 Renal Causes

Impaired K+ Excretion

RAASi Blockade: Most common cause
• ACE inhibitors, ARBs, spironolactone • Aldosterone receptor antagonists
Low Distal Sodium Delivery: Volume depletion
• Dehydration reduces distal Na+ delivery • Less K+ exchange in collecting duct
AKI/CKD: Reduced nephron mass
• eGFR <30: high risk • Oliguria/anuria
Type 4 RTA: Hypoaldosteronism
• Diabetes, NSAIDs, heparin • Normal anion gap acidosis
Calcineurin Inhibitors: Tacrolimus, cyclosporine
• Impairs distal K+ secretion
Trimethoprim/Pentamidine: ENaC blockade
• Blocks sodium channels in collecting duct
Gordon Syndrome: Pseudohypoaldosteronism type II
• Thiazide-sensitive hypertension + hyperkalemia

🏥 Endocrine Disorders

Hormonal Dysregulation

Addison's Disease: Primary adrenal insufficiency
• Low cortisol AND aldosterone • Hyperpigmentation, hypotension
Congenital Adrenal Hyperplasia: 21-hydroxylase deficiency
• Salt-wasting crisis in newborns • Virilization
Hypoaldosteronism: Selective mineralocorticoid deficiency
• Diabetes, HIV, elderly • Normal cortisol
Hyporeninism: Low renin state
• Diabetic nephropathy • NSAIDs, β-blockers

🔬 Pseudohyperkalemia

Falsely Elevated Lab Values

Hemolysis: Most common pseudo-cause
• Check hemolysis index • Repeat with careful draw
Thrombocytosis: Platelet clumping
• PLT >1,000,000 • Use heparinized tube
Extreme Leukocytosis: WBC breakdown
• WBC >100,000 • Leukemia, lymphoma
Fist Clenching: During phlebotomy
• Muscle contraction releases K+
Difficult Draw: Prolonged tourniquet
• Cellular release from ischemia
Hereditary Spherocytosis: Fragile RBCs
• Family history, spherocytes on smear
Stored Blood: Transfusion-related
• Blood >7 days old • Massive transfusion protocol

📈 Increased K+ Intake

Salt Substitutes: KCl instead of NaCl
• "NoSalt", "Morton Salt Substitute"
IV Potassium: Iatrogenic
• High-dose K+ replacement
High-K+ Foods: Usually not sole cause
• Bananas, oranges, potatoes in CKD
Blood Transfusions: Especially massive
• Each unit contains ~5-7 mEq K+
Herbal Supplements: Noni juice, alfalfa
• Often overlooked in history

🔄 Transcellular Shifts

Acidosis: K+ shifts out of cells
• Each 0.1 pH ↓ = ~0.6 mEq/L K+ ↑
Insulin Deficiency: DKA
• Total body K+ often low despite high serum
β-blocker Overdose: Impaired cellular uptake
Hypertonicity: Water shifts out
• Hyperglycemia, mannitol
Succinylcholine: Depolarizing paralytic
• Especially in burn/trauma patients
Digitalis Toxicity: Na-K-ATPase inhibition
• Check digoxin level • Avoid calcium if suspected
Intense Exercise: Muscle K+ release
• Heat stroke, dehydration • Usually transient

🧬 Genetic/Congenital

Hereditary Disorders

Hyperkalemic Periodic Paralysis: Sodium channel mutations
• Episodes triggered by K+ intake, cold, rest after exercise
Pseudohypoaldosteronism Type I: Mineralocorticoid resistance
• Autosomal recessive • Salt wasting, failure to thrive
Pseudohypoaldosteronism Type II: Gordon syndrome
• Thiazide-sensitive hypertension + hyperkalemia
Sickle Cell Disease: Renal tubular dysfunction
• Type 4 RTA pattern • Chronic hemolysis

💊 Additional Medications

Often Overlooked Drug Causes

Heparin (UFH/LMWH): Aldosterone suppression
• Usually after 4+ days • Check aldosterone level
NSAIDs: Multiple mechanisms
• Reduced renin, prostaglandin inhibition • Type 4 RTA
Immunosuppressants: Beyond calcineurin inhibitors
• Sirolimus, everolimus
α-agonists: Clonidine, methyldopa
• Central sympathetic suppression
Mannitol: Hyperosmolar-induced shift
• Especially in neuro ICU patients

🚨 Critical Care Causes

ICU-Specific Scenarios

Massive Tissue Trauma: Crush injuries
• Earthquake victims • Prolonged entrapment
Reperfusion Injury: After ischemia
• Tourniquet release • Revascularization procedures
Ventilator-Associated: Respiratory acidosis
• Acute CO2 retention • Check ABG
Post-Cardiac Arrest: Cellular injury
• Global hypoxic-ischemic injury

🚨 HIGH-YIELD Clinical Correlations

Volume Depletion + RAASi:
Classic combo - dehydration ↓ distal Na+ delivery + ACE-I blocks aldosterone = severe hyperkalemia

Pseudohyperkalemia Clues:
Normal ECG + extreme K+ (>8) + no symptoms = likely false positive

Rhabdomyolysis Triad:
Hyperkalemia + AKI + dark urine = check CPK, treat aggressively

Addison's Disease Clues:
Hyperkalemia + hyponatremia + hypotension + hyperpigmentation

Gordon Syndrome:
Hyperkalemia + hypertension + normal GFR = think thiazide trial

Digitalis Toxicity Alert:
Hyperkalemia + dig toxicity = NO CALCIUM (causes "stone heart")

📊 EKG Manifestations of Hyperkalemia

1. Mild Hyperkalemia

5.5-6.0 mEq/L

Early manifestations include tall, peaked T waves, best visualized in precordial leads. QT interval may shorten slightly. Often asymptomatic but requires monitoring.

• T wave height >5mm limb leads, >10mm precordial leads • Narrow base • First ECG change

🎯 Calcium Success Marker: QRS narrowing is the primary indicator of membrane stabilization, NOT T wave flattening

2. Moderate Hyperkalemia

6.1-7.0 mEq/L

Progression to PR interval prolongation and diminished P wave amplitude. QRS complex begins to widen as conduction velocity decreases. ST segment depression may be present.

• PR >200ms • P wave amplitude decreased • QRS begins widening • ST depression

3. Severe Hyperkalemia

7.0-8.0 mEq/L

Absence of P waves, marked QRS widening resembling bundle branch block or sine wave pattern. Heart blocks may occur. These changes represent pre-terminal rhythms requiring immediate intervention.

• No visible P waves • QRS >120ms • Bundle branch block pattern • Sine wave emerging

4. Critical Hyperkalemia

>8.0 mEq/L

Terminal wide QRS complexes merging with T waves creating sine wave pattern. Ventricular fibrillation or asystole may follow without immediate treatment.

• Sine wave pattern • QRS-T wave fusion • VFib/asystole risk • LIFE-THREATENING

🔍 Diagnostic Workup

📋 Essential Labs

Repeat K+: Confirm result, rule out hemolysis
BMP: Check BUN/Cr, bicarb, glucose
Magnesium: Often overlooked contributor
ABG: If acidosis suspected
CPK: If rhabdomyolysis suspected

⚡ Immediate Assessment

12-Lead ECG: Look for peaked T waves
Bladder Scan: Check for retention FIRST
Cardiac Monitor: Continuous rhythm monitoring
Vital Signs: Blood pressure, heart rate
Muscle Strength: Weakness, paralysis
Reflexes: Diminished or absent

🔍 Etiology Investigation

Medication Review: ACE-I, ARB, K+ sparing diuretics
Kidney Function: AKI, CKD assessment
Endocrine: Adrenal insufficiency, hypoaldosteronism
Tissue Breakdown: Rhabdomyolysis, tumor lysis
GI Function: Bowel obstruction (affects Lokelma)
Dietary History: Salt substitutes, supplements

💊 Treatment Mechanisms & Timing

🛡️ Membrane Stabilization

Calcium (No K+ Effect)

Calcium Gluconate: 30mL IV (peripheral OK) - 9% elemental Ca
Calcium Chloride: 10mL IV (central line only) - 27% elemental Ca
⚡ KEY: CaCl₂ has 3× MORE elemental calcium than gluconate
Success Marker: QRS narrowing (not T wave flattening)
Onset: 1-3 minutes
Duration: 30-60 minutes
Mechanism: Stabilizes cardiac membrane
Caution: Avoid in digoxin toxicity

🎯 Clinical Pearl: Monitor for QRS narrowing as the primary indicator of calcium effectiveness. T wave changes are less reliable and occur later.

🔄 Potassium Shifting

Evidence-Based Intracellular Shifting

📊 Evidence Summary: Insulin is most reliable; albuterol variable; bicarbonate controversial unless severe acidosis

Insulin + Glucose: MOST RELIABLE
• K+ ↓: 0.6-1.2 mEq/L • Onset: 15-30 min • Duration: 4-6 hrs • ~90% response rate
• Standard: 10U regular insulin IV + 25g dextrose (if glucose <250)
Albuterol: VARIABLE effectiveness
• K+ ↓: 0.5-1.0 mEq/L • Onset: 30-60 min • Duration: 2-4 hrs • Only 60-80% respond
• Dose: 10-20mg nebulized • Higher doses (20mg) more effective
• Less reliable in ESRD patients • Use as adjunct to insulin
Sodium Bicarbonate: CONTROVERSIAL - Limited evidence
• Only effective if severe metabolic acidosis (pH <7.1-7.2)
• Minimal effect in normal pH • May cause volume overload, alkalosis
• Dose: 50-100 mEq IV if pH <7.1 • Avoid in mild acidosis
Respiratory Acidosis Treatment: Address underlying cause
• Mechanical ventilation: ↑ minute ventilation, ↓ PCO₂
• Each 0.1 pH ↑ = ~0.6 mEq/L K+ ↓ • Treat airway obstruction, respiratory depression
• BiPAP/CPAP for acute respiratory failure • Bronchodilators if indicated

🎯 Clinical Evidence & Recommendations:

First-Line (Grade A):
• Insulin + glucose combo
• Most predictable response
• Works in all patient populations

Second-Line (Grade B):
• Albuterol as adjunct
• Bicarbonate only if pH <7.1
• Treat respiratory acidosis

⚡ Synergistic Effect: Insulin + albuterol together more effective than either alone (additive K+ reduction)

🗑️ Potassium Removal

Eliminates K+ from Body

Lokelma: 10g PO IMMEDIATELY (don't wait!)
Patiromer: Once daily dosing
Hemodialysis: Most effective for severe cases
Lokelma onset: 1 hour (small intestine)
Dialysis: 1 mEq/L in 60 min
Note: Foley catheter first if no EKG changes

🆚 Potassium Binder Comparison: New Generation vs Traditional

Parameter	Lokelma (SZC)	Veltassa (Patiromer)	Kayexalate (SPS)
FDA Approval	2018	2015	1950s
Exchange Ion	Sodium + Hydrogen	Calcium	Sodium
Site of Action	Small intestine	Colon	Colon
Onset of Action	1 hour (0.4 mEq/L)	~7 hours	~2 hours
Dosing Frequency	TID loading, then daily	Once daily	Every 6-8 hours
Bowel Obstruction	Won't work	May still work (colon)	May still work (colon)
Major Side Effects	Edema, fluid retention	Hypomagnesemia	Colonic necrosis risk
Clinical Use	Acute & chronic (give ASAP)	Chronic management	Acute (use with caution)

⚖️ Dialysis vs Conservative Management Decision

The choice between aggressive intervention (dialysis) and conservative management depends critically on EKG changes and ability to establish urine output:

🚰 Conservative Management

When appropriate:

No EKG changes
K+ 5.5-7.0 mEq/L
Able to establish UOP
No severe symptoms

Start with: Foley catheter

🏥 Aggressive Management

When needed:

ANY EKG changes
K+ >7.5 mEq/L
Anuric/oliguric
Severe symptoms

Prepare for: Emergent dialysis

Key Point: Many cases of hyperkalemia can be managed without dialysis if treated early and aggressively with Foley catheter placement, Lokelma, and shifting agents.

🚰 Urinary Obstruction: The Great Mimicker

Often overlooked but rapidly reversible cause that can prevent the need for dialysis

5-10%

of AKI cases in ED

22%

of AKI in men >60

0.8-1.1

mEq/L reduction in 4-6 hrs

800+

mL retention = significant improvement

Clinical Pearl: Relief of obstruction alone can be more effective than insulin-glucose therapy and may completely avoid the need for dialysis. Always perform bladder scan in unexplained hyperkalemia.

⚠️ Common Pitfalls & Evidence-Based Corrections

🚫 Avoid These Mistakes

Central line first: Place Foley BEFORE central line if no EKG changes
Delaying Lokelma: Give IMMEDIATELY, don't wait 1-2 hours
Bicarbonate routine use: Only effective if pH <7.1-7.2
Expecting albuterol to work: Only 60-80% respond (vs 90% for insulin)
Missing respiratory acidosis: Treat underlying ventilation issues
Calcium in Digitalis Toxicity: Can precipitate "stone heart"
Insulin without Dextrose: Risk of severe hypoglycemia

👀 Monitor Closely

Urine Output: After Foley placement
QRS Width: Calcium success = QRS narrowing (not T waves)
Glucose: Hourly × 6h after insulin (90% respond)
Albuterol Response: Only 60-80% will respond
Respiratory Status: If acidosis present, treat underlying cause
Potassium: Every 2-4 hours initially
ECG: Continuous monitoring if changes present

✅ Evidence-Based Success

Insulin + Glucose: Most reliable shifting agent (Grade A evidence)
QRS Narrowing: Primary indicator of calcium effectiveness
K+ Reduction >0.5 mEq/L: Within 1 hour of treatment
Bicarbonate Response: Only if severe acidosis (pH <7.1)
Respiratory Improvement: Each 0.1 pH ↑ = 0.6 mEq/L K+ ↓
Urine Output >0.5 mL/kg/hr: After Foley placement
Avoided Dialysis: Conservative management successful

🧮 Enhanced Hyperkalemia Calculator

Comprehensive Treatment Protocol Calculator

Serum K+ (mEq/L): 6.2

Patient Weight (kg): 70

ECG Changes:

Bladder Scan (mL): 150

Kidney Function:

Clinical Symptoms:

Suspected Etiology:

Calculating comprehensive treatment protocol...

🎯 Enhanced Key Learning Points

🚰 Foley First Principle

First catheter = Foley (not central line)
If no EKG changes, establish UOP first
May prevent need for dialysis
Check bladder scan in all cases

💊 Lokelma Timing

Give IMMEDIATELY, don't wait
Works in small intestine
Won't work in bowel obstruction
1-hour onset for K+ reduction

⚡ Emergency Priorities

EKG changes = immediate calcium
CaCl₂ has 3× MORE elemental Ca than gluconate
QRS narrowing = calcium success (not T waves)
Stabilize → Foley → Shift → Remove
Continuous cardiac monitoring
Don't wait for labs to treat severe cases

🔍 Etiology Recognition

Cellular death: Rhabdo, tumor lysis, gut ischemia
Renal: RAASi blockade, volume depletion, CKD
Endocrine: Addison's disease, CAH
Pseudohyperkalemia: Hemolysis, thrombocytosis
Genetic: Hyperkalemic periodic paralysis
Critical care: Burns, reperfusion injury

⚡ Hyperkalemia