Potassium Disorders

DrYasser Matter

Nephrology and Kidney Transplantation SpecialistUrology and Nephrology center Mansoura

University -Egyptyassermatter86@gmail.com

yassermatter@mans.edu.eg

Outlines • General principals and physiology.• Hypo & Hyperkalemia : causesManifestations and diagnostic approachManagement • Some updates .

General principals and physiology

• 1 mmol k+ = 1 meq k+ = 40 mg k+ .• Total body k+ = 50 meq x body weight kg. • 95 - 98% of the body potassium is found

inside the cells. • Normal blood potassium level : 3.5 - 5.0

milimoles/litre( concentration of K is about 150mmol/L of H2O inside the cell).

• Adequate daily intake of k+ in adults :4700mg.

• The normal ratio between extracellular and intracellular concentrations is important for maintenance of the resting membrane potential and neuromuscular functioning.

• Intracellularly, potassium participates in several vital functions, such as cell growth, maintenance of cell volume, DNA and protein synthesis, enzymatic function and acid-base balance.

Distribution of total body potassium in organs and body

compartments

Factors controlling k metabolism

•Factors that shift K+into cells:–Insulin.–Aldosterone.–Epinephrine (through Beta-adrenergic stimulation).–Alkalosis.

•Factors that shift K+out of cells:–Insulin deficiency (diabetes mellitus)–Aldosterone deficiency (Addisons disease)–Beta-adrenergic blockade–Acidosis–Cell lysis

Cellular Potassium Shifts

Aldosterone stimulates K secretion

Transtubular Potassium Gradient TTKG (normally 6-12 )

• TTKG is indirect indicator of aldosterone activity .• TTKG = (UrineK / SerumK) * (UrineOsm / SerumOsm).

Hypokalemia from extrarenal causes

results in renal potassium conservation and a TTKG less than 2. A higher value suggests renal potassium losses,

as through hyperaldosteronism

The expected TTKG during hyperkalemia is

greater than 10.An inappropriately low TTKG in a hyperkalemic

patient suggests hypoaldosteronism or a

renal tubule defect.

After 0.05 mg 9α-fludrocortisone>10 ----- Hypoaldosteronism is likely.No change -------Suggests a renal tubule defect

Potassium and food

Amphotericin B

B agonists ; B12 ; Penicillin

Carbenoxolone ; CS.

Diuretics

Exogenous insulin

Folic acid

G-csf

A nti-inflamm.non-steroidals

B blockers ; blockers of RAAS

CNI; co-trimoxazole

DIuretics: k+ sparing

EPleronone(&spironolactone);EPO

Fluconazole

G Anaesthetic:succinyl choline

Heparins ; herbs

Potassium and drugs

hyperkalaemiahypokalaemia

Hormones: epinephrine

HYPOKALEMIA

Hypokalemia (K level < 3.5 mmol/L)

causes

• Pseudohypokalemia• Redistribution • Intake • Loss (renal & non renal)• Hyperaldosteronism• Drugs

The most common cause is acute leukemia; the large numbers of abnormal leukocytes take up potassium when the blood is stored in a collectionvial for prolonged periods at room temperature. Rapid separation of plasma and storage at 4° C is used to avoid Pseudohypokalemia.

Manifestations

Hypokalemia ECG changes

Treatment of Hypokalemia

• Every 1mmEq/ L [K+] depletion = 10 % Reduction of total body K+store.

• [Total body K+content = 50mEq/ KG]• For a 60 kg person, total body K+store = 60 x 50=

3000 mEq. Therefore, 1 mEq/ L [K+] depletion = 3000 x 10% = 300 mEq. = Total K+ deficit.

• Oral or enteral administration is preferred if the patient can take oral medication and has normal GI tract function. Acute hyperkalemia is highly unusual when potassium is given orally.

• parenteral KCl should be administered in dextrose-free solutions.

Indications for IV potassium• Hypokalemic periodic paralysis.• Severe hypokalemia in a patient requiring urgent

surgery.• Acute myocardial infarction and significant

ventricular ectopy.• Severe diarrhea.• Severe myopathy with muscle necrosis.

K supplement in the market

• 1 bottle ringer 2 meq• 1 bottle kadlax 13.5 meq• 1 amp KCL 10 meq• 1 tab slow k 7.5 meq• 5 ml of potassium syrup 4 meq

Hyperkalemia

Hyperkalemia (K level >5.0 mmol/L)

Ranges are as follows: 5.5 – 6 mEq/L - Mild condition . 6 - 6.5 mEq/L - Moderate condition. 6.5 mEq/L and greater - Severe

condition.

causes• Pseudohyperk

alemia• Redistribution • Intake • Renal retension• Hypoaldosteronism• Drugs

Pseudohyperkalemia

Causes Sever Leukocytosis Sever Thrombocytosis Hemolysis :Ischemia from prolonged tourniquet timeIN patients with RA or IMN or abnormalRBC membrane potassium permeability (IVH)

Pseudohyperkalemia• There is raised serum (clotted blood) potassium concentration with concurrently normal plasma (non-clotted blood) potassium concentration

• It is the clotting process with subsequent release of potassium from cells and platelets that causes an increase in the serum potassium concentration by an average of 0.4 mmol/L.

• Pseudo-hyperkalaemia can be excluded by performing simultaneous measurements of plasma potassium in a lithium heparin anti-coagulated specimen and in a clotted sample.

Pseudohyperkalemia

• This will provide two values with the lower being in the heparinised specimen.

• Pseudo-hyperkalaemia is detected when the serum potassium concentration exceeds that of the plasma by more than 0.4 mmol/L.• The difference in results may be in the order of

several mmol/L. A full blood count should also be performed to exclude a haematological disorder.

PseudohyperkalemiaTechnique of blood drawing• Mechanical trauma during venipuncture can result

in the release of potassium from red cells and a characteristic reddish tint of the serum due to the concomitant release of hemoglobin.

• Potassium moves out of muscle cells with exercise. repeated fist clenching during blood drawing can acutely raise the serum potassium concentration by more than 1 to 2 meq/L in that forearm

Pseudohyperkalemia• venipuncture without a tourniquet, repeated

fist clenching, or trauma will demonstrate the true serum potassium concentration.

• If a tourniquet is required, the tourniquet should be released after the needle has entered the vein, followed by waiting for one to two minutes before drawing the blood sample.

Manifestations

Hyperkalemia ECG changes

ECG in a patient with severe hyperkalaemia (serum K+ 9.1 mmol/L) illustrating peaked T waves (a), diminished P waves (b) and wide QRS complexes (c).

Treatment of Hyperkalemia

AVOID POTASSIUM

There are five key steps in the treatment of hyperkalaemia (never walk away without completing all of these steps).

STEP 1 -Protect the heart; intravenous calcium salts

• We recommend that intravenous calcium chloride or calcium gluconate, at an equivalent dose (6.8mmol), is given to patients with hyperkalaemia in the presence of ECG evidence of hyperkalaemia. (1A)

• ca chloride salt has been recommended in the setting of haemodynamic instability, including cardiac arrest , because the active calcium is released immediately on infusion, unlike calcium gluconate, which requires liver metabolism to release the calcium.

• IV calcium antagonises the cardiac membrane excitability thereby protecting the heart against arrhythmias .

• It is effective within 3 minutes as shown by an improvement in the ECG appearance (e.g. narrowing of the QRS complex). The dose should be repeated if there is no effect within 5-10 minutes.

ECG on admission (a) and following 30ml 10% calcium gluconate IV (b) patient with serum K+ 9.3 mmol/L

STEP 2 – Shift K+ into cells

• Insulin-glucose infusion

• B2 agonist

• Sodium bicarbonate

Insulin-glucose infusion &salbutamol

• We recommend that insulin-glucose (10 units soluble insulin in 25g glucose) by intravenous infusion is used to treat severe (K+ ≥ 6.5 mmol/L) hyperkalaemia. (1B)

• We recommend nebulised salbutamol 10-20mg is used as adjuvant therapy for severe (K+ ≥ 6.5 mmol/L) hyperkalaemia. (1B)

• We recommend that salbutamol is not used as monotherapy in the treatment of severe hyperkalaemia. (1A)

• The efficacy of insulin-glucose is increased if given in combination with salbutamol. The peak K+ lowering effect with combination therapy at 60 minutes was found to be 1.2 mmol/L with nebulised beta-agonist therapy.

• Up to 40% of patients with ESRD do not respond to salbutamol, even in the absence of beta-blocker therapy, and the mechanism for this resistance is unknown.

• A frequent mistake when administering nebulizedβ2-adrenoceptor agonists is underdosage (salbutamol 10-20mg )

1 ml farcolin 6 mg salbutamol

So , at least 2 ml farcolin should be used

Sodium bicarbonate

• We suggest that intravenous sodium bicarbonate infusion is not used routinely for the acute treatment of hyperkalaemia. (2C)

• Do not use(NaHCO3) therapy unless the patient is frankly acidotic (pH <7.2) or unless substantial endogenous renal function is present.

STEP 3 – Remove K+ from body, resins (30-60 gm )

• We suggest that cation-exchange resins are not used in the emergency management of severe hyperkalaemia, but may be considered in patients with mild to moderate hyperkalaemia. (2B)

• multiple doses were required over several days with the effect on lowering the serum K+ noted over 1 to 5 days.

• These resins exchange sodium(Kayexalate) or calcium(resonium), respectively, for potassium in the GI tract to remove K . It can be administered orally or rectally as a retention enema.

• Constipation is common; therefore, resins are usually given in combination with a cathartic, (20% sorbitol).

• If given as an enema, sorbitol should be avoided, because rectal administration of cation exchange resins with sorbitol can cause colonic perforation

STEP 3 – Remove K+ from body, Hemodialysis

• Acute hemodialysis is the primary method of potassium removal when renal function is significantly impaired, either from AKI or advanced CKD, and severe hyperkalemia.

• Serum potassium can decrease as much as 1.2 to 1.5 mmol/h.

STEP 4 - Blood monitoring; serum K+

• We recommend that the serum K+ is monitored closely in all patients with hyperkalaemia to assess efficacy of treatment and look for rebound hyperkalaemia. (1B)

• We suggest that serum potassium be assessed at least 1, 2, 4, 6 and 24 hours after identification and treatment of hyperkalaemia. (2C)

STEP 4 - Blood monitoring; blood glucose

• We recommend that the blood glucose concentration is monitored at regular intervals (0, 15, 30, 60, 90, 120, 180, 240, 300, 360 minutes) for a minimum of 6 hours after administration of insulin-glucose infusion in all patients with hyperkalaemia. (1C)

Some Updates

Zirconium cyclosilicate(ZS-9)• ZS-9 exchanges both sodium and hydrogen

ions for potassium at intestine in CKD patients.

• Dose : 10- 15 gm Once daily.• S/E : no serious se reported but edema may

occur.• Neither trial evaluated the long-term

efficacy and safety of ZS-9, and neither studied patients with acute hyperkalemia or ESRD.

Patiromer• FDA approved October 2015and will be available

at January 2016• Patiromer binds potassium in the colon in

exchange for calcium in CKD patients.• Dose : 8.4 g once daily (maximum dose: 25.2 g/day).• S/E : Constipation (the commonest ),

Hypomagnesemia (Patiromer binds to magnesium in the colon)

• The effect of Patiromer in patients with acute hyperkalemia or ESRD was not evaluated

References

• Potassium and its disorders. Presentation of Prof. Essam Nour Eldin at acid base and electrolytes disturbance conference ,Cairo, October ,2014 .

• ANDREOLI AND CARPENTER ’ S CECIL ESSENTIALS OF MEDICINE , 8th edition,2010.

• COMPREHENSIVE CLINICAL NEPHROLOGY , 5th edition ,2015.

• Davidsons Principles and Practice of Medicine ,22nd edition ,2014.

References

• Uptodate , 2016.• CLINICAL PRACTICE GUIDELINES , TREATMENT OF

ACUTE HYPERKALAEMIA IN ADULTS , UK Renal Association ,2014 .