Topic 18   Nutritional Support in Intensive Care Patients

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Module 18.1 Metabolic Response to Stress, Energy Requirements

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Jean-Charles Preiser
René Chioléro
Pierre Singer

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1. Physiologic response to stress

Extensive physiological changes occur in critically ill patients, particularly in those suffering from sepsis, trauma and burns. All the body systems are involved, particularly the circulation, the endocrine, metabolic and immune systems. This response is mainly activated from tissue inflammation and from the central nervous system. It plays a key role for the adaptation of the organism to the various forms of stress, including surgery, trauma and many types of critical illnesses, as shown by the inability of patients with cortico-adrenal failure to face minimal stress.
Tissue injury induces an acute local inflammatory response which activates macrophages and endothelial cells which in turn activate cascades of inflammatory mediators, including cytokines, coagulation factors, kinins and others endogenous substances.

Figure 1

Figure 2

Both pro-inflammatory cytokines (TNF-a IL-1 and IL-6) and anti-inflammatory cytokines (IL-4 and IL-10) are released to insure an adequate adaptation to the inflammatory stress (Fig. 1,Fig. 3).
The neuro-endocrine response is characterised by the activation of the sympatho-adrenal system, hypothalamo-pituitary axis and other endocrine glands (1.5). It leads to the release of the stress hormones epinephrine, norepinephrine, cortisol, vasopressin, growth hormone and glucagon (Fig. 2).

Figure 3

There is a synergy between the sympatho-adrenal system and the pituitary-adrenal axis: activation of the sympathetic system leads to a parallel stimulation of the corticotropic axis and vice-versa. The overall response is a dynamic process, allowing a rapid and prolonged adaptation to stress: adrenergic, growth hormone and vasopressin response time are very short (seconds), while the corticotropic response has a delay of some hours. Factors triggering this response include mental and psychological stress, exercise, pain, hypovolemia, hypothermia, hypoglycemia, and severe metabolic and electrolytes disorders. The magnitude of the neuro-endocrine response is related to the type of injury and severity of stress.

The neuro-endocrine response plays a critical role in maintaining the circulation and perfusion of vital organs, as well as the energy metabolism (Fig. 3). The thyroid axis is downregulated during acute stress, leading to the sick euthyroid syndrome. This may decrease energy metabolism during prolonged stress and critical illness.

 

2. Metabolic response: energy metabolism

The metabolic response to stress is extensive, involving all the major pathways of metabolism. The overall response is characterized by an enhanced metabolic rate associated with increased release of endogenous substrates for energy metabolism and increased inter organ substrate exchanges.

Figure 4

Insulin resistance leads to increased plasma glucose concentration and gluconeogenesis and endogenous glucose production. Lipolysis is activated with concomitant release of fatty acids for energy metabolism.
In healthy resting subjects, the main determinant of basal energy expenditure is the fat-free mass (FFM) (Fig. 4). FFM includes the tissues with the most active metabolic rate, mainly skeletal muscle and viscera. In subjects with normal FFM, REE amounts tO₂0 kcal/kg per day, or 1400 kcal for a 70 kg subject.

The specific contribution of the different organs and tissues to REE is highly variable, ranging from 5 kcal/kg per day for fat tissue to 500 kcal/kg for the myocardium (Fig. 5). As a whole the vital organs, that account for only 5% of body weight, consume 60% of REE.
Except during the initial phase after injury (the ebb phase), the energy metabolism is stimulated after the initial resuscitation (flow phase). During this flow phase, resting energy expenditure (REE) is increased in critically ill patients, amounting to 120-150% of normal basal values after severe trauma or sepsis. Resting metabolic rate is even higher in patients with major burns, reaching 140-170%.

Contribution of organs and tissue to resting energy expenditure Organ BW % % total REE Organ MR Kcal/kg/d Heart 0.4 10% 400-600 Kidneys 0.4 8% 400 Brain 1.9 20% 240 Liver 2.3 21% 200 Skeletal muscle 40 22% 13 Adipose 21 4% 4.5 Others 33 16 12

Figure 5

Figure 6

Stress hormones, pro-inflammatory cytokines and other mediators mainly cause such hypermetabolism. Infusion of the stress hormones cortisol, glucagon and epinephrine in healthy subjects induces metabolic changes mimicking important aspects of the metabolic response to injury (Fig. 6, Fig. 7). The duration of the flow phase varies according to the evolution of the acute illness: it is short lasting after major uncomplicated surgery (days), lasts several weeks after major trauma and sepsis and even months after major burns until the full skin healing. Variability of REE is extensive, both between different diagnosis categories of patients and over time in a given patient (Fig. 8).

Figure 7

Figure 8

In healthy subjects, the metabolic rate is increased by feeding, cold exposure, exercise and by growth in children (Fig. 9). Additional factors influence REE in acutely ill patients (Fig. 10, Fig. 11). The main factors include body temperature, organ failure, pain and supportive and drug therapies. Fever increases metabolic rate by 10-15% per degree C, hypothermia does the reverse. Pain, respiratory failure, acute liver failure are all associated with hypermetabolism.

Conditions affecting energy expenditure in healthy subjects   REE Change Basal metabolic rate -10% Sleeping -5 - 10% Nutrition +3 - 20% Exercise +100 - 1500% Pregnancy +10% Growth +5 - 15%

Figure 9

Conditions affecting energy expenditure in ICU patient   REE Change Fever (per °C) +10 to 15% Sepsis +20 to + 60% Trauma + 20 to 50% Burn +40 - 80% Treatments     - Mech. Ventilation (resp. failure) -25 - 35%   - Nutritional support (Burn) +20% Agitation + 50 - 100%

Figure 10

Drugs affecting EE in the ICU patient Drug Condition Change Opiates Analgesia - 9%     Post-op rewarming -26%   Post-op shivering -59% Sedation Mechanical ventilation -20 - 55% Barbiturates Brain injury -32% Musc. relaxants Brain injury -42% Catecholamines Circ failure +32% ß-blockers Head injury -6%   Burn (adult) -7%

Figure 11

Mechanical ventilation in patients with respiratory failure, sedation, opiates, muscular relaxants, decrease the metabolic rate, while catecholamines increase the metabolism. Physical activity is usually low in critically ill patients, but may be significant in agitated patients (Fig. 12). Beta-blockade in burned and trauma patients has been associated with decrease in resting energy expenditure (Fig. 13) and in protein catabolism (Fig. 14, Fig. 15).

Figure 12

Figure 13

Figure 14

Figure 15

There is little information on the change of the regional metabolic rate induced by the critical illness. Inflammatory diseases stimulate the regional metabolism, as shown by studies performed in patients with acute pneumonia, which show increased O₂ consumption in the lung (Fig. 16). Coma is associated with decreased brain O₂ consumption during the initial phase of brain injury.

Figure 16

3. Energy requirements

Clinical assessment of energy expenditure is difficult in critical care and requires the use of sophisticated techniques (see Table 1). Several equations allow the calculation of resting metabolic rate in healthy subjects, based on body weight, height, gender and age (Table 2, Fig. 17). It underestimates resting energy expenditure in most surgical patients. Correction factors for stress have been proposed, but they have been found to be inappropriate for clinical practice, fostering excessive feeding (Fig. 18).

Harris-Benedict equations These equations are gender specific and are based on body weight (kg), height (cm) and age (yr). They predict the resting energy expenditure (+ 10%) in subjects with normal body composition: Male: REE (kcal/day) = 66.5 + (13.8 x body weight) + (5.0 x body height) - (6.8 x age) Female: REE (kcal/day) = 655.1 + (9.6 x body weight) + (1.8 x body height) - (4.7 x age)

Figure 17

Table 1

Method Principle Conditions for use Calorimetric methods Direct calorimetry Determination of heat produced Closed environment (entire body in a closed chamber) Indirect calorimetry O2 consumption, CO2 production, nitrogen excretion Ventilation, fraction of inspired oxygen ( FiO2) <0.6 Non-calorimetric methods Isotopic (doubly-labelled water) CO2 production estimated from the difference between labelled hydrogen and labelled oxygen   Fick method Cardiac output ´ Difference in oxygen content between arterial and mixed venous blood Pulmonary artery catheter Physical activity Pedometer, accelerometer Not suitable for ICU patients Muscular activity Electromyography Not assessed in ICU

Table 2

Name Formula Harris-Benedict Males: 66.5 + (13.8x weight) + (5 x height) – (6.8 x age) Females: 655.1 + (9.6 x weight) + (1.9 x height) – (4.7 x age) Correction factors *: Postoperative: Estimated REE x 1.1 Multiple fractures: Estimated REE x1.1 to 1.3 Severe infection: Estimated REE x 1.3 to 1.6 Burns: Estimated REE x 1.5 tO2.1 Fever: Estimated REE x1.1/°C above 37°C Frankenfield –1000 + 100 (minute ventilation) + 1.3 (haemoglobin) + 300 (sepsis) Swinamer 945 (body surface area) – 6.4 (age) + 108 (temperature) + 24.2 (respiratory rate) + 817 (minute ventilation) – 4349 Fusco –983 – 4(age) + 32 (height in inches)+ 11 (weight) Ireton-Jones° 1925 – 10 (age) + 5 (weight) + 281 (sex)+ 292 (trauma) + 851 (burn) Unless otherwise specified, weight is expressed in kilograms, height is expressed in centimetres, body surface area is expressed in square meters and age is expressed in years. * If required, several correction factors can be used simultaneously ° Sex: 0 for females, 1 for males

Figure 18

In clinical practice, simple rules are used to estimate REE in critically ill patients:

• 20-25 kcal/kg per day in patients with low or moderate stress;
• 25-30 kcal/kg per day in patient with marked stress: multiple injury, brain injury, severe sepsis;
• 35-40 kcal/kg per day or more in patients with major stress, like extensive burns.

In patients with complicated evolution, requiring prolonged nutritional support, it is recommended to perform weekly indirect calorimetry measurements to avoid both gross over- or underfeeding.

It is difficult to match nutrient supply to the needs of acutely ill patients for several reasons:

• The energy requirement is difficult to predict, variability between patients is high, variability in a given patient along the stay is high and the energy expended for activity is difficult to predict;
• The route of feeding may alter energy delivery (enteral nutrition).Precise determination of energy requirement is possible at the bedside using indirect calorimetry.

Figure 19

This measurement is usually made over a short period (about 20-30 min) and 24 hr energy expenditure is extrapolated. This leads to a significant error, reaching 20-30%. A precise determination of the 24 hr metabolic arte would require a 24 hr measurement, which is not possible in clinical condition.

Calculation of the daily energy deficit, defined as the difference between the 24 hr energy expenditure and energy delivery, allows to estimate how appropriate is the caloric supply. Recent studies suggest that prolonged energy deficit is associated with clinical complications, particularly septic complications in critically ill patients (Fig. 19, Fig. 20, Fig. 21).

 

 

 

 

Figure 20

Figure 21

4. Adaptation to fasting

Healthy subjects have the ability to adapt to starvation, allowing survival in case of prolonged starvation. The mechanisms of adaptation include a progressive decrease in resting metabolism, stimulation of production and utilization of ketone bodies as fuel and a progressive reduction of protein catabolism.

Such adaptable mechanisms are blunted by the critical illness (Fig.22): ketosis is suppressed by stress hormones and cytokines, while protein catabolism stay elevated all over the course of critical illness. Thus starvation should be as short as possible in the most severely ill patients, who should receive adequate energy supply as soon as possible after the initial resuscitation.

Figure 22

5. Clinical case

A 48 years old woman was admitted to the hospital with fever 38.2 °C, vomiting and epigastric pain for 2 days after fat food consumption. She had not a past history of cholelitiasis. The BMI 51. kg/m². She was diagnosed to have severe acute pancreatitis ( SAP) due to a very high serum amylase level (6169 IU per liter) and lypase (2400 IU per liter).
On examination the vital functions were rather stable - respiratory rate of more than 27 per minute, BP 160/90 mmHG, pulse 120 /min. Laboratory findings shown leucocytosis 19 x 10 9/L, Hb 169 g/L, platelets 257 x 10 9/L, CRP 481 mg/L, procalcitonine 0.4 ng/ml, bilirubine 23 mkmol/L, blood glucose 15 mkmol/L, paO2 67mmHg, paCO2 26mmHg, lactate 2.5 mmol/L.

Q1:   Where has she to be admitted - general ward or ICU?

Q2:   What does it mean such high concentration of Hb?

Q3:   Does the patient need clinical nutrition now?

Q4:   Can you confirm an abdominal compartment syndrome?

Q5:   Is it time to start clinical nutrition now? How?

Q6:   How calculate energy requirements for such patient?

Q7:   What aim would you like to achieve with enteral nutrition?

Q8:   Is it a time for surgical intervention?

Q9:   What is going with patient?

Q10: Is it possible to continue enteral nutrition?

6. Self-assessment test

References

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