Practical Approach to

Determining Protein
Requirements of the
Critically ill
Juan B. Ochoa Gautier, MD, FACS, FCCM
Medical Director ICU
Hunterdon Medical Center

January 2023
 • This presentation is the sole responsibility of
the author (Juan B. Ochoa).

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Objectives:
• Verbalize suggested protein recommendations found in current
critical care nutrition guidelines.

• Assess results of recent nutrition studies and relate them to current

nutrition guidelines.

• Discuss potential benefits associated with determining appropriate

protein and calorie goals for the critically ill patient.
 Protein - Historical perspective
• Foods with higher protein content are historically considered of higher nutritional
value
• Coveted and more expensive
• Protein intake is higher in wealthier individuals
• First described by Atwater in 1887
• “…to teach the poor how they could obtain their requirement for
protein, the most expensive of their needs, more economically…”
• The BASIS of population nutrition focuses on providing adequate nutrient
balance at the lowest expense.
• Maximizing Carbohydrates and minimizing protein intake.
• Thus:
• It is often (if not universally) considered that providing higher amounts of
protein is WASTEFUL!

Carpenter KJ. J Nutr. 2003;133(10):3023-32.

https://www.wri.org/da
ta/people-are-eating-
more-protein-they-
need
• 1944 -1945 One-year experiment The Starvation Experiment
• 36 conscientious volunteers
• 24 weeks of semi-starvation
• 1570 Calories per day
• 50 grams of protein
• 30 grams of fat
• Micronutrient deficient
• Had to walk 22 miles/week

• Difficulties in completing the study

• Resorted to stealing food

• 12 weeks refeeding

• A study that helped understand the

progression towards malnutrition

• Anecdote. Patients gained fat mass

beyond their baseline after the
experiment
• Muscle mass remained impaired
The Minnesota Semistarvation Experiment - Bing video
 • “The Dietary Goals are stated in terms of specific
levels. However, each level represents a conclusion
based on the scientific evidence and the levels
recommended by the thirteen panels of scientific
experts…”

Dietary goals for the United States - NALDC (usda.gov)

Summary of Dietary Guidance Development | Dietary
Guidelines for Americans
The principles of Population Nutrition have been
used in Clinical Nutrition to “feed patients”

(FOOD SUBSTITUTION PARADIGM)

=
Cardenas, D, Ochoa Gautier, J. - Submitted
 PM - (Nutrition Journey) Intake and the effect of illness
Volitional Artificial Nutrition De-escalation Return to volitional intake

Caloric Excess

Normal

Caloric Deficit

Average 6 days

Health Acute Illness/Hospitalization Recovery Return to health

Biggs JS, Health Promot Pract. 2014;15(2):199-207 Ochoa JB, JPEN J Parenter Enteral Nutr. 2020;44(8):1369-75
Food Substitution as Medical Nutrition Therapy
• Traditional
• A ↓ in nutrition intake is pathologic
• MNT is aimed a Food Substitution
• Calories are essential
• Protein sparing effect of calories
• GOAL is to AVOID A CALORIC Deficit
• Calculate Caloric requirements
• Deliver these as soon as possible
• MNT should closely mimic “normal” food intake
• “Standard Formula”
• Use Parenteral Nutrition
• ASAP
• To fill the gap that Enteral Nutrition cannot fill Caloric Deficit - Pathologic
• FOOD DOES NOT CAUSE HARM
Alternative View on Medical Nutrition Therapy
• Alterations in Nutritional intake
• CAN BE ADAPTIVE and therefore physiologic
• MNT can cause harm
• Increasing inflammation
• Blocking autophagy
• Creating amino acid imbalances
• Increasing metabolic (organ function demands)
• Goals other than preventing a caloric deficit may be
more important
• Metabolic care
 Food Subtitution vs metabolic care (EPANIC Clinical Trial)
Michael P. Casaer, M.D.et., al
80 P – 0.007
70

60

P – 0.008
Percentage/days

50

40 P – 0.006
30

20 P – 0.02
10

0
Discharge Alive ICU LOS Infection Vent > 2 Days
Axis Title

Caloric Debt allowed

Late (EN) Early (PN)
No Caloric Debt
N Engl J Med 2011;365:506-17.
 Energy intake (first 7 days of acute illness)
Critical Care Guidelines (ASPEN/ESPEN
ASPEN

ESPEN
 Lower calories (carbohydrate) vs. a standard control
• The rate of glycemic events outside of 6.1 to 8.3 mmol/L were not different between groups (p = 0.5383).
• Significant increase in the mean rate of glycemic events > 4.4 and ≤ 6.1 mmol/L (+14%, p = 0.0007)
• A decrease in > 8.3 mmol/L in the experimental group (-13%, p = 0.0145).
• Mean rates of hypoglycemia (≤ 4.4 mmol/L) were not different (p = 0.23).

Rice TW, JPEN J Parenter Enteral Nutr. 2019;43(4):471-80.

 Lower calories (carbohydrate) vs. a standard control
• Differences in:
• Alkaline phosphatase (Alk Phos)
• Carbon dioxide (CO2)
• Bicarbonate (Bicarb)
Differences in laboratory values (Experimental – Control)
Day 1 2 3 4 5 6 7
Alk Phos -8% -8.2% -15.8% -21.5% -27.2% -20.9% -28.7%
Alk Phos p-value 0.3 0.3 0.07 0.02 0.005 0.04 0.02
CO2 -3.8% -7.5% -7.1% -10.1% -8.9% -10.5% -14.8%
CO2 p-value 0.3 0.05 0.06 0.01 0.04 0.02 0.004
Bicarb mmol/L 1.7 -0.4 -1.4 -3.1 -4.4 -3.1 -5.3
Bicarb p-value 0.2 0.7 0.3 0.06 0.01 0.08 0.01

• Also:
• Increase in detectable ketones in blood and urine.
• Tendency towards lower total proteinemia
• Significantly lower WBC counts
Rice TW. JPEN J Parenter Enteral Nutr. 2019;43(4):471-80.
 CONCLUSION

It is unnecessary to meet Caloric

goals within the first 7 days of
acute/critical illness X
CLEAR CONSENSUS

Compher C, JPEN J Parenter Enteral Nutr. 2021. Singer P,. Clin Nutr. 2019;38(1):48-79
What about Protein in the critically ill patient? 2 2
(Q T )
• Timing – How fast?
• Food substitution (parenteral nutrition) vs. metabolic care
• Quantity - How much?
• Average intake in the ICU (0.5 g/k/d)
• Minimal suggested 1.3 g/k/day
• Quality - What Type?
• Biological Value of protein (what does it mean?)
• Identifying single amino acid deficiencies and supplementation
• Tools - What product?
• Standard isocaloric vs. Very high Protein energy restricted formulas
 Protein Sparing effect of Glucose (PSEG) in Critical illness?
14C-Alanine Conversion to glucose

• Increased Conversion of Amino

acids to glucose Fed Critically ill Patients

• Therefore, muscle breakdown is

increased to “make glucose”
• NO EVIDENCE that there is an Starving Volunteer

effective PSEG in critical illness

Fed Volunteers
• To date virtually ALL enteral and
parenteral nutrition solutions
contain high amounts of CHO as
an energy source
Long, CL Metabolism
1976/ 25:193-201
The effect of Postoperative Intravenous Feeding (TPN) on Outcome
following Major Surgery evaluated in a Randomized Study
Sandstrom et. al. Ann. Surg. 217(2):185-195. 1993. Sweden

• Prospective randomized trial –

• 300 Patients
• Elective GI or urologic surgery
• Group 1 – Prophylactic TPN
• Group 2 – Moderate postop
starvation

• Higher Nitrogen loss observed when TPN

was used as “FOOD SUBSTITUTION”

Sandstrom – Nitrogen Loss

 PM - (Nutrition Journey) Intake and the effect of illness
Volitional Artificial Nutrition De-escalation Rehabilitation

Caloric Excess
<0.8 0.8 – 1.2 > 1.2 g/k/d

Normal
1 -2 days 3 – 5 days > 6 days

Caloric Deficit

Average 6 days

Health Acute Illness/Hospitalization Recovery Return to health

Biggs JS, Health Promot Pract. 2014;15(2):199-207 Ochoa JB, JPEN J Parenter Enteral Nutr. 2020;44(8):1369-75
 Nitrogen Balance correlates with Protein
intake
Long, CL. JPEN
1979:3:452-456
 Protein Intake A gradual increase during first seven days
Volitional Artificial Nutrition De-escalation Rehabilitation

Caloric Excess

“Supplementation (PN)”
Normal
X For how long?

Caloric Deficit
“Slow Ramp up”

Health Acute Illness/Hospitalization Recovery Return to health

Biggs JS, Health Promot Pract. 2014;15(2):199-207 Ochoa JB, JPEN J Parenter Enteral Nutr. 2020;44(8):1369-75
The PROTINVENT retrospective study

• Retrospective study
• 455 Patients
• Mechanically ventilated

• Increased ICU and 6 month mortality

Koekkoek, et. Al., Clin Nut 38; 883-890. 2019

 Amino Acid availability (Pool)

Medical Nutrition
Therapy
ARG Anabolism
P
Ribosome
GCN2
mTOR 3’ 5’
Ideal
Concentration

Catabolism

↑AUTOPHAGY
ALTERED

Proteasome

TRP ARG LYS ILE PHE VAL MET THR

Amino ACID
OXIDATION

Synthesis
25
NEA
 How much Protein can be digested and absorbed?

Journal of the International Society of Sports Nutrition 2008, 5:10

• Normal individuals
• Maximum digestive capacity = 15 g
Whey (bolus)
• Pre - digestion increases amino acid
absorption significantly
• Nitrogen retention is also increased
Occult Impaired digestive capacity may be frequent in critically ill patients

Wang S, et al. Crit Care 2013;17:4171

High protein intake is associated with low mortality
and energy overfeeding with high mortality
Weijs et al. Critical Care 2014 – 843 ICU patients -

10-20% Energy deficit decreases mortality Protein > 1.2 g/kg/d lower mortality

RECOMMENDATIONS - Higher amounts of Protein (> 1.2 g/k/d) with Lower Caloric Loads
Resting energy expenditure, calorie and protein consumption in
critically ill patients: a retrospective cohort study

RECOMMENDATIONS - Higher amounts of Protein (1.3 g/k/d) with Lower Caloric Loads

Zusman et al. Critical Care (2016) 20:367

 Protein Intake (first 7 days of acute illness)
Critical Care Guidelines (ASPEN/ESPEN
ASPEN

ESPEN

“Lowest 6-month mortality was found when increasing protein

intake from < 0.8 g/k/da on day 1-2 to 0.8 to 1.2 g/k/day on
day 3-5 and > 1.2 g/kg/day after day 5.”

Koekkoek, et. Al., Clin Nut 38; 883-890. 2019

Conclusions on Protein delivery in critically ill
patients
• Currently, clinicians tend to fail to meet adequate protein delivery
• 0.5 g/k/d. Heyland DK. Nutr Clin Pract. 2017;32(1_suppl):58S-71S.
• Most of the delivery of protein comes from Enteral Nutrition
• Protein supplements are inconsistently utilized making compliance and
adherence difficult to complete prescribed orders.
• Ochoa. Clinical Nutrition. 41: 2833 - . 2022
• Protein delivered should be of high biological value and easy to absorb
• Closest to the Optimal amino acid concentrations that maximize anabolic responses
• Is easily digested
• Protein Delivery should be:
• Gradual (First seven days), persistent (after 7 days)
 How are we going to achieve goals?

What are the formulas available that we

should utilize?
 New Nutritional Formulas ↑ Protein while lowering ↓Cal:N ratio

Standard < 20% Protein

160 Very High Protein > 25%

140
20 – 25 % High Protein
120

100

80

60

40

20

0
1 2 3 4 5 6 7 8 9 10 11 12 13
Calorie:Nitrogen Ratio Protein (g)/1000 ml
Available
Commercial 1.8
Enteral Formulas 1.6
1.4
1.2
• Categories (Protein concentration) 1
• Standard - Hi Calories/Low
Protein 0.8
• Hi Protein - Hi Calories/Hi 0.6
Protein
• VHP – Very High Protein/Low 0.4
calories 0.2
• Very High Protein (VHP) 35-37%
0
• Lower in caloric concentration 16-20 21-25 > 25
• Lower (CHO) – Sugars Calories Protein
• Lower Lipid concentrations
 Variations in New Very High Protein Formulas
(Caution)
• Similar amounts of Protein
• Protein
• Intact vs. hydrolyzed
• Lipids
• Types and amount
• Carbohydrates
• Amount

• Example – Differences in
glycemia and insulin release

Huhmann et al. Nutrition and Diabetes (2018) 8:45

 Distribution of Critically ill patients by BMI – Geisinger Health System
• Humanity’s relationship with food has changed
dramatically in the last 50 years.
5%
• An increase in food availability
• Food is cheaper
• Food is more and more processed
• Increased bioavailability 42% 27%
• Easy absorption
• Less time required in the preparation of
food
• The proportion of macronutrients (and 27%
micronutrients) in foods has also changed
• Favoring intake in sugar, fat, and protein
< 18.5 18.5 - 24.9 25 - 29.9 > 30
• The type of nutrients used in processed foods are
governed by COST and NOT by quality
Ochoa Gautier JB, Clin Nutr. 2022;41(12):2833-42
 The type of Formula Prescribed determines the Median
Daily Protein Delivered
120 Ochoa, et. Al., Clinical Nutrition. 41:2833- 2022

100 Standard Formula (< 20%), High Protein (21-25%), Very High Protein (> 25%)

80
Protein g/k/d

60

40

20

0
1 2 3 4 5 6 7
Day in ICU
16-20 21-25 > 25
Non-Protein Calories Delivered by type of Formula
Ochoa et. Al., 41:2833- . 2022

Additional Non-protein Calories

were delivered as “vehicles” for
the delivery of medications

e.g., Vasopressors in D5W

Propofol 10% lipids
 Effect of Protein intake on Mortality
Ochoa et. Al., 41:2833- . 2022

25.00%

20.00%
% Mortality

15.00%

10.00%

5.00%

0.00%
Low Intermediate High
Inpatient death 7.60% 7.40% 7.00%
30 day mortality 19.20% 16.90% 10.80%
Inpatient death 30 day mortality
Theoretical Case scenarios (based on admission
phenotype)
• 50-year-old female admitted with an ischemic stroke resulting in aphasia, hemiparesis
and aspiration pneumonia
• BMI 40, IBW 70 kgs. Type II Diabetes Mellitus, Hypertension, depression

• 62-year-old female with colon cancer, admitted to the ICU after Colon resection.
Transfusion related acute lung injury (TRALI). Reactive hyperglycemia (210 mg/dL).
• BMI 25, IBW 70 kgs. Healthy individual, active in sports

• 47-year-old female admitted with an acute abdomen secondary to “binging” on shrimp.

Intussusception and bowel necrosis requiring bowel resection.
• BMI 17, IBW 70 kgs. long history of anorexia nervosa.
 Number of Calories delivered by product
Calculated Protein goal (1.3 g/k/d)
Total CHO (grams) by Product Calculated Total Calories by Product
350.0 170% 2500.0
170%
2240.0
303.7
300.0
2000.0

250.0 100%
Total Grams 24 hrs

Total Cals 24 hrs

200.0 100% 1500.0 1400.0
70%
150.0 130.7 70% 1000.0
980

100.0 76.4
500.0

50.0

0.0
0.0 Osmolite Peptamen AF Peptamen Intense
Osmolite Peptamen AF Peptamen Intense
Standard Hi Very Hi Standard Hi Very Hi
Protein Protein Protein Protein
Assessing calorie and protein recommendations for survivors of
critical illness weaning from prolonged mechanical ventilation –
can we find a proper balance?

Clin Nutr ESPEN. 2021 October ; 45:

449–453.
doi:10.1016/j.clnesp.2021.07.001

Chronic LTAC Patients

Ventilator dependance

Higher protein intake was

associated positive nitrogen
balance
 What I do after seven days
Phenotypes
(Volitional intake)

Case # 1
Morbid Obesity
Maintain 1.3. g/k/d and 100% calories

Case # 2 Maintain 1.3 g/k/d and use Indirect Calorimetry

Normal

Maintain > 1.3 g/k/day but 70% of Calories

Case # 3
Protein/Energy
Malnutrition

Health Acute Illness/Hospitalization Recovery Return to health

Biggs JS, Health Promot Pract. 2014;15(2):199-207 Ochoa JB, JPEN J Parenter Enteral Nutr. 2020;44(8):1369-75
• Nutrition in ICU is NOT about
providing food substitution

• Nutrition in the ICU is about

METABOLIC CARE

44
 • First Seven days in the ICU (Evidence-based)
• Start MNT (ideally Enteral Nutrition) within 48 hours of
admission

Conclusions • CALCULATE Nutrition requirements based ON PROTEIN not on

Calories
• <0.8 g/k/d (IBW) first 48 hours
- Medical • 0.8 – 1.3 g/k/d (IBW) 3 to 5 days
• > 1.3 g/k/d (IBW) > 5 days

Nutrition • Meet 70% of caloric Goals (non-protein calories)

• SELECT a formula that has the appropriate Calorie : Nitrogen ratio (<

Therapy - 50:1)
• A very high protein with low C/N ratio is simply easy and
straight formula to use

MNT • After seven days (what I do)

• Consider the underlying energy stores (Actual body
weight/IBW) BMI
• Taylor nutrition requirements according to patient’s needs and
nutritional goals
• Change nutritional formula with a higher caloric content if
clinically indicated
THANK YOU
I will answer Questions

jbogatuier1@outlook.com
Beyond Nutrition Screening
Criteria For Nutrition Assessment
 PM - (Nutrition Journey) Intake and the effect of illness
Volitional Artificial Nutrition De-escalation Return to volitional intake

Caloric Excess

Normal

Caloric Deficit

Average 6 days

Health Acute Illness/Hospitalization Recovery Return to health

Biggs JS, Health Promot Pract. 2014;15(2):199-207 Ochoa JB, JPEN J Parenter Enteral Nutr. 2020;44(8):1369-75
 Nutritional History prior to ICU arrival _ Calories and Muscle
Mass (protein) – Phenotypical assessment (GLIM)

Nutritional Screening + assessment

Calories Protein Micronutrients

Obese Normal ???

?
68%

? • Vitamins
?
Normal Sarcopenia • Minerals
27%
Cachexia 5 % • Lipids ω-3 FA
Not routinely Measured • Amino acid balance
Muscle mass • Arginine
BMI – Weight (loss) CT scan • Tryptophan
Food intake Ultrasound
Functional Status Not Part of Screening
Selective assessment
Cederholm T, Clin Nutr. 2019;38(1):1-9.