Download Hypokalemia

Disorders of Electrolyte Homeostasis –
Potassium and Magnesium
Sara E Parli, PharmD
Assistant Professor (Adjunct)
Critical Care Pharmacist
Trauma/Acute Care Surgery
Potassium Physiology and Homeostasis

Primary intracellular cation—3,000
to 4,000 mEq in body
–
–
3.5-5 mEq/L in serum, about 2%
150 mEq/L intracellular

75% in skeletal muscle, 25% in liver, RBCs
Lancet 1998;352:135-40.
Potassium Homeostasis

Insulin stimulates Na/K/ATPase pump in liver,
muscle, adipose tissue
–
Transports Na out of cells, K into cells (3:2)



Determines electrical AP across cell membranes
Disturbances affect neuromuscular activity, especially cardiac
conduction
Catecholamines
–
Epinephrine
Lancet 1998;352:135-40.
Potassium Homeostasis


Aldosterone secreted from adrenals to promote
urinary potassium excretion
Acid-base disturbances affect potassium
–
–
–
Excess H+ in serum are exchanged for K+ to maintain
electroneutrality via H+/K+/ATPase pump
Acidosis → hyperkalemia
Alkalosis → hypokalemia
N Engl J Med 1998;339(7):451-58.
Potassium Pharmacokinetics

Readily absorbed
–

RDA=50 mEq/d, average intake 50-150 mEq/d
Kidney is primary route of elimination (90%)
10% excreted in feces
– Mostly filtered and primarily reabsorbed
in proximal tubule, loop of Henle
–
Loop diuretics
Diuretics

Loops
–
–

Thiazides
–
–

Inhibit Na-K-Cl carrier
Hypokalemia, hypomagnesemia,
metabolic alkalosis
Inhibit Na-Cl carrier
Hypercalcemia, hypokalemia
Potassium-sparing
–
–
Inhibit sodium channel directly or
decrease aldosterone activity
Hyperkalemia, gynecomastia
Furosemide (Lasix)
Bumetandie (Bumex)
Torsemide (Demadex)
Ethacrynic acid (Edecrin)
Thiazide diuretics
Chlorthalidone (Hygroton)
Indapamide (Lozol)
Hydrochlorothiazide
Metolazone (Zaroxolyn)
K-sparing diuretics
Amiloride (Midamor)
Triamterene (Dyrenium)
Spironolactone (Aldactone)
Eplerenone (Inspra)
Hypokalemia (Serum K+ <3.5 mEq/L)


Rare in healthy adults
~ 50% of patients on loop or thiazide diuretics
present with serum K+ <2.5 mEq/L
Category
Serum K+ level (mEq/L)
Mild
3 – 3.5
Moderate
2.5 – 3
Severe
< 2.5
Hypokalemia:
Pathophysiology

GI losses
–

Renal losses
–
–



Diarrhea, NG suctioning, emesis
High aldosterone
Hypomagnesemia
Inadequate K intake
Alkalosis
Medications
–
Diuretics


–
Inhibit Na reabsorption → increased Na delivery to distal tubule →
selective reabsorption of Na and K excretion in distal tubule
Volume contraction → aldosterone production → enhanced K
excretion
Corticosteroids
N Engl J Med 1998;339(7):451-58.
Hypokalemia:
Clinical Presentation and Diagnosis

Mild hypokalemia (3 to 3.5 mEq/L)
–
–
–

Usually asymptomatic
Nausea, vomiting, constipation
Weakness, muscle cramps
Moderate hypokalemia (2.5 to 3 mEq/L)
–
Cramping, weakness, myalgias, malaise
Hypokalemia:
Clinical Presentation and Diagnosis

Severe hypokalemia (< 2.5 mEq/L)
–
Electrocardiogram (ECG) changes


–
ST-segment depression/flattening, T-wave inversion, U-wave
elevation
Arrhythmias (atrial flutter, paroxysmal atrial tachycardia, heart
block, ventricular fibrillation, digitalis-induced)
Death
Hypokalemia:
Treatment

Replace magnesium first, then potassium
–
–

Mild to moderate: PO
Severe: IV
Prefer NS containing solutions (dextrose causes
insulin secretion, can worsen hypokalemia)
–
10meq/100ml ok for peripheral veins

–
Addition of 1 mL of 1% lidocaine to bag ↓ pain at infusion site
for greater concentrations
Rates > 10 mEq/hr require EKG monitoring
Hypokalemia:
Treatment

Dose
–
–
–
For every 1 mEq/L decrease below 3.5 mEq/L, there is a
total body deficit of 100-400 mEq
10 mEq K supplementation will correct about 0.1 mEq/L
Potassium sparing diuretics may be considered instead of
chronic oral replacement
Potassium salt
mEq/g (mmol/L)
Gluconate
4.3
Citrate
9.8
Bicarbonate
10.0
Acetate
10.2
Chloride
13.4
Oral
Potassium Salt
Product
Form
Potassium Content
Potassium
Chloride
K-Dur
Tablet, controlled release
10 mEq [750 mg]
KCl (generic)
Liquid
Capsule and tablet, controlled
release
20 (10%) and 40 (20%) mEq/15mL
10 mEq [750 mg]
Kay Ciel® 10%
Kay Ciel® 20%
Powder, for oral solution
Solution
20 mEq/packet
40 mEq/15mL
Micro-K® and Micro-K 10®
Capsule, extended release,
microencapsulated
8 [600 mg] and 10 mEq [750 mg]
K-lor™
Powder, for oral solution
20 mEq/packet
Klor-Con®
Klor-Con®/25
Klor-Con® M10
Klor-Con® M15
Klor-Con® M20
Klor-Con® 8
Klor-Con® 10
Powder, for oral solution
20 and 25 mEq/packet
Tablet, extended release,
microencapsulated
10 [750 mg], 15 [1125 mg], and 20
mEq [1500 mg]
Tablet, extended release, wax
matrix
8 [600 mg] and 10 mEq [750 mg]
K-Tab®
Tablet, extended release
10 mEq [750 mg]
Kaon-Cl® 10
Tablet, extended release
10 mEq [750 mg]
K-Lyte® and K-Lyte® DS
Tablet, effervescent:
25 and 50 mEq
Effer-K™
Tablet, effervescent:
25 mEq
Klor-Con®/EF
Tablet, effervescent:
25 mEq
Potassium
Bicarbonate
and Citrate
Hypokalemia:
Treatment Guidelines
Administer initial potassium
replacement dose
Monitor symptoms resolution
Monitor adverse effects
(hyperkalemia, ECG changes,
arrhythmias, bradycardia)
2 to 4 hours after dose →
Recheck serum K+
* When serum K+ 3 to 3.9 → each 10 mEq
of K+ supplement will ↑ serum K+ by 0.1
mEq/L
* When serum K+ < 2.9 → each 10 mEq
of K+ supplement will ↑ serum K+ by
0.05 mEq/L
Monitor oral potassium
effects (GI upset, diarrhea,
vomiting)
Monitor IV potassium effects
(ECG changes, irritation, pain,
thrombophlebitis)
Hyperkalemia (>5 mEq/L)


Less common than hypo, over replacement with IV
potassium is the most common cause
Overuse of potassium supplements in elderly
(diuretics, kidney disease)
Category
Mild
Moderate
Severe
Serum K+ level (mEq/L)
5.5 – 6
6.1 – 6.9
>7
Hyperkalemia:
Pathophysiology


Input > output
Increased intake
–
Nonadherence to dietary restrictions by patients with CKD


Decreased excretion (more common in AKI than CKD)
–

Fruits, vegetables, herbals and complimentary
ACE-Is, ARBs
Redistribution into extracellular space (acidosis, DM)
Hyperkalemia:
Clinical Presentation and Diagnosis


General signs/symptoms are due to effects of high K+
levels on cardiac (K+ depolarizes cells),
neuromuscular, smooth muscle cell function
Usually asymptomatic, patients may feel heart
palpitations/skipped heartbeats
ECG Changes
Mild (5.5 to 6
mEq/L)
Moderate (6.1
to 6.9 mEq/L)
Severe (> 7
mEq/L)
Hyperkalemia:
Treatment
 Severe
–
–
–
–
–
Calcium for EKG abnormalities
Hyperglycemia, insulin (5-10 units IV)
Albuterol inhalation (10-20mg nebulized
over 10 min), may cause tachycardia
Bicarbonate (if acidotic) 50-100 mEq
RRT if needed
Hyperkalemia:
Treatment

Mild-moderate
–
–
Loop diuretics
Sodium polystyrene sulfonate (SPS, Kayexalate)




Prepackaged SPS consists of 70% sorbitol suspension (induces
diarrhea → ↑ K+ excretion)
Caution in patients with ileus (cause intestinal dymotility)
Oral is better tolerated and more effective than enema
Each SPS gram → exchanges 1 mEq Na+ with 1 mEq K+ (in large
intestines)
Lancet 1998;352:135-40.
Disorders of Potassium Homeostasis


Primary intracellular cation, normal K= 3.5–5 mEq/L
Tightly regulated by Na/K/ATPase pump
–


Determines electrical action potential across
myocardium
Hypokalemia is common with diuretics and GI losses
–

Insulin, catecholamines, acid/base
Replace IV or PO depending on severity
Hyperkalemia can be due to over-correction with IV
potassium
–
Treat symptoms, promote excretion
Magnesium Homeostasis




Primarily distributed in ICF (67% in bone, 20% in
muscle)
Serum = 1.7-2.3 mg/dl (1% of total body in ECF)
30-40% ingested is absorbed in small intestine
Renal elimination
–
Majority of Mg2+ is reabsorbed in loop of Henle
Factors Affecting Magnesium Loop
Reabsorption

Serum Mg++ levels
–

Intraluminal Na+ and ECF volume status
–
–

↑ serum Mg++ → ↓ Mg++ reabsorption
↓ ECF volume → ↑ Mg++ reabsorption (due to ↓ luminal
flow and ↑ Na+ reabsorption (Na+ - K+ - 2Cl- -ATPase cotransport pump)
Low Na+ diet → ↑ Mg++ reabsorption
Parathyroid hormone (PTH) ↑ Mg++ reabsorption
Magnesium Physiology






Central role → cellular function, and cofactor in
numerous biochemical reactions (especially systems
depending on adenosine triphosphate (ATP)) and
enzymes
Mitochondrial and cell membrane function
Protein synthesis
PTH secretion
Nerve conduction, membrane stabilization
Inhibits calcium channels
Hypomagnesemia (<1.5 mg/dL)


More common in ICU
GI losses
–

Renal losses
–
–

Decreased absorption/intake (alcoholism), increased loss
Most common with loops, thiazides
Also with other drugs-foscarnet, aminoglycosides,
amphotericin, etc.
Commonly associated with hypocalcemia
Hypomagnesemia:
Clinical Presentation and Diagnosis


Typically asymptomatic but other electrolyte abnormalities
(hypokalemia, hypocalcemia) can be present and difficult to
assess if symptoms due to Mg++ deficiency alone
Most prominent symptom is hypocalcemia (possibly due to ↓
PTH secretion, ↓ 1,25-(OH)2 vitamin D levels, skeletal
resistance to PTH)
Category
Mild to Moderate
Severe
Serum Mg2+ level (mEq/L)
1 – 1.5
<1
Hypomagnesemia:
Signs and Symptoms

Neuromuscular
–

Gastrointestinal
–

Tetany, twitching, weakness, generalized seizures, coma,
ataxia, tremor
Nausea, vomiting
Cardiovascular
–
Heart palpitations, arrhythmias

–
Torsades de pointes, digoxin-induced, ventricular fibrillation
Moderate-severe hypomagnesemia

Prolonged PR interval, progressive widening of QRS complex,
flattened T waves
Hypomagnesemia:
Treatment

Mild-moderate 1 – 1.5 mg/dL
–
Magnesium oxide 400-800mg 3-4x day (60% elemental)


Severe < 1 mg/dKL
–
–


Diarrhea is dose limiting
IV solution (magnesium sulfate 1g = 8.12 mEq Mg2+)
May require 8-12g in the first day then 4-6g/day for 3-5
days
Decrease dose by 50% in kidney disease
Must correct hypomagnesemia before other
electrolyte disturbances
Hypermagnesemia (>2.4 mg/dL)


Uncommon
Occurs when intake exceeds kidneys’ ability to
excrete (stage 4-5 CKD, elderly)
–

Antacid use
Symptoms are rare when serum Mg < 3 mg/dl
Hypermagnesemia:
Treatment




Depends on severity
↓ Mg++ intake and remove sources of Mg++
Loop diuretics to promote excretion
Antagonize Mg++ physiologic effects with Ca2+
–
–
In emergent/urgent or symptomatic cases →
administer IV calcium chloride 10% 5 mL (500 mg
calcium chloride = 6.8 mEq Ca++) over 5 to 10 minutes,
may repeat once if symptoms unresolved
Avoid oral calcium
Hypermagnesemia:
Treatment
Severity
Treatment
Mild, non-emergent ↓ Mg++ intake (if present)
Loop diuretic therapy (i.e. furosemide)
Moderate-severe
Loop diuretic therapy (i.e. furosemide)
Hemodialysis
Urgent/emergent
or symptomatic
IV calcium, loop diuretic therapy
Disorders of Magnesium Homeostasis



Primarily intracellular, reabsorbed in loop of Henle
Normal serum magnesium = 1.7-2.3 mg/dl
Hypomagnesemia common with hypokalemia and
hypocalcemia – tetany, Torsades
–
–

Replace magnesium first!
PO, IV depending on severity
Hypermagnesemia uncommon
–
Promote excretion