Management of Hyperkalaemia and Hypokalaemia

Potassium homeostasis Obtained through the diet -GI absorption is complete - daily excess intake of

about 1 mEq/kg/d (60-100 mEq) - is excreted through the kidneys (90%) and the gut (10%).

K homeostasis is maintained predominantly through the regulation of renal excretion. The most important site of regulation is the cortical collecting tubule where aldosterone receptors are present.

Excretion is increased by the following: -Aldosterone -High Na delivery to the distal tubule, eg, diuretics -High urine flow, eg, osmotic diuresis -High serum K level -Delivery of negatively charged ions to the distal tubule, eg, bicarbonate

Excretion is decreased by the following: -Absence of aldosterone -Low Na delivery to the distal tubule -Low urine flow -Low serum K level -Renal failure

Pathophysiology-Hyperkalaemia

3 pathogenetic mechanisms can cause hyperkalemia.

Excessive intake: relatively high K intake in a patient with impaired mechanisms for the intracellular shift of K or renal K excretion.

Decreased excretion: renal failure; ingestion of drugs that interfere

with K excretion, eg, K-sparing diuretics, ACE-I, NSAIDS; or impaired responsiveness of the distal tubule to aldosterone, eg, type IV renal tubular acidosis observed with DM, sickle cell disease, chronic partial urinary tract obstruction.

Shift from intracellular to extracellular space: rhabdomyolysis and tumor lysis. However, more often, insulin deficiency or acute acidosis.

Clinical Features of Hyperkalaemia

Plasma K >6.5mmol/l needs urgent treatment-but 1st ensure it’s not an artefact (eg. due to hemolysis inside the bottle)

Neuromuscular manifestations: Weakness, paraesthesia, areflexia, ascending paralysis

Cardiac manifestations: Bradycardia, prolonged of AV conduction, complete heart block, wide complex tachycardia, ventricular fibrillation, and asystole

ECG: tall tented T waves, small P waves, depressed ST segments, widened QRS complexes, sine waves (biphasic waves, pre-cardiac arrest)

ECG has limitation in predicting cardiac toxicity. Thus patient should be treated even in the absence of ECG changes

Management

Goals:- To protect the heart from effects of K by

antagonizing its effects on cardiac conduction (Ca)

- To shift K from ECF to ICF (Na bicarbonate, insulin & glucose)

- To reduce total body K (cation exchange resin & dialysis)

- Treatment is urgent if K>6.5 mmol/L or ECG shows change of hyperkalaemia

RecommendationsMild to moderate hyperK (5.5-6.5mmol/L) with no ECG changes:

low K diet Cation exchange-resins Correction of acidosis in patient with metabolic acisosis +/- Glucose & insulin infusion stop drugs which may cause hyperkalaemia

K-sparing diuretics, spironolactone, triamterene, amiloride NSAIDS ACE-I ARB Cyclosporine or tacrolimus Pentamidine Trimethoprim/sulfamethoxazole Heparin Ketoconazole Metyrapone Herbs

Severe Hyperkalaemia (>6.5 mmol/L) or with ECG changes

Above treatmentsImmediate Calcium administrationGlucose and insulin infusionSodium bicarbonate infusionBeta agonist therapyDialysis

Calcium administration

10ml of 10% calcium gluconate IV over 2-5 minutes. A 2nd dose can be given after 5 mins if no change in ECG is seen. Effect of calcium occurs within minutes and lasts for 1 hour

Slower infusion rates in patients on digitalis to avoid hypercalcaemia-induced digitalis toxicity

Calcium should not be given before after bicarbonate in the same IV line to avoid precipitation

Glucose and Insulin infusion

Rapid acting insulin 10u + 50cc of 50% dextrose IV infused over 30-60min (in pt with renal failure, higher dose of glucose needs to be given, e.g. 100-150 ml of dextrose)

Onset within 30-60 min & lasts for several hours The above regime can be repeated 6-8 hourly Bolus hypertonic glucose solution may

transiently exacerbate hyperK by its osmotic effect on cells

After insulin & dextrose infusion, maintain pt. on continuous dextrose infusion, e.g.D5%

Sodium bicarbonate infusion

IV infusion of bicarbonate 100-200 mmol/l over 30 min produces metabolic alkalosis which lowers K in ECF

Onset of action occurs within 30 min & lasts for 1-2 hours

It is less effective in patients with renal failure

Cation-exchange resins (Resonium A)

Bind potassium in exchange for another cation in GI tract, thereby removing K from body

Can be given orally (sodium polystyrebe [Resonium A] 15-30 g 3-4 times daily) or as enemas (Resonium A 30 -60 g in 200 ml 3-4 times daily)

Hemodialysis or peritoneal dialysis

When consvative measures fail, underlying cause is not reversible or in persistent hyperkalaemia

Beta-agonist therapy IV salbutamol 0.5 mg in 15 min or 10 mg neb

( with or without glucose & insulin infusion) has been shown to be effective in reducing K level (IV is preferred in pt with ESRD)

If effective, plasma K will fall by 0.5-1.5 mmol/l in 15-30 min & effect will last for several hours

Pathophysiology -Hypokalaemia

Poor K intake - seen in very elderly individuals unable to cook for themselves or unable to chew or swallow well or in pt.s receiving TPN, where K supplementation may be inadequate for a prolonged period of time.

Increased excretion – increase renal K losses incl. enhanced Na delivery to the collecting duct, as with diuretics; mineralocorticoid excess, as with primary or secondary hyperaldosteronism; or increased urine flow, as with an osmotic diuresis.

GI losses – diarrhea,vomiting (produces volume depletion and metabolic alkalosis)

Shift from extracellular to intracellular space- Beta-adrenergic stimulation

e.g.AMI, beta-agonists, insulin treatment e.g. DKA, exogenous glucose, alkalosis, hypokalaemic periodic paralysis-intermittent weakness lasting up to 72 hours

Clinical Features of Hypokalaemia

If K < 2.5 mmol/L, urgent treatment is required. Note that hypokalaemia exacerbates digoxin toxicity.

Malaise, fatigue Neuromuscular disturbances: Weakness, hyporeflexia,

paraesthesias, cramps, restless legs syndrome, rhabdomyolysis, paralysis

GI : Constipation, ileus Polyuria, plydipsia, metabolic alkalosis ECG changes: small or inverted T waves, prominent U

wave, depressed ST segments, prolonged PR intervals Arrhythmias: 1st & 2nd degree heart block, AF, ventricular

tachycardia, ventricular fibrillation

Important facts 1g KCL contains 14 mmol (14 mEq) of K If serum K level does not appreciably rise after adequate K therapy

(e.g. 72-96 h after oral therapy), concomitant Mg depletion should be suspected.

If hypoK & low urinary K excretion (<20 mmol/L), hypoK of extrarenal origin must be suspected

In asymptomatic pt. with K 3-4 mmol/L, who are vulnerable to cardiac arrythmias e.g. CCF, digitalis treatment (e.g. digoxin), h/o MI or IHD- K supplements should be recommended

If K < 3 mmol/L, K supplements should be recommended KCl – preffered choice except in metabolic acidosis ( potassium

bicarbonate or potassium citrate is preferred) & hypophosphataemia, e.g. DKA (use potassium phosphate)

K is an intracellular ion; a low serum K reflects a much grater total K deficit

Correction of large deficits may require several days as up to 50% of administered K is excreted in the urine

Management Oral therapy

-method of choice for mild to moderate depletion (plasma K>2.5 mmol/L)-Oral KCl 1-2g hrly until return of serum K to at least 3.5 mmol/L-Slow release K (1 tab = 8 mmol) -40-200 mmol daily of KCl may be rqd over periods of days or weeks e.g. 20-40 mmol 2-4 x daily depending on severity of depletion ( as frequent as 2-4 hrly may be rqd)-Monitor K levels closely to prevent hyperK-K-sparing diuretics (e.g. amiloride, triamterene & spironolactone) may be an alternative for pt.s in whom hypoK develops secondary to renal losses

IV therapy-Method of choice in pt.s with severe hypoK ( <2.5 mmol/L), with ECG changes, & in pt.s who are not able to take orally & who are symptomatic, e.g. cardiac arrythmias with rapid ventricular response, famililal periodic paralysis, & severe myopathy-In asymptomatic pt.s without ECG changes, K should be given as follows:

-at a concentration of < 40 mmol/L (< 3g KCl/L) of dextrose free carrier fluid

-at a rate of <20 mmol/hr (10 mmol/hr recommended)-Plasma K should be monitored regularly; ECG monitoring advised

-In emergency e.g. cardiac arrythmias, severe myopathy, -K can be given at a rate of 40 mmol/hr (i.e KCl 3 g/hr) & in concentration of 200-400 mmol/L (by mixing 20-40 mmol or 1.5-3.0 g KCl in 100 ml of saline)-use large central vein: Femoral venous infusion is

preferable than upper body central vein to avoid deleterious effects on cardiac conduction

Important notes Potential risk of IV K : acute hyperkalaemia, which is

most likely in pt.s with renal insufficiency To avoid venous pain, irritation & sclerosis,

concentrations of > 60 mmol/L should not be given through a peripheral vein

Preferably fluid should be dextrose free as fast infusion of dextrose would result in endogenous insulin secretion, thus simulating an insulin/gllucose infusion.

IV administration of K at a rate of > 10 mmol/hr requires continuous ECG monitoring

As soon as ECG normalize, cardiac rhythm returns to normal or respiratory muscle strength is restored, IV infusion is gradually tapered & discontinued. Oral KCl is then initiated.

Complications:

Complications of hyperkalemia range from mild ECG changes to cardiac arrest. Weakness is common as well.

Complications of therapy include the following: Failure to control hyperkalemia Hypokalemia due to excessively aggressive therapy Hypercalcemia due to excessive calcium administration Hypocalcemia from excessive bicarbonate therapy Chest discomfort or tachycardia due to beta-agonist therapy Hypoglycemia or hyperglycemia complicating glucose and insulin administration Metabolic alkalosis and tetany due to excessive sodium bicarbonate

administration Volume depletion, metabolic alkalosis, renal insufficiency, hypocalcemia,

hypomagnesemia, and hypophosphatemia due to aggressive loop diuretic use Colon perforation due to Kayexalate administration

Complications of Hypokalaemia Increased susceptibility to cardiac arrhythmias is observed with

hypoK in CCF, IHD/ AMI, aggressive therapy of hyperglycemia, such as with DKA,digitalis therapy

Low K intake has been implicated as a risk factor for the development of HPT and/or HPT EOD.

Muscle weakness, depression of the deep-tendon reflexes, and even flaccid paralysis can complicate hypoK. Rhabdomyolysis can be provoked, especially with vigorous exercise.

Abnormalities of renal function often accompany acute or chronic hypoK

HypoK decreases gut motility, leading to or exacerbating an ileus. HypoK also is a contributory factor in the development of hepatic

encephalopathy in the setting of cirrhosis. HypoK has a dual effect on glucose regulation.

HypoK decreases insulin release. It also decreases peripheral insulin sensitivity.

HypoK has widespread actions in many organ systems, which, over time, result in cardiovascular disease.

Patient Education:

Inform patients regarding the following: Instruct patients on symptoms of hypokalemia or hyperkalemia.

Palpitations or notable cardiac arrhythmias Muscle weakness Increasing difficulty with diabetes control Polyuria

Dietary sources of K, including salt substitutes Medications that impair renal excretion, including ACE-I, ARBs,

NSAIDS, and K-sparing diuretics Clinical situations in which pt.s might be at risk for the

development of hyperK, which incl.volume depletion and acute renal insufficiency complicating GI fluid losses; increasing doses of ACE-I or K-sparing diuretics; and addition of a medication that decreases renal excretion or cellular uptake in patients who already are taking such drugs.