Exploratory study to evaluate the efficacy and safety of nutritionally administering 1.5 g protein/kg/day vs. 1.0 g protein/kg/day in the catabolic phase of the critically ill patient on mechanical ventilation.

INTERVENTION: Trade Name: SmofKaviben Central Product Name: SmofKaviben Central Pharmaceutical Form: Emulsion for infusion INN or Proposed INN: ALANINE CAS Number: 56‐41‐7 Current Sponsor code: ALANINE Other descriptive name: ALANINE Concentration unit: g gram(s) Concentration type: range Concentration number: 3.5‐17.5 INN or Proposed INN: ARGININE CAS Number: 74‐79‐3 Current Sponsor code: ARGININE Other descriptive name: ARGININE Concentration unit: g gram(s) Concentration type: range Concentration number: 3.0‐15.0 INN or Proposed INN: GLYCINE CAS Number: 56‐40‐6 Current Sponsor code: GLYCINE Other descriptive name: GLYCINE Concentration unit: g gram(s) Concentration type: range Concentration number: 2.8‐13.8 INN or Proposed INN: HISTIDINE CAS Number: 71‐00‐1 Current Sponsor code: HISTIDINE Other descriptive name: HISTIDINE Concentration unit: g gram(s) Concentration type: range Concentration number: 0.8‐3.7 INN or Proposed INN: ISOLEUCINE CAS Number: 73‐32‐5 Current Sponsor code: ISOLEUCINE Other descriptive name: ISOLEUCINE Concentration unit: g gram(s) Concentration type: range Concentration number: 1.3‐6.2 INN or Proposed INN: LEUCINE CAS Number: 61‐90‐5 Current Sponsor code: LEUCINE Other descriptive name: LEUCINE Concentration unit: g gram(s) Concentration type: range Concentration number: 1.9‐9.4 INN or Proposed INN: LYSINE ACETATE CAS Number: 57282‐49‐2 Current Sponsor code: LYSINE ACETATE Other descriptive name: LYSINE ACETATE Concentration unit: g gram(s) Concentration type: range Concentration number: 1.7‐8.4 INN or Proposed INN: METHIONINE CAS Number: 63‐68‐3 Current Sponsor code: METHIONINE Other descriptive name: METHIONINE Concentration unit: g gram(s) Concentration type: range Concentration number: 1.1‐5.4 INN or Proposed INN: PHENYLALANINE CAS Number: 63‐91‐2 Curre CONDITION: Acquired Weakness in the Intensive Care Unit (DAUCI) of the critically ill patient. ; MedDRA version: 20.0 Level: PT Classification code 10077255 Term: Intensive care unit acquired weakness System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Not possible to specify PRIMARY OUTCOME: Main Objective: To compare the occurrence and degree of Acquired Acute Critical Care Unit Weakness (ICUCI or ICUAW) in 2 groups of patients treated with different doses of protein (1.5.g/kg/day vs. 1.0 g/kg/day). Primary end point(s): The primary endpoint will be Intensive Care Unit‐Acquired Acute Care Weakness (ICUAW) as defined by a Medical Research Council (MRC Scale) score of less than 48, measured from ventilator weaning, every 4‐6 days, on day 28 or at ICU discharge. (ANNEXES 4 and 4a) Secondary Objective: To compare the rate of:; ; ‐ Infectious complications appeared in each of the two groups. ; ‐ Days of mechanical ventilation; ‐ Metabolic and/or gastrointestinal complications; ‐ Intra‐ICU, in‐hospital, 30 and 90 day mortality; ‐ Intra‐ICU and hospital days; ‐ Urinary nitrogen excretion during time in ICU ; ‐ Quality of life at hospital discharge and 90 days Timepoint(s) of evaluation of this end point: Every 4‐6 days, on day 28 or at ICU discharge. SECONDARY OUTCOME: Secondary end point(s): Secondary objectives will be studied by:; ; ‐ Muscle strength will be measured by Dynamometry ICU, Hospital and at 90 days, and mobility will be measured by IMS (Intensive Mobility Scale) at ICU discharge, hospital discharge and at 90 days. (ANNEX 5) ; ; ‐ Incidence of new nosocomial infections (as defined by the Centers for Disease Control and Prevention (CDC). (ANNEX 6) ; ; ‐ Surgical wound infection; ‐ Primary bacteremia; ‐ Cardiovascular system infection; ‐ Central nervous system infection ; ‐ Gastrointestinal Tract Infection ; ‐ Skin and soft tissue infection ; ‐ Pneumonia associated with mechanical ventilation; ‐ Lower respiratory tract infection without evidence of pneumonia (tracheobronchitis); ‐ Urinary tract infection; ‐ Sinusitis; ; ‐ Duration and type of infection. (Onset and end) ; ‐ Days of mechanical ventilation; ‐ ICU and hospital stay days; ‐ Mortality (ICU, hospital, 90 days) Timepoint(s) of evaluation of this end point: At ICU discharge, hospital discharge and at 90 days. INCLUSION CRITERIA: Must meet all criteria for inclusion: 1. Critically ill patient, adult > 18 years of age. 2. Admission to the ICU during the previous 48 hours. 3. Patients on invasive mechanical ventilation with a minimum expected duration of > 3 days. 4. Patient with a minimum expected duration of clinical nutrition of > 7 days from 48 hours after admission. 5. Written informed consent from the patient or the patient's legal representative or deferred written consent from the patient or the patient's legal representative. 6. Central venous access available for continuous infusion of study drugs. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50