Table 3.

Nutrition therapy of critical ill patients, ESPEN recommendations [16].

Target	Patients Staying in the ICU, Mainly for More than 48 h (Considered at Risk for Malnutrition);
Overall recommendations	Careful and progressive re-introduction of nutrition;
	Severely malnourished and starved patients are at risk of refeeding syndrome;
	EN should be ceased in patients with uncontrolled shock, uncontrolled hypoxemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate > 500 mL/6 h, bowel ischemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access 1);
	Key points should be aimed for: (1) oral nutrition as early as possible while considering the risks of complications (e.g., Aspiration); (2) early EN at a low rate and progressive increase within 48 h if oral nutrition is not possible while considering the risk of complications; this progressive increase should be ruled by local protocols; (3) determination of the optimal starting point and dose of (supplemental) PN based on the risk of complications from oral or EN, state of acute illness and presence of previous under/malnutrition; 1)
Nutritional risk determination	Anamnesis, report of unintentional weight loss or decrease in physical performance before ICU admission;
	Physical examination;
	General assessment of body composition (if possible) to detect the loss of lean body mass and sarcopenia;
	Assessment of muscle mass and strength (if possible); considering the abovementioned parameters (the critically ill patient is compared to a geriatric patient);
	Main tools: grading of malnutrition according to the ESPEN GLIM recommendations (see Table 5, page 54, ESPEN guideline) or previous 2015 ESPEN criteria of malnutrition; Clinical Frailty Score (mainly in elderly patients);
	Additional tools: handgrip dynamometer (muscle function); Bioelectrical impedance (only in a stable patient not suffering from fluid compartment shifts);
	Criteria of malnutrition according to the 2015 ESPEN definition: BMI < 18.5 kg/m2 or suffering from an unintentional weight loss > 10% irrespective of time, or > 5% over the last 3 months combined with either a BMI < 20 if < 70 years of age, or < 22 if > 70 years old;
	Tools for screening the risk of malnutrition during hospital stay: the nutritional screening tools (NRS 2002); malnutrition universal screening tool (MUST); or pragmatic approach: patients staying in the ICU > 2 days, undergoing mechanical ventilation, infected, underfed > 5 days, and/or presenting with a severe chronic disease;
Risk of overfeeding	To avoid overfeeding, early full EN shall not be used but shall be prescribed within 3 to 7 days;
	In the early phase of critical illness the provision of excessive amounts of nutrients by any route should be avoided;
Refeeding syndrome	Energy supply should be restricted for 48 h and then progressively increased; measurements of electrolytes (potassium, magnesium, phosphate) during initiation of feeding is necessary to detect development of refeeding syndrome; refeeding hypophosphatemia is a warning signal (<0.65 mmol/L or a drop of > 0.16 mmol/L); electrolytes monitoring two to three times a day and supplemented if needed;
Route and initiation time of nutrition therapy	Oral diet preferred (patients who are able to eat) over EN or PN; if the patient is able to cover 70% of his needs from day three to seven, without risks of vomiting or aspiration;
	EN if oral intake is not possible; early EN (within 48 h) should be preferred over delaying EN and early PN; enteral feeding should be delayed when GRV is > 500 mL/6 h and application of prokinetics should be considered;
	PN should be implemented within 3 to 7 days if contraindications to oral and EN exist; low-dose PN (if EN is not feasible) should be implemented in patients with high nutrition risk (e.g., NRS 2002 ≥ 5) or severely malnourished because of the risks of overfeeding and refeeding;
Type of access	Gastric access-use as the standard approach to initiate EN;
	Postpyloric feeding-in patients with gastric feeding intolerance despite the use of prokinetic agents; postpyloric (mainly jejunal feeding) can be performed in patients at high risk for aspiration: inability to protect the airway, mechanical ventilation, age > 70 years, reduced level of consciousness, poor oral care, inadequate nurse:patient ratio, supine positioning, neurologic deficits, gastroesophageal reflux, transport out of the ICU, use of bolus intermittent EN; the small bowel feeding is associated with a reduced risk of pneumonia compared to gastric feeding;
Administration of EN (bolus or continuous feeding)	Continuous rather than bolus EN is recommended; decreased risk of diarrhea comparing continuous versus bolus administration;
Prokinetics use	Erythromycin should be intravenously administered (usually at dosages of 100–250 mg three times a day) as a first line prokinetic therapy; recommended to patients with gastric feeding intolerance; should be used for 24–48 h or maximum 4 days; if a large (>500 mL) GRV still persists, the use of post-pyloric feeding should be considered over withholding EN;
	Metoclopramide can be used alternatively, or in combination with erythromycin;
	Effectiveness of prokinetics is decreased after 3 days and should be discontinued;
Energy expenditure (EE) estimation	Several parameters must be considered in order to estimate caloric needs: the nutritional status prior to ICU admission (body weight and its alterations); the number of days of hospitalization before ICU admission and/or in the ICU; the endogenous nutrient production and autophagy; the energy balance during ICU stay; the time elapsed and energy balance during hospital stay; the occurrence of refeeding syndrome (or at least hypophosphatemia) at the time of feeding;
	Indirect calorimetry (IC) is recommended in critically ill mechanically ventilated patients;
	If IC is not available use VO2 (oxygen consumption) from pulmonary arterial catheter or VCO2 (carbon dioxide production) derived from the ventilator (REE = VCO2 × 8.19);
	If IC and VO2 or VCO2 measurements are not available, use of simple weight-based equations (such as 20–25 kcal/kg/day);
Isocaloric or hypocaloric nutrition therapy?	Isocaloric nutrition if indirect calorimetry is used; after the early phase of acute illness can be progressively implemented; 1) after day 3, caloric delivery can be increased up to 80–100% of measured EE;
	Hypocaloric nutrition (not exceeding 70% of EE), if predictive equations are used to estimate the energy need, should be administered in the early phase of acute illness especially for the first week of ICU stay;
Energy/protein goal	Should be achieved progressively and not before the first 48 h to avoid over-nutrition 1);
	Full targeted medical nutrition therapy is considered to achieve more than 70% of the resting energy expenditure (REE), but not more than 100% 1);
Protein requirements	1.3 g/kg protein equivalents per day (delivered progressively);
	1.2–1.5 g protein/kg/day in older people who are malnourished or at risk of malnutrition
Carbohydrates requirements	Should not exceed 5 mg/kg/min;
	Citrate (used in continuous veno-venous hemo-dia-filtration (CVVH)) increases carbohydrate load and should be included as a non-nutritional calorie intake;
Fat requirements	High-fat administration can lead to lipid overload and especially unsaturated fat to impaired lung function and immune suppression1);
	The best ratio of fat can be established by monitoring of triglycerides and liver function tests;
	Propofol (lipid solution-1.1 kcal/mL) is associated with calorie overload;
Glutamine (GLN)	Additional enteral GLN should not be administered (exception: burn and trauma patients);
EPA/DHA	EN enriched with omega-3 FA within nutritional doses can be used;
	High doses omega-3 enriched enteral formulas should not be given on a routine basis and by bolus administration;
Micronutrients	Should be provided daily with PN;
	The repletion of micronutrients (i.e., Trace elements and vitamins) in conditions of chronic and acute deficiency is recommended;
Antioxidants	As high dose monotherapy should not be implemented without proven deficiency;
	Intense inflammation reduces the circulating levels (below reference ranges) of the antioxidant micronutrients (in particular copper, selenium, zinc, vitamins E and C);
Vitamin D	A high dose of vitamin D3 (500,000 IU) as a single dose within a week after admission can be supplemented if there are low plasma levels (25-hydroxy-vitamin D < 12.5 ng/mL, or 50 nmol/L);
Supplemental PN	In patients who do not tolerate full dose EN during the first week in the ICU, the safety and benefits of initiating PN should be weighed on a case-by-case basis 1);
	PN should not be started until all strategies to maximize EN tolerance have been attempted 1);
	When the level of energy needs provided by EN is below 60% 3 days after ICU admission, supplementary PN should be initiated to reach a maximum of 100% of the energy needs (measured by indirect calorimetry whenever possible) 1);
Obese and overweight patients	An iso-caloric high-protein diet is recommended;
	Energy requirements are guided by indirect calorimetry (if not available use “adjusted body weight”*); protein requirements are guided by urinary nitrogen losses or lean body mass determination (if not available, 1.3 g of protein/kg “adjusted body weight”*/day);
	*“adjusted body weight” = (actual body weight-ideal body weight) × 0.33 + ideal body weight
	Ideal body weight for obese patients = 2.2 ×BMI + 3.5 × BMI × (height−1.5 m)
	Or use pragmatic approach: energy requirements = 20 ÷ 25% × (actual body weight-ideal body weight) + ideal body weight
	Early EN, gastrointestinal tolerance and progressive increase in nutrition recommended similarly as in all other ICU patients;
Physical activity	May improve the beneficial effects of nutritional therapy;
Special conditions	1) EN should be delayed if shock is uncontrolled and hemodynamic and tissue perfusion goals are not reached, whereas low dose EN can be started as soon as shock is controlled with fluids and vasopressors/inotropes, while remaining vigilant for signs of bowel ischemia; in the case of uncontrolled life-threatening hypoxemia, hypercapnia or acidosis, whereas EN can be started in patients with stable hypoxemia, and compensated or permissive hypercapnia and acidosis; in patients suffering from active upper GI bleeding, whereas EN can be started when the bleeding has stopped and no signs of re-bleeding are observed; in patients with overt bowel ischemia; in patients with high-output intestinal fistula if reliable feeding access distal to the fistula is not achievable; in patients with abdominal compartment syndrome; if gastric aspirate volume is above 500 mL/6 h;
	1) Low dose EN should be administered in patients: receiving therapeutic hypothermia and increasing the dose after rewarming, with intra-abdominal hypertension without abdominal compartment syndrome, whereas temporary reduction or discontinuation of EN should be considered when intra-abdominal pressure values further increase under EN; with acute liver failure when acute, immediately life-threatening metabolic derangements are controlled with or without liver support strategies, independent of grade of encephalopathy;
	1) Early EN should be performed in patients: receiving ECMO (extracorporeal Membrane Oxygenation); with traumatic brain injury; with stroke (ischemic or hemorrhagic); with spinal cord injury; with severe acute pancreatitis; after GI surgery; after abdominal aortic surgery; with abdominal trauma when the continuity of the GI tract is confirmed/restored; receiving neuromuscular blocking agents; managed in prone position; with open abdomen; and regardless of the presence of bowel sounds unless bowel ischemia or obstruction is suspected in patients with diarrhea;
	1) in non-intubated patients not reaching the energy target with an oral diet, oral nutritional supplements should be considered first and then EN;
	1) in non-intubated patients with dysphagia, texture-adapted food can be considered; if swallowing is proven unsafe, EN should be administered;
	1) in non-intubated patients with dysphagia and a very high aspiration risk, postpyloric EN or, if not possible, temporary PN during swallowing training with removed nasoenteral tube can be performed;
Laboratory parameters monitoring	Blood glucose after ICU admission or after nutrition therapy initiation and at least every 4 h, for the first 2 days in general;
	Insulin: when glucose levels exceed 10 mmol/L; insulin therapy initiation when blood glucose exceeds 150 or 180 mg/dL (10 mmol/L); blood glucose should target a concentration of 6–8 mmol/L;
	Electrolytes (potassium, magnesium, phosphate): at least once daily for the first week; refeeding hypophosphatemia: two to three times a day and supplemented if needed

¹⁾ exact recommendations indicated in “ESPEN guideline on clinical nutrition in the intensive care unit” (2019).