Definition

Chronic Illness and Nutritional Therapy

Nutritional therapy for critically ill patients is characterized by significant heterogeneity regarding etiology, severity, phase of the critical illness, and pre-existing comorbidities. Critically ill patients are treated in Intensive Care Units (ICUs) and increasingly in Intermediate Care Units. From a metabolic perspective, these patients should not be systematically separated, as any critical illness, depending on severity, triggers a significant stress and inflammatory response ^1-3. This stress response is reflected in the phases of critical illness:

1. Acute Phase, divided into an early and late phase, historically known as the "ebb" and "flow" phases.
2. Chronic Phase or Rehabilitation Phase ².

The initial ebb phase is characterized by hemodynamic and metabolic instability, manifesting in a highly catabolic metabolic state with hyperglycemia and peripheral insulin resistance ⁴. In the subsequent flow phase, metabolic stabilization occurs, accompanied by significant muscle mass loss. After the acute phase, the late phase, marked by a decrease in inflammation, promotes increased anabolism and entry into the rehabilitation phase ⁵. However, if inflammation and catabolism persist, it results in a prolonged hospital stay, termed the "Prolonged Inflammatory and Catabolic Syndrome" (PICS) ². These distinct phases, influenced by varying degrees of catabolic metabolic changes, significantly affect the caloric and protein requirements of critically ill patients ².

Given the impact of caloric and protein deficits, as well as overnutrition, on morbidity and mortality, the term "nutrition support" has been replaced by "medical nutritional therapy" in recent years. This change acknowledges the importance and complexity of assessing nutritional status, recognizing the high prevalence of malnutrition, and addressing constantly changing nutritional needs ².

Despite current research, more studies are urgently required to further adapt and optimize nutritional therapy for critically ill patients, addressing heterogeneous demands for protein and calorie targets, timing, and type of nutritional interventions ².

Screening and Nutritional Status Assessment

A high proportion of critically ill patients present with malnutrition upon admission, and additional energy and protein deficits may develop during their stay (50% and 60%, respectively) ^{6, 7}. Patients with a stay longer than 48 hours in Intensive and Intermediate Care have a high risk of malnutrition. Nutritional screening (Nutritional Risk Screening: NRS 2002) should be conducted upon admission to identify malnourished patients early.

In addition to the NRS 2002, other screening tools are available, such as the "Nutrition Risk in the Critically Ill" (NUTRIC) Score ⁸, the "Subjective Global Assessment" (SGA) Score ⁹, or the "Mini-Nutrition Assessment" (MNA) Score (short form or long form) ¹⁰. However, none of these scores have been validated for critically ill patients, nor do they identify patients who would benefit from intensified nutritional therapy ¹¹.

Nutritional requirements of critically ill patients. Adjustments are necessary for malnourished patients, physical activity, and patient age. The weight used is the Adjusted Body Weight (AjBWJ) for patients with a BMI ≥28; otherwise, the pre-hospitalization body weight is applied ³. KG = body weight; d = day

Vitamins, Minerals, and Trace Elements

Medical nutritional therapy for critically ill patients includes the adequate provision of vitamins, minerals, and trace elements, preferably enterally or parenterally if necessary. ¹²

• Daily Requirement Considerations:

1. Individual Deficits: The heterogeneity of critical illnesses and pre-existing conditions should be considered when estimating daily requirements. The potential for Refeeding Syndrome in critically ill patients should also be taken into account (Table 6a). ¹²
2. Therapy-Associated Deficits: Renal replacement therapies or certain medications (e.g., diuretics, proton pump inhibitors, metformin, isoniazid, HIV therapies, antiepileptic drugs, thymoglobulin) may increase the risk of deficiencies (Table 6b). ¹²

Goals of Nutritional Therapy

• Maintain/improve nutritional status and body function.
• Prevent malnutrition and nutrient deficiencies.
• Determine caloric goals from day 3 using indirect calorimetry.
• Progressive increase/optimization of nutrient intake according to the phases of critical illness (from day 4: 80-100% of caloric target).
• Avoid underfeeding and overfeeding.
• Metabolic monitoring, particularly blood glucose levels.
• Reduce systemic inflammation and hypermetabolic stress.

Energy Requirements

Determining the energy needs of critically ill patients is challenging, as energy expenditure depends on various factors such as underlying illness, inflammatory status, medication, body composition, and nutritional status at admission, which are dynamic over time. ¹³ Although predictive formulas are widely used for estimating energy needs in nutritional therapy, many studies have shown that they are often inaccurate. ^14-17 Moreover, none have been validated specifically for critically ill patients. ^{2, 3}

When using predictive formulas, hypocaloric nutritional therapy (<70% of estimated energy needs) is preferred over isocaloric nutrition during the first week in the ICU or Intermediate Care Unit to avoid overfeeding. ²

Indirect Calorimetry (IC) is the recommended standard for determining energy requirements. ^{18, 19} The ESPEN guidelines also recommend a gradual introduction of hypocaloric nutrition even when using IC during the early phase of acute illness, transitioning to isocaloric nutrition in the post-acute phase.

The "International Multicenter Study Group for Indirect Calorimetry" (ICALIC) has recently developed a new indirect calorimetry system to meet clinical needs. ¹³ The ICALIC group recommends IC measurements on the 3rd or 4th day after admission, repeating as soon as the clinical condition changes, or at least once a week and before extubation. ^{6, 7} To optimize nutritional management, it is recommended to adjust energy goals based on the results of the latest IC measurement. ¹³

Protein Requirements

Based on current studies and without technical or laboratory means to determine the individual protein needs during illness progression, ESPEN guidelines recommend a gradual intake of 1.3 g/kg/day protein equivalent during critical illness. ² Additionally, early mobilization of patients in combination with reaching protein targets is suggested to preserve muscle mass. ^{2, 20}

Nutrient Delivery: What, When, and How

The type, amount, and timing of nutrient delivery have been extensively debated in recent decades. However, achieving energy and protein targets with Enteral Nutrition (EN) alone can be challenging during ICU or Intermediate Care stays, often leading to underfeeding in most patients. ^{21, 22} Recent randomized controlled trials (RCTs) have shown that complication rates do not increase with the chosen form of nutrition ^{23, 24} and that avoiding under- or overfeeding is more critical than the type of nutritional therapy selected. ^{25, 26}

Recommendations for Nutritional Therapy in Critically Ill Patients According to International Guidelines ^{2, 3}

1. Oral Nutrition: Energy and protein requirements should be met through oral nutrition whenever possible.
2. Dietary Supplements: Supplements may be used to cover energy and protein needs. ²⁷
3. Enteral Nutrition: Early enteral nutrition (within 48 hours) is recommended for all critically ill patients with a functioning gastrointestinal tract and inadequate oral intake.
4. Parenteral Nutrition: For patients who cannot tolerate targeted enteral nutrition during the first week, additional parenteral nutrition should be considered, but only after attempting all strategies to enhance enteral tolerance.
5. Stepwise Parenteral Nutrition: If oral nutrition is not possible and enteral nutrition is contraindicated, parenteral nutrition should be gradually initiated within the first week.

Oral Nutrition

A high-protein, high-energy diet improves nutritional status. If possible, nutritional counseling should be integrated throughout the treatment to optimize intake and prevent complications.

• Practical Tips: Use mouth sprays for dry mouth, adapt food consistency (pureed, finely chopped, extra sauce), and ensure adequate fluid intake.
• Dysphagia Screening: Screen for swallowing difficulties and adjust diet as necessary.
• Supplements: Oral nutritional supplements (2-3 times daily after meals, served chilled with a straw), enrich foods and drinks with protein powder.
• Optimize Intake: Ensure dedicated meal times, minimize distractions, include favorite foods, and involve family members or provide assistance if needed.

Enteral Nutrition

Enteral nutrition maintains nutritional status when oral intake is insufficient, commonly in critically ill patients with severe illness or sedation. Nasal tubes (nasogastric or nasojejunal) are typically used.

Two large randomized studies comparing enteral and parenteral nutrition found higher rates of hypoglycemia, vomiting, and gastrointestinal complications (e.g., diarrhea, bowel ischemia) with enteral nutrition. Achieving protein and calorie targets was also more challenging in ventilated ICU patients receiving enteral nutrition. ^{23, 24}

Dysphagia screening after extubation is recommended, with appropriate therapy initiated before resuming oral nutrition.

Parenteral Nutrition

Parenteral nutrition is used when oral and/or enteral nutrition is insufficient. It helps maintain nutritional status in cases of intestinal failure or inadequate enteral intake.

Indications: Vomiting/regurgitation with aspiration risk, persistent shock with splanchnic hypoperfusion, ileus, severe malabsorption, bowel ischemia, chronic obstruction, and short bowel syndrome.

ESPEN experts recommend early initiation of parenteral nutrition (within 3-7 days) if contraindications to oral or enteral nutrition exist. Supplemental parenteral nutrition (SPN) may be considered if enteral nutrition is insufficient during the first ICU week. ²

Common adverse effects include mechanical complications (e.g., catheter obstruction/infection, thrombosis) ²⁸ and metabolic issues such as fluid imbalance, electrolyte disturbances, and dyslipidemia. ²⁹ Systematic monitoring can help mitigate these risks. Hepatobiliary complications are often linked to overfeeding during parenteral nutrition. ³⁰

Overfeeding and Underfeeding

Both overfeeding and underfeeding are common in critically ill patients. Overfeeding, defined as energy intake >110% of requirements, can lead to complications such as hyperglycemia, hypertriglyceridemia, and increased mortality. ³² Underfeeding (<70% of caloric target) often results from enteral intolerance, respiratory management, or interruptions for surgery. ³³

Careful monitoring and individualized nutritional strategies are essential to minimize risks and improve outcomes.

Monitoring

• Repeated measurement of energy requirements using indirect calorimetry (see Nutritional Therapeutic Measures).
• During the acute phase of critical illness, inflammation causes micronutrient shifts from plasma into various compartments, limiting the accuracy of measurements for total body stores. For ICU stays longer than 7 days, levels of zinc, copper, iron, folic acid, vitamin B12, and vitamin D should be measured and supplemented if necessary (modified from ¹²). For long-term illnesses, repeat measurements are recommended only after 6 months.
• For patients on parenteral nutrition, triglycerides and liver enzymes should be measured 1-2 times per week.
• In prolonged catabolism (from approximately 5 days), if artificial nutrition (enteral or parenteral) is indicated, it should be slowly increased over several days with the following parameters monitored (Caution: Refeeding Syndrome):
• Phosphate < 0.6 mmol/L or a decrease < 30% below normal value.
• Two or more electrolytes below normal range:
• Phosphate < 0.8 mmol/L
• Potassium < 3.5 mmol/L
• Magnesium < 0.75 mmol/L

Special Considerations for Clinical Nutrition in Critically Ill Patients

Refeeding Syndrome

Refeeding Syndrome is a potentially life-threatening condition that occurs during the transition from catabolism to anabolism (resumption of nutrient intake) in malnourished patients. Electrolyte disturbances (especially hypophosphatemia, hypokalemia, and hypomagnesemia) and fluid shifts can lead to cardiovascular, respiratory, hematological, and neuromuscular symptoms. The absence of a clear definition limits evidence-based screening and therapeutic recommendations. When reintroducing nutrition in critically ill patients (particularly at-risk groups like anorexia nervosa, alcoholism, elderly or obese patients, or those with chronic malnutrition), the potential for Refeeding Syndrome should always be considered. Nutritional therapy should be individualized and include continuous electrolyte monitoring and correction ^{34, 35}:

1. Initial caloric intake should be limited to 20 kcal/hour for at least two days.
2. Once phosphate supplementation is no longer required, caloric intake can be gradually increased to the target over 2-3 days:
• 40 kcal/hour for 24 hours, followed by
• 60 kcal/hour for another 24 hours, then
• 80% of the calculated or measured caloric needs for 24 hours, with 100% of the target amount reached by day 4.

Obesity/Bariatrics

With the rising number of bariatric surgeries, up to 30% of patients experience metabolic complications ³⁷. Critically ill obese patients also require specific nutritional considerations, such as assessing biomarkers for metabolic syndrome, comorbidities, sarcopenia, and chronic inflammation ³. For energy needs, indirect calorimetry is preferred. Alternatively, predictive equations like Mifflin-St Jeor (MSJ) or Harris-Benedict may be used ¹. ESPEN guidelines recommend a high-protein, isocaloric diet with 1.3 g/kg adjusted body weight/day ². Lifelong multivitamin supplementation and, if necessary, intravenous iron should be prescribed post-bariatric surgery to prevent deficiencies.

Geriatric Patients

Patients aged 65 and older make up a large proportion of critically ill patients and are often malnourished at admission. This, combined with acute illness, leads to significantly higher complication risks ³⁸. A "Frailty Score" can supplement malnutrition screening ³⁹. ESPEN guidelines recommend 1.2-1.5 g protein/kg/day, with higher targets for critically ill patients. Rehabilitation and physiotherapy are essential ^{40, 41}.

Vitamin D deficiency, common in geriatric patients, is linked to poor outcomes. ESPEN guidelines recommend a single dose of 500,000 IU during the first ICU week for levels < 12.5 ng/ml or < 50 nmol/L ².

Chronically Critically Ill Patients

This new patient group requires individualized, high-protein nutrition delivered orally or enterally, balanced fluids, metabolic control, and intensive mobilization programs ^{1, 3}.

Additional Subgroups of Critically Ill Patients

• Renal Insufficiency: Use standard nutritional solutions unless fluid overload or electrolyte issues arise. For renal replacement therapy, protein needs increase (< 2.5 g/kg/day), and micronutrient supplementation should also be increased ^{2, 3}.
• Chronic Alcohol Abuse: High risk of thiamine deficiency (up to 500 mg/day recommended), alongside electrolyte correction and addressing malnutrition ^{42, 43}.
• Severe Burns/Liver Failure: Follow ESPEN-specific guidelines ⁴⁴.

Nutrition and Physiotherapy

Nutritional therapy should be combined with tailored endurance and resistance training to rebuild muscle mass and improve metabolic function ¹.

Role of Dietitians

Interdisciplinary collaboration with dietitians is essential for optimizing medical nutritional therapy for critically ill patients ¹.

Transfer or Discharge

Continue or adjust medical nutrition therapy after transfer or discharge. Long-term nutritional support is often needed to meet energy and protein goals. Consider physical and neurological status, and provide nutritional education to patients, caregivers, and family members ^{13, 45, 46}.

Medications/Supplements

• Antiemetics for nausea/vomiting
• Acid secretion inhibitors for mucosal protection
• Agents for bowel motility normalization
• Prokinetics for severe gastrointestinal reflux