Larose Study guide and overall important points

•Fractional Excretion of Na

(FeNa) = 1-2% (Normal range) •FENa = 100 X Sodium(U) X Creatinine (Sr)/ Sodium (Sr) X Creatinine (U) U=urine USS/SSU UrsodiumxSerumC/ SrSodiumxUrinCreatinine

Base deficit

(desired HCO₃⁻ - actual HCO₃⁻) (desired 22-26, usually 24)

HypoNa Tx hypertonic hypotonic Isotonic

*a. hypertonic hyponatremia* Usually secondary to hyperglycemia or hypertonic infusions (Mannitol, glucose, glycine). Serum Na falls 1.6mEq/L for every 100mg/dl increase in glucose or mannitol. (Increased serum glucose causes ICF fluid movement into the ECF) *b. hypotonic hyponatremia* - Most common form of hyponatremia POsm < 280 mOs/Kg Three categories based on ECV: - Hypovolemic (causes: Fluid losses (diarrhea, thiazide diuretics**, excessive sweating, salt-wasting syndrome) - Hypervolemic hyponatremia (Causes: renal impairment, CHF, cirrhosis, nephrotic syndrome, edema) - Isovolemic (euvolemic) (most common cause is SIADH. See Table 66-3 for Potential Causes of SIADH) Check Hx, PE, urine osmolality, urine Na, BUN, SrCr and Sr electrolytes *c. isotonic hyponatremia* POsm = 280-285mOs/Kg Secondary to: - hyperlipidemia - hyperproteinemia - isotonic infusions of glucose, mannitol, glycine.

Treatment of Hypercalcemia: Calcitonin-salmon (Myacalcin)

- Reduces bone resorption and increases renal clearance of calcium - Dose: 4U/Kg IV followed by 4U/Kg po q12h - 25% of patients do not respond - FDA Advisory Board in 2013 confirmed that benefits may outweighs risk of cancer and that benefits vs risks should be evaluated for each individual patient

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NG is 55 YO 5'11" 240-Lb BM with a history of diabetes, HTN, Acid-Reflux Disease and RF. Labs: Na 150, K5.6, Cl 110, CO22, BUN 52, SrCr 3.2, Mg 3.5, Ca 8.9, PO4 3.4 After discontinuing the drugs from the therapy, which of the following drugs would you add to his current therapy? Select all that apply. A.Losartan B.Metoprolol C.Kayexalate D.Lansoprazole E.Metolazone F.None of the above

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NG is 55 YO 5'11" 240-Lb BM with a history of diabetes, HTN, Acid-Reflux Disease and RF. Labs: Na 150, K5.6, Cl 110, CO22, BUN 52, SrCr 3.2, Mg 3.5, Ca 8.9, PO4 3.4 Which of the following drugs should be discontinued from his current therapy? Select all that apply. A.Spironolactone B.MOM C.Amlodipine D.Lisinopril E.All of the above F.None of the above

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Slide 161 algorithm hypoCa

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hypertonic hyponatremia Usually secondary to hyperglycemia or hypertonic infusions (Mannitol, glucose, glycine). Serum Na falls 1.6mEq/L for every 100mg/dl increase in glucose or mannitol. (Increased serum glucose causes ICF fluid movement into the ECF)

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hypotonic hyponatremia - Most common form of hyponatremia POsm < 280 mOs/Kg

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slide 168 Dose recommendations for Vitamin D in CKD-associated Hypocalcemia

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Treatment of Hypercalcemia PHO

. Phosphates - Used in life-threatening hypercalcemia after failure to diuresis and hydration - Dose: 1.5g elemental phosphorus IV over 6-8h - Obtain Serum phosphate level q2h. Goal of therapy is to get serum level b/w 5- 6mg/dl - In non-life threatening hypercalcemia and phosphate < 3mg/dl give po - Fleet phosphosoda capsules 4-8/day provides 1-2g of elemental phosphorus per day - Obtain/check Serum phosphorus level after 2-3 days of therapy - Do not give to patients with high serum phosphate and renal failure • •Deaths have occurred due to Calcium-phosphate precipitation in lungs and irreversible ARDS

Treatment of Hypernatremia

.•Treatment of hypernatremia is dependent on extracellular volume status and rate of development of the hypernatremia •One of three types of hypernatremia may be present •Hypovolemic hypernatremia •Hypervolemic hypernatremia •Isovolemic hypernatremia

Crystalloids:

1) indications - First line therapy for fluid resuscitation (as initial therapy without colloids) - Add colloids if shock persists or returns after several Liters (6-7 L) of crystalloids. 2) distribution To expand intravascular space, use isoosmotic solutions. Only one fourth (25%) stays intravascularly because crystalloids equilibrate with the extracellular space by moving freely through the semipermeable membranes 3) complications Peripheral edema Pulmonary edema Hyperglycemia (Dextrose) Hyperchloremic metabolic acidosis (Saline) Metabolic alkalosis (Lactated Ringers) 4) Advantages: Crystalloids are less costly than colloids and have fewer side effects than colloids

1. Crystalloids Indx 2. Colloids

1. - First line therapy for fluid resuscitation (as initial therapy without colloids) - Add colloids if shock persists or returns after several Liters (6-7 L) of crystalloids. 2. To augment body's own response of releasing albumin from the liver to the intravascular space within three hours of hypovolemia a) Severe hypovolemia persisting after large amounts of crystalloids. b) Low effective circulating volumes but with excess of Na+ and H2O to mobilize fluid - Ascites - CHF/JVD/Edema (Pulmonary and/or lower extremity) - Post-cardiac bypass c) Patient is unable to synthesize albumin - Liver transplants, Hepatic resection, liver diseases, - Malnutrition (controversial) d) Severe hemorrhage or coagulopathy: Treat with PRBC and FFP to help increase Hct and correct coagulopathy

Normal Range: 1. Mg 2. Ca 3. Cl 4. K 5. Na 6. Phosphate 7. HCO3 (bicarb)

1. 1.3 - 2.1 mEq/L or 0.65-1.05 mmol/L {(1.4-1.8 mEq/L or 1.7-2.3 mg/dL or 0.70-0.95 mmol/L) (DiPiro)} 2. 9.2-11 mg/dL (2.3-2.8mmole/L) 3. 95 to 103 mEq/L 4. 3.8 - 5.0 mEq/L (mmol/L) 5. 136 -142 mEq/L (136-142 mmol/L) (135-145 mEq/L) 6. 2.3 - 4.7mg/dL or 0.74 -1.52 mmole/L 7. 22-26 mEq/L

Guideline for IV Calcium replacement based upon ICa++ levels 1. 3.5-3.9 mg/dL 2. 3.0-3.4 mg/dL 3. 2.5-2.9 mg/dL 4. < 2.5 mg/dL

1. 4 g Ca Gluconate recheck With next AM Labs 2. 6 g Ca Gluconate recheck 4 Hours After Replacement 3. 8 g Ca Gluconate recheck 4 Hours After Replacement 4. 10 g Ca Gluconate and call physician recheck 4 Hours After Replacement • •Infuse 2 gm per hour •Patients on hemodialysis/peritoneal dialysis, creatinine clearance of <20mgL/min, chronic adrenal insufficiency, electrical burns, rhabdomyolysis, DKA, crush injury, hypothermia, are excluded from receiving magnesium IV and/or PO.

Magnesium Replacement Guideline 1. 1.6-1.9 mg/dL 2. 1.0 - 1.5 mg/dL 3. < 1 mg/dL

1. 4 grams IV over 2 hours 2. 4 grams IV over 2 hours 6 grams IV over 3 hours 3. 8 grams IV over 4 hours. Recheck Mg level 6 hours after replacement

Replacement of K Based on Potassium levels 1. 3.3-3.9 mEq/L 2. 3.0-3.2 mEq/L 3. 2.6-2.9 mEq/L 4. <2.6 mEq/L

1. 40 meq KCl PO/PT/IV (enteral route preferred) recheck with next AM labs 2. 60 meq KCl PO/PT/IV (IV route preferred) recheck Immediately and with next AM labs 3. 80 meq KCl IV and NHO recheck Immediately and with next AM labs 4. 100 mEq KCL IV and NHO recheck Immediately and with next AM labs

Phosphorus Replacement Guideline 1. K-Phos Neutral Tablet 2. K-Phos Injection (per mL) 3. Na Phos Injection

1. Pho: 250 mg (8mmol), K: 1.1 mEq, Na: 13mEq 2. Pho: 3 mmol, K: 4.4, Na:- 3. Pho: 3 mmol, K: -, Na:4mEq

Daily requirement Mg

20-40mEq

Treatment of Hypermagnesemia (cont.)

A. Calcium - 100-200mg IV as Ca Gluconate or Ca Chloride over 5-10 min B. Dialysis - Peritoneal of hemodialysis if renal functions are poor C. Removal of Mg++ source D. Prevention - Avoid Mg containing compounds in patients with renal failure (Ex. Antacids containing Mg, i.e MOM)

Treatment of Hypercalcemia

B. hemodialysis or peritoneal dialysis - Used in renal failure and life-threatening hypercalcemia C. corticosteroids - Increase urinary excretion and decrease intestinal absorption - Used for hypercalcemia associated with malignancy. - Onset is variable and not immediate- If no response after a week taper and D/C - Hydrocortisone 100mg IV q6 for 24 hr then prednisone 60mg po qd

Chloride deficit

CD=0.2L/KgxWt(kg)x(103-observed Cl)

are solutions that exert some degree of intravascular oncotic pressure

Colloids

are electrolyte solutions

Crystalloids

Treatment of Hypercalcemia: Biphosphonates

F. Biphosphonates decrease bone resorption by inhibiting osteoclast activity 1. Zoledronic acid (Zometa, Reclast) Dose Range: 4-8mg IV administered over 15-30 min. T1/2 = 146 hours - Dose for postmenopausal osteoporosis: 5mg IV over 15 min once a year. - Dose for hypercalcemia in malignancy: 4 mg IV X 1. Wait for 7 days before administering another dose. - Dose for metabolic bone disease: 4 mg IV X 1 every 3-4 weeks Cautions: Decrease dose if CrCl <60 ml/min Maintain adequate hydration Monitor renal function

Treatment of Hypercalcemia: Biphosphonates

F. Biphosphonates decrease bone resorption by inhibiting osteoclast activity 2. Pamidronate (Aredia) 60 or 90 mg IV over 2-4 hours X1. Wait for 7 days before administering another dose. T1/2 = 21-35 hours. Indication: Hypercalcemia in malignancy - Do not use in patients with serum creatinine >5mg/dL - Do not use in patients with multiple myeloma with serum creatinine >3mg/dL - Monitor renal function

Treatment of Hypercalcemia: Biphosphonates

F. Biphosphonates decrease bone resorption by inhibiting osteoclast activity 3. Etidronate (Didronel) Indications: - Paget's Disease: 5-10mg/kg/d up to 6 months or 11-20mg/kg/d up to 3 months - Hypertophic ossification Spinal cord Injury (SCI): 20mg.kg/day for 2 weeks, then 10mg/kg/day for 10 weeks. - Hypertophic ossification in hip surgery: 20mg/kg/day for 1 month pre-op and continue same dose for 3 months post-op. - Use caution in chronic renal injury

Treatment of Hypercalcemia: Biphosphonates

F. Biphosphonates decrease bone resorption by inhibiting osteoclast activity 4. Ibandronate (Boniva): Indications: - Treatment and prevention of osteoporosis in post-menopausal women Dose: 2.5 mg QD PO or 150 mg every month T1/2 = 37-157 hours Take on an empty stomach for 60 minutes - Treatment of osteoporosis in post-menopausal osteoporosis Dose: 3mg IV over 15-30 seconds every 3 months - Contraindicated in CrCl <30 ml/min

Treatment of Hypercalcemia: Biphosphonates

F. Biphosphonates decrease bone resorption by inhibiting osteoclast activity 5. Alendronate (Fosamax, Fosamax Plus, Fosamax D): Indications: - Treatment and prevention of osteoporosis in post-menopausal women: 5 mg PO QD or 35mg PO QW, - Treatment of osteoporosis in men: 10 mg QD or 70mg QW - Treatment of Paget's Disease in men and women 40mg PO QD X 6 month - Do not use if CrCl is <35 ml/min - Fosamax D has 2800 Units of Vitamin D - T1/2 > 10 years

Treatment of Hypercalcemia: Biphosphonates

F. Biphosphonates decrease bone resorption by inhibiting osteoclast activity 6. Risedronate (Actonel, Actonel with Calcium) Indications: - Treatment and prevention of osteoporosis in post- menopausal women: Dose: 5 mg PO QD or 35mg PO QW, - Treatment of steroid-induced osteoporosis: Dose: 5 mg QD - Treatment of Paget's Disease in men and women Dose: 30mg PO QD X 2 months

Treatment of Hypercalcemia: Biphosphonates

F. Biphosphonates decrease bone resorption by inhibiting osteoclast activity 1. Zoledronic acid (Zometa, Reclast) 2. Pamidronate (Aredia) 3. Etidronate (Didronel) 4. Ibandronate (Boniva) 5. Alendronate (Fosamax, Fosamax Plus, Fosamax D) 6. Risedronate (Actonel)

Fluid Replacement for Loss of body fluid (Gastric, small bowel and colon, biliary and pancreatic)

Gastric losses secondary to vomiting, drainage or fistulas •Treat with D5W 1/2NS + 20 mEq of KCl If alkalosis, treat with D5W NS + 40 Meq of KCl to provide enough chloride to correct the alkalosis Small bowel and colon •Lactated Ringer's for small bowel •LR of 1/2 NS + 20 mEq KCl/L + 25mEq NaHCO3/L for colon losses or diarrhea Biliary and pancreatic losses •Treat with Lactated Ringer's. Do not use lactated Ringer's in alkalosis.

Treatment of Hypercalcemia: Mithramycin(plicamycin®)

Mithramycin is a secondary treatment after hydration and diuresis. - an antitumor agent that inhibits bone resorption - Dose 25mg/kg of BWt IV over 3 hours - The hypocalcemic effect occurs approximately 24 hours after the dose - Use is limited because of thrombocytopenia, platelet dysfunction, hepatic and renal toxicity

Na(sodium) deficit

Na Deficit = (Na Desired - Na measured) X TBW). TBW is based on patient's age. See Table 66-5

Know difference in electrolyte content(NaCl vs Lactated ringers, and D5W)

NaCl: 0.9%(normal saline)= 154mEq/L Na, 154 Cl 0.45%=Na=77, Cl=77 3%: Na=512, Cl= 512 D5W: none w/0.45%: 77,77 w/0.2%:?, cl=34 Plasmalyte: Na=140, k=5, Mg=1.5, Cl=98, acetate=27, gluconate=23 Normal/euxobic: Na=140, k=4, Ca=2.3, Mg=1, Cl=104 Lactated ringer: Lactate=28 Ca=4.8 Na=130, K=4, Ca=1.5, cl=109

Anion gap

[Na+ K] - [HCO+Cl]

Treatment of Hyperphosphatemia

a. Acute with Sx of hypocalcemia 1) acetazolamide 15 mg/kg q3-4h - increases phosphate excretion 2) dialysis b. Mild or chronic - Usually seen in chronic renal failure or neoplastic calcinosis - low phosphate diet - aluminum binding antacids (Aluminum OH) chronic hyperphosphatemia - Usually related to hyperparathyroidism seen in chronic renal failure (CKD). Treat with - Low phosphate diet/ restrict phosphate (dairy products, chocolate, nuts, cola) - Phosphate binders inhibit the absorption of phosphate from the gut (do not use if food has already been ingested. Resume with next dose.) - Three types of binders: - Aluminum-based - Calcium-based - Aluminun-free, calcium-free

Phosphorus Replacement Guideline Serum Phos 1. 2-2.5 mg/dL 2. 1.6 - 1.9 mg/dL 3. <1.6 mg/dL

mEq of K-Phos 1. ≈30 mEq (≈7 mEq/hr based on 4h infusion) 2. ≈44 mEq (≈11 mEq/hr based on 4h infusion) 3. ≈60 mEq (≈15 mEq/hr based on 4h infusion)

Drugs used in Central and Nephrogenic DI (Table 66-9)

slide 71

osmolality

~ 2 [Na+ ] + [glucose in mg/L/18] + [BUN/2.8] + [Ethanol/ 3.8] (other version doesnt use ethanol)

Treatment of Hypervolemic Hypernatremia

• 1) Loop diuretic + D5 W or D5 1/4 NS is the treatment of choice •Furosemide 20-40 mg IV Q6H •Monitor serum sodium every 2-4 hours •Continue diuretic until signs of fluid overload resolve •Once serum concentration is less than 148mEq/L and symptoms have resolved serum sodium can be measured every 6-12 hours 2) dialysis (renal failure) to remove excess volume

Treatment of Symptomatic Hyponatremia

• If patient has Symptomatic hyponatremia Patients are usually asymptomatic until Na+ levels fall to <120mEq/L or Na levels fall sharply. Treat pt enough to control severe symptoms; then proceed more slowly. • 3% NaCl raising serum Na+ by 2mEq/L/hr until Na+ of 125 mEq/L is reached or by 4-6mEq/L over 24 hours (3% NaCl must be given through a central line) •Increase in serum sodium should not exceed 2 mEq/L/hr and 9 mEq/L (6-12mEq/L) in any given 24-hr period and no more than 18mEq/L in 48 hours. Neurological deficit should improve with such increase in sodium levels. •determine underlying cause & correct/treat •correct sodium status based on etiology- Slowly. Monitor Na every 2-4 hours and osmolality every 4-6 hours for 24-48 hours initially. Check vital signs and neurological signs frequently during the first 12-24 hours. *Overzealous correction of hyponatremia can cause seizures, myelinolysis and permanent brain damage. (when duration of hyponatremia is unknown use no more than 6-8mEq/L in 24 hours to avoid ODS) (0.9% NaCl is not effective in patients with SIADH and may worsen their hyponatremia. Use loop diuretic (furosemide or bumetanide) to increase elimination of water and to prevent volume overload from the 3% NaCl. Bolus: 150 mL over 20 minutes, then 100 mL over 10-20 min every 30 min. until symptoms resolve. Serum Na should not increase by no more than 5mEq/L. Once resolved, give 0.9% NaCl. Oral sodium tabs.)

TABLE 66-4 General Guidelines for Treatment of Hyponatremia (DiPiro. Accesspharmacy.mhmedical.com. Accessed 3/18/22)

• management, treat the underlying cause of hyponatremia. • •Appropriate treatment of hypotonic hyponatremia requires balancing the risks of hyponatremia vs the risk of ODS. •Patients who acutely develop moderate-to-severe hyponatremia and/or patients who have severe symptoms are at greatest risk and potentially benefit most from more rapid correction of hyponatremia. •Correction of hypovolemic hypotonic hyponatremia is usually best accomplished with 0.9% NaCl, as these patients have both sodium and water deficits. •Active correction of euvolemic and hypervolemic hypotonic hyponatremia in patients who do not require rapid correction is usually best accomplished by water restriction. Demeclocycline, VRA, or 0.9% NaCl plus a loop diuretic can be used if the initial response to water restriction is not adequate. •In patients with severe symptoms or severe hyponatremia, 3% NaCl (possibly combined with a loop diuretic) should initially be used to more rapidly correct the hyponatremia. A loop diuretic can be administered concurrently with 3% NaCl to enhance the serum sodium correction by increasing free water excretion. •Long-term management will be required for patients in whom the underlying cause of hyponatremia cannot be corrected. Depending on the cause, water restriction, increasing sodium intake, and/or a VRA may be used

Treatment of Euvolemic Hypernatremia

•1) H2 O orally •2) D5W parenterally •*** Rate of correction is dependent on whether hypernatremia is: Acute - correct rapidly over few hours Chronic - correct slowly - over at least 48 hours and no faster than 2 mOsm/hr

Treatment of Chloride Imbalances

•Abnormality of Chloride is usually associated with sodium and/or acid-base imbalances. •Correcting underlying problems and sodium and/or acid-base imbalances will correct chloride imbalances. •Chloride is never replaced alone. It's always in combination with sodium and/or potassium or in TPN.

Phosphorus Replacement Guideline

•Always look at potassium level to determine IV phosphorus product to use. •Use K-Phos if K+ <4.0 mEq/L •Use Na Phos if K+ > than 4.0 mEq/L •IV replacement: Dilute in 250 ml/NS or D5W. Infuse over 4-6 hours •PO/PT replacement: K-Phos Neutral tablet •Patients on hemodialysis/peritoneal dialysis, creatinine clearance of <20mgL/min, chronic adrenal insufficiency, electrical burns, rhabdomyolysis, DKA, crush injury, hypothermia, are excluded from receiving phosphorus IV and/or PO. •Patients who are not in intensive care should not be receiving IV Phosphorus injection

How to Calculate Daily Fluid Requirements

•Basal Daily Requirement of Fluid needed per day (BDR): •Neonate (1-10 Kg) = 100 mL/kg •Child (10-20 kg) = 1000 mL + 50 mL for each Kg > 10 •Adult (> 20 Kg) 1500 mL + 20 mL for each Kg > 20 •70kg man would need 1500mL + [20mL X (70kg-20kg)] = 2500 mL or 2.5L •Fluid deficits must be replaced in addition to the BDR •To calculate unknown fluid deficit from other sources, use daily weights, the weight change constitutes the fluid deficit (1 Kg = 1 L of fluid) -•Fluid deficit (mL) = normal TBWt - present TBWt -•This is usually done in hospitalized patients

Treatment of Hyperphosphatemia

•Calcium-based products: •First line agent to use in hyperphosphatemia •Calcium Acetate (Phoslo, Phoslyra, others) - 2,001-2668 mg PO TID w/meals •Calcium Carbonate (Tums, others) - 500mg PO (Tab/chew) TID with meals •SE: Constipation, hypercalcemia, nausea •Aluminum-based products: •Aluminum Hydroxide (alternagel, others) •300-600 mg TID with meals •Aluminum-free, Calcium-free products: •Sucroferric oxyhydroxide (Velphoro) - 500 mg PO TID with meals •Ferric Citrate (auryxia) 2 Gm PO TID w/meals up to 12 grams per day •Lanthanum carbonate (Fosrenol) - 500 - 1,000 mg PO TID/Chew thoroughly (GI perforation, fecal impaction, GI obstruction, ileus), constipation •Sevelamer carbonate (Renvela) and Sevelamer hydrochloride (Renagel) •800-1,600 mg PO TID with meals •SE: N/V/D, dyspepsia, constipation, abdominal pain, flatulence

Treatment of Hypercalcemia: Cinacalcet (Sensipar®)

•Cinacalcet (INN) is a drug that acts as a calcimimetic by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues (Van Wagenen et al. (2001), U.S. Pat. 6,211,244). •Cinacalcet is used alone or with other medications to treat secondary hyperparathyroidism in patients with chronic kidney disease who are being treated with dialysis. Cinacalcet is also used to treat high levels of calcium in the blood of patients who have parathyroid cancer. Cinacalcet is in a class of medications called calcimimetics. It works by signaling the body to produce less parathyroid hormone in order to decrease the amount of calcium in the blood. (www.medlineplus.gov/druginfo) •ADR: upset stomach, vomiting, diarrhea, dizziness, weakness, chest pain (3) •Uncommon SE: burning, tingling, or unusual feelings of the lips, tongue, fingers, or feet,muscle aches or cramps,sudden tightening of the muscles in the hands, feet, face, or throat, seizures, infection of dialysis access (3) •DOSAGE FORMS AND STRENGTHS: Tablets: 30, 60, and 90 mg tablets (3); Dose: 30-18mg PO daily w/food •CONTRAINDICATIONS: Sensipar treatment initiation is contraindicated if serum calcium is less than the lower limit of the normal range. (3)

Treatment of Hypokalemia

•Confirmation of serum K+ and UO •Supplementation of K+ oral (PO) - If GIT is working give 80-120mEq/day. Each 10mEq PO or IV should increase serum K+ by 0.1 mEq/L Intravenous (IV) - if GIT is not working and hypokalemia is severe, Administer in saline without dextrose 5-10mEq KCl/hr diluted in 100-150mL NS **Rate greater than 10 mEq/hr should be administered via a central line (central vein, i.e. jugular, femoral) (because of phlebitis and pain associated with peripheral administration of higher concentration). Patient has to have EKG monitoring. ***Rate rarely exceed 20mEq/hr and should never exceed 40mEq/hr If patient is hypomagnesemic, give 4mL as MgSO4 50% diluted in 10 ml of NaCl 0.9% over 20 minutes, then start 40mEq KCL infusion followed by Mg replacement •Serum potassium may be expected to increase by 0.25 mEq/L for each 20 mEq IV KCL infused. •Hypokalemia is often associated with hypomagnesemia, which increases the risk of malignant ventricular arrhythmias.1 •Check potassium and magnesium in any patient with an arrhythmia •Top up the potassium to 4.0-4.5 mmol/L and the magnesium to > 1.0 mmol/L to stabilize the myocardium and protect against arrhythmias - this is standard practice in most CCUs and ICUs.1 •If potassium is <4.0mEq/L and Phosphorus is ≥2.5 mg/dL, give KCl as indicated per guideline on the next slide.2 •If potassium is <4.0 mEq/L and Phosphorus is ≤ 2.5 mg/dL give Kphos.2

corrected calcium

•Corrected Ca(mg/dl) = [0.8 (4- measured Serum Albumin (Gm/dL)] + reported Ca (mg/dL)

Treatment for DI

•Desmopressin (a longer acting form of vasopressin) may be taken as a nasal spray twice a day or sometimes as a tablet. The dose is adjusted to maintain the body's water balance and a normal urine output. Dose: DDAVP intranasal (100mcg/ml) 10mcg/insufflation daily, titrated to 20mcg BID based on serum sodium concentration (preferred treatment). (Lower doses can be given through a rhinal tube). IV or subcu can be given if intranasal or oral therapy is not possible or in patients with central diabetes insipidus who are undergoing surgery or are unconscious. •Taking too much vasopressin can lead to fluid retention, swelling, and other problems. •Sometimes central diabetes insipidus can be controlled with drugs that stimulate production of vasopressin, such as chlorpropamide, carbamazepine, clofibrate, indomethacin, amiloride and thiazide diuretics. These drugs are unlikely to relieve symptoms completely in people whose diabetes insipidus is severe. (See table 66-9)

Other Treatments of Hypocalcemia

•Dietary intake of calcium = 600-900 mg daily •Calcium products are available in many forms •Calcium Carbonate (tums and others) contains 40% elemental calcium. Absorption is acid-dependent and is recommended to take with food/meals •Calcium citrate (calcitrate, others) contains 21% elemental calcium. Absorption is not acid dependent and can be taken with or without food. Calcium citrate is absorbed better than calcium carbonate and may be preferable when the pH of the stomach is elevated (as in elderly patients and those on PPIs) •Do not exceed 500-600 mg/dose •Vitamin D increase the absorption of calcium (800-2000 Units daily) •Adults > 50 YO require doses up to 1200 mg of calcium per day •Patients with vitamin D deficiency (rickets, CKD, osteomalacia, osteoporosis) should receive higher doses of vitamin D daily (5,000 IU) or weekly (50,000 IU) for 8-12 weeks in the form of Vit D3 (Cholecalciferol) or Vit D2 (Ergocalciferol, 25(OH) vita D) followed by 1000-2000 IU daily. •Vitamin D products: •Calcitriol (Rocaltrol®, active form of Vit D3) to increase calcium absorption and inhibit PTH secretion. Indications: CKD and hyperparathyroidism •Vitamin D analogs - Paricalcitol (Zemplar®), doxercalciferol (Hectorol®), calcifediol (Rayaldee®) - cause less hypercalcemia than calcitriol •Sunlight exposure to get Vita D3 (30 min/day). However, caution=risk of skin cancer •Ergocalciferol (D2) is from plant sterols. Cholecalciferol (D3) (from sunlight)

Calculating ECF deficit

•ECF deficit (mL) = ECF normal - ECF current •ECF = 0.33 X TBW •For a 50Kg person who lost 5kg (50-5 = 45kg) •ECF = [50 X 0.4 L/Kg X 0.33] - [45 kg X 0.4L/kg X 0.33)] = 660 mL

ECF(extracellular fluid deficit)

•ECF deficit (mL) = ECF normal - ECF current •ECF = 0.33 X TBW •For a 50Kg person who lost 5kg (50-5 = 45kg) •ECF = [50 X 0.4 L/Kg X 0.33] - [45 kg X 0.4L/kg X 0.33)] = 660 mL

•Colloids are solutions that exert some degree of intravascular oncotic pressure

•Ex: Albumin Hespan PRBC (hypovolemic shock when HgB <7gm/dL, active bleeding or HgB <10 gm/dL if cardiovascular disease) Plasma

Treatment of Hypercalcemia: Denosumab (Prolia®)

•For the treatment of postmenopausal women with osteoporosis at high risk for fracture, male osteoporosis and cancer related bone loss •With 1 dose every 6 months, Prolia® follows your PMO patients all year long. •60 mg subcutaneous injection in the upper arm, upper thigh, or abdomen by a healthcare professional •Pre-existing hypocalcemia must be corrected prior to initiating therapy with Prolia®. Adequately supplement all patients with calcium and vitamin D •Multiple vertebral fractures have been reported following Prolia® discontinuation

Treatment of Hypovolemic Hypernatremia

•Goal is to restore ECV •Use isotonic saline until euvolemia •Use Hypotonic saline or D5W to correct hypernatremia. The amount of fluid given here is dependent on the water deficit. •H2O deficit (L)= 0.6 x BW (Kg) x (Current P Na -1) 140 •Aqueous Pitressin (for hypovolemia due to diabetes insipidus) •5U SQ q4-6h or a drip (25U in 250ml at a rate of 1U/hr) to maintain UO between 100-200 ml/hr

calculate water deficit$

•H2O deficit (L)= 0.6 x BW (Kg) x [(Current P Na -1)/140]

Treatment of Asymptomatic Hyponatremia

•If patient has asymptomatic hyponatremia, Correct underlying problem •Mild asymptomatic hyponatremia (Na <125 mEq/L) can be safely corrected over a few days with oral rehydration solution or increased sodium intake •Hypertonic or isotonic hyponatremia •Correct underlying disorders •Give insulin if due to hyperglycemia •Hypovolemic hypotonic hypovolemia •Give Isotonic saline (0.9% NaCl) •Hypervolemic hypotonic hyponatremia •A) Restrict water. B) Consider diuresis •Isovolemic hypotonic •Restrict water to <500ml/day

Treatment of Hypocalcemia

•If the calcium levels are low, give 1-1.5 g of elemental calcium daily. (a) Calcium carbonate has 40% elemental calcium. (b) Calcium citrate has 21% elemental calcium (c ) Calcium gluconate has 9% elemental calcium. •When a person is on calcium therapy, one has to make sure that the phosphate level is less than 5 because calcium phosphate can be formed and precipitated into the tissue, causing soft tissue calcification (d) Give vitamin D to increase calcium absorption but give enough calcium to allow absorption. - Calcitriol and vita D analogs in patients with hypocalcemia associated with renal failure •Acute - 200-300mg of Ca or 20-30ml of 10% Ca gluconate 90mg/10ml ampule or 5-10ml of 10% 360mg/10cc amp. •Chronic - 1500- 3000mg/day + vitamin D or add Ca to a liter of maintenance IV fluid to run over several hours •** with hypocalcemia always treat concomittant hypomagnesemia and hyperphosphatemia •IV Ca should be given slowly over several minutes because it potentiates hypertension and dig toxicity. • ** Do not mix in the same line with sodium bicarbonate because it will precipitate as the Ca salt

Treatment of Hypercalcemia: Denosumab (Xgeva®)

•Indication: Bone complications, also known as skeletal-related events (SREs), are defined as radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression. •Convenient 120 mg subcutaneous injection administered once every 4 weeks1 •Intended for subcutaneous route only and should not be administered intravenously, intramuscularly, or intradermally •The mean elimination half-life of XGEVA® was 28 days.1 •XGEVA® is a fully human† monoclonal antibody and is not cleared by the kidneys.1,4-8 •Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®.1 •The most common adverse reactions in patients receiving XGEVA® were fatigue/asthenia, hypophosphatemia, diarrhea, nausea, anemia, back pain. The most common serious adverse reaction was dyspnea, pneumonia. The most common adverse reactions resulting in discontinuation were osteonecrosis, osteonecrosis of the jaw, tooth abscess and hypocalcemia. •XGEVA® is contraindicated in patients with known clinically significant hypersensitivity to XGEVA®.1

Treatment of Hypercalcemia: Etelcalcetide(Parsabiv)

•MOA: Parsabiv is in a calcimimetic. It works by signaling the body to produce less parathyroid hormone in order to decrease the amount of calcium in the blood. •Use: Pts with ESRD on dialysis: 2.5-15mg IV 3X weekly •Decreases PTH, Ca and PO4 •Warnings: Hypocalcemia, GI Bleeding, decreased bone turnover, worsening HF •SE: muscle spasms, paresthesia, N/V/D •Monitor: Ca, PO4, PTH

Treatment of Hypomagnesemia

•MgSO4 supplementation •Acute with symptoms: 2g (8mEq/g) as 20% solution over 2-5min followed by 10g during the next 24 hours with normal renal function. then 4-6g/day for 4-5 days. •MgSO4 supplementation •Chronic with symptoms: 3-6g for 3 days (10-160mEq/day) MOM: 10ml= 28mEq of Mg++ Mg Oxide: 600mg = 28mEq •Prophylaxis: 1-2g of MgSO4 in IV fluid per day **IV Mg causes hypotension therefore monitor BP •IV Magnesium administration is given as a one-time dose •The IV bag contains 2g/50mL premixed •IV magnesium is infused at a rate of 2gm per hour (2 g/hr) •Orally, elemental magnesium is given as magnesium oxide or Milk of Magnesia. Associated with diarrhea which limits oral administration of magnesium. •Patients on hemodialysis/peritoneal dialysis, creatinine clearance of <20mgL/min, chronic adrenal insufficiency, electrical burns, rhabdomyolysis, DKA, crush injury, hypothermia, are excluded from receiving magnesium IV and/or PO. •Patients who are not in intensive care and closely monitored should not receive magnesium IV

Treatment of Hypercalcemia

•Nonpharmacologic Therapy •Removal of parathyroid glands •Surgery to remove tumor-producing Calcium or PTHrP •Dialysis •Pharmacologic Therapy •Hydration (Crystalloids) •Diuresis (loop diuretics) •Calcitonin (SQ or IM) •Phosphates (IV and oral) •Biphosphonates •Gallium Nitrate •Mithramycin •Denosumab •Corticosteroids (Prednisone) •Cinacalcet

Treatment of Hyperkalemia (also algorithm on slide 110, table slide 114)

•Rule out pseudo-hyperkalemia •Treatment approach depends on level of K+ and ECG changes a. K+ < 6.5 with no ECG changes repeat level on heparinized blood b. K+ < 6.5 and ECG changes consisting only of peaked T waves 1) Kayexalate PO or PR 2) find underlying cause c. K+ > 6.5 or any level with peak T waves and more - treat aggressively •Hyperkalemia is the major life-threatening problem people with acute renal failure (ARF) have. •When K+ serum concentration is greater than 6-6.5 mEq/L, treatment is indicated. •Levels above 8 mEq/L are emergencies. •Avoid/discontinue any potassium-containing drugs or supplements in these patients. •Avoid/discontinue K sparing diuretics, such as spironolactone, dyrenium, moduretic. •Hyperkalemia should be treated in the following ways: •Furosemide (other loop diuretic) •Kayexalate or Patiromer •You can also add kayexalate to any of the following treatment when indicated •Calcium gluconate •Glucose infusion •Insulin Cocktail •Hemodialysis or peritoneal dialysis •Albuterol •Hemodialysis •Kayexalate (Na polystyrene) is an exchange resin. K+ comes in contact with the resin and displaces Na+, which lowers serum levels of K+. Excreted in feces. •Can be used PO, 20-50 g with 70% sorbitol. It is used with sorbitol because kayexalate causes constipation. Sorbitol causes osmosis and overcomes the constipation. •Kayexalate can be used as an enema (Per Rectum = PR) - 100 g in water as an enema QID - lowers serum potassium by 1-2 mEq/day. •Symptoms of kayexalate overdose may include: mental/mood changes, muscle weakness, fast/irregular heartbeat, slowed breathing, paralysis. •Calcium gluconate IV Give 10cc of 10% because Ca+ will antagonize the cardiotoxic effect of K+. Given to correct EKG changes. After initial dose, wait five minutes and give another dose if no effect is noted. •Glucose infusion 50cc of D50W IV. If the patient has an adequate insulin supply, insulin increases and pulls K+ in with the glucose and shifts K+ back into the cell. Acutely lowers potassium in the blood. •Insulin Cocktail -1000 ml D10W + NaHCO3 and SQ with regular insulin. This is called an insulin cocktail. May be used in both diabetic and non-diabetic patients. •Albuterol 10-20mg via nebulizer over 10 minutes. Acutely lowers potassium. Can be used with insulin if necessary. •Hemodialysis or peritoneal dialysis. This is used as a last resort. •You can also add kayexalate to either treatment

IV Fluid Therapy (Replacement of Previous Losses)

•Should be based on whether: •Patient is hemodynamically stable (Normal or close to normal BP, HR, RR, CO, Temperature, I/O, etc.) •Patient is hemodynamically unstable (Abnormal BP, HR, RR, CO, Temperature, I/O, etc.)

Treatment of Hypercalcemia: Gallium Nitrate

•The action of gallium in gallium nitrate on bone metabolism decreases the hypercalcemia associated with cancer. Gallium inhibits osteoclastic activity and therefore decreases hydroxyapatite crystal formation, with adsorption of gallium onto the surfaces of hydroxyapatite crystals.[Warrel,Rp et al, Ann Intern Med, 1987] Also, the increased concentration of gallium in the bone leads to increasing the synthesis of collagen as well as the formation of the bone tissue inside the cell. It has been reported that a protracted infusion was effective against cancer-associated hypercalcemia.[Warrel,Rp et al, J. Clin. Onc 1988] •ADR: Renal failure, anemia, hypotension

Fluid deficit

•To calculate unknown fluid deficit from other sources, use daily weights, the weight change constitutes the fluid deficit (1 Kg = 1 L of fluid) •Fluid deficit (mL) = normal TBWt - present TBWt

If Patient is Hemodynamically Stable

•Volume deficit can be restored more slowly (over 24-36hrs) with 1/2 of estimated volume lost replaced within the first 8 hours and remaining 1/2 over remaining time. •Hx, PE, etc. necessary to document weight loss, lab data for electrolytes and osmolality. •Isotonic or hypertonic imbalance is determined based on degree of Weight loss/ECF loss, dehydration, plasma Na+ and osmolality.

Treatment of Hypophosphatemia

•one (1) mmole of phosphate= 31mg of elemental phosphorus •Elemental phosphorus •0.16 mmole/Kg (5mg/kg) over 6 hours, if severe (PO4 level <1mg/dl) •PO4 = 1-2mg/dl - administer 0.08 mmole/kg (2.5mg/kg) over 6 hours •Increase dose by 25-50% if pt symptomatic •Decrease dose by 25-50% if pt hypercalcemic •mild asymptomatic hypophosphatemia give PO phosphosoda - 5ml (4.2mmole/ml) tid •correct concurrent hypocalcemia

Treatment of Hypercalcemia A. hydration and Na/Ca diuresis

● •Most effective initial treatment- can achieve urinary Ca excretion of 2G/day 1) normal saline with K+ 1L/hr then 200-400ml/hr until patient is euvolemic (may require CVP monitoring) 2) Lasix 50-100mg q 1-2 hrs to maintain UO> 500ml/hr May lower Sr Ca by 1-3mg/dl 3) D5 1/2 NS + 20meq/L KCL + 20meq/L magnesium at 200ml/hr ***Monitor K+ , Mg++ , and PO4 levels