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THERAPEUTICS I FALL 2003FLUID/ELECTROLYTE BALANCE

Jack Burke, Pharm.D., BCPS

Required Reading: Joy MS, Hladik GA. Disorders of Sodium, water, calcium and phosphorous homeostasis. In: DiPiro JT, et al. Pharmacotherapy: A Pathophysiologic Approach. 5 ed. , 953-62th

Ability Outcomes

1. Assess a patient’s volume status and serum sodium concentration

2. Evaluate the appropriateness of patient-specific drug therapy (including fluids) for a patient’s fluid balance,and modify therapy as necessary.

3. Select/recommend appropriate drug therapy for patients requiring IV fluid for maintenance fluid orcorrection of hypovolemia or hypernatremia.

4. Monitor for expected efficacy, toxicity, and adverse effects associated with chosen IV fluid therapy.

Content Questions

1. Describe the % distribution of fluid in the various body compartments

2. Explain the factors which influence movement of fluid between the compartments.

3. What is the normal range (including units) for: serum sodium, serum potassium, serum chloride, CO 2content, calcium, inorganic phosphate, BUN, serum creatinine, Plasma Osmolality,

4. Explain what serum sodium represents and the significance of any changes.

5. Calculate fractional excretion of sodium and explain its significance.

6. Given a serum sodium concentration, BUN, and serum glucose concentration, calculate plasma osmolality.

7. Calculate basal fluid requirements for a patient based on body weight.

8. Identify clinical manifestations (symptoms, physical findings and laboratory data) that are consistent withhypovolemia.

9. Explain how an elevation in blood glucose can effect serum sodium concentration and serum osmolality

10. List potential causes of hypernatremia.

11. Explain the significance of a free water deficit and be able to calculate it based on patient-specific data.

12. List the clinical manifestations associated with hypernatremia.

13. What is the desired rate for correction of serum sodium concentration (in mEq/L per hour)?

14. Explain why too rapid correction of hypernatremia can result in serious neurologic sequelae.

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15. Explain why normal saline is preferred over Dextrose 5% in water (D5W) in the initial treatment ofhypovolemia.

16. Explain how the following IV fluids will distribute throughout the fluid compartments of the body: Normalsaline, ½ normal saline, D5W, Ringers solution, lactated ringers

Identify/Collect Data

Brainstorm Possible Solutions

Reflection/Evaluation of the ProblemDoes the solution answer the problemIs the solution the best possible: consider patient factors, acuity of problem

PMH, Meds, h/o fluid intake, weight (changes), BP, +/- JVD, ralesedema, sodium, glucose, BUN, Urine lytes, I/O; TG, Protein

Categorize/Organize DataCategorize data as Subjective or Objective;Organize according to history, physical findings, laboratory data

Interpret DataFilter relevant from irrelevant data: Identify normal/abnormal dataPerform needed calculations: Wt loss/gain, CrCl, FeNa, Sosm

Is the Problem solvable?: reversible cause vs manageable problem; Rx unnecessary; preventionList criteria for solution: aggressive vs conservative; PO vs IV; cost constraintsCompare to other problems:List possible Solutions: non-drug (change fluid intake); change current therapy; add new therapy

Assess Medical ProblemsIdentifies complete problem listDetermines etiology and risk factors of problem(s)Assess status of problem(s)Relates pathophysiology to the clinical presentation

Evaluate for Drug-Related ProblemsDetermines appropriateness of drug use and regimenIdentifies untreated medical problemsDetermines efficacy of current therapyRecognizes the presence of adverse drug effectsAssesses compliance

Re-Analysis of Data for Solving Problem

Select/Recommend TherapyPlan for existing therapyAddition of new drug therapyJustifies decisions based on analysis of dataIdentifies clinical end-points

Monitors for expected efficacy and potential adverse effectsIdentifies goals of therapyIdentifies problem-specific parameters to assess improvementIdentifies drug-specific parameters to assess for possible ADR’sIdentifies additional data needed

AnalysisQuestion Validity, Accuracy, or consistency of dataRelate data and define patterns: Acute vs ChronicIntegrate information by interpreting relationships/patternsRecognize Assumptions: Identify missing or incomplete dataDevelop a differential of problems: Iso-/hypo-/hyper-tonic hypo-/iso-/hyper-volemic; hypo-/hyper-natremia vs normal sodium

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Extracellular fluid Intracellular Fluid

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DISORDERS OF SODIUM/WATER HOMEOSTASIS

I. INTRODUCTION

A. Body Fluid Distribution

B. Assessing Fluid/Electrolyte Balance

1. Determining Basal Fluid Requirementsa. based on weight

0-10 kg: 100 ml/kg10-20 kg: 1000 ml + 50 ml/kg x (Wt - 10)> 20 kg: 1500 ml + 20 ml/kg x (Wt - 20)

b. based on BSA: 1500 ml/m2

Basal Fluid Requirements:

Estimate the daily fluid requirements for a euvolemic patient with a body weight of 70 kg.

2. Monitoring Fluid Statusa. Symptoms: dry mouth, edema, changes in urine outputb. Physical Findings: weight (changes); temperature

blood pressure (orthostatic changes); heart rate mucous membranes (moist vs dry); jugular venous distension (presence/absence) pulmonary exam: rales; edema: (presence/absence)

c. Laboratory: electrolytes; BUN, serum creatinine; serum osmolalityUrine osmolalityurine electrolytes (U , FeNa)Na

FeNa = (Urine Na)/(Urine Cr) x 100

(Serum Na)/(Serum Cr)

d. Sensible Losses: Intake/Output; urine outpute. Insensible losses: 500-1000 ml/dayf. Parameters: intake/output; weight

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Calculating fractional excretion of sodium

1. Calculate the Fractional Excretion of Sodium (FeNa) for a 96 year-old female with a history of congestiveheart failure and aggressive diuretic therapy. Urine sodium: 11 mEq/l; serum sodium 140 mEq/l; Urinecreatinine 13.6 mg/dl; serum creatinine 2.1 mg/dl.

3. Calculating plasma osmolality

Osmolality (mOsm/kg) = 2*[Na ] + [BUN/2.8] + [glucose/18]+

Calculate the serum osmolality for a patient with a serum sodium of 135 mEq/l, BUN of 12 mg/dl,and plasma glucose of 90 mg/dl.

II. Intravenous fluids

A. Choice of IV fluids

Fluid Sodium Chloride Potassium Calcium Lactate Osmolality free (mEq/l) (mEq/l) (mEq/l) (mOsm/l) water

content

0.9% NaCl 154 154 ----- ----- ----- 308 0%(Normal Saline)

0.45% NaCl 77 77 ----- ----- ----- 154 50%½ NS

0.225% NaCl 38.5 38.5 ---- ----- ----- 77 75%¼ NS

D5W ----- ----- ---- ----- ---- 250 100%Dextrose 5%

Ringers Solution 147 155 4 4 ----- 310 5%

Lactated Ringers 130 105 4 3 28 275 15%(LR)

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B. Distribution of IV Fluids: Based on sodium content

Choice of IV fluid is based on the osmolality created by the sodium content which will influencehow the fluid administered will distribute throughout the body space.

QUESTION:WHICH PERCENTAGE OF THE FLUID ADMINISTERED WOULD YOU EXPECT TO STAY IN THEEXTRA-CELLULAR SPACE?

a. Normal Saline: _________%b. ½ Normal Saline _________%c. ¼ Normal Saline _________%d. D5W _________%e. Ringers Soln _________%f. LR _________%

QUESTION:SOME SOLUTIONS ARE AVAILABLE WITH DEXTROSE IN ADDITION TO THE SODIUMCHLORIDE. HOW WOULD YOU EXPECT THAT TO CHANGE THE DISTRIBUTION OF THEFLUID?

C. Providing basal fluid requirements with intravenous fluids

1. Choice of Fluids0.45% sodium chloride (½NS) Dextrose 5%/ 0.45%sodium chloride (D5½NS)0.45% sodium chloride (¼NS)Dextrose 5%/0.225% sodium chloride (D5 ¼NS)

Rationale for choice:

2. IV fluid rate:ml/hr = Basal fluid requirements/ 24 hours

3. Additives:Potassium chloride: 20 mEq per liter IV fluid (if patient has normal serum potassium)

A 55 year-old male (height 6'0", weight: 78 kg) is admitted to the hospital for cholecystectomy and will be NPOperioperatively. He is currently euvolemic and has no other chronic medical problems. Recommend acontinuous IV fluid regimen for him to meet his basal fluid requirements. This should include: type of fluid,any additives, IV administration rate.

IV fluid:_____________________ with ___________ mEq/L infused at _________________ml/hour

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D. Correction of Hypovolemia (With normal serum sodium concentration)

1. Choice of initial IV fluidsNormal SalineLactated RingersRinger’s solution

2. IV fluid rate

Severe Hypovolemia: 500-1000 ml/hr until hemodynamically stable, followed by a lowerrate

Moderate Hypovolemia: 2-3 times maintenance fluid requirements

Mild Hypovolemia: 1-2 times maintenance fluid requirements

Large volume IV fluids that are used for fluid administration rather than as a vehicle for drugadministration are primarily available in liter bags. However, rates of administration are usually definedin ml/hr. Rates of administration can vary for IV fluids. Rates may be as low as KVO (keep vein open)or TKO (to keep open) which is a rate of approximately 20-30 ml/hr. But for rapid fluid replacement,IV fluid may be administered via a large vein at 500-1000 ml/hr. Rates this fast are usually done for ashort period of time (< 1-2 hrs) until the patient is hemodynamically stable.

QUESTION: IF YOU DETERMINE A PATIENT’S MAINTENANCE FLUID REQUIREMENT IS 2000 ML/DAY,HOW FAST (ML/HR) WOULD YOU HAVE TO ADMINISTER THE IV FLUIDS TO MEET THOSE NEEDS?

HOW WOULD YOU ADJUST THAT RATE IF THE PATIENT WAS VOLUME DEPLETED (HYPOVOLEMIC)?

HOW WOULD YOU ADJUST THAT RATE IF THE PATIENT WAS VOLUME OVERLOADED?

IF 20 MEQ OF KCL IS ADDED TO EACH LITER OF IV FLUID, HOW MUCH K WOULD THE PATIENTRECEIVE PER DAY?

III. Hypernatremia

A. Development of hypernatremia

HYPERVOLEMICHYPERNATREMIA

DETERMINE SERUM OSMOLALITY

ASSESS VOLUME STATUS

HYPOVOLEMICHYPERNATREMIA

EUVOLEMICHYPERNATREMIA

Renal lossesdiureticsglucosuriaARF/CRFpartial post-renal obst

Adrenal insufficiencyGI lossesResp lossesInsensible loss

Diabetes insipidus Renal FailureIatrogenicMineralocorticoid excess

HYPERVOLEMICHYPERNATREMIA

DETERMINE SERUM OSMOLALITY

ASSESS VOLUME STATUS

HYPOVOLEMICHYPERNATREMIA

EUVOLEMICHYPERNATREMIA

HYPERVOLEMICHYPERNATREMIA

DETERMINE SERUM OSMOLALITY

ASSESS VOLUME STATUS

HYPOVOLEMICHYPERNATREMIA

EUVOLEMICHYPERNATREMIA

DETERMINE SERUM OSMOLALITY

ASSESS VOLUME STATUS

HYPOVOLEMICHYPERNATREMIA

EUVOLEMICHYPERNATREMIA

Renal lossesdiureticsglucosuriaARF/CRFpartial post-renal obst

Adrenal insufficiencyGI lossesResp lossesInsensible loss

Diabetes insipidus Renal FailureIatrogenicMineralocorticoid excess

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B. Assessment of the patient with hypernatremia

C. Clinical Manifestations

1. CNS dysfunction: restlessness, irritability, tremulousness, spasticity, hyperreflexia, ataxia,seizures, coma, death

2. Polyuria in diabetes insipidus

3. Polydipsia

4. Severity of clinical manifestations is related to the severity of hypernatremia and the rate ofdevelopment.

5. Urine osmolality: variable, based on cause of hypernatremia

6. Volume status: variable, based on cause

NormalBrainNormalosmolality

Water Loss

Highosmolality

Accumulationof electrolytes

Highosmolality

Accumulationof organicosmoles

CerebralEdema

Immediate effect ofhypertonic state

RapidAdaptation

SlowAdaptationRapid

correction ofhypertonicity

Slow Correctionof hypertonicity

water

Adrogue HJ. N Engl J Med 2000; 342: 1493-9.

ECF Volume

Low Normal/increased

Uvol < 3 l/day Uvol > 3 l/day

Uosm > 450 Uosm

> 300

Postural Hypotension

Na/H20 depletion 1º H20depletion

Uvol > 3 l/day

Uosm < 250 Uosm > 300

Osmotic diuresisDI

Responseto ADH

CentralDI

NephrogenicDI

yes noyes no

Osmoticdiuresis

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D. PATHOPHYSIOLOGY

E. ASSESSMENT

Severity of Hypovolemia

2 Normal Saline Normal Saline

Persistent Hypernatremia

¼ Normal SalineDextrose 5% in Water

SevereMild/Mod

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F. TREATMENT OF HYPOVOLEMIC HYPERNATREMIA: ECF volume depletion; losses of sodium and water

1. Goals: Extracellular volume expansionReplace free water deficit

2. Choice of IV Fluids

a. Rate of AdministrationDesired rate of correction of hypernatremia = 0.5 mEq/l/hour

G. Replacement of Free Water

1. Choice of IV Fluids Free water contentDextrose 5% in Water 100%¼ Normal saline 75%½ normal saline 50%

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2. Calculation of free water deficit

NOTE: FREE WATER DEFICIT is a measure of the volume of water lost relative to sodium isotonically.In other words, how much water would have to be replaced in order to decrease the serum sodiumconcentration to 140 mEq/l. It does NOT measure volume deficit. Patients with hypernatremia willhave a free water deficit regardless of whether or not they are hypovolemic, isovolemic, orhypervolemic. It should only be used in the assessment of patients with hypernatremia and NOT patientswith hyponatremia or a normal serum sodium concentration.

H O deficit (liters) = (Weight)(%TBW)(serum Na - 1)2140

% TBW = 0.6 l/kg for children and men < 70 yrs= 0.5 l/kg for men > 70 yrs and females < 70 yrs= 0.45 l/kg for females > 70 yrs

3. Replacement of free water is based on the calculated deficit and the free water content of thefluid, and the desired rate of correction of the deficit.

Rate = (Free water deficit in ml) = _______ ml/hour(Desired time of correction)(free water content)

Free Water deficit CalculationCalculate the free water deficit for a 75 year-old male (weight 60 kg) with a serum sodium of 160 mEq/l.

How fast would you have to infuse each of the following IV fluids to provide enough free water to replace thisdeficit over 40 hours?

Dextrose 5% in Water:

½ normal saline

¼ normal saline

Dextrose 5%/ 0.45% sodium chloride

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DISORDERS OF POTASSIUM BALANCEJack Burke, Pharm.D.

Reading Assignment: Brophy DF, Gehr TWB. Disorders of potassium and magnesium homeostasis. In:Dipiro JT, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 5 edition. pp. th

981-93.

Cohn JN, Kowey PR, Whelton PK, Prisant M. New guidelines for potassiumreplacement in Clinical Practice: A contemporary review by the National Council onPotassium in Clinical Practice. Arch Intern Med 2000; 160: 2429-36.

ABILITY OUTCOMES

1. Assess a patient’s hypokalemia or hyperkalemia and current drug therapy.

2. Evaluate the appropriateness of patient-specific drug therapy for a patient’s hypokalemia or hyperkalemia, andmodify therapy as necessary.

3. Select/recommend appropriate drug therapy for patients with hypokalemia or hyperkalemia

4. Monitor for expected efficacy, toxicity, and adverse effects associated with chosen therapy for hypokalemia orhyperkalemia.

5. Educate patients and health professionals regarding drug therapy of hypo-/hyper-kalemia.

CONTENT QUESTIONS:

1. List the factors that influence serum potassium concentration and its distribution in the body.

2. Describe the effect that an elevation or decrease in serum potassium has on the resting membrane potential.

3. Describe the clinical manifestations associated with hypokalemia and hyperkalemia.

4. Based on serum potassium concentration, estimate the total degree of potassium depletion.

5. What is the recommended maximal rate of intravenous potassium administration without cardiac monitoring?With cardiac monitoring?

6. Explain why chloride is the preferred salt form for potassium replacement.

7. Describe the causes of hypokalemia and the mechanisms by which it develops.

8. Calculate transtubular potassium gradient and explain how it is used to distinguish the cause of hypokalemia andhyperkalemia.

9. List adjunctive therapies (in addition to potassium supplementation) that can be used to treat hypokalemia.

10. Describe the mechanism and duration of action of beta agonists, calcium, sodium bicarbonate,insulin/glucose, sodium polystyrene sulfonate in the treatment of hyperkalemia.

Identify/Collect Data

Reflection/Evaluation of the ProblemDoes the solution answer the problemIs the solution the best possible: consider patient factors, acuity of problem

PMH, Meds, Serum K, Serum Mg, HCO3, ABG’s, BUN, S.Cr, EKG

Categorize/Organize DataCategorize data as Subjective or Objective;Organize according to history, physical findings, laboratory data

Interpret DataFilter relevant from irrelevant data: Identify normal/abnormal dataPerform needed calculations: CrCl

Brainstorm Possible SolutionsIs the Problem solvable?: reversible cause vs manageable problem; Rx unnecessary; preventionList criteria for solution: aggressive vs conservative; PO vs IV; cost constraintsCompare to other problems:List possible Solutions: non-drug (change diet intake); change current therapy; add new therapy add/dec PO/IV supplement; add/del potassium sparing agent; add/del Mag; Treat hyperkalemia: Calcium, NaHCO3, insulin/dextrose, kayexalate, dialysis

Assess Medical ProblemsIdentifies complete problem listDetermines etiology and risk factors of problem(s)Assess status of problem(s)Relates pathophysiology to the clinical presentation

Evaluate for Drug-Related ProblemsDetermines appropriateness of drug use and regimenIdentifies untreated medical problemsDetermines efficacy of current therapyRecognizes the presence of adverse drug effectsAssesses compliance

Re-Analysis of Data for Solving Problem

Select/Recommend TherapyPlan for existing therapyAddition of new drug therapyJustifies decisions based on analysis of dataIdentifies clinical end-points

Monitors for expected efficacy and potential adverse effectsIdentifies goals of therapyIdentifies problem-specific parameters to assess improvementIdentifies drug-specific parameters to assess for possible ADR’sIdentifies additional data needed

AnalysisQuestion Validity, Accuracy, or consistency of dataRelate data and define patterns: Acute vs ChronicIntegrate information by interpreting relationships/patternsRecognize Assumptions: Identify missing or incomplete dataDevelop a differential of problems: Hypokalemia, Normal Potassium Balance, Hyperkalemia

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I. Potassium Physiology

A. Physiologic Functions of Potassium

1. Cellular Metabolism

2. Establishing resting membrane potential

E = -61 x logmr[K]c + 0.01[Na]c

r[K]e + 0.01[Na]e

3. Distribution of potassium

For each of the conditions below, draw a line (from the serum into the cell OR from the cell tothe serum) indicating which direction the condition will cause the potassium to move. Indicatethe mechanism.

Condition Serum Cell Mechanism

Increased insulin

Decreased insulin

Increased Epi/NE

Decreased pH

Increased pH

Increased Sosm

Decreased Sosm

II. Hypokalemia

A. Etiology

QUESTION: FOR EACH OF THE FOLLOWING CAUSES, DESCRIBE THE MECHANISM RESPONSIBLE FOR THEDEVELOPMENT OF HYPOKALEMIA.

Cause Mechanism1. Beta-agonists (albuterol)

2. Theophylline

3. Insulin

4. Diuretics (HCTZ, furosemide)

5. High dose penicillins

ProminentU Wave

BiphasicT wave

ST depression

ProminentU Wave

BiphasicT wave

ST depression

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6. Mineralocorticoids

7. Aminoglycosides

8. Amphoterecin-B

9. Cis-platinum

10. Sodium polystyrene sulfonate

11. Sorbitol

12. Diarrhea

13. Vomiting/NG suction

14. Hypomagnesemia

15. Metabolic alkalosis

B. Renal Handling of Potassium

1. Trans-tubular potassium gradient (TTKG)

TTKG =[K ]urine/(Uosm/Sosm)+

[K ]+serum

Normal: 6-8 mEq/L

C. Clinical ManifestationsQUESTION: WHAT ARE COMMON CLINICAL MANIFESTATIONS ASSOCIATED WITH HYPOKALEMIA?

Cardiovascular effects

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Muscular effectsWeaknessMyalgiasCrampsParalysisRhabdomyolysis

Metabolic effectsAbnormal carbohydrate metabolismHypomagnesemiaHypercalcemiaHyperlipidemiaAchlohydria

Renal effectsNephrogenic diabetes insipidusDecreased protein synthesisNegative nitrogen balanceIncreased ammonia production by kidneys

II. Selecting/Recommending Therapy for the treatment of hypokalemia

A. Estimate the extent of deficit

QUESTION: WHY IS THE SERUM POTASSIUM CONCENTRATION AN IMPRECISE MEASURE OF TOTALBODY POTASSIUM?

HOW DOES THIS INFLUENCE YOUR ESTIMATE OF NEED FOR SUPPLEMENTATION?

1 MEQ/L DECREASE IN SERUM POTASSIUM REPRESENTS AN AVERAGE POTASSIUM DEFICIT OF ________MEQ

B. Choice of salt form

Potassium bicarbonate (K-lyte effervescent tabs; Klor-con/EF): 6.5 mEq; 25 mEq

Potassium chloride Capsules, ER: (Micro-K): 8 mEq, 10 mEqFor Solution: (K-lor, Kay Ciel, Klor-Con): 20 mEq per packetSolution: (Kaochlor, Kay Ciel) 10% = 6.7 mEq/ 5 ml

(Kaon-Cl) 20% = 13.3 mEq/ 5 mlTablets: (Slow-K, Kaon-Cl, K-Dur, K-Tab): 8, 10, 20 mEq

QUESTION: Why is the chloride salt the preferred salt form for potassium supplementation

[K+]

3.5-4.0mEq/L

Salt subsitutesDietary sources

3-3.5mEq/L

?Cardiacdisease

none 40-100mEq20 mEq/day

For prevention

2.5-3.0mEq/L

?Symptoms

PO IV

no yes

< 2.5mEq/L

IV

intolerant

[K+]

3.5-4.0mEq/L

Salt subsitutesDietary sources

3-3.5mEq/L

?Cardiacdisease

none 40-100mEq20 mEq/day

For prevention

2.5-3.0mEq/L

?Symptoms

PO IV

no yes

< 2.5mEq/L

IV

intolerant

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C. Dosing and Administration

C. Oral supplementation

D. Intravenous supplementation

IV supplementation of potassium can occur as an additive to large volume IV fluids or as a separate IV infusionof a smaller fluid volume. For most cases of mild to moderate hypokalemia, potassium (usually as the chloridesalt) is added to liter bags of IV fluid already being administered if not administered orally. So doses are definedin terms of ____mEq of KCl to be added to each liter of IV fluid. The dose is then determined by both theconcentration of potassium and the rate of IV fluid administration. In most cases, this will not exceed themaximum allowable rate.

For more severe hypokalemia, the potassium chloride dose is dissolved in 100-250 ml of IVF and administeredat a rate not to exceed the maximum rate discussed below.

QUESTION: ACCORDING TO DIPIRO’S TEXT, POTASSIUM CAN BE ADMINISTERED INTRAVENOUSLY AT ARATE OF _________MEQ/HR WITHOUT THE USE OF CONTINUOUS CARDIAC MONITORING.

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E. Adjunctive treatment

QUESTION: LIST 3 DRUGS WHICH CAN BE USEFUL ADJUNCTIVELY OR ALTERNATIVELY TO POTASSIUMSUPPLEMENTATION FOR THE TREATMENT OF HYPOKALEMIA.

1.

2.

3.

CASE DISCUSSION CASES

Develop a regimen to supplement potassium for each of the following patient circumstances:

a. Patient with chronic diuretic therapy for hypertension with a serum potassium of 3.2 mEq/L

b. Otherwise healthy patient with serum potassium of 3.6 mEq/L

c. Hospitalized patient who is NPO and receiving IV fluids. Serum potassium is 3.2 mEq/L

d. Patient with CHF receiving diuretic therapy admitted to hospital with serum potassium of 2.8 mEq/L

e. Hospitalized patient who has NG suction and found to have serum potassium of 2.2 mEq/L

III. Hyperkalemia

A. Etiology1. Increased intake2. Movement from ICF to ECF3. Decreased urinary excretion

a. renal failureb. volume depletionc. hypoaldosteronismd. Type 1-distal RTAe. ACE inhibitors (captopril, lisinopril, etc.)f. Angiotensin receptor blockers (irbesartan)g. Potassium-sparing diuretics (triamterene, amiloride, spironolactone)h. Non-steroidal antiinflammatory agentsi. trimethoprim/sulfamethoxazole

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B. Clinical Manifestations

1. Muscle Weakness

2. Cardiac Arrhythmias

C. Diagnosis/Evaluation

1. Assess the patient for symptoms, i.e.- ECG

2. Confirm true hyperkalemia

3. Evaluate for possible reversible causes

4. Evaluate renal function

5. Transtubular potassium gradient (TTKG)

6. Fractional excretion of potassium (FeK)

Abnormal EKG? IV Calcium

Continuous EKG monitoring

Hyperglycemia? IV insulin° BS

IV insulin + dextrose

Consider albuterol or NaHCO3

Sodium polystyrene sulfonate or Dialysis

Monitor [K] q 2 hrs until < 5.5 mEq/L

yesno

yesno

Abnormal EKG? IV Calcium

Continuous EKG monitoring

Hyperglycemia? IV insulin° BS

IV insulin + dextrose

Consider albuterol or NaHCO3

Sodium polystyrene sulfonate or Dialysis

Monitor [K] q 2 hrs until < 5.5 mEq/L

yesno

yesno

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III. Selecting/Recommending therapy for the treatment of Hyperkalemia

A. Mild/Chronic Hyperkalemia

1. no acute therapy indicated

2. identify potentially reversible causes

3. Dietary potassium restriction

3. Diuretics-enhances renal sodium excretion

4. Sodium Polystyrene Sulfonate (Kayexalate)

-a non-absorbable, ion-exchange resin which binds potassium in the GI tract to enhance excretion of potassiumOnset: 2-3 hoursdose: 25-50 grams orally or rectally PRN

B. Acute/Severe Hyperkalemia

1. COMBINATION THERAPY IS UTILIZED

2. Calciuma. raises the threshold potential (less negative) and restores cardiac excitability

b. Onset of action: 1-2 minutes

c. Duration of Action: 10-30 minutes

d. Dose/AdministrationCalcium Gluconate 1 (4.7 mEq/gram) IV over 5 minutes

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3. Insulin/Glucose

a. stimulates cellular uptake of potassium, redistributing total body stores of potassium

b. Onset of Action: 30 minutes

c. Duration of Action: 2-6 hours

d. Dose/AdministrationDextrose 50% 50 ml (25 g) IV over 5 minutes with10 units of Regular insulin IV/SQorDextrose 10% in water with 25-50 units/liter of solution at 100-500 ml/hr

4. Sodium Bicarbonate

a. increases serum pH and stimulates redistribution of potassium intracellularlyb. Onset of Action: 30 minutesc. Duration of Action: 2-6 hoursd. Dose/Administration

50-100 mEq IV over 2-5 minutes

5. Albuterola. Beta stimulation promotes intracellular distribution of potassiumb. Onset of action: 30 minutesc. Duration of action: 1-2 hoursd. Dose/administration: 10-20 mg via nebulizer over 10 minutes

6. Hemodialysis

a. Increases potassium elimination b. Onset of Effect: Immediatec. Duration of Dialysis: variable (2-4 hours)

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CASE DISCUSSION 2

In groups of 2 students each, read the following case and answer the question that follows:

HIK is a 73 year-old male (Ht 5'10", Wt 178 lbs) with a history of hypertension, diabetes, and renal failure notyet requiring hemodialysis. He notes progressive muscle weakness over the past several weeks and is broughtto the office in a wheelchair because of difficulty walking.

Current Meds: furosemide 80 mg PO BID Diltiazem CD 240 mg PO daily Captopril 25 mg PO TID

Lab: Na+ 134, K 8.2, Cl 102, CO 20, BUN 53, S.Cr. 4.8, BS 168+ -2

Provide a recommendation for the management of this patient’s hyperkalemia?

For the drug(s), provide a dosage regimen (dose, route, frequency, rate of administration, duration of therapy)

Part 2: How would your management differ if the patient’s potassium was:

a. 7.2 mEq/L?

b. 6.2 mEq/L?

IV. Summary

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Therapeutics I Fall 2003Fluid/Electrolyte Disorders

DISORDERS OF MAGNESIUM BALANCE Jack Burke, Pharm.D.

ABILITY OUTCOMES1. Assess a patient’s hypomagnesemia and hypermagnesemia and current drug therapy.

2. Evaluate the appropriateness of patient-specific drug therapy for a patient’s hypomagnesemia orhypermagnesemia, and modify therapy as necessary.

3. Select/recommend appropriate drug therapy for patients with hypomagnesemia or hypermagnesemia.

4. Monitor for expected efficacy, toxicity, and adverse effects associated with chosen therapy for hypomagnesemiaor hypermagnesemia.

5. Educate patients and health professionals regarding drug therapy of hypo-/hyper-magnesemia

CONTENT QUESTIONS

1. What is the physiologic function of magnesium?

2. What are the common causes of hypomagnesemia and hypermagnesemia?

3. What are common drug-induced causes of hypomagnesemia?

4. Describe the clinical manifestations of hypermagnesemia that commonly occur at various serum magnesiumconcentrations.

5. Explain the mechanism of action of IV calcium in the treatment of hypermagnesemia.

I. Hypomagnesemia

A. Physiology of Magnesium

QUESTION: MAGNESIUM IS AN _______-CELLULAR CATION AND ONLY ________% IS PRESENT INBLOOD.

B. Etiology

The following are the most common mechanisms responsible for hypomagnesemia:reduced intakedecreased gastrointestinal absorptionIncreased gastrointestinal lossesIncreased loss from primary renal tubular disordersDrug-induced renal losseshormone-induced renal lossesInternal distribution

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For each of the following conditions, indicate which of the above mechanisms is responsible for causinghypomagnesemia: (See text for complete list of causes)

Prolonged NG suction

pancreatic insufficiency

renal tubular acidosis

cisplatin

aldosteronism

nephrotic syndrome

diuretics

glucose, insulin, AA administration

C. Clinical Manifestations of Hypomagnesemia

QUESTION: WHAT ARE COMMON CLINICAL MANIFESTATIONS OF HYPOMAGNESEMIA FOR EACH OFTHE FOLLOWING CATEGORIES?

1. NeuromuscularMuscle twitching tremorHyperreflexia ParesthesiaTetany SeizuresComa NystagmusAtaxia Vertigo

2. PsychiatricApathyDepressionDeliriumAgitationConfusionHallucinations

3. CardiacPVC’s, ventricular fibrillation, ventricular tachycardiaTorsade de PointesPredisposition to digoxin toxicityPR, QT interval prolongation; widening of QRS complexCoronary vasospasm

4. Electrolyte homeostasisRefractory hypokalemiaRefractory hypocalcemia

D. Treatment of Hypomagnesemia

1. Available preparations (1 mMol = 2 mEq = 24 mg magnesium)parenteral: magnesium sulfate: 8.13 mEq/g saltoral: magnesium oxide: 46 mEq/g salt

magnesium acetate: 9.35 mEq/g saltmagnesium chloride: 9.75 mEq/g salt

SER U M M g C O N C EN TR A TIO N

< 1 m Eq/L 1-1.5 m Eq/L + aSx

Life-threatening Sx?

R x____ R x____ R x____

yes no

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ProductsMagnesium hydroxide (MOM) 390 mg/5ml; 800 mg/5 ml; 1.2 g/5 ml

(30 ml = 1.05 g= 87 mEq)

Magnesium oxide: 140 mg caps; 400, 420 mg tablets49.6 mEq = 25 mMol = 1000 mg Mag oxide20 mEq = 10 mMol = 400 mg Mg Ox = 240 mg Mg

Magnesium sulfate: 500 mg MgSO4 = 4.06 mEq Mg = 49.3 mg elemental Mg

2. Magnesium supplementation

II. Hypermagnesemia

A. EtiologyQUESTION: WHAT ARE COMMON CAUSES OF HYPERMAGNESEMIA?

Decreased renal excretion

Excessive intake

Other:

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B. Clinical manifestationsQUESTION: DESCRIBE THE CLINICAL MANIFESTATIONS OF HYPERMAGNESEMIA ASSOCIATED WITHTHE FOLLOWING SERUM CONCENTRATION LEVELS. (See page 992)

> 3 mEq/L

> 4 mEq/L

> 4.5 mEq/L

> 5 mEq/L

> 7 mEq/L

> 10 mEq/L

> 14 mEq/L

> 15 mEq/L

C. Management

QUESTION: WHICH PATIENTS SHOULD RECEIVE TREATMENT FOR HYPERMAGNESEMIA?

QUESTION: WHAT CAN BE USED FOR THE ACUTE TREATMENT OF HYPERMAGNESEMIA?

I Calcium Homeostasis

A. normal total serum calcium conc: 8.5-10.5 mg/dl

Note: Calcium is present in the serum bound to albumin and free (unbound). The normal serum concentration isa measure of total calcium: bound and unbound. It assumes a constant percentage of free calcium, which isthe active form. When serum albumin is low, the percentage of the total calcium in the blood that is unboundincreases. Therefore, it takes a lower total concentration to achieve a normal free level of calcium. Whenserum albumin is low, the serum calcium must be “corrected” to compare it to the normal range.

B. correction for hypoalbuminemia required: for each 1 gm/dl albumin falls below 4.0 gm/dl, add 0.8 mg/dlto the measured serum calcium and compare to usual normal values

Case: How would you interpret a serum calcium concentration of 7.0 mg/dl in a patient with a serum albumin of 2gm/dl?