Metabolic Support in the Era of Fluid and Electrolyte Shortages Roland N. Dickerson, Pharm.D., BCNSP, FCCP, FASHP, FCCM, FASPEN Professor, University of Tennessee College of Pharmacy and Clinical Coordinator/Clinical Pharmacist, Nutrition Support Service, Regional One Health, Memphis, TN Disclosures: I have no commercial relationships relevant to the topic being presented. Presentation Summary: Parenteral nutrition component shortages have resulted in clinicians across the health care continuum scrambling to provide safe and efficacious nutrition support therapy. The intent of this part of the program is to discuss various strategies and techniques for managing fluid and electrolyte shortages, including identifying treatable causes for electrolyte disorders, developing appropriate target goals for the patient, and implementing various treatment strategies including challenges with oral/enteral electrolyte products. The presenters of this session will also serve as facilitators to solicit audience responses and engage attendees into a discussion about their experiences and techniques for metabolic support in this era of parenteral nutrition component shortages. Learning objectives: At the conclusion of the presentation, the learner will be able to:

1. Identify the most common electrolyte shortages 2. Describe the clinical relevancy between electrolyte depletion and organ dysfunction 3. Contrast “optimal” and “essential” electrolyte dosing algorithms during shortages 4. Discuss methods for managing electrolyte disorders

Fast Facts: During electrolyte shortages, one should:

• Use the enteral/oral route if practical or possible • Identify the “most appropriate” electrolyte target concentration for the patient • Address the etiology for the electrolyte disorder

Learning Assessment Questions:

1. Which problem has been associated with use of electrolyte sources from outsourcing (503B) facilities? a. Electrolyte concentrations may not be the same as conventional sources b. Labelling requirements are not required to be in line with USP standards c. Packaging of products may be unconventional (e.g., syringes versus vials) d. All of the above

2. Why is it difficult to consistently achieve a serum phosphorus concentration > 4 mg/dL in

critically ill patients without renal dysfunction? a. The renal threshold serum phosphate concentration is ~3 to 3.5 mg/dL b. Some critically ill patients exhibit augmented renal clearance c. Exaggerated cytokine and catecholamine production suppresses serum phosphate

concentration d. All of the above

3. During an intravenous calcium gluconate shortage, the hospital has implemented a temporary

provision for using intravenous calcium chloride. Which is the correct dosage adjustment to deliver the same amount of elemental calcium?

a. No dosage adjustment is necessary b. The prescribed calcium chloride dose (in g) should be 3 times higher than calcium gluconate c. The prescribed calcium chloride dose (in g) should be 1/3 the dose of calcium gluconate d. Calcium chloride should be administered as a continuous intravenous infusion

4. Why is enteral potassium administration safer than parenteral administration?

a. The bioavailability is about 60% of the total dose b. Blood stream delivery is controlled by rate of absorption and feed-forward regulation c. Slow release wax-matrix tablets are preferred for tube fed patients d. Gastric and jejunal delivery of KCL liquid are interchangeable

5. Which large volume intravenous fluid would be best as a replacement fluid for a patient with

significant small bowel intestinal fluid losses? a. Lactated Ringers solution b. 0.9% NaCL with 20 mEq KCl/L c. 0.9% NaCL with 40 mEq KCl/L d. 0.45% NaCL with 20 mEq KCl/L

Learning Assessment Answers:

1. D. All of the above choices have been associated with medication errors when using electrolyte sources from 503B facilities (facilities that compounds sterile products for institutions).

2. D. All of the above factors are reasons why it may be difficult to achieve a serum phosphorus concentration of 4 mg/dL.

3. C. The prescribed calcium chloride dose should be 1/3 the dose of calcium gluconate as 1 g of calcium gluconate provides 4.65 mEq of elemental calcium whereas 1 g of calcium chloride provides 13.6 mEq of elemental calcium.

4. B. A rapid inadvertent pulse dose of potassium cannot be accomplished with oral or enteral administration due to timing of absorption and feed forward regulation of enteral potassium administration unlike intravenous administration. Bioavailability with enteral or oral potassium supplementation is ~95% or better under most circumstances. Wax matrix tablets when crushed will clog the feeding tube and is a poor product choice. Jejunal administration of hypertonic drug solutions like potassium chloride liquid can cause cramping and diarrhea.

5. A. Because of significant sodium, chloride, and bicarbonate content of intestinal fluids, it would be prudent to choose a more “balanced” replacement solution containing lactate (converts to bicarbonate in the liver) to prevent an acidemia particularly if adjustments to the PN solution are limited.

Key References:

1. Brown EW, McClellan NH, Minard G, Maish GO, Dickerson RN. Avoiding Patient Harm With Parenteral Nutrition During Electrolyte Shortages. Hosp Pharm. 2018;53:403-407.

2. Busch RA, Curtis CS, Leverson GE, Kudsk KA. Use of Piggyback Electrolytes for Patients Receiving Individually Prescribed vs Premixed Parenteral Nutrition. JPEN. 2015;39:586-590.

3. Curtis CS, Busch RA, Crass RL, Webb AP, Kudsk KA. Use of Premixed Parenteral Nutrition During a Phosphate Shortage in a Non-Critically Ill Population. Nutr Clin Pract. 2016;31:218-222.

4. Patino AM, Marsh RH, Nilles EJ, Baugh CW, Rouhani SA, Kayden S. Facing the Shortage of IV Fluids - A Hospital-Based Oral Rehydration Strategy. N Engl J Med. 2018;378:1475-1477.

5. Plogsted S, Adams SC, Allen K, et al. Parenteral Nutrition Electrolyte and Mineral Product Shortage Considerations. Nutr Clin Pract. 2016;31:132-134.

Metabolic Support in the Era of Parenteral Nutrition Component Shortages

• Fluid and Electrolytes – Roland Dickerson, PharmD, BCNSP,FASPEN

• Amino Acids, Trace Minerals, and Cysteine – Steven Plogsted, PharmD, BCNSP, CNSC

• Resources for Managing Shortages of PN Components and Multi-Component Products – Beverly Holcombe, PharmD, BCNSP, FASPEN

• Open Discussion Among Session Participants and Speakers

Active Shortages Top 5 Drug Classes

101

1217

2

23

15

11

26

29

0

5

10

15

20

25

30

35

40

45

50

Antimicrobials Chemotherapy Cardiovascular CNS E-Lytes, Nutrition,Fluids

Active Shortages December 31, 2018

University of Utah Drug Information ServiceErin.Fox@hsc.utah.edu, @foxerinrGreen = injectable, yellow = non-injectable

Metabolic Support in the Era of Fluid and Electrolyte Shortages

Roland Dickerson, PharmD, BCNSP, FCCP, FASHP, FCCM, FASPEN

Professor of Clinical Pharmacy and Translational Science

University of Tennessee College of Pharmacy

Clinical Coordinator and Clinical Pharmacist, Nutrition Support Service

Regional One Health

Memphis, TN

Disclosures

• No conflicts of interest to disclose.

Learning Objectives

• Identify the most common electrolyte shortages

• Describe the clinical relevancy between electrolyte depletion and organ dysfunction

• Contrast “optimal” and “essential” electrolyte dosingalgorithms for electrolyte disorders during shortages

• Discuss methods for managing electrolyte disorders

Some Common Principles During Intravenous Electrolyte Shortages

(go to www.nutritioncare.org for a more detailed compilation)

• Use the oral/enteral route if practical or possible

• Reserve for patients requiring PN or with a therapeutic need

• Identify the “most appropriate” target goal for the patient

• Reconsider “automatic” use of standardized dosing algorithms

• Address the etiology for the electrolyte disorder

• Consider if use of a commercially available multi-electrolyteproduct would be acceptable

• Beware of products provided by outsourcing 503B manufacturers

• Think “outside of the box”

Beware of Outsourcing Facilities

• Electrolyte solutions compounded with SWFI from powder sources

• Electrolyte concentrations may not be same as conventional sources

• Labeling requirements are not required to be in line with USP standards for 503B facilities

Think “Outside of the Box”

• Determine the etiology for the electrolyte disorder and treat the etiology if possible (direct example: diarrhea; indirect example: high non-obstructive gastric output with ? NGT placement)

• Evaluate supplemental IV fluids – could a commercially available large volume IV solution be substituted for the current supplemental fluid? (examples: 0.45% NaCl or 0.9% NaCl with 20 mEq/L or 40 mEq/L of KCL or Lactated Ringers solution)

• Drug substitution: Could a potassium-sparing diuretic be substituted (e.g., in lieu of HCTZ)?

Intracellular Electrolytes“The Big Questions”

• Is it necessary to keep serum potassium @ 4 mEq/L, phosphorus @ 4 mg/dL, magnesium @ 2 mg/dL, ionized calcium @ > 1.12 mmol/L in all patients?

• Are the etiologies for the electrolyte disorders beingadequately addressed?

• Is intravenous treatment of the electrolyte disorder necessary for the patient?

Phosphorus

• Commonly in shortage

• Particularly essential for muscle contractility (cardiac and diaphragmatic), oxygen transport (2,3 DPG)

• Increased demand in patients with traumatic and thermal injuries, undergoing hepatic resection, receiving carbohydrate-based feedings, insulin therapy, or in those with refeeding syndrome

Etiologies for Hypophosphatemia(most are untreatable short-term)

• Malnourished patients

• Alcoholism

• Refeeding Syndrome

• Drugs (calcium, antacids, phos-binders)

• Hepatic Resection

• Critical Illness/Traumatic and Burn Injury

• Hyperparathyroidism

• Cancer (fibroblast growth factor-23)

Should We Target a Serum Phosphorus Concentration of 4 mg/dL During Intravenous

Phosphorus Shortages?

• Serum phosphorus < 2 mg/dL detrimentally influences

organ function

• Where did the target of 4 mg/dL come from?

Why do we target a serum phosphorus concentration of 4.0 in ICU patients if the normal

range is ~2.5 to 4.5 mg/dL?

Aubier et al. NEJM. 1985;313:420-4.

Variable Before After P <

Phos 1.0 + 0.4 3.8 + 1.4 0.01

HR 102 + 17 105 + 13 N.S.

CI 3.8 + 1.9 4.5 + 1.8 0.01

Zazzo et al. Inten Care Med. 1995:21:826-31.

Why it is Difficult to Achieve a Serum Phosphorus Concentration of 4 mg/dL in ICU Patients

• Cytokines/catecholamines

• Increased energyexpenditure

• Augmented renal clearance

• Renal phosphate threshold concentration

Barak et al. Amer J Med. 1998;104:40-7.

Dickerson et al. JPEN. 2002;26:17-29.

Crawford et al. Crit Care Med. 2019;47(1: Suppl 1):863.

Dickerson et al. JPEN. 2001;25:153-9.

IV Phosphorus Dosing for Hospitalized Patients• Serum Phosphorus

Concentration (mg/dL)

• 2.3 to 3 mg/dL

• 1.6 to 2.2 mg/dL

• < 1.5 mg/dL

• Dosage (mmol/kg)

“High needs”

• 0.32

• 0.64

• 1

◼ Dosage

(mmol/kg)

General/ICU

◼ 0.16

◼ 0.32

◼ 0.64

Infuse Intravenous Phosphorus at 7.5 mmol/hr~ HALF DOSES FOR PATIENTS WITH KIDNEY IMPAIRMENT!

Clark CL et al. Crit Care Med.

1995;23:1504-11.

Brown KA et al. JPEN.

2006;30:209-14.

Sodium Glycerophosphate

• Available for use in the US (due to IV phosphate shortages) from Fresenius Kabi

• Organic form of phosphorus – used extensively in Europe

• Compatible in PN solutions

• 20 ml single use plastic vial (1 mmol/mL of Phosphorus; 2mEq sodium per mmol of phosphorus)

Intravenous Phosphorus Sources

Electrolyte mEq per mmol Phos

Concentration and volume units

(in vials)

Typical prescribing units (mmol)

Amounts given per prescribing units (mEq)

Potassium

Phosphate

1.47 mEq

K

3 mmol/mL

15 mL, 50 mL

15, 30, 45, 60 of P 22, 44, 66, 88 of K

Sodium

Phosphate

1.33 mEq

Na

3 mmol/mL

15 mL, 50 mL

15, 30, 45, 60 of P 20, 40, 60, 80 of Na

Sodium

Glycerophosphate*

2 mEq

Na

1 mmol/mL

20 mL

20, 40, 60 of P 40, 80, 120 of Na

K H2 (P04)

Potassium

Phosphate

Monobasic

K2 H (P04)

Potassium

Phosphate

Dibasic

mEq = (mg/molecular weight) X Valence = mmol X valence

* Only available in single use vials

Enteral Phosphorus Options

• Phos-NaK = 250 mg Phos (8 mmol) + 7.1 mEq K, 7.1 mEq Na. Available in powder or capsule. Dissolve 1 packet or open capsule into ~75 mL of water

• Kphos Neutral = Potassium and Sodium Phosphate tablets =250 mg Phos (8 mmol) + 13 mEq Na + 1.1 mEq K.

• Practical for significant deficiency?

• Diarrhea

Should We Target a Serum Phosphorus Concentration of 4 mg/dL During Intravenous

Phosphorus Shortages?

Perhaps a target serum phosphorus concentration of

> 3 mg/dL is acceptable?

Calcium:Another common IV electrolyte in shortage

• “Normal” values:

Total calcium: 8.5 to 10.5 mg/dL

Ionized calcium: 1.12 to 1.32 mmol/L

• Modified Orell equation: (0.8 mg/dL decrease in total calcium for every 1 g/dL decrease in serum albumin conc) – not accurate for ICU patients

HypocalcemiaSigns/Symptoms and Etiologies

• Chvostek’s/Trouseau’s

• Cramping/tetany

• Seizures

• CHF, hypotension

• Increased Q-T interval,arrhythmias

• Coagulation disorders

• Metabolic bone disease

• Parathyroidectomy

• Hypomagnesemia

• Malabsorption (?)

• Vitamin D deficiency

• Acute and chronic pancreatitis

• Renal failure

• Hyperphosphatemia

When Should Hypocalcemia Be Treated?

• Significant or symptomatic hypocalcemia or ionized calcium concentration < 1 mmol/L

• Massive blood transfusion with pre-existing myocardial disease

• Calcium channel blocker overdose

• Receiving inotropic agents and/or vasopressors?

• Adjunct to emergent management of severe hyperkalemia

• Coagulopathy or high risk for bleeding?

• Prevention of worsening hypocalcemia???

Calcium Gluconate Dosing GuidelinesContinuous Infusion NOT Necessary!

Ca

Dose

(g)

Ionized Ca

1 – 1.12

mM/L

(n=29)

Ionized Ca

< 1mM/L

(n= 8)

1 8/8 (100%) -

2 15/21 (71%) 2/5 (40%)

3 - 0/2 (0%)

4 - 1/1 (100%)20 patients iCa < 1 mM/L

4g Ca Gluconate over 4 hours

iCa 0.90 + 0.8 to 1.16 + 0.11 mM/L

14/20 (70%) corrected after a single 4 g dose

19/20 (95%) > 1 mM/L

2 pts iCa = 1.34 and 1.38 mM/L after 4 g dose

Dickerson RN et al. JPEN.2005;29:436-431.

Dickerson RN et al. JPEN.2007;31:228-233.

Dickerson RN et al. Nutrition.2007;23:9-15.

IV Calcium Dosing Recommendations(without shortage)

Ionized

Ca Conc

(mmol/L)

Calcium Gluconate

Dose

1.00 – 1.12 2 g IVPB over 2 hrs

< 1.00 4 g IVPB over 4 hrs

Dickerson RN et al. JPEN.2005;29:436-431.

Dickerson RN et al. JPEN.2007;31:228-233.

Dickerson RN et al. Nutrition.2007;23:9-15.

Treatment Considerations for Hypocalcemia(for lower risk patients)

• If symptomatic or if the ionized calcium is < 1 mmol/L treat with calcium and magnesium (if serum magnesium is below normal)

• If asymptomatic/ionized Ca > 1 mmol/L, may just treat with magnesium – iCa should correct within 2 days of therapy with magnesium

Calcium Gluconate vs Calcium Chloride

Calcium Gluconate Calcium Chloride

Concentration 10% Concentration 10%

Volume 10 mL Volume 10 mL

g per 10 mL 1 g per 10 mL 1

mEq 4.65 mEq 13.6

Prescribing Prescribing

1 g in 50 or 100 mL NS.

Infuse over 1 hr

0.33 g in 50 or 100 mL NS. Infuse over 1

hr

2 g in 100 mL NS. Infuse over 2 hrs 0.67 g in 100 mL NS. Infuse over 2 hrs

4 g in 250 mL NS. Infuse over 4 hrs 1.34 g (use 0.67 g X 2 doses)

Oral Calcium Therapy(not suggested for an iCa < 1 mmol/L)

• For more stable, non-critically ill patients

• Calcium carbonate (40% elemental Ca)

• 500 mg to 1 g three to four times daily to achieve an elemental calcium intake of 1200 to 1500 mg/day

• Often taken in conjunction with oral vitamin D

Potassium

• Keep serum K > 4.0 mEq/L?

• “Normal” serum concentration: 3.5 to 5.2 mEq/L

• Hypokalemia (serum K < 3.5 mEq/L) occurs in 21% of hospitalized patients* (may be more frequent in patientsreceiving nutrition therapy)

• ECG changes not consistent with presence of hypokalemia*

• Most cases of hypokalemia-induced rhythm changes occur in those with underlying heart disease*

*Viera AJ et al. Am Fam Physician. 2015;92:487-495

HypokalemiaEtiologies (The “At Risk” Population)

• Decreased intake – rare with oral diet (kidneys adapt)

• Increased requirements due to building of new muscle/tissue (refeeding syndrome) or hypermetabolic states

• Increased gastrointestinal losses

• Hypomagnesemia

• Medications (diuretics, insulin, beta adrenergic agonists, catecholamines, amphotericin B)

• Intracellular shift with alkalemia

• Increased urinary losses (diabetes insipidous)

Hypomagnesemic Hypokalemia

• About 50% of clinically significant hypokalemic patients have hypomagnesemia

• Magnesium is co-factor for Na-K-ATPase pump

• Intracellular magnesium binds Renal Outer Medullary Potassium (ROMK) channels in distal nephron and inhibits K efflux

• If hypomagnesemic, hypokalemia is refractory to potassium therapy alone

• If hypomagnesemic, must treat both!

Huang et al. J Am Soc Nephrol. 2007;18: 2649-52.

Empiric IV Dosing Guidelines for Potassium

Serum K

(mEq/L)

Potassium Dosage

(mEq)*

3.5 – 3.9 40 to 60 mEq X 1 dose

3.0 – 3.4 40 mEq X 2 doses

< 3 40 mEq X 3 doses

* Given at 10 mEq/hr. Use half doses for renal

impairment; may need to be adjusted based on

body size, nutrition therapy, and ongoing losses.

Patients with TBI had an attenuated response.

Excluded patients with confounding factors.

Johnston CT et al. JPEN.2017;41:796-804 .

Potassium Therapy and PN

• “Additional” potassium may be added to the PN solution

• Different salt forms available: chloride, acetate, phosphate

• “Standard K” ~ 40 mEq/L or 80 to 100 mEq/d (0.5 to 1.2mEq/kg/d)

• “Repletion K” ~ 60 to 80 mEq/L or 120 to 160 mEq/d (1.5 to 2 mEq/kg/d)

• Consider using commercially available KCl containing IV solutions (e.g., D5 0.45% NaCl with 20 or 40 mEq of KClper liter) if necessary

Oral or Enteral Potassium Therapy

• 95% to 100% bioavailable enterally

• “Safer” and often preferred over IV unless contraindicated or severe/symptomatic potassium deficiency

• Slow-release tabs are generally better tolerated or more palatable than effervescent or liquid, but wax-matrix tabs (higher incidence of GI erosions) –Don’t administer via tube!

• KCL liquid can be given via intra-gastrically (flush tube well if EN)

• Do not administer via the small bowel -diarrhea (osmolality) Greenlee M al. Ann Intern Med 2009;150:619-625

Hypomagnesemia

• Normal serum conc.: 1.8 to 2.4 mg/dL

• When do patients become symptomatic?Serum magnesium < 1.2 to 1.5 mg/dL?*

• Should the target serum magnesium concentration be > 2 mg/dL in patientswithout heart disease, hypokalemia, hypocalcemia, or symptoms?

*Martin KJ et al. J Am Soc Nephrol 2009; 20: 2291–2295

Hypomagnesemia

Signs/Symptoms Etiologies

• Gastrointestinal losses

• Sepsis/critical illness

• Drugs – lactulose, laxatives, diuretics, cyclosporin, tacrolimus,foscarnet, amphotericin B, cisplatin, carboplatin, ifosfamide, cetuximab, pentamidine

• Alcohol

• Pancreatitis

• Thermal injury

• Muscle weakness, cramping,parasthesias

• Positive Chvostek’s andTrousseau’s signs

• Tetany

• Q-T prolongation; cardiac arrhythmias (PVCs, v tach, v fib)

• Hypocalcemia

• Hypokalemia

Empiric Dosing Guidelines for IV Magnesium Sulfate

Half doses for those with renal

impairment; Infuse at ~ 1 g/hr

Sacks GS et al. Nutrition.1997;13:303-8.

Serum

Magnesium

Conc (mg/dL)

Dosage of IV

Magnesium

Sulfate (g/kg)

1.6 – 1.8 0.05

1 – 1.5 0.1

< 1 0.15

Trauma patients, serum Mag < 1.5 mg/dL

(mean, 1.1 mg/dL)

Given IV infusion of 0.125 or 0.19 g/kg

Magnesium Therapy(during shortage)

• Magnesium therapy generally take 4 to 7 days of therapy to replenish deficit following initial IV loading dosage

• Serum magnesium < 1.5 mg/dL (~1 – 1.5 mEq/kg deficit)

• Serum magnesium < 1mg/dL (~2 mEq/kg deficit)

• Serum magnesium concentrations take 24 to 48 hrs to equilibrate post intravenous dose

• Oral magnesium replenishment may be tried for a serum concentration > 1.2 to 1.5 mg/dL if patient is asymptomatic and if the etiology for the hypomagnesemia is not GI-related (empiric recommendation)

Oral Magnesium Therapy

Salt form Strength Elemental

Mag

Usual Dosing

Gluconate 500 mg 2.2 mEq 1-2 tabs TID

Oxide 400 mg

140 mg

19.8 mEq

6.9 mEq

1-2 tabs BID to

TID

Chloride tablet 2.6 mEq 2 tabs daily

Multi-Electrolyte Intravenous Solutions

Ingredients Plasma-Lyte APlasma-Lyte148

Isolyte S (Canada)

Normosol-R Lactated Ringers

Sodium (mEq/L) 140 140 140 130

Potassium (mEq/L) 5 5 5 4

Chloride (mEq/L) 98 106 98 109

Acetate (mEq/L) 27 27 27 0

Lactate (mEq/L) 0 0 0 28

Magnesium (mEq/L) 3 3 3 3

Influence of Multi-Chamber Bag PN Solutions upon Electrolyte Needs for (All) PN Patients

(change due to amino acid shortage)

Electrolyte

Concentration

(mEq/L)

Individual

PN

Two

chamber

MCB-PN

Three

chamber

MCB-PN

Sodium 0 – 130 35 32

Potassium 20 - 80 30 24

Calcium 5 4.5 4

Magnesium 0 - 15 5 8

Phosphorus

(mmol/L)

0 - 30 15 10

Acetate 51 to 80* 39

Chloride 39 46

Variable Individual

PN

MCB-PN P

Patients (n) 59 81

PNs (n) 457 490

Electrolyte

piggybacks

(K, Mag,

Phos)

7.0 + 3.1 13.8 + 6.8 0.001

Target Electrolyte Concentrations:

K > 4.0 mEq/L, Phos > 3.0 mg/dL,

Magnesium > 2.0 mg/dL

*dependent on amino acid concentration Busch RA et al. JPEN. 2015;39:586-590.

Influence of Multi-Chamber Bag PN Solutions upon KPhos Prescribing for Non-Critically Ill Patients

(change due to KPhos shortage)

• Previously well-nourished, stable post-op patients with delayed return of bowel function after bowel surgery

• Target Phosphorus Concentration: Phos > 3.0 mg/dL? (not given)

• Given 30 mmol of Phos given daily via MCB-PN (2 L/d),16,440 mmol of phos conserved for the year

• Because of a 14 fold increase in cost of Kphos (during shortage period), use of MCB-PN solutions resulted in overall cost savings compared to individualized PN prescriptions.

Electrolyte

Concentration

(mEq/L)

D10%

AA 4.25%

D15%

AA 5%

Sodium 35 32

Potassium 30 30

Calcium 4.5 4.5

Magnesium 5 5

Phosphorus

(mmol/L)

15 10

Acetate 70 80

Chloride 39 39

Curtis CS et al. Nutr Clin Pract. 2016;31:218-22.

Electrolyte Shortage-Induced Acid-Base Disorders

• Sodium Acetate

• Sodium Chloride

• Potassium Acetate

• Potassium Chloride

• Magnesium Chloride

• Sodium Bicarbonate

• Acetate/Lactate/Citrate: Substitute for Bicarbonate

Brown EW et al. Hosp

Pharm. 2018;53:403-7.

65 yo male. Prolonged ileus. An average of ~800 mL/d NG suction

and ~1600 mL/d jejunostomy drainage (for abd decompression).

PN (1.3 X BEE, 1.8 g/kg/d of protein, and 1.9 L/d of fluid).

Supplemental fluids: 0.9% NaCl + 0.45% NaCl. Total chloride

and acetate intakes from PN and supplemental IV fluids (mEq/d):

430 mEq and 60 mEq. Stable PN for 2 months.

SHORTAGE: No K Acetate, No Na Acetate!ABG pH 7.28, pCO2 36, HCO3 17: mild non-AG

(hyperchloremic) metabolic acidosis

Sodium bicarbonate 50 mEq daily X 3 days

Supplemental fluid changed to Lactated Ringers soln– 2 liters/day

(provided 56 mEq of lactate and reduced chloride by 90 mEq

daily).

ABG: 7.36, pCO2 54, HCO3 30 (vent weaning trials) Brown EW et al. Hosp Pharm.2018;53:403-7.

Shortage of Intravenous Fluids

0.9% NaCl (large volume) shortage

• Initiation of oral rehydration fluid protocol*

• 30% reduction in IV fluid use; 15% reduction in emergency dept*

0.9% NaCl (small volume) shortage

• Repackaging of large volume 0.9% NaCl to piggyback bags

• Purchase pre-mixed medications

• Syringe pumps or small volume infusion devices for medications

*Patino AM et al. New Engl J Med. 2018;378:1475-7.

Mazer-Amirshahi M et al. New Engl J Med. 2018;378:1472-4.

Metabolic Support in the Era of Fluid and Electrolyte Shortages

Beverly Holcombe, PharmD, BCNSP, FASHP, FASPEN Clinical Practice Specialist, American Society for Parenteral and Enteral Nutrition Resources for Managing Shortages of Parenteral Nutrition Components and Multi-component Products Disclosure: I have no commercial relationships to disclose. Presentation Overview/Summary Shortages of parenteral nutrition (PN) have been ongoing for almost three decades. Historically, they were intermittent and short-lived. Since 2010, almost every component used in the preparation of PN admixtures has been in short supply and the duration of shortages has been months to years. Providing PN therapy is particularly challenging as multiple ingredients used in the PN may simultaneously be in limited supply and the availability of PN components must be considered during every step of the PN use process from ordering the PN prescription to administering this therapy to a patient. Several federal and healthcare professional organizations have developed resources to assist clinicians in managing shortages. This session will discuss these resources, their features and how to use them in developing institutional efforts and PN product-specific guidance for optimizing patient care and minimizing the potential for adverse health outcomes during shortages. Learning Objectives At the conclusion of the presentation, the learner will be able to:

1. explain the role of the FDA in preventing and mitigating medication shortages. 2. identify resources for guidance in selecting appropriate alternative(s) during shortages of PN

components and multi- components products. 3. identify resources for developing policy and procedures for managing shortages of PN

components and multi-component products.

Key Takeaways/Fast Facts • Shortages of PN components and multi-component products continue and despite efforts from

federal agencies, healthcare providers, group purchasing organizations and pharmaceutical industry no enduring solution(s) to preventing shortages has been identified.

• The American Society of Health-System Pharmacists (ASHP) provides clinical and administrative guidance, tools and information on medication shortages. and healthcare organization management of drug shortages. (https://www.ashp.org/Drug-Shortages/Shortage-Resources).

• The American Society for Parenteral and Enteral Nutrition (ASPEN) offers resources for general and component-specific management of shortages of PN components and multi-component products.

• Report any adverse Learning Assessment Questions

1. The Food and Drug Administration Safety and Innovation Act (FDASIA) gives the FDA Commissioner the authority to require a pharmaceutical manufacturer to make more of a medication.

A. True B. False

2. Which organization publishes conservation and management strategies specifically for managing shortages of PN components and multi-component products?

A. Institute for Safe Medication Practices (ISMP) B. American Hospital Association (AHA) C. American Society of Health-System Pharmacists (ASHP) D. American Society for Parenteral and Enteral Nutrition (ASPEN)

3. Medication errors or adverse event associated with shortages of PN components and multi-component products should be reported to the Agency for Healthcare Quality and Research (AHRQ).

A. True B. False

4. The best resource for a healthcare system pharmacy developing policies and procedures for identifying and managing shortages of PN components and multi-component PN products is the

A. American Hospital Association (AHA). B. American Pharmacists Association (APhA). C. American Society of Health-System Pharmacists (ASHP). D. American Society for Parenteral and Enteral Nutrition (ASPEN).

5. The FDA Drug Shortage web site list of medications in short supply includes only medications that are considered medically necessary.

A. True B. False

Learning Assessment Answers:

1. Answer = False; Rationale: FDASIA requires pharmaceutical manufacturers to notify the FDA of a potential shortage or permanent discontinuance or interruption in the production of medications. The FDA cannot require manufacturers to make a drug, produce more of a drug or change how the drug is distributed.

2. Answer = D; Rationale: All organizations, ISMP, ASHP and AHA, provide resources on drug shortages. However, ASPEN is the organization that publishes guidance specific to managing shortages of PN components and multi-component products.

3. Answer = False; Rationale: Medication errors and adverse patient outcomes associated with shortages should be reported to the Institute for Safe Medication Practices Medication Error Reporting Program and the FDA MedWatch. Although AHRQ’s mission is to produce evidence to make health care safer, higher quality, more accessible, equitable, and affordable it does not collect information on medication-related adverse events.

4. Answer = C; Rationale: ASHP provides resources outlining the responsibilities and tasks for pharmacists and pharmacy technicians for each phase of drug shortage management. AHA and APhA have public policy statements regarding drug shortages but not management strategies. ASPEN’s PN component shortage management strategies are specific to PN components but do not guidance for every phase of the management process.

5. Answer = True; Rationale: The FDA’s priority is on medications considered medically necessary, which are those intended to prevent or treat a debilitating disease or condition. The ASHP drug shortage list includes any medication with a supply issue that affects how pharmacies prepare and dispense a product or when prescribers must choose an alternative therapy due to supply issues.

References 1. Holcombe B, Mattox T, Plogsted S. Drug shortages: effect on parenteral nutrition therapy. Nutr

Clin Pract. 2018; 33(1):53-61. 2. United States FDA. Frequently asked questions about drug shortages.

https://www.fda.gov/Drugs/DrugSafety/DrugShortages/ucm050796.htm#q4. Accessed February 10, 2019.

3. American Society of Health-System Pharmacists Drug Shortages. https://www.ashp.org/Drug-Shortages. Accessed February 10, 2019.

4. American Society for Parenteral and Enteral Nutrition. Nutrition product shortages. http://www.nutritioncare.org/public-policy/product-shortages/. Accessed February 10, 2019.

Steve Plogsted PharmD, NCNSP, CNSC Clinical Pharmacist Nutrition Support Service Nationwide Children’s Hospital, Columbus, OH Resources for Metabolic Support in the Parenteral Nutrition Component Shortages, Amino Acids, Trace Minerals and Cysteine Disclosure: I have no commercial relationships to disclose. Presentation Overview/Summary Shortages of parenteral nutrition (PN) components pose a great threat to the health of anyone who relies of parenteral therapy. In order for the nutrition specialists to mitigate these threats they first must have an understanding of the normal requirements for their patients. This session will review the recommended intakes for protein, trace elements and cysteine and will discuss alternative products and routes of administration. The session will also briefly some electrolyte replacement strategies. Learning Objectives At the conclusion of the presentation, the learner will be able to:

1. Review the protein requirements of the adult and pediatric patient 2. Discuss the micronutrient needs of the adult and pediatric patient 3. Formulate plans for the use of alternative intravenous shortage components 4. Discuss potential safety issues when utilizing alternative strategies to address parenteral

component shortages

Key Takeaways/Fast Facts • Shortages continue to stifle efforts to provide adequate nutrition to our patients. Often we have to

employ alternative strategies to provide for the patient’s well-being and in doing so may place the patient’s safety at risk.

• Little formal information is available to help mitigate these risks Learning Assessment Questions

1. The American Society for Parenteral and Enteral Nutrition (ASPEN) provides guidelines for the safe use of nutritional components.

A. True B. False

2. Multichamber Bag Parenteral Nutrition (MCB-PN) Products are a collection of closed system products that provides full nutrition support to meet the needs of most patients needing parenteral nutrition.

A. True B. False

3. Zinc deficiency in neonates can result in the patient developing A. Hypotonia B. Anemia C. Growth failure D. Glucose metabolism

4. What percent of the average adult’s protein content makes up the body cell mass (BCM) A. 12.5% B. 25% C. 80-85% D. 50%

5. According to the World Health Organization the safe level for protein intake for a 1 year old is A. 2..25 g/kg

B. 1.65 g/kg C. 1.14 g/kg D. 1 g/kg

Learning Assessment Answers:

1. Answer = True; ASPEN as an organization is dedicated to providing evidence based nutrition support for our patients.

2. Answer = F; Although the products currently available in the marketplace provide a wide range of options in providing nutrition support they don’t meet the needs of a majority of patients, particularly the neonatal and pediatric patient.

3. Answer = C. Zinc plays an important role in linear growth of the neonate. Copper deficiency can result in hypotonia and anemia whereas chromium deficiency can lead to abnormal glucose metabolism.

4. Answer = D. Approximately 50% of the body’s protein makes up the body cell mass. Of the body cell mass skeletal muscle makes up 80-85%

5. Answer = C. According to the World Health Organization the safe level for protein intake for a 1 year old is 1.14 g/kg with the average requirement of only 0.95 g/kg.

References 1. Ayers P, Holcombe B, Plogsted S, Guenter P, eds. A.S.P.E.N. Parenteral Nutrition Handbook,

2nd ed. A.S.P.E.N., Silver Spring, MD, 2014. Mueller CM, ed. A.S.P.E.N. Adult Nutrition Support Core Curriculum, 2nd ed. A.S.P.E.N., Silver Spring, MD, 2012

2. Hoffer J. Human Protein and Amino Acid Requirements. JPEN 2016; 40(4):460-475. 3. Helms R, Tillman E, Patel A, KernerJ. Protein Digestion, Absorption, and Metabolism. In The

A.S.P.E.N. Pediatric Nutrition Support Core Curriculum, 2nd ed, Ed M Corkins, 31-44. 4. Joint FAO/WHO/UNU Expert Consultation on Protein and Amino Acid Requirements in Human

Nutrition (2002 : Geneva, Switzerland), Food and Agriculture Organization of the United Nations, World Health Organization & United Nations University. (2007). Protein and amino acid requirements in human nutrition : report of a joint FAO/WHO/UNU expert consultation. Geneva : World Health Organization. http://www.who.int/iris/handle/10665/43411.

5. Ayers P, Adams S, Boullata J, et al. A.S.P.E.N. Parenteral nutrition safety consensus recommendations. J Parenter Enteral Nutr. 2014;38(3):296-333

6. Mena K, Espitia O, Vergara J. Management of Ready-to-Use Parenteral Nutrition in Newborns: Systematic Review. J Parenter Enteral Nutr 2018; 42(7):1123-1132.

7. Chhim R, Crill C. Premixed Parenteral Nutrition Solution Use in Children. J Pediatr Pharmacol Ther 2015; 20(5):378-384.

8. Vanek V, Borum P, Buchman A, Fessler T, Howard L, Jeeejeebhoy K, Kochevar M, Shenkin A, Valentine C, Novel Nutrient Taskforce, Pafrenteral Multi-Vitamin and Trace- Element Working Group, and the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors. A.S.P.E.N. Position Paper: Recommendations for Changes in Commercially Available Parenteral Multivitamin and Multi–Trace Element Products. Nutr Clin Pract. 2012;27:440-491.

9. Otten JJ, Pitzi Hellwig J, Meyers LD, eds. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: National Academies Press; 2006

10. Sriram K, Lonchyna A. Micronutrient Supplementation in Adult Nutrition Therapy: Practical Considerations. J Parenter Enteral Nutr 2009 33: 548-562

11. Greene HL, Hambidge M, Schanler R, Tsang R. Guidelines for the use of vitamins, trace elements, calcium, magnesium, and phosphorus in infant and children receiving total parenteral nutrition: report of the Subcommittee on Pediatric Parenteral Nutrient Requirements from the Committee on Clinical Practice Issues of the American Society for Clinical Nutrition. Am J Clin Nutr. 1988;48:1324-1342

12. Notes from the Field: Zinc Deficiency Deficiency Dermatitis in Cholestatic Extremely Premature Infants After a Nationwide Shortage of Injectable Zinc — Washington, DC, December 2012

CDC Mortality and Morbidly Weekly. Weekly Feb 22, 2013; 62(7):136-137. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6207a5.htm

13. Aoki T. Copper Deficiency and Clinical Practice. JJMAJ 2004; 47(8):365-370. 14. Corkins M, Martin V, Szeszycki E. Copper Levels in Cholestatic Infants on Parenteral Nutrition.

J Parenter Enteral Nutr. 2013;37:92-96 15. Capone K, Sriram S, Patton T, Weinstein D, Newton E, Wroblewski K, Sentongo T. Effects of

Chromium on Glucose Tolerance in Infants Receiving Parenteral Nutrition Therapy. Nutr Clin Pract. 2018;33:426–432

16. Moukarzel A. Chromium in Parenteral Nutrition: Too Little or Too Much. Gastroenterology 2009; 137:S18-S28

17. Davis C, Javid D, Horsley S. Selenium Deficiency in Pediatric Patients With Intestinal Failure as a Consequence of Drug Shortage. K, Parenter Enteral Nutr. 2014;38:115-118.

18. Masumoto K, Nagata K, Higashi M, Nakatsuji T, Uesugi T, Takahasi Y, Nishimoto Y, Kitijima J, Hikino S, Hara T, Nakashima K, Nakashima K, Oishi R, Taguchi T. Clinical Features of Selenium Deficiency in Infants Receiving Long-Term Nutritional Support. Nutrition. 2007;23:782-787.

19. Chen C, Harris M, Partipilo M, Welch K, Teitelbaum D, Blackmer A. Impact of the Nationwide Intravenous Selenium Product Shortage on the Development of Selenium Deficiency in Infants Dependent on Long-Term Parenteral Nutrition. Parenter Enteral Nutr. 2016;40(6):851-859.

20. Riedijk MA, Voortman G, van Beek RHT, Baartsman MGA, Wafelman LS, van Goudoever JB. Cysteine Requirements in Enterally Fed Very Low Birth Weight Infants. Pediatrics. 2008;121 (3):e561-567.

Metabolic Support in the Era of PN Component Shortages:

Amino Acids, Trace Elements and Cysteine

ASPEN 2019 Nutrition Science & Practice Conference

Steven Plogsted, PharmD, BCNSP, CNSCClinical Pharmacist, Nutrition Support Service

Nationwide Children’s Hospital

Columbus, Ohio

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Disclosures

I have no commercial relationships to disclose

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Learning Objectives

1. Review the protein requirements of the adult and pediatric patient

2. Discuss the micronutrient needs of the adult and pediatric patient

3. Formulate plans for the use of alternative intravenous shortagecomponents

4. Discuss potential safety issues when utilizing alternative strategies toaddress parenteral component shortages

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ASPEN Recommendations for Conservation of PN Products

Consider oral or enteral administration Prioritize patients, saving supplies for those most vulnerable patients Eliminate adding injectable electrolytes/minerals to enteral nutrition products Minimize the use of additives to daily maintenance IV fluids Reevaluate replacement algorithms or treatment protocols Carefully evaluate alternative supplies of individual and multiple electrolyte products that are available, including standardized, commercially available PN products

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Protein Needs-Adult

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Patient Population Dose

Stable Patients 0.8-1 g/kg/d

Critically Ill 1.5-2 g/kg/d

Severe malnutrition, acute or chronic kidney injury-with or without renal replacement therapies, hepatic disease, trauma, obese, burns, etc.

See Clinical Guidelines/Scientific literature

Ayers 2012

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Basic Protein Needs-Adult

• Approx 50% of the protein in the body makes up the body cell mass (BCM)oRepresents ~50% of a healthy male and 40% of a healthy female

• The other 50% of the protein in the body is structural and metabolically inactive

• Skeletal muscle makes up 80-85% of the BCM in normal adults whereas the remaining 15-20% consists of fat free mass of the organs, plasma proteins blood cells and immunological cells

• Estimated minimum protein requirement of ~0.66 g/kg/day

• Obligatory losses are ~0.3 g/kg/day

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Hoffer 2016WHO 2002

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Stressed Protein Needs

• Generally accepted to be 1.5-2.5 g/kg or greater depending onmultiple factorsoTrauma

oSepsis

- Synthesis of 1 g fibrinogen would require the degradation of 2.6 g muscle protein

oBurs

oOpen wounds

oCRRT

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Hoffer 2016Preston 1998 ©

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9 AS

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Protein Needs

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2010 Pediatric Core Curriculum

Protein needs of the pediatric patient (g/kg/day)

Very low birth weight 3-4

Preterm 2.5-3

Infant/neonate 2-2.5

Infant 1.5-2

Preschool/school age 1-1.5

Adolescent 0.8-1.5

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Basic Protein Needs-Peds

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WHO 2002

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Basic Protein Needs-Peds

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Basic Protein Needs-Peds

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Amino Acid Needs-Neonate

• If given dextrose alone, infants lose 1-2% endogenous protein stores daily

• 1 g/kg/day achieves protein balance

• 2.5-4 g/kg/day allows accretion (i.e., newborn energy requirement)

• CAN START SOON AFTER BIRTH (within hours)o Prevents state of catabolism after birth

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Amino Acid Needs-Neonate

• Plasma amino acid profiles of neonates vary with gestational age

• Neonates have immature metabolic systems -lack hepatic enzymes needed to convert methionine to cysteine that is converted to taurine (conditionally essential amino acids)

• Neonates given “adult/standard” amino acid solutions tend to have

abnormal amino acid profiles and poor growth

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Current Amino Acid Formulations-Pediatric/Neonates

• Trophamine

• Aminosyn PF

• Premasolodesigned to match plasma amino acid profiles of healthy breast fed infants

ocontain less methionine/glycine/phenylalanine

ocontain conditionally essential amino acids taurine, glutamate,

aspartate

ocontain a higher percentage of the branch chain amino acids

leucine/isoleucine/valine

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Current Amino Acid Formulations -”Adult”

• Travasol

• Aminosyn

• Freamine

• Plenamine

• Clinisol

• Prosol

• Procalamine (for peripheral or central)

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Multichamber Bag Parenteral Nutrition (MCB‐PN) Products

ASPEN Definition

“A standardized parenteral nutrition formulation available from a manufacturer and

requiring fewer compounding steps before administration. Examples of these products are concentrated amino acids (with or without electrolytes), concentrated dextrose and with or without intravenous lipid emulsions in multi-chamber bags.

The term “premixed” should be avoided as these products require activation and mixing

prior to administration”

ASPEN recommends to consider utilizing in patients depending on needs and resources

ASPEN shortage recommendations-consider one of these products if appropriate

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Multichamber Bag Parenteral Nutrition Products

Clinimix-E

• Amino acids, dextrose and electrolytes• Multiple amino acid/dextrose combinations

• Adult based formulation

• Open chamber for lipid addition

• Clinimix

• Amino acids and dextrose• Multiple amino acid/dextrose combinations

• Adult based formulation

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Multichamber Bag Parenteral Nutrition Products

• Kabiven• Amino acids, dextrose, lipids and electrolytes

oSingle combination

oAdult based formulation

• Perikabiven• Amino acids, dextrose, lipids and electrolytes

oSingle combination

oAdult based formulation

oCan be used via both central and peripheral routes

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Multichamber Bag Parenteral Nutrition Products

• Advantageso Convenient

o Improved safety

• Disadvantageso May not meet the needs of certain patients

o Cost?

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Multichamber Bag Parenteral Nutrition Products Use in Pediatrics

• Response to component shortage• 69 patients and 74 courses of therapy• Age range 1.1 - 18 yrs• 5.6-7.2 days duration• 20% discontinuation rate d/t lab abnormalities• 22% required additional fluids• 38% required change to individualized therapy based on labs results• 98% of protein goal met• 67% met calorie goals

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Chhim 2015

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Multichamber Bag Parenteral Nutrition Products Use in Pediatrics

• Electrolyte imbalances seen

• 33% Metabolic alkalosis

• 20% Hyperkalemia

• 20% Hyperphosphatemia

• 13% Hypokalemia

• 7% Hypophosphatemia and hyponatremia

• 7% Hyperphosphatemia and metabolic alkalosis

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Chhim 2015

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Multichamber Bag Parenteral Nutrition Products Use in Pediatrics

Conclusion:

• Appeared to be safe and effective for at least a short period of time

• Patients require close monitoring

• Another option during PN component shortages

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Multichamber Bag Parenteral Nutrition ProductsWhen Electrolyte Supplementation Needed

Clinimix-E

• Uses inorganic phosphate and calcium gluconate

Kabiven

• Uses organic phosphate and calcium chloride

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Compatibility Concerns

• Calcium and magnesiumo Calcium chloride and magnesium sulfate

- Calcium sulfate (used to make Plaster of Paris)

• Zinc and phosphoruso Zinc hypophosphate

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Sodium Salt Substitutes

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Product Concentration

Table salt ~100 mEq/tsp

Salt tablets 17 mEq/1 gram

Sodium bicarbonate tablets 7.71 mEq/650 mg

0.9% NaCl injection 0.154 mEq/mL

3% NaCl injection 0.5 mEq/mL

5% NaCl Injection 0.85 mEq/mL

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Electrolyte Alternatives

Potassium

• 10 mEq/100 mL injection

• Various oral potassium chloride products

• Potassium citrate effervescent tab

• Potassium Salt substitutes

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Additional Oral Salt Substitutes

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Product mEq per tsp mg per tsp

Table Salt 102 sodium 2360 sodium

Morton Lite Salt 50 sodium35 potassium

1160 sodium1400 potassium

Morton’s Salt Sub 62.5 potassium 2440 potassium

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Concentrated Electrolytes-Caution

• Use when only absolutely necessary

• Communicate, communicate, communicate

• Return to standard concentrations as soon as possible thencommunicate, communicate, communicate

• ISMP Alert-May 24, 2018. Safe Handling of Concentrated ElectrolyteProducts From Outsourcing Facilities During Critical Shortageso Labeling requirements different from medical manufacturers

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Trace Element RequirementsCurrent Recommended Adult Daily Oral and Parenteral Micronutrient Requirements

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Trace Element Requirements

Pediatric

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Premature Infant Term Infant Children(Maximum dose)

Zinc, mcg/kg/day 400 250 50 (5000 mcg)

Copper, mcg/kg/day 20 20 20 (300 mcg)

Chromium, mg/kg/day 0.2 0.2 0.2 (5 mcg)

Manganese, mcg/kg/day 1 1 1 (50 mcg)

Selenium, mcg/kg/day 2 2 2 (30 mcg)

Green 1988

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Trace Element Shortage Zinc

CDC Report

• 3 infants 23-24 wks gestation with cholestasis

• 2 developed biopsy proven dermatitis

• Improvement with oral supplementation

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CDC 2013

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Why is Zinc So Important

• Essential cofactor in approximately 300 enzyme-dependent processes

• Fetal zinc accumulation via placental transport is maximal at 24–34 weeks of gestation

• Inadequate zinc supplementation leads to cutaneous changes, diarrhea, immunologic impairment, growth failure, and poor woundhealing

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CDC 2013

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Trace Element Shortage Copper

• Most common features with deficiency include anemia, leucopenia, bone lesions (scorbutic-like bone changes and occipital horn), and vesical diverticula

• In children, some commonly noted findings are hypotonia, psychomotor retardation, and hypothermia

• During shortage copper may not needed in newborns for the first 3weeks (preemies may need earlier)

• Presence of cholestasis does not ensure adequate copper concentrations

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Aoki 2004Corkins 2013

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Trace Element Shortage Chromium

• Involved in carbohydrate metabolism

• In very low birth weight newborns chromium deficiency has been associated with increased risk for intraventricular hemorrhage, late-onset bacterial sepsis, necrotizing enterocolitis, and death

• Improved glucose tolerance and carbohydrate delivery demonstratedin very low birth weight newborns supplemented with chromium

• In adults, is there a need to supplement d/t contamination in the PN

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Capone 2018Moukarzel A 2009

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Trace Element Shortage Selenium

• Essential nutrient that serves several important

• Functions, including anti-oxidative defense through the

• Actions of glutathione peroxidase as well as thyroid hormone

• Metabolism through the actions of iodothyronine deiodinase.3-5

• Deficiency implicated as a cause of cardiomyopathy and death

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Davis 2014

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Trace Element Shortage Selenium

Do we need to supplement?

• 5 pediatric patients >1 yr age with intestinal failure

• Full PN support

• All 5 developed severe biochemical selenium deficiency

• No morbidity associated with the deficiency

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Davis 2014

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Trace Element Shortage Selenium

Do we need to supplement?

• 6 infants with selenium deficiency were studied retrospectively

• Onset of selenium deficiency in five patients occurred at <6 mo of age

• All patients had developed growth retardation and alopecia withpseudo-albinism

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Masumoto 2007

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Trace Element Shortage Treatment Options

• Importation

• Oral products

• Sublingual admin?oZinc sublingual dots

oZinc SL solution-1 mL hold under tongue

oSL Selenium and chromium

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L-Cysteine

• Conditionally essential amino acid in neonatesoImproves nitrogen retention

• Normal dose is 40 mg/g of protein

• Improves calcium/phos solubility and dosing by decreasing pH

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L-CysteineOther Uses Contributing to Shortage

• Increases chloride load of solutiono Occasionally used a source of chloride ions when traditional sources can’t

be used

- NaCl, KCl, Arginine

• Used as a catheter clearing agent replacing 0.1N HCL which is problem to compound when following USP <797> guidelineso Has approximately the same pH as 0.1N HCL

o Cheap

o Already in a sterile ready-to-use vial

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L-Cysteine Shortage Considerations

• If there is some product available, restrict L-cysteine supplementation in PN to neonates <1 kg or those neonates >1 kg who are at high risk for cysteine deficiency such as neonates who are post-surgical or those with sepsis.

• Normal needs for PN L-cysteine are estimated to be 30-40 mg/g of protein provided. However, studies have documented that as little as 20 mg/g of protein provided is adequate.

• Assess each patient as to the indication for PN and provide nutrition via the oralor enteral route when possible.

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L-Cysteine Shortage Considerations

• Purchase only as much L-cysteine injections supply as needed. In the interestof fair allocation to all patients nationally, please do not stockpile.

• Reconsider / discourage using L-cysteine as an agent to re-establish intravascular access catheter patency.

• If cysteine is needed strictly to improve calc:phos solubility consider using the imported organic phosphate.

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L-Cysteine Shortage Safety Issue

• If cysteine dose is reduced may affect solubility tablesoConsider not using the cysteine compatibility tables in the ACD

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Conclusion

Parenteral nutrition component shortages continue to frustrate the efforts of nutrition support specialists in proving adequate care

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References

1. Ayers P, Holcombe B, Plogsted S, Guenter P, eds. A.S.P.E.N. Parenteral Nutrition Handbook, 2nd ed. A.S.P.E.N., Silver Spring, MD, 2014. Mueller CM, ed. A.S.P.E.N. Adult Nutrition Support Core Curriculum, 2nd ed. A.S.P.E.N., SilverSpring, MD, 2012

2. Hoffer J. Human Protein and Amino Acid Requirements. JPEN 2016; 40(4):460-475.

3. Helms R, Tillman E, Patel A, KernerJ. Protein Digestion, Absorption, and Metabolism. In The A.S.P.E.N. PediatricNutrition Support Core Curriculum, 2nd ed, Ed M Corkins, 31-44.

4. Joint FAO/WHO/UNU Expert Consultation on Protein and Amino Acid Requirements in Human Nutrition (2002 : Geneva, Switzerland), Food and Agriculture Organization of the United Nations, World Health Organization & United Nations University. (2007). Protein and amino acid requirements in human nutrition : report of a joint FAO/WHO/UNUexpert consultation. Geneva : World Health Organization. http://www.who.int/iris/handle/10665/43411.

5. Preston T, Slater C, McMillan D, Falconer S, Shenkin A, Fearon K. Fibrinogen Synthesis Is Elevated in Fasting Cancer Patients WithAn Acute Phase Response. J Nutr 1998; 128:1355-1360.

6. Ayers P, Adams S, Boullata J, et al. A.S.P.E.N. Parenteral nutrition safety consensus recommendations. J ParenterEnteral Nutr. 2014;38(3):296-333

7. Mena K, Espitia O, Vergara J. Management of Ready-to-Use Parenteral Nutrition in Newborns: Systematic Review. JParenter Enteral Nutr 2018; 42(7):1123-1132.

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References

8. Chhim R, Crill C. Premixed Parenteral Nutrition Solution Use in Children. J Pediatr Pharmacol Ther 2015; 20(5):378-384

9. Vanek V, Borum P, Buchman A, Fessler T, Howard L, Jeeejeebhoy K, Kochevar M, Shenkin A, Valentine C, Novel Nutrient Taskforce, Pafrenteral Multi-Vitamin and Trace- Element Working Group, and the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors.A.S.P.E.N. Position Paper: Recommendations for Changes in Commercially Available Parenteral Multivitamin and Multi–Trace Element Products. Nutr Clin Pract. 2012;27:440-491.

10. Otten JJ, Pitzi Hellwig J, Meyers LD, eds. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements.Washington, DC: National Academies Press; 2006

11 .Sriram K, Lonchyna A. Micronutrient Supplementation in Adult Nutrition Therapy: Practical Considerations. J Parenter Enteral Nutr 2009 33: 548-562.

12. Greene HL, Hambidge M, Schanler R, Tsang R. Guidelines for the use of vitamins, trace elements, calcium, magnesium, and phosphorus in infant and children receiving total parenteral nutrition: report of the Subcommittee on Pediatric Parenteral NutrientRequirements from the Committee on Clinical Practice Issues of the American Society for Clinical Nutrition. Am J Clin Nutr. 1988;48:1324-1342

13. Notes from the Field: Zinc Deficiency Deficiency Dermatitis in Cholestatic Extremely Premature Infants After a Nationwide Shortage of Injectable Zinc — Washington, DC, December 2012 . CDC Mortality and Morbidly Weekly. Weekly Feb 22, 2013;62(7):136-137. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6207a5.htm

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References

14. Aoki T. Copper Deficiency and Clinical Practice. JJMAJ 2004; 47(8):365-370.

15 .Corkins M, Martin V, Szeszycki E. Copper Levels in Cholestatic Infants on Parenteral Nutrition. J Parenter Enteral Nutr. 2013;37:92-96

16 .Capone K, Sriram S, Patton T, Weinstein D, Newton E, Wroblewski K, Sentongo T. Effects of Chromium on Glucose Tolerance in Infants Receiving Parenteral Nutrition Therapy. Nutr Clin Pract. 2018;33:426–432

17 .Moukarzel A. Chromium in Parenteral Nutrition: Too Little or Too Much. Gastroenterology 2009; 137:S18-S28

18. Davis C, Javid D, Horsley S. Selenium Deficiency in Pediatric Patients With Intestinal Failure as a Consequence of Drug Shortage. K,Parenter Enteral Nutr. 2014;38:115-118.

19. Masumoto K, Nagata K, Higashi M, Nakatsuji T, Uesugi T, Takahasi Y, Nishimoto Y, Kitijima J, Hikino S, Hara T, Nakashima K, Nakashima K, Oishi R, Taguchi T. Clinical Features of Selenium Deficiency in Infants Receiving Long-Term Nutritional Support. Nutrition. 2007;23:782-787.

20. Chen C, Harris M, Partipilo M, Welch K, Teitelbaum D, Blackmer A. Impact of the Nationwide Intravenous Selenium Product Shortageon the Development of Selenium Deficiency in Infants Dependent on Long-Term Parenteral Nutrition. Parenter Enteral Nutr. 2016;40(6):851-859.

21. Riedijk MA, Voortman G, van Beek RHT, Baartsman MGA, Wafelman LS, van Goudoever JB. Cysteine Requirements in Enterally FedVery Low Birth Weight Infants. Pediatrics. 2008;121 (3):e561-567

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