Wound Care Pressure Ulcers One Slide Presentation

William E. Code, MD, FRCPC Denise Code, MSc, RD Patricia A .L. Kongshavn, Ph.D

present

Resolving Pressure Ulcers with a Bioactive Cystine-Rich and Cost-Effective Protein Supplement Continuing Medical Education Seminar Sponsored by

NuMedTec Toll free 877.687.2277

Resolution of Pressure Ulcers For healing to occur, there are five major related steps, each dependent on the prior step. All steps require energy, protein and an anabolic stimulus. 1. Inflammation (white blood cells, soluble factors – antibodies, ‘growth factors’) 2. Cellular Proliferation (angiogenesis, fibroblast proliferation, epithelialization) 3. Connective Tissue Formation (collagen production, interstitial matrix synthesis) 4. Wound Contraction (fibroblasts) 5. Wound Remodeling (increased collagen cross-linking, etc.)

Requirements for Successful Resolution of Pressure Ulcers Provide high quality protein for rebuilding cells and tissues Prevent or correct protein energy malnutrition (PEM) Maintain antioxidant defenses (raise intracellular GSH*) Strengthen the immune system to fight against infection *Glutathione is a tripeptide: glycine, glutamate and cysteine.

Cystine & Glutathione • Cystine (2 molecules of cysteine joined by a disulfide bond –”bioactive cysteine”) is the optimal form of the amino acid cysteine. • Bioactive cysteine is needed to make intracellular glutathione. • Glutathione enhances the functioning of the immune system and is a major antioxidant and detoxifying agent.

SEE THE SLIDE: CYSTINE OR CYSTEINE

Importance of Preserving the Disulfide Bond in Cystine Disulfide Bond

CYSTEINE

„

„

E N I T S Y C

CYSTEINE

Pasteurization/heat and instantization/stress break the disulfide bond and destroy cysteine’s bioavailability, causing cysteine to be oxidized in the gut during digestion Once oxidized, cysteine becomes metabolized and loses its bioavailability

Cystine or Cysteine

the Crucial Bioactive Difference

O

Cystine O H H

N H

C

O

C

H

C

H

Cysteine (CYS) H

H

H

N

C

H

H

C

H

H H

H

N

C

H

O

C

O

H

S

H

S

H

+

S C

O

+ 2H

S

H

C

H H H

C6H12N2O4S2 • Relatively rare in proteins • Useful to make glutathione, i.e. “bio-active” • Maintains positive N balance

H

C

H

N

C

H

O

C

O

H

C3H7NO2S • Found in many proteins • Useful source of energy

Most Cysteine is Catabolized during Digestion „

„

Cysteine – minus disulfide bond is catabolized during the digestive process and not available for synthesis of intracellular glutathione Cystine – (bioavailable cysteine) disulfide bond remains intact through digestion and cystine preserved for intracellular glutathione synthesis (i.e. “bioavailable”)

Cystine Controls Nitrogen Balance and LBM • If cystine is available, conditions favor retention of nitrogen and an increase in lean body mass. • If cystine is depleted, conditions favor loss of nitrogen and a decrease in lean body mass.1

1Droge

W, Holm E. Role of cysteine and glutathione in HIV infection and other diseases associated with muscle wasting and immunological dysfunction. FASEB J. 1997 Nov;11(13) 1077-89.

Cystine controls nitrogen balance. Adapted from Droge W and Holm E. FASEB J 11:1077-89, 1997

amino acid pool cyst(e)ine glutamate

α-ketoglutarate H2O SO42/H+

CO2

NH4+

glutamine

-

citrulline

HCO3

carbamoylphosphate

ornithine

arginine

UREA This diagram demonstrates the relationship between cystine and nitrogen balance to be as follows: 1. ↑ cystine, 2. ↑ protons (H+), 3. ↓ bicarbonate, 4. ↓ carbamoylphosphate, 5. ammonium ion (NH4+) is saved; this results in positive nitrogen balance with maintenance or increase in weight. 1. ↓ cystine, 2. ↓ protons (H+), 3. ↑ bicarbonate (HCO3-), 4. ↑ carbamoylphosphate, 5. ammonium ion (NH4+) enters into the urea cycle and is lost from the body; this results in negative nitrogen balance with decrease in weight and possible cachexia.

The Cell and

Oxidative Stress DNA Mitochondria Free radicals are bi-products of cellular metabolism

FUNCTIONS OF GLUTATHIONE Oxidation ¾

The major antioxidant used by the cell to neutralize and destroy damaging oxygen radicals that are continually being generated by the mitochondria during normal metabolic processes

¾

Also keeps vitamins C and E in their active state

¾

Plays a crucial role in maintaining an optimal prooxidant/anti-oxidant balance within the cell

FUNCTIONS OF GLUTATHIONE Detoxification ¾

A very important detoxifying agent , responsible for ridding the body of many xenobiotics, toxins, both exogenous and endogenous

FUNCTIONS OF GLUTATHIONE Immune System Modulation ¾

Enhances the function of the immune system

¾

Glutathione is required in many of the intricate steps of an immune response such as multiplication of lymphocytes

¾

50% of glutathione in lymphocytes is replaced every 5-1/2 hours!

FUNCTIONS OF GLUTATHIONE Cell Regulation ¾

Regulates many of the cell’s vital functions such as: - DNA synthesis and repair - protein synthesis - enzyme activation and regulation

CLINICAL CONDITIONS ASSOCIATED WITH LOW GLUTATHIONE VALUES • • • • • • • •

Pressure Ulcers PEM HIV with wasting Diabetes Burns and Sepsis Cystic Fibrosis Cancer Chronic Fatigue Syndrome

• • • • • • • •

Autism Hepatitis Ulcerative Colitis Crohn’s Disease COPD Idiopathic Pulmonary Fibrosis Adult Respiratory Distress Syndrome Myocardial Ischemia

Low glutathione is also associated with pathogenesis of other degenerative diseases including MS, Parkinson’s, Alzheimer’s, arteriosclerosis, cataracts and aging.

Summary: Benefits of a Bioactive Cystine Protein Supplement for Resolution of Pressure Ulcers 1. High quality source of amino acids for synthesis of proteins (growth factors, enzymes, structural proteins, collagen, and many other proteins) 2. Rich source of cystine →GSH (counteracts oxidative stress, regulates pro-oxidant/antioxidant balance in cells, etc.) 3. Rich source of cystine and other amino acids →maintain LBM and counteract PEM 4. Strengthens the immune system (inflammation, infection)

Case Studies Resolution of Multiple Chronic Pressure Ulcers, Improvement in Cognitive Function, and Reversal of Weight Loss with a Bioactive Cystine-Rich Protein Supplement

Patricia Kongshavn, Ph.D. Karen Wilkie, M.S.

Time Course for Resolution of Chronic Pressure Ulcer

Resolution of Chronic Pressure Ulcer 3

Patient: JL

r Started Supplement

Medical History

2 Area (cm2)

A 91-year-old female patient with dementia, osteoarthritis, peptic ulcer and anxiety, had a stage III pressure ulcer on the right buttock, measuring 3.4 x 3.2 cm on admission to LTC. Approximately 8 months later the pressure ulcer had not resolved. The patient was then given a specific WPI supplement rich in bioactive cystine, 37g BID. This supplement was used until the ulcer was healed about one month later.

2.5

1.5

1

0.5

0 -5

-4

-3

-2

-1

0 Weeks

1

2

3

4

5

Resolution of Multiple Chronic Pressure Ulcers and Improvement in Cognitive Function Patient: DO Medical History A 64-year-old African male was transferred to LTC with dehydration, hyponatremia, urinary tract infection, diabetes mellitus, history of multiple cerebral vascular accidents, severe contractures, multiple decubitus ulcers, history of MRSA (methicillin-resistant Streptococcus aureus), aphasia, vascular dementia, azotemia and possible sepsis. The patient was PEG tube fed. The Medical Director reported that the patient had been transferred multiple times between the hospital and the LTC facility and that multiple pressure ulcers had been present for over a year. He also reported that the patient was not communicative in any manner, over this period. The patient was placed on a specific WPI supplement rich in bioactive cystine, 37g BID until he was transferred out of the LTC facility 35 days later. Wound healing was monitored at weekly intervals. Owing to the large number of pressure ulcers being observed, the wound sizes are shown only at a time shortly before starting the supplement and at the end of the observation period. Some of the pressure ulcers healed and others improved greatly over the time he received the supplement. (see table next slide) Cognitive Observations The patient was also observed to show surprisingly improved cognitive skills. Initially he was unable to indicate his needs to the staff but, eight days after starting the supplement, he began to communicate with facial expressions. At 14 days he was able to make eye contact. At 21 days he was alert, able to focus on movements, and responded ‘yes’ and ‘no’ to statements by nodding and shaking his head. At 23 days he also then responded to staff by raising his eyebrows and shrugging his shoulders.

Time Course for Resolution of Multiple Chronic Pressure Ulcers

Time Course for Resolution of Multiple Chronic Pressure Ulcers

14

30

12

25

Lt Buttock Site A 8

Lt Buttock Site B

6

Lt Hip

20

Area (cm2)

Area (cm2)

10

4

Lt Inner Buttock Rt Heel

15

Rt Buttock Site 1 10

5

2 0

0 -2

35

Days

-8

Days

35

Time Course for Resolution of Multiple Chronic Pressure Ulcer

Time Course for Resolution of Multiple Chronic Pressure Ulcer

6 0.15

Area (cm2)

4

Rt Outer Ankle

3 2

Area (cm2)

5

Rt Buttock Sit 2

0.1

0.05 1 0

0 -5

9

Days

-8

30

Days

Resolution of Chronic Pressure Ulcer Patient: GS

Time Course for Resolution of Chronic Pressure Ulcer

Medical History 6

5

r Started Supplement r UTI

4 Area (cm2) .

A 67-year-old male patient had a history of insulin-dependent diabetes, coronary heart disease, hypertension, chronic anemia, and carcinoma of the prostate and bladder with repeated urinary tract infections. In July 2003 both legs were amputated owing to progressive necrotizing soft tissue infections of both lower legs, the right leg below the knee and the left leg above the knee. A decubitus ulcer on the coccyx was identified and surgically debrided in July 2003 at which time it measured 10 x 15 x 6 cm. This wound failed to heal and 11 months later the patient was started on a specific WPI supplement rich in bioactive cystine, 37g BID until healing was complete.

3

2

1

0 -5

0

5 Weeks

10

Resolution of Non-Healing Wound Patient: JS Medical History A 64-year old female patient had history of peripheral vascular disease, post-operative anemia, coronary artery disease and hypertension, congestive heart failure, depression and anxiety, hypercholesteremia, insomnia, tobacco use and failure to thrive. She was admitted with a chronic

After two days in LTC the patient was given one serving of a specific WPI supplement rich in bioactive cystine, 37g BID until the wound had resolved. Throughout the healing process, there were no signs of infection and the edema was only moderate.

Time Course for Resolution of Non-Healing Wound 70

s Started Supplement

60 Area in sq inches

non-healing wound with a history of MRSA (methicillin-resistant Staphylococcus aureus), resultant from a saphenous vein harvest graft taken 6 months previously. The wound area was large, necrotic/black in appearance, suggesting some infection. It was debrided twice, 3 days apart, and then an axillofemoralfemoral-femoral bypass was performed with bilateral profundoplasties, in order to restore blood supply to the area. The wound measured 18 x 4 x 0.4 inches. The patient was transferred from hospital to LTC ten days later.

50 40 30 20 10 0 0

5

10 Weeks

15

Resolution of Chronic Pressure Ulcer Patient: LF Medical History A 76-year-old female patient with a history of Guillain-Barre syndrome, diabetes, chronic obstructive pulmonary disease, depression, osteoarthritis, neuropathy, SIADH and anemia, was observed to have a stage III pressure ulcer on the coccyx which failed to heal for 7 months. She was kept on an Alamo bed during this period. She was placed on a specific WPI supplement rich in bioactive cystine, 37g BID until healing was. Two weeks after starting the supplement she had improved sufficiently to be removed from the Alamo bed. She continued to heal and the time course for complete healing is shown below. Time Course for Resolution of Chronic Pressure Ulcer 4.5

s Started Supplement

4 3.5

Week -3 -2 -1 0 1 2

Area (cm2)

3 2.5 2 1.5 1 0.5 0 -5 -4 -3 -2 -1

0

1

2

3

Weeks

4

5

6

7

8

9 10

Comments 5 sites of tunneling 4 sites of tunneling 3 sites of tunneling 3 sites of tunneling No sites of tunneling Granulating well

Resolution of Multiple Pressure Ulcers Time Course for Resolution of Chronic Pressure Ulcers

Patient: VP Medical History

25

s Started Supplement

Area (cm 2)

A 79-year old female patient had a history of coronary heart disease, essential 20 hypertension, chronic obstructive A pulmonary disease, arthritis, chronic hip 15 pain, mouth pain, depressive disorder and dementia. She was admitted with a fracture of the right femur at the distal end 10 of a previous total hip replacement and was operated on to repair the femur. Ten 5 B days later the surgical wound was healed C and the patient was transferred to LTC. At 0 this time she was observed to have a -5 0 5 10 15 20 coccyxeal stage III pressure ulcer Weeks measuring 4 x 4 cm, and two smaller stage III ulcers on the left buttock. She was A - coccyxeal stage III B - left buttock stage II started on a specific WPI supplement rich C - left buttock stage II in bioactive cystine, 37g BID. She developed two additional small ulcers on the left buttock on week four, both of which healed one week later. After 5 weeks the left buttock ulcers were healed and she was switched to Ensure because the Director of Nursing felt that she would finish healing without continuing the supplement. This did not happen, so at 13 weeks she was re-started on the supplement, 37g BID until the coccyxeal ulcer was healed.

Resolution of Coccyx Split Wound Patient: FF Medical History An 85-year-old female patient with a history of Parkinson’s disease, dementia, hypothyroidism, urinary tract infections and chronic renal failure, developed a pressure ulcer stage I (0.3 x 0.2 cm) which was observed to have progressed to a coccyx split. Two months later she was placed on a specific WPI supplement rich in bioactive cystine, 37g QD. The wound healed in 26 days.

Reversal of Weight Loss Patient: AM Medical history A 91-year-old female had a medical history of chronic obstructive pulmonary disease, chronic hip pain, congestive heart failure, depression, senile dementia, anemia, hypercholesterolemia and hemiarthroplasty (right) hip. The patient was only on ‘comfort care’. She was placed on a specific WPI supplement rich in bioactive cystine, 37g BID in order to counteract serious weight loss and weighed at weekly intervals.

90

85 Body Weight (lbs) -

At a Care Conference approximately 3 weeks after starting the supplement, it was stated that the patient had multiple episodes of refusing meals. At that same time the caregiver reported that the patient had gained 9 lbs with the new supplement, even though she only ate 23% of her meals. Moreover, despite the fact that she was overcoming a bout of pneumonia she still gained weight.

Time Course for Weight Gain

80

75

70

u Started Supplement

65 -15

(5)

0

5

Weeks

11

Improved Outcome for Healing of Pressure Ulcers in Patients Fed a Cystine-Rich Protein Supplement Before Background •

Female, 92

•

COPD, TIA, cerebrovascular accident, anxiety, aortic stenosis, depression

•

2 Stage II pressure ulcers

•

Treatment: 20g BID of a specific WPI supplement rich in bioactive cystine

•

Rate of Healing: coccyx 0.4 sq cm/mo, and left buttock 10.7 sq cm/mo

39 Days Later Days 0 42

Days 0

(1 x 0.5)

Healed

21

Stage II, Coccyx 0 0.25 Wound Area (cm sq)

(3 x 2.5)

Healed Stage II, Left Buttock

0.5

0 4 Wound Area (cm sq)

8

Complete Balanced Protein of Highest BV Amino Acid Profile in grams per 37g Serving of ProNutra® Amino Acid

Quantity

Amino Acid

Quantity

ASP

2.286

TYR

.558

THR

1.494

PHE

.558

SER

.954

HIS

.324

GLU

3.546

LYS

1.710

GLY

.360

ARG

.306

ALA

1.008

PRO

1.134

VAL

1.134

CYS

.450

ILE

1.224

MET

.450

LEU

1.962

TRP

.360

Nutritional Information Calories Calories from fat Total fat Saturated fat Polyunsaturated fat Monounsaturated fat Trans fatty acids Cholesterol Total carbohydrate Dietary fiber Sugars Protein Vitamin A Vitamin C Vitamin E Thiamin Niacin Riboflavin Calcium Sodium Potassium Magnesium Phosphorus Zinc Iron

/ 100 gm 368 134 15.00 g 3.60 g 0.62 g 5.16 g 4.89 g 1.60 mg 30.00 g 3.37 g 49.00 g 2780 IU 695 mg 69 IU ND ND ND 280.0 mg 155.0 mg 498.0 mg 96.0 mg 340.0 mg 22.5 mg 0.8 mg

/ 37 gm 136 50 5.55 g 1.33 g 0.23 g 1.91 g 1.81 g 0.6 mg 11.10 1.24 g 18.13 g 1000 IU 250 mg 25 IU ND ND ND 103.6 mg 57.4 mg 184.3 mg 35.5 mg 125.8 mg 8.3 mg 0.3 mg

ProNutra® (provides Bioactive Cystine) – Nutrition Facts Serving Size 1 bottle 37g, Fruit Flavored

Nutritional Breakdown

1 Bottle (37g)

Amount Per Serving

Nutrient

RDI

Patented WPI Calories from Fat 50

Calories 140

% Daily Value* Total Fat 6g

9%*

Saturated Fat 1.5g

7%*

Cholesterol 0mg

0%

Sodium 55mg

2%

Total Carbohydrate 10g

3%*

Dietary Fiber 0g

0%

5000 IU

1000 IU

Vitamin C

60mg

250mg

Vitamin E

30 IU

25 IU

1000mg

121mg

Iron

18mg

2mg

Zinc

15mg

9mg

Calcium

Omega 3 FA

11% of fat

Omega 6 FA

22% of fat

Ratio 6:3 Total Fat

Vitamin A 20%

Œ

Vitamin C 417%

Calcium 12%

Œ

Iron 11%

Vitamin E 84%

Œ

Zinc 60%

*Percent Daily Values are based on 2,000 calorie diet. Your daily values may be higher or lower depending on your calorie needs:

18g

Vitamin A

Sugars 1g Patented WPI 18g

Product Level

Calories

2:1 < 65g (based on 2,000 calorie diet)

6g 140

INGREDIENTS: Patented WPI (Whey Protein Isolate), Shortening Powder (Partially hydrogenated canola oil, lactose, sodium caseinate, dipotassium phosphate). Erythritol (a sugar alcohol), Citric Acid, Natural & Artificial Flavors, Soy Lecithin, Ascorbic Acid, Canola Oil, Alpha-Tocopheryl Acetate, Yellow Lake #6, Sucralose, Zinc Citrate, Vitamin A Palmitate.