Potassium is the major INTRACELLULAR cation in the body. Remember that sodium is primarily outside of the cell. Well, potassium finds its home at higher concentrations within cells throughout the body. Along with sodium, it regulates intracellular volume, plays an important role in not only nerve conduction, but also contraction of skeletal and cardiac muscle cells and plays an important role in many metabolic processes. The normal range is 3.5-4.9 mEq/L.
Just as an example of how potassium helps with nerve and muscle contraction, lets take a look at what happens in a neuron. In order for a signal to be passed from one nerve cell to the next, and eventually reach its final destination, such as a muscle in your finger telling it to contract, the cell must depolarize.
This is done by the rapid shifts of ions in and out across the neuron cell membrane. You will notice in the image that potassium is not the only player here, but it is quite an important one. The systematic shift in these ions across a cell membrane will cause the cell to polarize, then depolarize, and transmit the electrical action potential to the adjacent cell to do the same. Without potassium, you couldn’t sent nerve signals, your muscles couldn’t contract, your heart couldn’t beat.
HYPERKALEMIA
Hyperkalemia is when the concentration of potassium is too high. This can be due to renal failure, where potassium is no longer filtered or excreted through the kidneys, excessive potassium replacement. Remember that potassium likes to be inside of cells, so trauma causing massive tissue damage, such as a crush injury that causes large amounts of cellular damage can cause dangerously high levels of potassium to spill into systemic circulation. This is the premise behind reperfusion syndrome. Where a patients extremities are crushed and trapped by a large object, such as a fallen building or the dash of a car for a prolonged period of time, and when the object is removed and the blood that was trapped in the pinned extremity is released into systemic circulation, a toxic level of potassium reaches the heart resulting in cardiac arrest. Remember, lethal injection in the death penalty is done by potassium injection.
Causes:
- Lab error (most common)
- Excess K+ replacement
- Cellular breakdowns (rhabdo, chemo, transfusions
- Extracellular shift (acidosis, digoxin, B-blockade)
- Impaired excretion (renal failure, hypoaldosteronism, drugs)
- PseudohyperK (hemolysis, leukocytosis, thrombocytosis)
Signs of cardiac dysrhythmias are typically not seen until the potassium level reaches a level of about 6.5. The first EKG changes include a prolonging of the PR interval, shortening of the QT segment and Peaking of the T waves. This occurs at a potassium level of 6.5-7.5 At a level of 7.5-8.0, the P-waves begin to flatten and the QRS begins to widen. At levels greater than 8.0, the QRS segment begins to widen so much that it is difficult to appreciate a normal QRS segment, and it starts to become more of a sine wave appearance, which rapidly degrades into v-fib and then asystole. Treatment of suspected hyperkalemia starts with an EKG.
Hyperkalemia Treatment
If there are no significant EKG changes, and the potassium level is significantly elevated, the blood specimen should be redrawn prior to treatment as many factors can lead to a false reading. A prolonged tourniquet time while searching for a vein to start an IV, for example can cause a falsely elevated reading as cells leak potassium into the hypoxic arm, causing a higher local concentration that does not represent the true systemic concentration.
If the re-draw confirms hyperkalemia, treatment consists first or Calcium (either gluconate or chloride) which stabilizes the cardiac membrane, but does nothing to actually decrease potassium levels.
Insulin is given next as insulin will drive potassium into cells, and this hides it. This is only a temporizing measure, as it doesn’t decrease the actual whole body level of potassium, only temporarily decreases the amount of potassium in systemic circulation. Giving 10 units of insulin to a patient who is not hyperglycemic could be a big problem, so we always give glucose with the insulin when it is used for hyperkalemia.
Bicarbonate and inhaled albuterol also helps to hide potassium in cells, providing a temporary fix. Lasix is sometimes used as it increases the amount of potassium excreted at the kidneys. Kayexalate binds potassium in the GI tract, preventing its re-absorption, but this process is very slow and literature is mixed on its actually clinical efficacy. Finally, dialysis is indicated for significant hyperkalemia and will actually rapidly remove potassium from the body.
Step 1: Stabilize Cardiac Cell Membrane
- Give if there are EKG changes
- Calcium chloride: (10%) 5-10 mL IV (onset 1-3 min, duration 30-50 min)
- Calcium gluconate: (10%) 10-20 mL IV (onset 1-3 min, duration 30-50 min)
- Caution Ca use in Hyperphosphatemia as it precipitates out
- Caution Ca use in digoxin use (especially with Ca gluconate
Step 2: Shift K+ Intracellularly
- Give if K >6 with any EKG changes or > 7 without EKG changes
- Bicarbonate: 5—100 mEq IV (onset 5-10 min, duration 1-2 hours)
- Regular insulin: 10 u & 1 amp D50 (onset 30 min, duration 4-6 hours)
- Albuterol: neb 10-20 mg over 10 min (onset 30 min, 2-4 hour duration)
Step 3: Enhance Elimination
- Kayexalate: 25-50 g PO/PR (don’t give with ileum or bowel obstruction)
- Lasix: 40 mg IV
- Hemodialysis
- Hydrocortisone: 100 mg if concern of adrenal insufficiency
Admission Criteria:
- Admit most cases
Discharge Criteria:
- Mild hyperkalemia (< 5.5)
- Response to treatment demonstrated
- Known correctible cause
- Further rises not anticipated
- Early follow-up possible
Clinical Pearls: Calcium use in HyperKalemia
Should I use CaCl or Ca-Gluc?
- CaCl contains 3 x the elemental Ca (13.6 vs 4.6 mEq in 10 mL of a 10% solution)
- CaCl more likely to cause tissue necrosis with extravasation (best to have a CVC)
- Ca-Gluc preferred if stable
- CaCl preferred if unstable – make sure IV is a good one
What dose of Calcium should I use?:
- CaCl: 0.5-1 g (5-10 mL) of a 10% solution – 1 amp
- CaGluc: 1-2 g (10-20 mL) of a 10% solution – 1-2 amps
- Dose based on normalization of EKG changes (anything more than peaked T waves)
- Repeat dose every 3-5 minutes until EKG normalizes (onset of action is 1-3 minutes)
- Effects only last 30-50 minutes – should give cocktail if you are giving calcium
- Re-dose every 30-60 minutes if EKG changes return
Is calcium helpful if patient calcium level is normal?
- Short answer is yes
- Hypocalcemia increases cardiotoxicity of hyperK+
- Effective even in normocalcemic patients – directly antagonizes membrane actions of hyperK
Can I use Calcium in Dialysis patients?
- Yes – with caution
- However, ONLY give if there are significant EKG changes
- Most dialysis patients will also have concomitant hyperphosphatemia
- Call nephrology ASAP to arrange dialysis
Can I use Calcium in patient on Digoxin?
- Current recommendations are to use calcium for the same indications as those not on Digoxin (widening QRS or P wave loss)
- HOWEVER, hypercalcemia potentiates cardiotoxic effects of digitalis – so only give if you really need to
- SO, consider a dilute infusion of 1 amp CaGluc in 100 cc of D5W over 20-30 minutes
- Consider Digibind if K > 5.5
Wait…doesn’t Calcium use with Digoxin cause “stone-heart”?
- Basis of the theory…
- Digoxin inhibits Ca transport out of myocytes AND form Ca-channels in lipid bilayers – import Ca
- Ca was found to increase digoxin toxicity in animal models
- Only 5 total case reports showing a temporal increase in mortality (all from the 1930-1950’s)
- Issues with this theory…
- Several case reports also showing no harm
- Of the 5 case reports, no report of digoxin levels and only 2 showed a temporal increase in mortality
- Animal models have not been able to reproduce early models (Hack et al, 2004)
- Early animal models were severely hypocalcemic (> 15 mM/L) prior to Digoxin administration (Noel, 1970)
- Levine et al, 2011
- Showed no dysrhythmias or increased mortality with chronic Digoxin use and IV Calcium (2020 patients)
- Only level of K associated with increased mortality (OR 1.5 for each 1 mEq/L increase in serum K)
- Only 1 case was digoxin toxic (no clear evidence to date either way if dig toxic)
HYPOKALEMIA
Hypokalemia is seen at serum potassium levels less than 3.5. This can be seen with overdiuresis, inadequate dietary intake of potassium, in GI wasting with diarrhea and vomiting and in other metabolic conditions. There may be an associated metabolic alkalosis where potassium is lost as a compensatory mechanism in the kidney in exchange for sodium, which we will talk more about later.
Remember that potassium is vital for cell depolarization. Without potassium, neurons don’t fire. The patient becomes confused and drowsy. Muscles don’t contract, and you will see weakness and fatigue. Cardiac muscle doesn’t contract efficiently, and the patient is more prone to arrhythmias. Even smooth muscles of the GI tract don’t contract, and peristalsis doesn’t occur. The patient develops and ileus, and associated nausea and vomiting.
Symptoms:
- Renal losses:
- Diuretics
- Renal tubular damage – RTA I and II, nephritis, drugs (Tylenol, NSAIDs, hydroxychloroquine, Ampho B, gentamicin)
- Hyperaldosteronism
- Hypomagnesemia
- Polyuria – osmotic diuresis (mannitol, hyperlycemia, psychogenic)
- Congenital – bartter and gitelman syndrome, liddle syndrome
- GI Losses:
- Diarrhea
- Vomiting
- Ureterosigmoidostomy
- Cystic fibrosis
- Intracellular shift:
- Alkalosis
- Insulin
- Adrenergic Excess – trauma, MI, sepsis, cocaine
- Hypothermia
Clinical Pearls: Laboratory clues seen in HypoKalemia
Hypokalemia Treatment
Treatment is with replacement of Potassium and identifying preventable causes (hold diuretics or laxatives, treat vomiting or diarrhea). Potassium is significantly more efficiently absorbed through the GI tract, than through IV administration. So, if the patient can take oral medications, we prefer this route. However, it may be beneficial to give potassium both PO as well as IV. IV potassium must be given over a long period of time to help minimize risks associated with the IV infusion and is typically given at a rate of 10 mEq per hour at a maximum of 40-50 mEq per treatment. There are dextrose containing potassium formulations, however, this should really just be avoided as it can cause an anaphylactic reaction in patients who have an allergy to corn products.
ORAL POTASSIUM FORMULATIONS
Potassium Chloride:
- Liquid:
- More bioavailable, but more nausea
- Rapid rise in K, but will fall after 4 hours from transcellular shift
- Tablet:
- More sustained effect
- Slowly absorbed
- Potential for small bowel ulceration
- Dosage:
- Mild-Mod: 10-20 mEq q6-12 hr
- Mod-Sev: 40-60 mEq q8-12 hr
- Continue until K remains 3 – 3.5
- Use in acidotic patients (RTA)
- Ineffective if accompanying metabolic alkalosis
- Often used as prophylaxis against Ca-Ox renal stones
IV POTASSIUM FORMULATIONS
Potassium Chloride:
- IV recommended if severe
- Potassium Chloride preferred IV form
- 10 mEq/hr usually tolerated well
- If > 20 mEq/hr needed, use central line
- Dosage:
- Adult: 10 mEq will increase ↑ [K+] by o.1
- Child: 0.1-0.2 mEq/kg/h
- Cardiac Arrest: 20 mEq IV over 2-3 minutes
Potassium Phosphate:
- Used only if accompanying severe hypophosphatemia
Admission Criteria:
- K+ < 2.5
- Associated severe Hypo/Hypertension
- Severe symptoms
Discharge Criteria:
- Asymptomatic
- Able to replace orally
- Reversible cause identified
- Early follow-up possible
Clinical Pearls: Treatment of HypoKalemia
How much does serum [K+] change with supplementation?
For each 10 mEq dose of potassium given IV, will increase the serum concentration of potassium by 0.1 mEq. So if a patients potassium level is 3.1, we can estimate that giving them 40 mEq of IV potassium will increase their serum concentration back to 3.5. Oral potassium replacement is much less predictable, so we can’t use this rule for estimating enteral potassium replacement
In a 2016 study quantifying the change in serum potassium level after IV versus Oral potassium administration, authors concluded serum levels were similar increases in both IV and PO replacement. Further, in patients who are on medications that waste potassium (i.e. Lasix), oral potassium was better than IV at increasing serum potassium levels.
Don't forget about Magnesium!!!
K+ is freely filtered through the kidney. Most of this K+ is reabsorbed by the proximal tubule. However, in the late distal tubule, Mg inbitis ROMK channels and prevents K+ wasting in the urine. Without Mg, these channels stay open and K+ is wasted in the urine. Your K+ replacement will be useless if your patient is Mg deficient.
Miscellaneous pearls:
- Acidosis:
- Correct Hypokalemia before treating acidosis to avoid life-threatening hypokalemia from transcellular shifts
- Minimize glucose containing fluids:
- Glucose administration will stimulate insulin release à K+ moves into cell
- Large oral dosing:
- Large doses of PO potassium can be given safely in patients with normal renal function
- Limited only by GI intolerance
- Periodic Paralysis and States of Adrenergic Excess:
- Relatively small doses are required since transcellulaar shifts are transient
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