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POTASSIUM HOMEOSTASIS Mohammed Almeziny BsPharm R,Ph. Msc PhD Clinical Pharmacist Introduction POTASSIUM is required for neuromuscular tissues. intracellularly (98%). approximately 3500 mmol. 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 1-2 mmol/kg. (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. Clinical presentation Usually are asymptomatic between 3.5-3 mmol/l Malaise, weakness, fatigue and myalgia. Renal tubular disorders, myocardial excitability, and metabolic abnormalities (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. 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 Treatment and Prevention Correct coexisting magnesium depletion. Give potassium salts, primarily by the oral route. POTASSIUM CHLORIDE is the supplement of choice (Stanaszek & Romankiewicz, 1985; Beck et al, 1982). Intravenous indication Intravenous potassium chloride is indicated primarily when oral therapy is not feasible. Also indicated for the treatment of DIGITALIS-induced arrhythmias. (Cohen, 1979; McCarron, 1975). 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). 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). Potassium infusion I.V. order I.V fluid Rout of infusion Ward Concentration Peripheral Infusion rate / Central ECG monitoring mmol/L mmol/h Yes/no 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 Food, Standard Amount Potassium (mg) Calories Sweetpotato, baked, 1 potato (146 g) 694 131 Tomato paste, ¼ cup 664 54 Beet greens, cooked, ½ cup 655 19 Potato, baked, flesh, 1 potato (156 g) 610 145 White beans, canned, ½ cup 595 153 Yogurt, plain, non-fat, 8-oz container 579 127 Tomato puree, ½ cup 549 48 Clams, canned, 3 oz 534 126 Yogurt, plain, low-fat, 8-oz container 531 143 Prune juice, ¾ cup 136 530 Food, Standard Amount Potassium (mg) Calories Carrot juice, ¾ cup 517 71 Blackstrap molasses, 1 Tbsp 498 47 Halibut, cooked, 3 oz 490 119 Soybeans, green, cooked, ½ cup 485 127 Tuna, yellowfin, cooked, 3 oz 484 118 Lima beans, cooked, ½ cup 484 104 Winter squash, cooked, ½ cup 448 40 Soybeans, mature, cooked, ½ cup 443 149 Rockfish, Pacific, cooked, 3 oz 442 103 Cod, Pacific, cooked, 3 oz 439 89 Bananas, 1 medium 422 105 Food, Standard Amount Potassium (mg) Calories Spinach, cooked, ½ cup 419 21 Tomato juice, ¾ cup 417 31 Tomato sauce, ½ cup 405 39 Prunes, stewed, ½ cup 398 133 Peaches, dried, uncooked, ¼ cup 398 96 Pork chop, center loin, cooked, 3 oz 382 197 Milk, non-fat, 1 cup 382 83 Apricots, dried, uncooked, ¼ cup 378 78 Rainbow trout, farmed, cooked, 3 oz 375 144 Pork loin, center rib (roasts), lean, roasted, 3 oz 371 190 Food, Standard Amount Potassium (mg) Calories Buttermilk, cultured, low-fat, 1 cup 370 98 Cantaloupe, ¼ medium 368 47 1%-2% milk, 1 cup 366 102-122 Lentils, cooked, ½ cup 365 115 Honeydew melon, 1/8 medium 365 58 Kidney beans, cooked, ½ cup 358 112 Plantains, cooked, ½ cup slices 358 90 Split peas, cooked, ½ cup 355 116 Orange juice, ¾ cup 355 85 Yogurt, plain, whole milk, 8 oz container 352 138 Continuous Subcutaneous Infusion Effective in elderly patients who do not need acute potassium repletion. Monitoring Parameters 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). HYPERKALEMIA Introduction Hyperkalemia is a potentially lifethreatening 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 Some hospitals > 5mmol/L (Cox, 1981). Clinical Manifestation cardiac excitability, possibly progressing to ventricular fibrillation and asystole. 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. 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). Causes cont’d Pseudohyperkalemia: Improper blood collection (eg, ischemic blood draw from venipuncture technique) Laboratory error Leukocytosis Thrombocytosis. 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 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. Enhance the effects of the cardiac glycoside by causing arrhythmias SODIUM BICARBONATE Shift potassium intracellularly. Onset of action is within minutes and lasts approximately 15-30 min. Blood pH should be monitored to avoid excess alkalosis. 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. 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. SODIUM POLYSTYRENE SULFONATE SPS is a cation exchange resin. Onset 2-12 h, (longer when administered rectally). SORBITOL is added to combat the constipating effect of the cation-exchange resin (Gilman et al, 1990) Multiple doses of SPS are usually necessary. 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. 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 HEMODIALYSIS Peritoneal and hemodialysis are effective methods. Slow to be practical in treatment of acute poisoning. Patients who cannot tolerate fluids or have kidney dysfunction may benefit from dialysis (Ellenhorn & Barceloux, 1988). Summary Chronic Vs Acute Symptomatic Vs Asymptomatic Level Questions?