POTASSIUM HOMEOSTASIS

Mohammed Almeziny BsPharm R,Ph. Msc PhD

Consultant clinical Pharmacist

Introduction

POTASSIUM is required for neuromuscular

tissues.

Intracellularly (98%).

Approximately 3500 mmol.

45 to 55 mmol/kg and varies with

age, sex, muscle mass.

50 mmol is located in extracellular.

(Hak & Dunham, 1983; Scribner et al, 1956).

Protective effect of potassium

An antihypertensive effect.

Inhibitory effect on free radical formation.

Reduce the relative risk of stroke mortality.

Offer a protective effect on renal arterioles

Daily requirement

Infants: 2-6 mmol/kg/day

Children: 2-3 mmol/kg/day

Adults: 40-80 mmol/day

(1mmol =1mEq 39.1 mg)

HYPOKALEMIA

DEFINITION

Hypokalemia is defined as a serum

potassium concentration less than 3.5

mmol/L. Normal levels range from 3.5 to 5

mmol/L

(Young & Koda-Kimble, 1988)

CAUSES

The most common cause of hypokalemia is drug therapy.

Shifting of potassium from extracellular to intracellular.

Reduction in potassium intake (Lindman, 1976; Lawson et al, 1979; Nardone et al, 1978;

AMA, 1983)

Blood pH effect

0.1 unit potassium of approximately 0.6 mmol/L;

0.1 unit corresponds to slightly less 0.6mmol/L.

Pseudohypokalemia

Leukemic patients whose leukocyte count ranges from 100,000 to 250,000 cells/µL.

The potassium in serum is taken up by the large number of leukemic cells when the blood specimen is allowed to stand at room temperature.

Clinical presentation

Usually are asymptomatic between 3.5-3 mmol/l

Malaise, weakness, fatigue and myalgia.

Renal tubular disorders, myocardial excitability, and metabolic abnormalities

The incidence of ventricular arrhythmia increases with the degree of hypokalemia.Rhabdomyolysis can occur below 2 mmol/L.

(AMA, 1983; Stanaszek & Romankiewicz, 1985)

Calculate adult K deficit in hypokalemia

1 mmol/L fall in serum potassium from 4 to 3 mmol/L =200 mmol.

< 3mmol/L, = 200 to 400 mmol for each 1 mmol/L

*After correct acid-base status of measured serum level.

Treatment and Prevention

Correct coexisting magnesium depletion.

The route of potassium administration depends on the acuity and severity of hypokalemia

Oral supplementation is usually preferred.

Parenteral potassium can be given as chloride, acetate, or phosphate.

POTASSIUM CHLORIDE is the supplement of choice

(Stanaszek & Romankiewicz, 1985; Beck et al, 1982).

Treatment and Prevention

For prevention of hypokalemia during diuretic therapyAdults: 20-40 mmol/day in 1-2 divided doses

Potassium repletion should be guided by close monitoring of serum concentrations and analysis of patient’s urine for potassium content to help assess the need for additional replacement.The potassium concentration should be monitored every 4 hours, more frequently in patients with severe potassium depletion or when a rapid infusion is given >10 mmol/L

Intravenous indication

The parenteral route is indicated for patients who cannot tolerate high dosages of oral potassium

Severe or symptomatic hypokalemia

Also indicated for the treatment of DIGITALIS-

induced arrhythmias.

(Cohen, 1979; McCarron, 1975).

June 1, 1998, Volume 55, Issue 11

Most hospitals removing KCl concentrate from patient units

, ISMP reports

Institute for Safe Medication Practices (ISMP).

JAMA / volume:280 (page: 1444)Promoting Patient Safety by Preventing Medical Error Lucian L. Leape, MD; et al October 28, 1998

Checklist

Independent verification.

Concentration calculations

Infusion rates

Correct line attachments.

WHO Collaborating Centre for Patient Safety Solutions, Control of Concentrated Electrolyte Solutions, Patient Safety Solutions, volume 1, solution 5, May 2007

INTRAVENOUS. POTASSIUM CHLORIDE MUST BE DILUTED BEFORE INFUSION.If serum potassium is > 2.5 mmol/L and neuromuscular and cardiac abnormalities are minimal (and renal function is not impaired),Concentrations not exceeding 40 mmol/L and at a rate of 10 to 15 mmol/hour. Doses should not exceed 100 to 300 mmol/day (AMA, 1983). The preferred diluents is sodium chloride

INTRAVENOUS. Cont’d

If serum potassium is < 2 mmol/L and muscle paralysis or cardiac abnormalities are present.

Concentrations not exceeding 60 mmol/L at a rate of 40 mmol/hour. Doses should not exceed 400 mmol/day (AMA, 1983).

Administration of potassium in high concentration should be given after strict evaluation.

Intravenous Rate of Administration

Should be kept within 10 to 20 mmol/hour. Frequent biochemical and ECG monitoring is necessary when rates >10 mmol/hour.The faster rates should be continued for only short periods of time

(Lawson, 1976; Lawson & Henry, 1977; van der Linde et al, 1977; Porter, 1976; Beeson et al, 1958; Schwartz, 1976; Dipiro et al, 1989).

Paediatrics dosing

Neonatal: Prevention of hypokalemia

Prevention of hypokalemia during diuretic therapy: 1-2 mmol/kg/day in 1-2 divided doses

Neonatal:Treatment of hypokalemia

Oral: 2-5 mmol/kg/day in divided doses; not to exceed 1-2 mmol/kg as a single dose.

If deficits are severe or ongoing losses are great, I.V. route should be considered preferred route of administration

Neonatal:Treatment of hypokalemia cont’d

Intermittent I.V. infusion): 0.5-1 mmol/kg/dose

Infuse at 0.3-0.5 mmol/kg/hour (maximum dose/rate: 1 mmol/kg/hour)

Repeated as needed based on frequently obtained lab values.

Severe depletion or ongoing losses may require >200% of normal daily limit needs

Prevention of hypokalemia

During diuretic therapyInfants and Children: 1-2 mmol/kg/day in 1-2 divided doses

Treatment of hypokalemia:

Infants and Children:Oral: 2-5 mmol/kg/day in divided doses; not to exceed 1-2 mmol/kg as a single dose

Treatment of hypokalemia: cont’d

Infants and Children:Intermittent I.V. infusion: 0.5-1 mmol/kg/dose (maximum dose: 40 mmol)

Infuse at 0.3-0.5 mmol/kg/hour (maximum dose/rate: 1 mmol/kg/hour)

Repeated as needed based on frequently obtained lab values;

Severe depletion or ongoing losses may require >200% of normal daily limit needs

Preparation and dispensing

I.V. Potassium intravenous preparations MUST BE DILUTED BEFORE ADMINISTRATION.

Mixing of potassium intravenous preparations is always the responsibility of Pharmacy I.V. section.

The additive port of the infusion bag should be held uppermost.

Preparation and dispensing cont’d

where potassium chloride solutions are prepared using potassium chloride ampoules, Potassium Chloride injection should be injected downwards into the bag the solution MUST be inverted at least 10 times to ensure potassium chloride is thoroughly mixed throughout the solution. Unshaken bags are prone to layering of added concentrate and are extremely hazardous.

Preparation and dispensing cont’d

Extra potassium MUST not be added to pre-mixed solutions containing potassium.

Potassium chloride ampoules MUST never be added to a hanging bag.

The preferred vehicle is normal saline

Dextrose solution should be avoided as the vehicle, unless is the patient has hypernatremia

glucose-induced insulin secretion will promote intracellular potassium uptake

Administration

Maximum recommended concentration (peripheral line): 80 mmol/L

Maximum recommended concentration (central line): 150 mmol/L

In severely fluid-restricted patients (with central lines): 200 mmol/L some studies 400 mmol/L

Monitoring

Continued therapy should be guided by clinical assessments plus potassium levels. Since potassium is an intracellular cation, the potassium level should be checked after one hour of stopping infusion or maximum within 12 hours of starting therapy.

Serum potassium level (s) shall be monitored every 24 hours for all patients receiving IV potassium supplements

Monitoring cont’d

In case of severe hypokalemia less than or equal 2.5 mmol/L baseline ECG is advisable.

ECG monitoring is required in children if the rate of infusion is 0.5mmol/kg per hour or greater

Continuous ECG monitoring should be used for intermittent doses >0.5 mmol/kg/hour.

Potassium infusion I.V. order

I.V fluid Concentration mmol/L

Rout of infusion

Peripheral/ Central

Infusion rate mmol/h

Ward ECG monitoring Yes/no

Standardisation

Standardisation

Without consistency there can be NO Quality

Non standardisation is a prime reason for waste

Reasons of non standardisation in IVWork practices not standardised (Potassium chloride)

Everyone uses their discretion

No predictability

Standardised Work

The current one best way to safely complete an activity with the proper outcome and the highest quality, using the fewest possible resources.

It is not absolute but the basis for kaizen (改善 ) (continuous improvement).

Standardised Work cont’d

One of the best strategy to reduce errors in addition it help to reduce the work load.

All standardised work must benefit the patients, nurses, physicians, other team members and the institute.

The advantages of premixed I.V. admixtures

preparation-time savings,

Assurance of properly reconstituted drugs,

Lengthy expiration dating,

Appropriate labelling.

Increased health care professional participation in direct patient care

Providing safe, effective and high-quality patient care.

Standardised Work cont’d

Premixed preparations

Batch preparations in PSMMC pharmacy.

20 mEq/L Potassium Chloride in 0.45% Sodium Chloride Injection, USP20 mEq/L Potassium Chloride in 0.9% Sodium Chloride Injection, USP40 mEq/L Potassium Chloride in 0.9% Sodium Chloride Injection, USP10 mEq/L Potassium Chloride in 5% Dextrose Injection, USP20 mEq/L Potassium Chloride in 5% Dextrose Injection, US20 mEq/L Potassium Chloride in 5% Dextrose and 0.2% Sodium Chloride Injection, USP20 mEq/L Potassium Chloride in 5% Dextrose and 0.45% Sodium Chloride Injection, USP30 mEq/L Potassium Chloride in 5% Dextrose and 0.45% Sodium Chloride Injection, USP40 mEq/L Potassium Chloride in 5% Dextrose and 0.45% Sodium Chloride Injection, USP10 mEq/L Potassium Chloride in 5% Dextrose and 0.45% Sodium Chloride Injection, USP40 mEq/L Potassium Chloride in 5% Dextrose and 0.9% Sodium Chloride Injection, USP20 mEq/L Potassium Chloride in 5% Dextrose and 0.9% Sodium Chloride Injection, USP, 1000 mL VIAFLEX Plastic Container

20 mEq/L Potassium Chloride in Lactated Ringer's and 5% Dextrose Injection, USP, VIAFLEX Plastic Container, 1000mLHighly Concentrated Potassium Chloride Injection, 10 mEq/ 50 mL, VIAFLEX Plus Container

ICUHighly Concentrated Potassium Chloride Injection. 20 mEq/50 mL, VIAFLEX Plus ContainerHighly Concentrated Potassium Chloride Injection, 40 mEq/100 mL, VIAFLEX Plus ContainerHighly Concentrated Potassium Chloride Injection, 10 mEq/100 mL, VIAFLEX Plus ContainerHighly Concentrated Potassium Chloride Injection, 20 mEq/100 mL VIAFLEX Plus Container

ORAL

Liquid, enteric-coated, and slow release preparation.Slow release:

1) Sugar-coated (slow-K) or film coated (K-Tab) tablets;

2) KCL incorporated into wax matrix, controlled release tablets (K-Dur)

3) A gelatin capsule containing microencapsulated KCL crystals that are coated with a water polymer

Monitoring for oral

Should be monitored at least every two weeks in ambulatory patients with mild deficiencies and in patients requiring prophylactic.

After a pattern is established, monitoring every 3 to 6 months is adequate (Stanaszek & Romankiewicz, 1985).

Dietary intake

Dietary intake alone will not induce hyperkalemia unless renal excretion is impaired.

Usually, the GFR must be less than 10 to 15 mL/minute

Unless there is concurrent hypoaldosteronism or distal tubular potassium secretory defects.

Food, Standard Amount Potassium

(mg) Potassium

mmol Calories

Sweetpotato, baked, 1 potato (146 g) 694 17.75 131

Tomato paste, ¼ cup 664 16.98 54

Beet greens, cooked, ½ cup 655 16.75 19

Potato, baked, flesh, 1 potato (156 g) 610 15.60 145

White beans, canned, ½ cup 595 15.22 153

Yogurt, plain, non-fat, 8-oz container 579 14.81 127

Tomato puree, ½ cup 549 14.04 48

Clams, canned, 3 oz 534 13.66 126

Yogurt, plain, low-fat, 8-oz container 531 13.58 143

Prune juice, ¾ cup 530 13.55 136

Food, Standard Amount Potassium

(mg) Potassium

mmol Calories

Carrot juice, ¾ cup 517 13.22 71

Blackstrap molasses, 1 Tbsp 498 12.74 47

Halibut, cooked, 3 oz 490 12.53 119

Soybeans, green, cooked, ½ cup 485 12.40 127

Tuna, yellowfin, cooked, 3 oz 484 12.38 118

Lima beans, cooked, ½ cup 484 12.38 104

Winter squash, cooked, ½ cup 448 11.46 40

Soybeans, mature, cooked, ½ cup 443 11.33 149

Rockfish, Pacific, cooked, 3 oz 442 11.30 103

Cod, Pacific, cooked, 3 oz 439 11.23 89

Bananas, 1 medium 422 10.79 105

Food, Standard Amount Potassium

(mg) Potassium

mmol Calories

Spinach, cooked, ½ cup 419 10.72 21

Tomato juice, ¾ cup 417 10.66 31

Tomato sauce, ½ cup 405 10.36 39

Prunes, stewed, ½ cup 398 10.18 133

Peaches, dried, uncooked, ¼ cup 398 10.18 96

Pork chop, center loin, cooked, 3 oz 382 9.77 197

Milk, non-fat, 1 cup 382 9.77 83

Apricots, dried, uncooked, ¼ cup 378 9.67 78

Rainbow trout, farmed, cooked, 3 oz 375 9.59 144

Food, Standard Amount Potassium

(mg) Potassium

mmol Calories

Buttermilk, cultured, low-fat, 1 cup 370 9.46 98

Cantaloupe, ¼ medium 368 9.41 47

1%-2% milk, 1 cup 366 9.36 102-122

Lentils, cooked, ½ cup 365 9.34 115

Honeydew melon, 1/8 medium 365 9.34 58

Kidney beans, cooked, ½ cup 358 9.16 112

Plantains, cooked, ½ cup slices 358 9.16 90

Split peas, cooked, ½ cup 355 9.08 116

Orange juice, ¾ cup 355 9.08 85

Yogurt, plain, whole milk, 8 oz container 352 9.00 138

HYPERKALEMIA

Introduction

Hyperkalemia is a potentially life-

threatening illness, which can be

difficult to diagnose clinically because of

paucity of reliable signs and symptoms.

Definition

Hyperkalemia is defined as a serum potassium concentration greater than 5.5 mmol/L

(Cox, 1981).

Clinical Manifestation

Cardiac excitability, possibly progressing to

ventricular fibrillation and asystole.

Coexisting hyponatremia, hypocalcemia, and

hypomagnesemia all reduce the threshold

potential, thereby increasing the patient’s

susceptibility to the cardiac effects of

hyperkalemia.

Mortality/Morbidity

Reported death rates rate range up to 67% if

severe hyperkalemia is untreated.

Gender: Male = Female

Causes Decreased or impaired potassium excretion.

Acute or chronic renal failure (most common).Potassium sparing diuretics.Urinary obstruction. Sickle cell disease. Addison disease (chronic adrenal

insufficiency).Systemic lupus erythematosus (SLE).

Causes cont’d

Additions of potassium into extracellular space:

potassium supplements (eg, PO/IV

rhabdomyolysis,

hemolysis (eg, venipuncture, blood transfusions,

burns, tumor lysis).

Causes cont’d

Transmembrane shifts

Acidosis.

Medication effects (eg, acute digitalis

toxicity, beta-blockers, succinylcholine).

Elevating the plasma tonicity by 15 to 20

mOsm/kg will increase the plasma

potassium concentration by 0.8 mmol/L

Causes cont’d

Pseudohyperkalemia: Improper blood collection (eg, ischemic

blood draw from venipuncture technique)Laboratory errorLeukocytosisThrombocytosis.

Classification of Hyperkalemia

Serum sodium is usually decreased, and acidosis is usually present.

The relationship between serum potassium and symptoms is not consistent.

Classification of Hyperkalemia cont’d

MINIMAL TOXICITY - < 6.5 mmol/L. MODERATE TOXICITY - 6.5-8 mmol/L give lassitude, fatigue, and weakness.SEVERE TOXICITY - >8 mmol/L, complete neuromuscular paralysis may dominate the clinical picture. Death from cardiac arrest occurs usually at 10 to 12 mmol/L. It may occur at lower levels if cellular potassium is severely depleted.

Treatment

Urgency of therapy depends on EKG findings and level of serum potassium.

If serum K is greater than 8 mmol/L. If the EKG shows the changes of

hyperkalemia.If the patient is extremely symptomatic.

Goal of therapy

Stabilizing the myocardium.The cardiac toxicity of hyperkalemia is a major cause of morbidity and mortality,

Shifting potassium from the extracellular to the intracellular compartment.

Promoting the renal excretion and GI loss of potassium.

Calcium

The first drug to be used for severe hyperkalemia (> 7.0 mmol/L) when the ECG also manifests significant abnormalities.

Antagonizes cardiac toxicity.

onset < 5 min and lasts 30-60 min.

Calcium chloride is the preferred salt.

Calcium chloride is very irritating, and should only be given via a central venous catheter.

CALCIUM cont’d

Dose of 10 to 20 mL of 10% calcium gluconate IV over the course of 1 to 3 minutes =(2.32 mmol)

10 gram (100ml) calcium gluconate = 930 mg elemental calcium = 46.50 mEq =  23.25 mmol.

CALCIUM cont’d

The dose can be repeated in 5 minutes if ECG changes do not resolve and as needed afterward for recurrence.

With no response after the second dose, additional attempts, however, are not beneficial..

Enhance the effects of the cardiac glycoside by causing arrhythmias.

SODIUM BICARBONATE

Shift potassium intracellularly.

Its efficacy in this setting has been questioned.

The usual dose, 44 to 50 mmol, is infused slowly over the course of 5 minutes and repeated in 30 minutes when necessary.

Blood pH should be monitored to avoid excess alkalosis.

May be beneficial in patients with severe metabolic acidosis (pH <7.20).

SODIUM BICARBONATE cont’d

Onset of action is within minutes and lasts approximately 15-30 min.

The hypokalemic effect is variable and may be delayed up to 4 hours,

It is reportedly ineffective in patients on maintenance hemodialysis.

INSULIN/DEXTROSE

Enhances intracellular potassium shift.

This regimen will lower serum potassium by 1 to 2 mmol/L within 30 to 60 minutes with the decrease lasting for several hours (Saxena, 1989).

ADULT DOSE

Administer 25 g of dextrose (250 ml of a 10% solution) I.V + 10 units of regular insulin over 30 minutes, and then continue the infusion at a slower rate. (Saxena, 1989).

Or, 50 ml of a 50% dextrose solution with 5 to 10 units of regular insulin may be administered I.V over 5 minutes.

If the serum glucose is more than15mmol/l glucose administration with insulin is not required

PEDIATRIC DOSE

0.5 to 1 g/kg/dose followed by 1 unit of regular insulin intravenously for every 4 grams of glucose infused; may repeat every 10 to 30 minutes (Barkin, 1986).

HYPEROSMOLARITY

It must be remembered that 50% dextrose (2525 mOsm/L) , and even 25% dextrose (1330 mOsm/L) , are very hyperosmolar and may be sclerosing to peripheral veins (Chameides, 1988).

Peripheral veins can tolerate up to (900 mOsm/L).

Administration of hypertonic solutions via central lines is preferred, if possible.

Calcium Polystyrene Sulphonate Powder “Calcium Resonium”

Onset of action: May be delayed 2-3 days due to GI transit time

Absorption: None

Excretion: Feces (100%)

Patient information:Take a laxative, drink plenty of water and increase intake of fibrous food to prevent constipation.

Calcium Polystyrene Sulphonate Powder “Calcium Resonium”

Treatment Initiation

if potassium level >6 mmol/L discontinue when potassium ≤5 mmol/L

Dose AdultsGeriatric

Oral administration: 15g once to four times daily as a slurry in waterRectal route: Single dose of 30g as a warm emulsion up to four times daily

Small children and infants

The practical exchange ratio of 1 mmol/L potassium/g of resin as the basis for calculation.

Calcium Polystyrene Sulphonate Powder “Calcium Resonium”

Children Oral (preferred route): Initial: 1 g/kg/day in divided doses; Maintenance: May reduce dose to 0.5 g/kg/day in divided dosesRectal: Initial: 1 g/kg/day in divided doses; Maintenance: May reduce dose to 0.5 g/kg/day in divided doses

Neonates: Rectal: 0.5-1 g/kg/dose

BETA-2-AGONIST

Appears to be a safe and reasonably effective means of treatment while waiting for dialysis or other potassium removing therapies to be initiated.

20 mg dissolved in 4 mL of saline over 10 minutes

Use with caution in hyperthyroidism, diabetes mellitus, or cardiovascular disorders.

Diuretics

Effects of diuretics are slow and frequently take an hour to begin.

Avoid use in patients with anuria

DIALYSIS

Peritoneal and hemodialysis are effective methods.

Slow to be practical in treatment of acute poisoning.

Dialysis with a glucose-free dialysate will remove 30% more potassium than one containing 200 mg/dL of glucose.

Patients who cannot tolerate fluids or have kidney dysfunction may benefit from dialysis (Ellenhorn & Barceloux, 1988).

Summary

Chronic Vs Acute

Symptomatic Vs Asymptomatic

Level

Summary of Treatment of Hyperkalemia

Questions?