HK1196274B - Product for parenteral feeding of obese intensive care patients - Google Patents

Description

Intensive care patients are generally unable to feed themselves and therefore require artificial nutrition. Many intensive care patients require parenteral nutrition because oral or enteral nutrition is either not available, not sufficient, or contraindicated. With parenteral nutrition, nutrition is administered via the bloodstream, bypassing the gastrointestinal tract.

Obese intensive care patients place special demands on parenteral nutrition. Obesity is defined as severe overweight, characterized by an excessive increase in body fat with pathological consequences. While obese intensive care patients generally do not differ from normal- or underweight intensive care patients with regard to the indication for parenteral nutrition, complications occur more frequently in obese intensive care patients receiving parenteral nutrition. Furthermore, the severity of complications occurring in intensive care patients receiving parenteral nutrition is often higher, for example, than in normal-weight intensive care patients receiving parenteral nutrition.

This is partly due to the fact that adequate parenteral nutrition of obese intensive care patients is difficult to achieve with conventional state-of-the-art parenteral nutrition solutions, which are essentially tailored to the needs of normal- or underweight patients.

However, the nutritional needs of obese intensive care patients differ significantly from those of underweight or normal-weight intensive care patients. Obese intensive care patients require different ratios and amounts of the macronutrients amino acids, carbohydrates, and lipids, partly because lipid and glucose metabolism are often impaired in this patient group.

In addition, the need for micronutrients, such as vitamins and trace elements, can differ from that of underweight or normal weight intensive care patients and is often increased.

If the needs of obese intensive care patients, which differ from those of underweight or normal weight patients, are not taken into account or are not taken into account sufficiently, this can lead to an increased occurrence of metabolic or infectious complications and thus to increased morbidity and mortality of the patients.

State-of-the-art parenteral nutrition solutions are offered that contain amino acids, lipids, and carbohydrates in specific amounts and ratios. Electrolytes can be included in the nutritional solutions or added to them prior to administration. Trace elements and vitamins are added to the parenteral nutrition solutions prior to administration or administered separately from the parenteral nutrition solution. These state-of-the-art parenteral nutrition solutions are not designed to meet the needs of obese intensive care patients, but rather to meet the nutrient and energy requirements of normal- or underweight intensive care patients.

The dosage recommendations for parenteral nutrition solutions provided in the state of the art are also not designed for the nutrition of obese intensive care patients. For example, dosage instructions for parenteral nutrition solutions often refer to the body weight of the intensive care patient.

However, body weight is not a suitable reference for determining the required amount of nutrition in obese patients, as it is pathologically elevated in obese intensive care patients. Administering nutrition based on actual body weight can therefore lead to a massive oversupply of macronutrients. Furthermore, body weight in obese intensive care patients is often difficult to determine by weighing.

While it is conceivable to provide tailored nutrition to obese intensive care patients using individual solutions in which amino acids, carbohydrates, and lipids are administered via separate containers, this requires complex calculations of the required volumes of nutritional solutions by the prescribing physician and administration from several different containers. This entails increased time expenditure for nursing staff, an increased risk of administration and dosage errors, and increased consumption of nutritional solutions, resulting in increased costs. This is because the volumes contained in the individual containers are not coordinated and residual volumes of the individual solutions must be discarded.

In view of these disadvantages of state-of-the-art parenteral nutrition solutions, a parenteral nutrition solution for administration to obese intensive care patients should be provided that takes into account the special nutritional needs of this patient group and is at the same time simple, safe and economical in handling and dosing.

Disclosure of the invention

1. (i) 500 mL - 834 mL einer Aminosäurelösung umfassend 50 g - 83 g Aminosäuren,
2. (ii) 167 mL - 278 mL einer Glukoselösung umfassend 67 g - 111 g Glukose, und
3. (iii) 83 mL - 139 mL einer Lipidemulsion umfassend 17 g - 28 g Lipide.

The invention comprises a parenteral nutrition solution for use in administration to an obese intensive care patient, the nutrition solution comprising per 1000 mL:

1. (i) 500 mL - 834 mL of an amino acid solution comprising 50 g - 83 g of amino acids,
2. (ii) 167 mL - 278 mL of a glucose solution comprising 67 g - 111 g glucose, and
3. (iii) 83 mL - 139 mL of a lipid emulsion comprising 17 g - 28 g of lipids.

1. (i) 667 mL einer Aminosäurelösung umfassend 67 g Aminosäuren,
2. (ii) 222 mL einer Glukoselösung umfassend 89 g Glukose, und
3. (iii) 111 mL einer Lipidemulsion umfassend 22 g Lipide.

The parenteral nutrition solution can contain per 1000 mL:

1. (i) 667 mL of an amino acid solution comprising 67 g of amino acids,
2. (ii) 222 mL of a glucose solution containing 89 g glucose, and
3. (iii) 111 mL of a lipid emulsion comprising 22 g of lipids.

In a preferred embodiment, the amino acid solution comprised by the parenteral nutrition solution comprises, per 1000 mL of the amino acid solution, at least one component selected from the group consisting of about 5 g of isoleucine, about 7.4 g of leucine, about 9.31 g of lysine acetate (corresponding to about 6.6 g of lysine), about 4.3 g of methionine, about 5.1 g of phenylalanine, about 4.4 g of threonine, about 2 g of tryptophan, about 6.2 g of valine, about 12 g of arginine, about 3 g of histidine, about 14 g of alanine, about 11 g of glycine, about 11.2 g of proline, about 6.5 g of serine, about 0.4 g of tyrosine and about 1 g of taurine, or a combination thereof.

It is also preferred that the lipid emulsion comprised by the parenteral nutrition solution comprises, per 1000 mL of the lipid emulsion, at least one component selected from the group consisting of about 60 g of soybean oil, about 60 g of MCT, about 50 g of olive oil, and about 30 g of fish oil, or a combination thereof.

The parenteral nutrition solution may further comprise electrolytes. In a preferred embodiment, the parenteral nutrition solution comprises, per 1000 mL, electrolytes selected from the group consisting of about 32.8 mmol sodium to about 48 mmol sodium, about 24 mmol potassium to about 36 mmol potassium, about 4.1 mmol magnesium to about 6.1 mmol magnesium, about 2 mmol calcium to about 3 mmol calcium, about 8.2 mmol phosphate to about 15.6 mmol phosphate, about 0.032 mmol zinc to about 0.048 mmol zinc, about 4.1 mmol sulfate to about 6.1 mmol sulfate, about 28.8 mmol chloride to about 43.2 mmol chloride, about 84.8 mmol acetate to about 127.2 mmol acetate, or a combination thereof.

A particularly preferred parenteral nutrition solution comprises per 1000 mL of electrolytes selected from the group consisting of about 36.9 mmol sodium to about 45.1 mmol sodium, about 27 mmol potassium to about 33 mmol potassium, about 4.6 mmol magnesium to about 5.6 mmol magnesium, about 2.3 mmol calcium to about 2.8 mmol calcium, about 9.2 mmol phosphate to about 14.3 mmol phosphate, about 0.036 mmol zinc to about 0.044 mmol zinc, about 4.6 mmol sulfate to about 5.6 mmol sulfate, about 32.4 mmol chloride to about 39.6 mmol chloride, about 95.4 mmol acetate to about 116.6 mmol acetate, or a combination thereof.

A particularly preferred parenteral nutrition solution comprises per 1000 mL of electrolytes selected from the group consisting of about 36.9 mmol sodium to about 45.1 mmol sodium, about 27 mmol potassium to about 33 mmol potassium, about 4.6 mmol magnesium to about 5.6 mmol magnesium, about 2.3 mmol calcium to about 2.8 mmol calcium, about 10.2 mmol phosphate to about 13 mmol phosphate, about 0.036 mmol zinc to about 0.044 mmol zinc, about 4.6 mmol sulfate to about 5.6 mmol sulfate, about 32.4 mmol chloride to about 39.6 mmol chloride, about 95.4 mmol acetate to about 116.6 mmol acetate, or a combination thereof.

Even more preferably, the parenteral nutrition solution comprises per 1000 mL of electrolytes selected from the group consisting of about 41 mmol sodium, about 30 mmol potassium, about 5.1 mmol magnesium, about 2.5 mmol calcium, about 13 mmol phosphate, about 0.04 mmol zinc, about 5.1 mmol sulfate, about 36 mmol chloride, about 106 mmol acetate, or a combination thereof.

Most preferred is a parenteral nutrition solution comprising 41 mmol sodium, 30 mmol potassium, 5.1 mmol magnesium, 2.5 mmol calcium, 13 mmol phosphate, 0.04 mmol zinc, 5.1 mmol sulfate, 36 mmol chloride and 106 mmol acetate per 1000 mL of the nutrition solution.

The parenteral nutrition solution can comprise 25 to 35 energy percent from amino acids, 40 to 45 energy percent from glucose, and 22 to 30 energy percent from lipids per 100 energy percent. Preferably, the nutrition solution comprises 28 to 34 energy percent from amino acids, 41 to 44 energy percent from glucose, and 25 to 27 energy percent from lipids per 100 energy percent. More preferably, the nutrition solution comprises 32 energy percent from amino acids, 42 energy percent from glucose, and 26 energy percent from lipids per 100 energy percent.

The parenteral nutrition solution has an energy content of 700 kcal to 975 kcal per 1000 mL. Preferably, the nutrition solution has an energy content of 800 kcal to 880 kcal per 1000 mL. Most preferred is a nutrition solution having an energy content of 820 kcal to 860 kcal per 1000 mL.

1. (i) in der ersten Kammer die Aminosäurelösung,
2. (ii) in der zweiten Kammer die Glukoselösung, und
3. (iii) in der dritten Kammer die Lipidemulsion,

wobei die Aminosäurelösung, die Glukoselösung und die Lipidemulsion vor der Verwendung zur Verabreichung an einen adipösen Intensivpatienten vereinigt und gemischt werden.The parenteral nutrition solution can be contained in a three-chamber bag comprising a first chamber, a second chamber and a third chamber.

1. (i) in the first chamber the amino acid solution,
2. (ii) in the second chamber the glucose solution, and
3. (iii) in the third chamber the lipid emulsion,

wherein the amino acid solution, the glucose solution and the lipid emulsion are combined and mixed prior to use for administration to an obese intensive care patient.

If the parenteral nutrition solution contained in the three-chamber bag contains electrolytes, these can be contained in the first and/or second chamber of the three-chamber bag.

• die erste Kammer 750 mL - 2250 mL einer Aminosäurelösung umfasst, enthaltend 56,3 g - 281,3 g Aminosäuren,
• die zweite Kammer 250 mL - 750 mL einer Glukoselösung umfasst, enthaltend 75 g - 375 g Glukose, und
• die dritte Kammer 125 mL - 375 mL einer Lipidemulsion umfasst, enthaltend 18,8 g - 93,8 g Lipide,

wobei der Dreikammerbeutel, bezogen auf das Gesamtvolumen der ersten, der zweiten und der dritten Kammer, pro 1000 mL mindestens 50 g Aminosäuren umfasst.The invention further comprises a three-chamber bag comprising a first chamber, a second chamber and a third chamber, wherein

• the first chamber contains 750 mL - 2250 mL of an amino acid solution containing 56.3 g - 281.3 g of amino acids,
• the second chamber comprises 250 mL - 750 mL of a glucose solution containing 75 g - 375 g glucose, and
• the third chamber comprises 125 mL - 375 mL of a lipid emulsion containing 18.8 g - 93.8 g of lipids,

wherein the three-chamber bag contains at least 50 g of amino acids per 1000 mL, based on the total volume of the first, second and third chambers.

Preferably, the three-chamber bag comprises, based on the total volume of the first, second and third chambers, at least 60 g of amino acids per 1000 mL, particularly preferably at least 63 g of amino acids, even more preferably at least 65 g of amino acids.

In a preferred embodiment, the three-chamber bag comprises a first, a second, and a third chamber, wherein: the first chamber comprises 1500 mL of an amino acid solution containing 135 g - 187.5 g of amino acids, preferably 150 g of amino acids, the second chamber comprises 500 mL of a glucose solution containing 150 g - 250 g of glucose, preferably 200 g of glucose, and the third chamber comprises 250 mL of a lipid emulsion containing 37.5 g - 62.5 g of lipids, preferably 50 g of lipids, or wherein: the first chamber comprises 750 mL of an amino acid solution containing 67.5 g - 93.8 g of amino acids, preferably 75 g of amino acids, the second chamber comprises 250 mL of a glucose solution containing 75 g - 125 g of glucose, preferably 100 g of glucose, comprises, and the third chamber comprises 125 mL of a lipid emulsion containing 18.8 g - 31.3 g of lipids, preferably 25 g of lipids, or wherein the first chamber comprises 2250 mL of an amino acid solution containing 202.5 g - 281.3 g of amino acids, preferably 225 g of amino acids, the second chamber comprises 750 mL of a glucose solution containing 225 g - 375 g of glucose, preferably 300 g of glucose, and the third chamber comprises 375 mL of a lipid emulsion containing 56.3 g - 93.8 g of lipids, preferably 75 g of lipids.

The parenteral nutrition solution is suitable for administration to an obese intensive care patient. In a preferred embodiment, the parenteral nutrition solution is administered to an obese intensive care patient with a hypercatabolic and/or hypermetabolic metabolic state. In a particularly preferred embodiment, the parenteral nutrition solution is administered to an obese intensive care patient who is critically ill and/or who has a condition selected from the group consisting of trauma, burns, infection, sepsis, and surgical intervention, or a combination thereof.

The parenteral nutrition solution can be given to an obese intensive care patient with

Obesity grade I, obesity grade II and obesity grade III.

In a further preferred embodiment, the amount of parenteral nutrition solution to be administered daily is determined by a parameter selected from the group consisting of body size of the obese intensive care patient, gender of the obese intensive care patient, degree of obesity of the obese intensive care patient or a combination thereof.

If the patient suffers from grade I or grade II obesity, the parenteral nutrition solution is administered to the patient in an amount of 25 mL to 35 mL per kg of ideal body weight (IBW) per day. Parenteral nutrition is preferred.

Nutritional solution is administered to the patient in an amount of 28 mL to 32 mL per kg IBW per day, particularly preferably in an amount of 30 mL per kg IBW per day.

If the patient suffers from grade III obesity, the parenteral nutrition solution is administered to the patient in a volume of 32 mL to 42 mL per kg IBW per day. Preferably, the parenteral nutrition solution is administered to the patient in a volume of 35 mL to 39 mL per kg IBW per day, most preferably in a volume of 37 mL per kg IBW per day.

If the patient is female and suffers from grade I or grade II obesity, the patient can be administered approximately 2100 mL of parenteral nutrition solution per day for a height of 180 cm, approximately 1950 mL for a height of 174 cm, approximately 1800 mL for a height of 168 cm, approximately 1650 mL for a height of 163 cm, or approximately 1500 mL for a height of 157 cm. If the patient is female and suffers from grade III obesity, the patient can be administered approximately 2590 mL of parenteral nutrition solution per day for a height of 180 cm, approximately 2405 mL for a height of 174 cm, approximately 2220 mL for a height of 168 cm, approximately 2035 mL for a height of 163 cm, or approximately 1850 mL for a height of 157 cm.

If the patient is male and suffers from grade I or grade II obesity, the patient can be administered approximately 2550 mL of parenteral nutrition solution per day for a height of 187 cm, approximately 2400 mL for a height of 182 cm, approximately 2250 mL for a height of 178 cm, approximately 2100 mL for a height of 173 cm, approximately 1950 mL for a height of 168 cm, or approximately 1800 mL for a height of 163 cm. If the patient is male and suffers from grade III obesity, the patient can be administered approximately 3145 mL of parenteral nutrition solution per day for a height of 187 cm, approximately 2960 mL for a height of 182 cm, approximately 2775 mL for a height of 178 cm, approximately 2590 mL for a height of 173 cm, approximately 2405 mL for a height of 168 cm, or approximately 2220 mL for a height of 163 cm.

Further embodiments of the invention will become apparent from the following detailed description.

Definitions

Parenteral nutrition refers to the administration of nutrition (e.g., suitable nutritional solutions) into the bloodstream, i.e., bypassing the gastrointestinal tract. This includes, for example, intravenous injection or infusion, as well as intra-arterial injection or infusion. Parenteral nutrition solutions are preferably administered through a central venous catheter.

Intra-arterial administration refers to administration into an arterial blood vessel, while intravenous administration refers to administration into a venous blood vessel. Injection refers to administration via syringe. This is usually done as a bolus dose. Continuous injection using syringe pumps is also possible. Infusion refers to the continuous administration of the drug into a blood vessel, which can be done, for example, via a peripheral or central venous catheter.

A parenteral nutrition solution is a nutritional solution suitable for parenteral nutrition. Due to its composition, a parenteral nutrition solution can be administered into a patient's bloodstream.

Obesity is defined as severe overweight, characterized by an excess of body fat above normal levels, with pathological consequences. According to the World Health Organization's definition (WHO (editor): Obesity: preventing and managing the global epidemic. Report of a WHO Consultation. In: WHO Technical Report Series. 894, 2000), obesity is determined based on the body mass index (BMI). Obesity is defined as a body mass index (BMI) of 30 kg/ ^m² or higher. Obesity can be divided into three levels of severity (grade I, grade II, or grade III), which are also classified based on BMI.

Grade I obesity is defined as a BMI of 30.0–34.99. Grade II obesity is defined as a BMI of 35.0–39.99. Grade III obesity is defined as a BMI of 40 or greater.

The body mass index (BMI) is a measure of a person's body weight in relation to their height and is calculated using the following formula: BMI = m/12

Where m denotes body mass in kg and I denotes body height in m.

• Für Männer :
• Für Frauen:

The ideal body weight (IBW) in kg for men and women can be calculated using the following formulas:

• For men:
• For women:

When calculating, body height in cm must be used.

An intensive care patient is a male or female patient receiving inpatient, intensive medical treatment. An "intensive care patient" as defined in this application may be a patient for whom there is a medical indication for parenteral nutrition. A medical indication for parenteral nutrition may exist if oral or enteral nutrition cannot be provided or is not provided sufficiently, or if oral or enteral nutrition is contraindicated.

The term "hypercatabolic metabolic state" describes an excessive catabolic metabolism.

A "hypermetabolic metabolic state" is understood to mean an increase in metabolism throughout the organism.

The term "critically ill" includes intensive care patients who have systemic inflammatory response syndrome (SIRS), sepsis, or multi-organ dysfunction syndrome (MODS), or who are at risk of developing SIRS, MODS, or sepsis.

Systemic inflammatory response syndrome (SIRS) is the term for a generalized systemic inflammatory reaction to a severe physical event (e.g., trauma). SIRS is the overarching term in relation to sepsis, as it describes the clinical syndrome of the critically ill patient (regardless of the cause). Non-infectious triggers include pancreatitis, ischemia, trauma and tissue injury, hemorrhagic shock, or burns. If SIRS is caused by a proven infection, it is referred to as sepsis . Multi-organ failure often occurs as a complication and consequence of SIRS and severe sepsis. Multi-organ dysfunction syndrome (MODS) can occur as a result of shock, sepsis, or SIRS and is characterized by limitations in organ function, organ dysfunction, and/or organ failure. The number of affected organs and the severity of the resulting organ impairment can vary.

The term "approximately" as used herein with reference to numerical values refers to a deviation from the stated numerical value, the magnitude of which is determined, among other things, by the accuracy of the method used to determine the numerical value. Preferably, "approximately" in the present invention refers to a deviation of ± 5% of the stated numerical value.

The energy percentage of a component of a nutritional solution is the percentage of that component in relation to the total energy content of the nutritional solution. The total energy content of the nutritional solution is 100%. The energy content of a food is the amount of energy the body can obtain when breaking it down. The energy content is expressed in calories (kcal) or joules (J).

A dipeptide is a compound consisting of two amino acids linked by a peptide bond. The dipeptide can be N(2)-L-alanyl-L-glutamine.

Fish oil is defined as fish oil containing omega-3 fatty acids. The fish oil can be obtained from marine fish, for example, from deep-sea fish. Fish oil , as defined in this application, is highly purified fish oil suitable for parenteral administration to humans.

Medium-chain triglycerides (MCTs) are triglycerides that contain medium-length fatty acid residues (6 to 12 carbon atoms in length). Examples of MCT fatty acids include caproic acid ( _C6 ), caprylic acid ( _C8 ), capric acid ( _C10 ), and lauric acid ( _C12 ), or a combination thereof.

Trace elements include chromium (Cr), cobalt (Co), iodine (I), iron (Fe), copper (Cu), manganese (Mn), molybdenum (Mo), selenium (Se), and zinc (Zn).

Dissolved salts dissociated into positively and negatively charged ions can also be referred to as electrolytes . Examples of electrolytes include sodium, potassium, magnesium, calcium, phosphate, zinc, sulfate, chloride, and acetate.

Vitamins include vitamin A, vitamin B ₁ , vitamin B ₂ , vitamin B ₃ , vitamin B ₅ , vitamin B ₆ , vitamin B ₇ , vitamin B ₉ , vitamin B ₁₂ , vitamin C, vitamin D, vitamin E and vitamin K.

Embodiments of the invention

The headings used below are for convenience only and should not be construed as limiting. Where ranges of values are mentioned below, each of the individual values encompassed by that range is also disclosed.

Composition of parenteral nutrition solution

Due to its special composition, the parenteral nutrition solution is particularly suitable for parenteral nutrition of obese intensive care patients.

The parenteral nutrition solution contains only components suitable for parenteral administration to humans. All components used have a purity level that makes the respective component suitable for parenteral administration. Those skilled in the art are familiar with components suitable for parenteral administration to humans and their required purity level.

The parenteral nutrition solution consists of an amino acid solution, a glucose solution and a lipid emulsion, and may also contain electrolytes.

If the parenteral nutrition solution contains electrolytes, these may be contained in the amino acid solution and/or the glucose solution.

In the parenteral nutrition solution, the amino acid solution, the glucose solution and the lipid emulsion can be present in combined and mixed form.

Trace elements and/or vitamins can be added to the parenteral nutrition solution prior to administration to an obese intensive care patient. Electrolytes can also be added prior to administration if they are not already present in the amino acid solution and/or the glucose solution, or if additional electrolytes are desired in addition to those already present in the parenteral nutrition solution.

Alternatively or additionally, electrolytes, trace elements and/or vitamins can also be administered separately from the parenteral nutrition solution.

(i) Amino acid solution

The amino acid requirement of obese intensive care patients is increased compared to normal weight intensive care patients and is at least 2 g/kg body weight (based on the patient's ideal weight) per day for intensive care patients with grade I or II obesity. For intensive care patients with grade III obesity, the amino acid requirement is even higher at at least 2.5 g/kg body weight (based on the patient's ideal weight) per day.

For example, an adequate supply of amino acids is important for maintaining lean body mass, especially muscle mass. Especially in intensive care patients with injuries, burns, or after surgery, an adequate supply of amino acids is also crucial for wound healing. It is therefore crucial that obese intensive care patients receive sufficient amounts of amino acids via parenteral nutrition.

In this context, the inventors have discovered that a parenteral nutrition solution containing 0.050 g to 0.083 g of amino acids per mL is well suited for administration to obese intensive care patients, since on the one hand the increased amino acid requirement of obese intensive care patients can be met, but on the other hand there is no excessive increase in end products of protein metabolism.

Surprisingly, it has been shown that a parenteral nutrition solution containing 0.060 g to 0.083 g of amino acids per mL, in particular 0.063 g to 0.080 g of amino acids, is particularly well suited for the parenteral nutrition of obese intensive care patients. A parenteral nutrition solution containing 0.065 g to 0.075 g of amino acids per mL is preferred. A parenteral nutrition solution containing 0.065 g to 0.070 g of amino acids per mL is particularly preferred. A parenteral nutrition solution containing 0.067 g of amino acids per mL is most preferred.

In a particularly preferred embodiment, the amino acid solution contained in the parenteral nutrition solution comprises, per 1000 mL of the amino acid solution, at least one component selected from the group consisting of: about 5 g of isoleucine, about 7.4 g of leucine, about 9.31 g of lysine acetate (corresponding to about 6.6 g of lysine), about 4.3 g of methionine, about 5.1 g of phenylalanine, about 4.4 g of threonine, about 2 g of tryptophan, about 6.2 g of valine, about 12 g of arginine, about 3 g of histidine, about 14 g of alanine, about 11 g of glycine, about 11.2 g of proline, about 6.5 g of serine, about 0.4 g of tyrosine and about 1 g of taurine or a combination thereof.

Very particularly preferred is an embodiment in which the amino acid solution contained in the parenteral nutrition solution comprises, per 1000 mL of the amino acid solution, 5 g isoleucine, 7.4 g leucine, 9.31 g lysine acetate (corresponding to 6.6 g lysine), 4.3 g methionine, 5.1 g phenylalanine, 4.4 g threonine, 2 g tryptophan, 6.2 g valine, 12 g arginine, 3 g histidine, 14 g alanine, 11 g glycine, 11.2 g proline, 6.5 g serine, 0.4 g tyrosine and 1 g taurine.

In a further preferred embodiment, amino acids in the form of dipeptides can be added to the parenteral nutrition solution prior to administration to an obese intensive care patient, in addition to the amino acids contained in the parenteral nutrition solution. 0.01 g to 0.04 g of dipeptide, preferably 0.015 g to 0.030 g of dipeptide, most preferably 0.02 g to 0.025 g of dipeptide, can be added to the parenteral nutrition solution per mL. In a particularly preferred embodiment, the dipeptide is N(2)-L-alanyl-L-glutamine.

(ii) Glucose solution

The parenteral nutrition solution is characterized by a comparatively low glucose content, which is lower than that of amino acid-rich parenteral nutrition solutions known from the state of the art.

In the parenteral nutrition solution for administration to obese intensive care patients, carbohydrates are provided in the form of glucose. The parenteral nutrition solution comprises 0.067 g to 0.111 g of glucose per mL. Preferably, the parenteral nutrition solution comprises 0.070 g to 0.105 g of glucose, or 0.080 g to 0.095 g of glucose per mL. Particularly preferred is a parenteral nutrition solution comprising 0.082 g to 0.093 g of glucose per mL. Most preferred is a parenteral nutrition solution comprising 0.089 g of glucose per mL.

While the administration of carbohydrates, for example in the form of glucose, is essential for adequate parenteral nutrition, even in obese intensive care patients, the comparatively low glucose content of this parenteral tube feed is extremely advantageous for administration to obese intensive care patients, as this patient group very often already has a disorder of glucose metabolism in the form of glucose intolerance or manifest diabetes mellitus, or this disorder occurs during parenteral nutrition.

(iii) Lipid emulsion

In addition to differing requirements for the supply of amino acids and carbohydrates during parenteral nutrition, obese intensive care patients also differ from normal or underweight intensive care patients in their lipid requirements. This is because, similar to carbohydrate metabolism, lipid metabolism is already disturbed in many obese intensive care patients before the event that requires parenteral nutrition occurs. Furthermore, obese intensive care patients receiving parenteral nutrition are at a higher risk than normal or underweight intensive care patients of developing a disorder of lipid metabolism due to inadequate parenteral nutrition that is not tailored to the specific needs of obese intensive care patients. Lipid metabolism disorders that are often present in obese intensive care patients even before the start of parenteral nutrition and that, if not already present, often occur as a result of parenteral nutrition include hypertriglyceridemia. Hypertriglyceridemia is often accompanied by elevated transaminases, bilirubin, thrombocytopenia, and thrombocytopathy.

Due to the special composition of the parenteral nutrition solution and the comparatively low energy content provided by lipids, the occurrence of nutrition-related lipid metabolism disorders in obese intensive care patients can be advantageously prevented. If a lipid metabolism disorder is already present, an exacerbation of the metabolic disorder can be prevented and a deterioration of the metabolic disorder due to parenteral nutrition can be avoided.

The parenteral nutrition solution comprises 0.017 g to 0.028 g of lipids per mL. Preferred is a parenteral nutrition solution that comprises 0.019 g to 0.026 g of lipids per mL, or that comprises 0.020 g to 0.024 g of lipids per mL. Particularly preferred is a parenteral nutrition solution that comprises 0.021 g to 0.023 g of lipids per mL. Most preferred is a parenteral nutrition solution that comprises 0.022 g of lipids per mL; this has proven particularly effective.

A parenteral nutrition solution in which the lipids comprised have a specific composition has proven particularly advantageous in the nutrition of obese intensive care patients. In this preferred embodiment, the lipid emulsion comprised in the parenteral nutrition solution comprises, per 1000 mL of the lipid emulsion, at least one component selected from the group consisting of: approximately 60 g of soybean oil, approximately 60 g of MCT, approximately 50 g of olive oil, and approximately 30 g of fish oil, or a combination thereof.

It is particularly preferred that the lipid emulsion comprises 60 g soybean oil, 60 g MCT, 50 g olive oil and 30 g fish oil per 1000 mL.

A lipid emulsion of this composition can prevent the occurrence or worsening of an existing inflammatory metabolic condition, which is often present in obese intensive care patients regardless of the underlying disease.

(iv) Energy content and energy percentage

State-of-the-art parenteral nutrition solutions are not designed to meet the specific nutritional needs of obese intensive care patients, among other reasons, because they have a comparatively high energy content. This is explained, among other things, by the fact that state-of-the-art parenteral nutrition solutions are generally tailored to the disease-related increased energy requirements of normal or underweight patients. For this patient group, for example, an energy requirement of 25 kcal to 30 kcal/kg of actual body weight per day is assumed.

If obese intensive care patients are fed accordingly, this results in an oversupply of energy, which, due to the composition of state-of-the-art parenteral nutrition solutions, is predominantly derived from carbohydrates and lipids. This increases the risk of nutrition-related metabolic and infectious complications in the group of obese intensive care patients.

The parenteral nutrition solution for administration to obese intensive care patients now provides a nutritional solution with an energy content particularly suitable for the nutrition of obese intensive care patients.

The energy content of the parenteral nutrition solution is 700 kcal to 950 kcal per 1000 ml, preferred is an energy content of 750 kcal to 900 kcal per 1000 ml, as is an energy content of 800 kcal to 880 kcal per 1000 ml. Particularly preferred is an energy content of 820 kcal to 860 kcal per 1000 ml, most preferred is an energy content of 845 kcal to 855 kcal per 1000 ml, such as 850 kcal or 851 kcal per 1000 ml.

The parenteral nutrition solution is particularly suitable for the nutrition of obese intensive care patients due to its composition in terms of the ratio of amino acids, glucose and lipids.

The parenteral nutrition solution can comprise, per 100 energy percent, i.e., based on the total energy content of the nutrition solution, 25-35 energy percent from amino acids, 40-45 energy percent from glucose, and 22-30 energy percent from lipids. A nutrition solution comprising, per 100 energy percent, 28-34 (28, 29, 30, 31, 32, 33, 34) energy percent from amino acids, 41-44 (41, 42, 43, 44) energy percent from glucose, and 23-27 (23, 24, 25, 26, 27) energy percent from lipids is preferred. Particularly preferred is an amino acid solution comprising 31 - 33 (31, 32, 33) energy percent from amino acids, 42 - 44 (42, 43, 44) energy percent from glucose and 25 - 27 (25, 26, 27) energy percent from lipids.

The most preferred parenteral nutrition solution is one that contains 32 percent energy from amino acids, 42 percent energy from glucose, and 26 percent energy from lipids. Administering a parenteral nutrition solution of this composition to obese intensive care patients results in an unexpectedly low rate of metabolic and infectious complications.

Due to the high energy percentage of amino acids and the comparatively low proportions of glucose and lipids, overnutrition or malnutrition in obese intensive care patients and the associated occurrence of nutrition-related metabolic complications such as hyperlipidemia, hyperglycemia, and glucose intolerance can be effectively prevented. In obesity-related metabolic disorders already present before the start of parenteral nutrition, the special composition of the parenteral nutrition solution can prevent the worsening of the respective metabolic disorder.

The composition of the parenteral nutrition solution can also prevent undersupply of obese intensive care patients, especially with amino acids, and the occurrence of protein-energy malnutrition.

In addition, the administration of parenteral nutrition solution can reduce the incidence of infection-related complications. Consequently, the morbidity and mortality rates of obese intensive care patients can also be reduced. Furthermore, a shortening of the length of stay in the intensive care unit can be achieved.

The composition of the parenteral nutrition solution and its high amino acid content facilitate the mobilization of the body's own fat in obese intensive care patients. The parenteral nutrition solution thus enables optimal mobilization of the body's own energy reserves, while simultaneously ensuring optimal preservation of the body's own proteins and muscle mass thanks to its high amino acid content.

Electrolytes, trace elements and vitamins

The parenteral nutrition solution may contain electrolytes. If the parenteral nutrition solution contains electrolytes, these can be contained in the amino acid solution and/or the glucose solution or added to the parenteral nutrition solution before administration to the obese intensive care patient. The addition can be carried out in a manner known to those skilled in the art, for example, via an injection port.

In a preferred embodiment, the parenteral nutrition solution comprises per 1000 mL of electrolytes selected from the group consisting of about 32.8 mmol sodium to about 48 mmol sodium, about 24 mmol potassium to about 36 mmol potassium, about 4.1 mmol magnesium to about 6.1 mmol magnesium, about 2 mmol calcium to about 3 mmol calcium, about 8.2 mmol phosphate to about 15.6 mmol phosphate, about 0.032 mmol zinc to about 0.048 mmol zinc, about 4.1 mmol sulfate to about 6.1 mmol sulfate, about 28.8 mmol chloride to about 43.2 mmol chloride, about 84.8 mmol acetate to about 127.2 mmol acetate, or a combination thereof.

A particularly preferred parenteral nutrition solution comprises per 1000 mL of electrolytes selected from the group consisting of about 36.9 mmol sodium to about 45.1 mmol sodium, about 27 mmol potassium to about 33 mmol potassium, about 4.6 mmol magnesium to about 5.6 mmol magnesium, about 2.3 mmol calcium to about 2.8 mmol calcium, about 9.2 mmol phosphate to about 14.3 mmol phosphate, about 0.036 mmol zinc to about 0.044 mmol zinc, about 4.6 mmol sulfate to about 5.6 mmol sulfate, about 32.4 mmol chloride to about 39.6 mmol chloride, about 95.4 mmol acetate to about 116.6 mmol acetate, or a combination thereof.

A particularly preferred parenteral nutrition solution comprises per 1000 mL of electrolytes selected from the group consisting of about 36.9 mmol sodium to about 45.1 mmol sodium, about 27 mmol potassium to about 33 mmol potassium, about 4.6 mmol magnesium to about 5.6 mmol magnesium, about 2.3 mmol calcium to about 2.8 mmol calcium, about 10.2 mmol phosphate to about 13 mmol phosphate, about 0.036 mmol zinc to about 0.044 mmol zinc, about 4.6 mmol sulfate to about 5.6 mmol sulfate, about 32.4 mmol chloride to about 39.6 mmol chloride, about 95.4 mmol acetate to about 116.6 mmol acetate, or a combination thereof.

Even more preferably, the parenteral nutrition solution comprises per 1000 mL of electrolytes selected from the group consisting of about 41 mmol sodium, about 30 mmol potassium, about 5.1 mmol magnesium, about 2.5 mmol calcium, about 13 mmol phosphate, about 0.04 mmol zinc, about 5.1 mmol sulfate, about 36 mmol chloride, about 106 mmol acetate, or a combination thereof.

Most preferred is a parenteral nutrition solution comprising 41 mmol sodium, 30 mmol potassium, 5.1 mmol magnesium, 2.5 mmol calcium, 13 mmol phosphate, 0.04 mmol zinc, 5.1 mmol sulfate, 36 mmol chloride and 106 mmol acetate per 1000 mL of the nutrition solution.

Trace elements and/or vitamins can be added to the parenteral nutrition solution prior to administration to the obese intensive care patient. This can be done in a manner known to those skilled in the art, for example, via an injection port.

It is preferred that trace elements and vitamins are added in sufficient quantities prior to administration, so that no additional administration of trace elements and vitamins to the obese intensive care patient is required.

The preferred parenteral nutrition solution can provide twice the daily recommended amount of trace elements and/or vitamins for normal-weight, healthy individuals of the same age and gender. It has been shown that obese intensive care patients particularly benefit from a parenteral nutrition solution that provides such a high amount of trace elements and/or vitamins, as obese intensive care patients in particular often suffer from multiple trace element and/or vitamin deficiencies.

Preferred embodiments

1. (i) 500 mL - 834 mL einer Aminosäurelösung umfassend 50 g - 83 g Aminosäuren,
2. (ii) 167 mL - 278 mL einer Glukoselösung umfassend 67 g - 111 g Glukose, und
3. (iii) 83 mL - 139 mL einer Lipidemulsion umfassend 17 g - 28 g Lipide.

The parenteral nutrition solution for administration to an obese intensive care patient may contain per 1000 mL:

1. (i) 500 mL - 834 mL of an amino acid solution comprising 50 g - 83 g of amino acids,
2. (ii) 167 mL - 278 mL of a glucose solution comprising 67 g - 111 g glucose, and
3. (iii) 83 mL - 139 mL of a lipid emulsion comprising 17 g - 28 g of lipids.

Thus, the parenteral nutrition solution for administration to an obese intensive care patient comprises per mL 0.05 g to 0.083 g of amino acids, 0.067 g to 0.111 g of carbohydrates in the form of glucose and 0.017 g to 0.028 g of lipids.

1. (i) 500 mL - 834 mL einer Aminosäurelösung umfassend 60 g - 83 g Aminosäuren,
2. (ii) 167 mL - 278 mL einer Glukoselösung umfassend 67 g - 111 g Glukose, und
3. (iii) 83 mL - 139 mL einer Lipidemulsion umfassend 17 g - 28 g Lipide.

The parenteral nutrition solution for administration to an obese intensive care patient may contain per 1000 mL:

1. (i) 500 mL - 834 mL of an amino acid solution comprising 60 g - 83 g of amino acids,
2. (ii) 167 mL - 278 mL of a glucose solution comprising 67 g - 111 g glucose, and
3. (iii) 83 mL - 139 mL of a lipid emulsion comprising 17 g - 28 g of lipids.

Thus, the parenteral nutrition solution for administration to an obese intensive care patient contains per mL 0.06 g to 0.083 g of amino acids, 0.067 g to 0.111 g of carbohydrates in the form of glucose and 0.017 g to 0.028 g of lipids.

The parenteral nutrition solution may contain 0.063 g to 0.080 g of amino acids, 0.070 g to 0.105 g of carbohydrates in the form of glucose, and 0.019 g to 0.026 g of lipids per mL.

1. (i) 500 mL - 834 mL einer Aminosäurelösung umfassend 63 g - 80 g Aminosäuren,
2. (ii) 167 mL - 278 mL einer Glukoselösung umfassend 70 g - 105 g Glukose, und
3. (iii) 83 mL - 139 mL einer Lipidemulsion umfassend 19 g - 26 g Lipide.

The parenteral nutrition solution for administration to an obese intensive care patient can therefore, for example, contain per 1000 mL:

1. (i) 500 mL - 834 mL of an amino acid solution comprising 63 g - 80 g of amino acids,
2. (ii) 167 mL - 278 mL of a glucose solution comprising 70 g - 105 g glucose, and
3. (iii) 83 mL - 139 mL of a lipid emulsion comprising 19 g - 26 g of lipids.

Preferred is a parenteral nutrition solution which comprises 0.065 g to 0.075 g of amino acids, 0.080 g to 0.095 g of carbohydrates in the form of glucose and 0.020 g to 0.024 g of lipids per mL.

1. (i) 500 mL - 834 mL einer Aminosäurelösung umfassend 65 g - 75 g Aminosäuren,
2. (ii) 167 mL - 278 mL einer Glukoselösung umfassend 80 g - 95 g Glukose, und
3. (iii) 83 mL - 139 mL einer Lipidemulsion umfassend 20 g - 24 g Lipide.

This is the case, for example, with the following preferred parenteral nutrition solution, which contains per 1000 mL:

1. (i) 500 mL - 834 mL of an amino acid solution comprising 65 g - 75 g of amino acids,
2. (ii) 167 mL - 278 mL of a glucose solution comprising 80 g - 95 g glucose, and
3. (iii) 83 mL - 139 mL of a lipid emulsion comprising 20 g - 24 g of lipids.

1. (i) 500 mL - 834 mL einer Aminosäurelösung umfassend 65 g - 70 g Aminosäuren,
2. (ii) 167 mL - 278 mL einer Glukoselösung umfassend 82 g - 93 g Glukose, und
3. (iii) 83 mL - 139 mL einer Lipidemulsion umfassend 21 g - 23 g Lipide.

Even more preferred is a parenteral nutrition solution for administration to an obese intensive care patient, which comprises per 1000 mL:

1. (i) 500 mL - 834 mL of an amino acid solution comprising 65 g - 70 g of amino acids,
2. (ii) 167 mL - 278 mL of a glucose solution comprising 82 g - 93 g glucose, and
3. (iii) 83 mL - 139 mL of a lipid emulsion comprising 21 g - 23 g of lipids.

In this particularly preferred embodiment of the parenteral nutrition solution, 0.065 g to 0.070 g of amino acids, 0.082 g to 0.093 g of carbohydrates in the form of glucose and 0.021 g to 0.023 g of lipids are included per mL.

1. (i) 667 mL einer Aminosäurelösung umfassend 67 g Aminosäuren,
2. (ii) 222 mL einer Glukoselösung umfassend 89 g Glukose, und
3. (iii) 111 mL einer Lipidemulsion umfassend 22 g Lipide.

A parenteral nutrition solution containing per 1000 mL is particularly preferred:

1. (i) 667 mL of an amino acid solution comprising 67 g of amino acids,
2. (ii) 222 mL of a glucose solution containing 89 g glucose, and
3. (iii) 111 mL of a lipid emulsion comprising 22 g of lipids.

In this particularly preferred embodiment, the parenteral nutrition solution for administration to an obese intensive care patient comprises per mL 0.067 g of amino acids, 0.089 g of carbohydrates in the form of glucose and 0.022 g of lipids.

In any of the above-mentioned embodiments, the parenteral nutrition solution may comprise electrolytes. These may be contained in the amino acid solution and/or the glucose solution.

Three-chamber bag

The parenteral nutrition solution can be provided in a three-chamber bag. The amino acid solution contained in the parenteral nutrition solution, the glucose solution, and the lipid emulsion can each be contained separately in a separate chamber of the three-chamber bag.

Any state-of-the-art three-chamber bag suitable for storing and administering parenteral nutrition solutions can be used.

The individual chambers (i.e., the first chamber, the second chamber, and the third chamber) of the three-chamber bag can be separated from each other by peel seals. Before administering the parenteral nutrition solution, the peel seals are opened by pressure, and the contents of the three chambers—the amino acid solution, the glucose solution, and the lipid emulsion—are combined and mixed.

In a first embodiment, the three-chamber bag comprises a first chamber, a second chamber and a third chamber, the first chamber comprising 750 mL - 2250 mL of an amino acid solution comprising 56.3 g - 281.3 g of amino acids, the second chamber comprising 250 mL - 750 mL of a glucose solution comprising 75 g - 375 g of glucose, and the third chamber comprising 125 mL - 375 mL of a lipid emulsion comprising 18.8 g - 93.8 g of lipids.

Based on the total volume of the first, second and third chambers, the three-chamber bag comprises at least 50 g of amino acids per 1000 mL, for example 50 g to 83 g of amino acids. A three-chamber bag is preferred which, based on the total volume of the first, second and third chambers, comprises at least 60 g, for example 60 g to 83 g, of amino acids per 1000 mL. A three-chamber bag is particularly preferred which, based on the total volume of the first, second and third chambers, comprises at least 63 g, for example 63 g to 83 g, of amino acids per 1000 mL. It is very particularly preferred that the three-chamber bag comprises at least 65 g of amino acids per 1000 mL, for example 65 g to 83 g, based on the total volume of the first, second and third chambers. Most preferred is a three-chamber bag which, based on the total volume of the first, second and third chambers, contains at least 67 g of amino acids per 1000 mL, for example 67 g to 83 g.

In a further preferred embodiment, the three-chamber bag comprises a first chamber, a second chamber, and a third chamber, wherein: the first chamber comprises 1500 mL of an amino acid solution containing 135 g - 187.5 g of amino acids, preferably 150 g of amino acids, the second chamber comprises 500 mL of a glucose solution containing 150 g - 250 g of glucose, preferably 200 g of glucose, and the third chamber comprises 250 mL of a lipid emulsion containing 37.5 g - 62.5 g of lipids, preferably 50 g of lipids.

Also preferred is an embodiment in which the three-chamber bag comprises a first chamber, a second chamber, and a third chamber, wherein: the first chamber comprises 750 mL of an amino acid solution containing 67.5 g - 93.8 g of amino acids, preferably 75 g of amino acids, the second chamber comprises 250 mL of a glucose solution containing 75 g - 125 g of glucose, preferably 100 g of glucose, and the third chamber comprises 125 mL of a lipid emulsion containing 18.8 g - 31.3 g of lipids, preferably 25 g of lipids.

Also preferred is an embodiment in which the three-chamber bag comprises a first chamber, a second chamber, and a third chamber, wherein: the first chamber comprises 2250 mL of an amino acid solution containing 202.5 g - 281.3 g of amino acids, preferably 225 g of amino acids, the second chamber comprises 750 mL of a glucose solution containing 225 g - 375 g of glucose, preferably 300 g of glucose, and the third chamber comprises 375 mL of a lipid emulsion containing 56.3 g - 93.8 g of lipids, preferably 75 g of lipids.

In a particularly preferred embodiment, the three-chamber bag further comprises electrolytes. Electrolytes can be contained in the first and/or second chamber of the three-chamber bag, i.e., in the amino acid solution and/or in the glucose solution.

Trace elements and/or vitamins can be added to the three-chamber bag prior to administering the parenteral nutrition solution to an obese intensive care patient. Vitamins and trace elements are preferably added in sufficient quantities to meet the patient's needs. If the amino acid solution and the glucose solution do not contain electrolytes, or if electrolytes are to be administered in addition to those already contained in the amino acid solution and/or the glucose solution, these can also be added to the parenteral nutrition solution prior to administration. The addition is carried out in a manner known to those skilled in the art, for example, via an injection port.

Advantages

The composition of the parenteral nutrition solution, which is tailored to the specific needs of obese intensive care patients, in particular the high amino acid content in combination with the comparatively low content of glucose and lipids, can surprisingly and advantageously lead to a reduction in the frequency of occurrence of nutrition-related metabolic and infectious complications caused by parenteral nutrition, and to a reduction in the morbidity and mortality of obese intensive care patients.

The parenteral nutrition solution is low in calories but rich in amino acids. This prevents oversupply of calories while effectively counteracting excessive loss of lean body mass, especially muscle mass, in obese intensive care patients.

The ratio of amino acids, carbohydrates, and lipids in the parenteral nutrition solution is particularly beneficial in preventing or reducing the occurrence of nutrition-related metabolic and infectious complications in this patient group. This is especially true when the parenteral nutrition solution provides 28 to 34 percent of energy from amino acids, 41 to 44 percent from glucose, and approximately 25 to 27 percent from carbohydrates.

The high amino acid content promotes wound healing and prevents the occurrence of a negative nitrogen balance. At the same time, the parenteral nutrition solution according to the invention can effectively prevent an oversupply of lipids and carbohydrates to obese intensive care patients, as occurs with the administration of prior art parenteral nutrition solutions tailored to the needs of underweight or normal-weight patients using standard dosage regimens or instructions.

When parenteral nutrition solution is administered, disorders of glucose metabolism such as hyperglycemia or glucose intolerance are avoided or reduced, as are disorders of lipid metabolism such as the occurrence of hypertriglyceridemia.

The special composition of the parenteral nutrition solution results in a synergistic effect of the high amino acid content, which is beneficial for obese intensive care patients, as well as the comparatively low carbohydrate and lipid content of the parenteral nutrition solution, which goes beyond a mere additive effect of the three individual effects. This is especially true with regard to the reduction of nutrition-related complications observed in obese intensive care patients, such as hypertriglyceridemia, hyperglycemia, and amino acid imbalance, which can be effectively prevented or reduced by the administration of parenteral tube feeding.

Parenteral nutrition solutions which have proven particularly effective are those which comprise an amino acid solution, a glucose solution and a lipid emulsion and which comprise 0.065 g to 0.070 g of amino acids, 0.082 g to 0.093 g of carbohydrates in the form of glucose and 0.021 g to 0.023 g of lipids per mL, wherein the amino acid solution comprised per 1000 mL of the amino acid solution approximately 5 g of isoleucine, approximately 7.4 g of leucine, approximately 9.31 g of lysine acetate (corresponding to approximately 6.6 g of lysine), approximately 4.3 g of methionine, approximately 5.1 g of phenylalanine, approximately 4.4 g of threonine, approximately 2 g of tryptophan, approximately 6.2 g of valine, approximately 12 g of arginine, approximately 3 g of histidine, approximately 14 g of alanine, approximately 11 g of glycine, approximately 11.2 g of proline, about 6.5 g of serine, about 0.4 g of tyrosine, and about 1 g of taurine, and wherein the comprised lipid emulsion comprises per 1000 mL about 60 g of soybean oil, about 60 g of MCT, about 50 g of olive oil, and about 30 g of fish oil.

Administration/dosage regimens

The parenteral nutrition solution is ideal for parenteral nutrition of obese intensive care patients.

The parenteral nutrition solution can be administered as the sole nutrition or in addition to enteral or oral nutrition of the obese intensive care patient.

In addition, electrolytes, trace elements, and/or vitamins can be administered to the obese intensive care patient separately from the parenteral nutrition solution. However, it is particularly preferred that electrolytes, trace elements, and/or vitamins be included in the parenteral nutrition solution when administering the parenteral nutrition solution, so that they do not need to be administered to the obese intensive care patient separately from the parenteral nutrition solution.

Parenteral nutrition solution can be administered as long as there is an indication for sole or supplementary parenteral nutrition and the intensive care patient is obese.

For example, the parenteral nutrition solution can be administered to an obese intensive care patient indicated for parenteral nutrition over a period of 1 day to several months. Due to its special composition tailored to the nutritional needs of obese intensive care patients, the parenteral nutrition solution can be used for long-term parenteral nutrition of these patients, even when administered as the sole nutrition. The parenteral nutrition solution is therefore also suitable for administration over a period of 1 month to 12 months, preferably also for administration over a period of 3 months to 12 months, or even 6 months to 12 months.

It is expected that the obese patient will lose weight when receiving the described parenteral nutrition by mobilizing the body's own energy reserves. The parenteral nutrition solution described here should be replaced with conventional parenteral nutrition as soon as the patient's BMI falls below 30 kg/ ^m² .

Administration can be continuous, i.e., for 24 hours a day without interruption. However, administration can also be discontinuous. For example, the parenteral nutrition solution is administered to an obese intensive care patient for 16 hours per day. No administration is made for the following 8 hours. Then, it is administered again for 16 hours.

The parenteral nutrition solution contains an amino acid solution, a glucose solution, and a lipid emulsion. These are provided in a single pouch, allowing for easy dosing. The parenteral nutrition solution can provide all the required macronutrients (amino acids, carbohydrates, and lipids) and, if desired, all the required electrolytes. Trace elements and vitamins can be added to the parenteral nutrition solution prior to administration.

This method of administration is simple and time-saving, as well as less prone to miscalculations or errors during the actual administration.

Unlike parenteral nutrition with separate solutions (separate administration of an amino acid solution, a carbohydrate solution, and a lipid emulsion), there are no residual volumes of the individual nutritional solutions that must be discarded later. This also applies when the parenteral nutrition solution is delivered via a three-chamber bag. While the amino acid solution, glucose solution, and lipid emulsion contained in the parenteral nutrition solution are stored in separate chambers within the three-chamber bag prior to administration, the volumes of the amino acid solution, glucose solution, and lipid emulsion contained in the three-chamber bag are coordinated so that no residual volumes of individual solutions arise.

If the parenteral nutrition solution is contained in a three-chamber bag comprising a first chamber, a second chamber, and a third chamber, with the first chamber containing the amino acid solution, the second chamber containing the glucose solution, and the third chamber containing the lipid emulsion, the amino acid solution, the glucose solution, and the lipid emulsion must first be combined and mixed before administering the parenteral nutrition solution to the obese intensive care patient. Methods for mixing parenteral nutrition solutions contained in a three-chamber bag are known to those skilled in the art. The parenteral nutrition solution is only administered to the obese intensive care patient after combination and mixing.

An obese intensive care patient may be a patient with a hypercatabolic and/or hypermetabolic metabolic state. An obese intensive care patient may be a patient who is critically ill and/or has a condition selected from the group consisting of trauma, burns, infection, sepsis, and surgical intervention, or a combination thereof.

The obese intensive care patient can be a patient with grade I obesity, grade II obesity or grade III obesity, and can be male or female.

The amount of parenteral nutrition solution to be administered daily to the obese intensive care patient can be determined by a parameter selected from the group consisting of patient height, patient sex, degree of obesity or a combination thereof.

The degree of obesity can be determined based on the patient's height and weight. Alternatively, the specialist can also determine the degree of obesity based on the patient's body fat quantity and/or body fat distribution.

The administration of parenteral nutrition solution according to the following schedule has proven particularly suitable for the parenteral nutrition of obese intensive care patients: If the patient suffers from grade I or grade II obesity, the parenteral nutrition solution is administered to the patient in an amount of 25 mL to 35 mL per kg IBW per day. Preferably, the parenteral nutrition solution is administered to the patient in an amount of 28 mL to 32 mL per kg IBW per day, particularly preferably in an amount of 30 mL per kg IBW per day.

If the patient suffers from grade III obesity, the parenteral nutrition solution is administered to the patient in an amount of 32 mL to 42 mL per kg IBW per day. Preferably, the parenteral nutrition solution is administered to the patient in an amount of 35 mL to 39 mL per kg IBW per day, most preferably in an amount of 37 mL per kg IBW per day.

If it is not clear whether a patient suffers from grade II or III obesity, as well as generally in the transition zone from grade II to grade III, a dosage between 30 and 37 mL/kg can be chosen.

This administration regimen ensures adequate nutrient supply to patients while simultaneously avoiding macronutrient oversupply.

In a particularly preferred embodiment, the amount of parenteral nutrition solution to be administered daily to the obese intensive care patient can be determined by the body size, gender and degree of obesity of the obese intensive care patient.

It is particularly preferred if the patient is female and suffers from grade I or grade II obesity to administer to the patient per day approximately 2100 mL of the parenteral nutrition solution for a body height of 180 cm, approximately 1950 mL for a body height of 174 cm, approximately 1800 mL for a body height of 168 cm, approximately 1650 mL for a body height of 163 cm or approximately 1500 mL for a body height of 157 cm. If the patient is female and suffers from grade III obesity, it is particularly preferable to administer approximately 2590 mL of parenteral nutrition solution per day for a patient with a height of 180 cm, approximately 2405 mL for a patient with a height of 174 cm, approximately 2220 mL for a patient with a height of 168 cm, approximately 2035 mL for a patient with a height of 163 cm, or approximately 1850 mL for a patient with a height of 157 cm.

If the patient is male and suffers from grade I or grade II obesity, it is particularly preferable to administer to the patient approximately 2550 mL of parenteral nutrition solution per day for a height of 187 cm, approximately 2400 mL for a height of 182 cm, approximately 2250 mL for a height of 178 cm, approximately 2100 mL for a height of 173 cm, approximately 1950 mL for a height of 168 cm or approximately 1800 mL for a height of 163 cm. If the patient is male and suffers from grade III obesity, it is most preferable to administer to the patient approximately 3145 mL of parenteral nutrition solution per day for a height of 187 cm, approximately 2960 mL for a height of 182 cm, approximately 2775 mL for a height of 178 cm, approximately 2590 mL for a height of 173 cm, approximately 2405 mL for a height of 168 cm or approximately 2220 mL for a height of 163 cm.

Using this highly preferred administration regimen, the occurrence of nutrition-related metabolic and infectious complications can be particularly effectively avoided, and the morbidity and mortality rates of obese intensive care patients can be particularly effectively reduced.

The above administration schedules refer to the administration of parenteral nutrition solution as the sole parenteral nutrition. If the obese intensive care patient is also fed enterally and/or orally, the percentage of energy supplied by parenteral nutrition relative to the total daily energy supplied by food is calculated, and only the corresponding percentage is administered according to the above administration schedules.

Examples Example 1: Preparation of a parenteral nutrition solution a) The following parenteral nutrition solutions are prepared:

Amino acids [g/L] 50 60 83 67 65 63 Glucose [g/L] 67 67 111 89 89 89 Lipids [g/L] 17 17 28 22 22 22

b) The following parenteral nutrition solutions are prepared:

Amino acids [g/L] 50 60 83 67 65 63 Glucose [g/L] 67 67 111 89 89 89 Lipids [g/L] 17 17 28 22 22 22 + + + + + +

c) Preparation of solutions A0 to F1 using a particularly preferred amino acid composition

Solutions A0 to F1 are prepared as described under a) and b). The amino acid source used is an amino acid solution containing per 1000 mL 5 g isoleucine, 7.4 g leucine, 9.31 g lysine acetate (equivalent to 6.6 g lysine), 4.3 g methionine, 5.1 g phenylalanine, 4.4 g threonine, 2 g tryptophan, 6.2 g valine, 12 g arginine, 3 g histidine, 14 g alanine, 11 g glycine, 11.2 g proline, 6.5 g serine, 0.4 g tyrosine, and 1 g taurine.

The solutions thus obtained are designated with the suffix "AS" and are referred to as A0AS to F1AS.

d) Preparation of solutions A0 to F1 using a particularly preferred lipid composition

Solutions A0 to F1 are prepared as described under a) and b). A lipid emulsion containing 60 g soybean oil, 60 g MCT, 50 g olive oil, and 30 g fish oil per 1000 mL is used as the lipid source.

The solutions thus obtained are designated with the suffix "LP" and are referred to as A0LP to F1LP.

e) Preparation of solutions A0 to F1 using the particularly preferred amino acid and lipid composition

Solutions A0 to F1 are prepared as described under a) and b). The amino acid source used is an amino acid solution containing per 1000 mL 5 g isoleucine, 7.4 g leucine, 9.31 g lysine acetate (equivalent to 6.6 g lysine), 4.3 g methionine, 5.1 g phenylalanine, 4.4 g threonine, 2 g tryptophan, 6.2 g valine, 12 g arginine, 3 g histidine, 14 g alanine, 11 g glycine, 11.2 g proline, 6.5 g serine, 0.4 g tyrosine, and 1 g taurine.

A lipid emulsion containing 60 g soybean oil, 60 g MCT, 50 g olive oil and 30 g fish oil per 1000 mL is used as a lipid source.

The solutions thus obtained are labeled "AS-LP" and referred to as A0AS-LP to F1AS-LP.

Example 2: Three-chamber bag

The following three-chamber bags are manufactured: Three-chamber bag 1 2 3 Total volume of parenteral nutrition solution [mL] 2250 1125 3375 Volume of solution in chamber 1 [mL] 1500 750 2250 Volume of solution in chamber 2 [mL] 500 250 750 Volume of solution in chamber 3 [mL] 250 125 375

Chamber 1 of the three-chamber bag contains an amino acid solution (100 g amino acids/L), chamber 2 a glucose solution (400 g glucose/L), and chamber 3 a lipid emulsion (200 g lipids/L). Based on the total volume of parenteral nutrition solution in the three-chamber bags 1, 2, and 3, there are 67 g/L amino acids, 89 g/L glucose, and 22 g/L lipids. Chambers 1 and/or 2 can also contain electrolytes.

The amino acid emulsion can have the following composition per 1000 mL: 5 g isoleucine, 7.4 g leucine, 9.31 g lysine acetate (equivalent to 6.6 g lysine), 4.3 g methionine, 5.1 g phenylalanine, 4.4 g threonine, 2 g tryptophan, 6.2 g valine, 12 g arginine, 3 g histidine, 14 g alanine, 11 g glycine, 11.2 g proline, 6.5 g serine, 0.4 g tyrosine and 1 g taurine.

The lipid emulsion can have the following composition per 1000 mL: 60 g soybean oil, 60 g MCT, 50 g olive oil and 30 g fish oil.

Example 3: Dosage regimens

The following table shows an exemplary dosage regimen according to which the parenteral nutrition solution according to the invention can be administered to obese intensive care patients. The ideal body weight of male and female patients can be found in the table based on the height of the obese intensive care patients. The recommended dosage of the parenteral nutrition solution based on the patient's height can also be found directly in the table. 187 85 2550 ml 3145 ml 182 80 2400 2960 178 75 2250 2775 173 180 70 2100 2590 168 174 65 1950 2405 163 168 60 1800 2220 163 55 1650 2035 157 50 1500 1850 * IBW = ideal body weight

Example 4: Administration examples a) Administration of parenteral nutrition solution to an obese male intensive care patient with a height of 178 cm.

Using the actual body weight of 150 kg, a BMI of 47.3 can be calculated for the 178 cm tall patient. The patient therefore has grade III obesity. Alternatively, the degree of obesity can also be determined based on the patient's body fat percentage and/or body fat distribution, which is not a problem for the clinical staff responsible for administering parenteral nutrition solutions. The table shown in Example 3 therefore results in a daily infusion volume of 2775 mL of parenteral nutrition solution for this patient.

b) Administration of parenteral nutrition solution to an obese female intensive care patient with a height of 163 cm.

Based on the actual body weight of 100 kg, a BMI of 37.6 can be calculated for the 163 cm tall patient. The patient therefore has grade II obesity. Alternatively, the degree of obesity can also be determined based on the patient's body fat percentage and/or body fat distribution. The table shown in Example 3 therefore results in a daily infusion volume of 1800 mL of parenteral nutrition solution for this patient.

Example 5: Impact on complications, morbidity and mortality

Solutions A0-F0 or A1-F1 are administered parenterally as the sole nutrition to male and female obese intensive care patients with grade I, grade II, or grade III obesity for a period of 2 weeks or 2 months, according to the dosage regimen shown in Example 3. If one of the solutions A0-F0 is administered, electrolytes, trace elements, and vitamins are additionally added to the parenteral nutrition solution in sufficient quantities prior to administration to the patient. If one of the solutions A1-F1 is administered, trace elements and vitamins are additionally added to the parenteral nutrition solution in sufficient quantities prior to administration to the patient.

During the administration period, the occurrence of nutritional complications such as hyperglycemia or hypertriglyceridemia is unlikely. Balanced nitrogen balance can be achieved through nutrition.

A slight weight reduction in patients is observed, with predominant preservation of lean body mass.

There is a reduced incidence of metabolic complications. This can lead to a reduction in the average length of stay in the intensive care unit compared to parenterally nourished obese intensive care patients who receive a comparator solution tailored to the needs of underweight catabolic patients.

All solutions are well-suited for administration to obese intensive care patients. Solutions with higher amino acid content (solutions B0-F0 and B1-F1) were particularly effective. The solutions with an amino acid content of 67 g/L, i.e., solutions D0 and D1, performed best.

Particularly good results in reducing metabolic complications are achieved when AS-LP solutions are administered, i.e., A0 AS-LP - F0 AS-LP or A1 AS-LP - F1 AS-LP. A particularly pronounced, more than additive, beneficial effect is observed in the form of a reduced incidence of metabolic and infectious complications compared to AS solutions (A0 AS - F0 AS or A1 AS - F1 AS) or LP solutions (A0 LP - F0 LP or A1 LP - F1 LP) alone.

Example 6: Comparison

Solutions A1 - F1 and A1 AS-LP - F1 AS-LP are administered parenterally as the sole nutrition to male and female obese intensive care patients with grade I, grade II, or grade III obesity for a period of 2 weeks or 2 months according to the dosage regimen shown in Example 3. Trace elements and vitamins are additionally added to the parenteral nutrition solutions in sufficient amounts prior to administration to the patient.

The incidence and/or severity of metabolic and infectious complications is lower in obese intensive care patients receiving one of the solutions A1 - F1 and A1 AS-LP - F1 AS-LP than in patients receiving a reference solution with identical amino acid content and a high lipid content of 40 g/L. This effect is particularly pronounced when one of the solutions A1 AS-LP - F1 AS-LP is administered, especially with solution D1 AS-LP.

Claims (14)

1. A parenteral nutrition solution for use in administration to an obese intensive-care patient, the nutrition solution comprising, per 1000 ml:

   (i) 500 ml to 834 ml of an amino acid solution comprising 50 g to 83 g of amino acids,

   (ii) 167 ml to 278 ml of a glucose solution comprising 67 g to 111 g of glucose, and

   (iii) 83 ml to 139 ml of a lipid emulsion comprising 17 g to 28 g of lipids,

   wherein, if the patient suffers from class I or class II obesity, 25 ml to 35 ml of the parenteral nutrition solution per kg of IBW, preferably from 28 ml to 32 ml per kg of IBW, particularly preferably 30 ml per kg of IBW are administered to the patient per day, or wherein, if the patient suffers from class III obesity, 32 ml to 42 ml of the parenteral nutrition solution per kg of IBW, preferably from 35 ml to 39 ml per kg of IBW, particularly preferably 37 ml per kg of IBW are administered to the patient per day.
2. The parenteral nutrition solution for the use according to claim 1, the nutrition solution comprising, per 1000 ml:

   (i) 667 ml of an amino acid solution comprising 67 g of amino acids,

   (ii) 222 ml of a glucose solution comprising 89 g of glucose, and

   (iii) 111 ml of a lipid emulsion comprising 22 g of lipids.
3. The parenteral nutrition solution for the use according to one of the preceding claims, wherein the amino acid solution comprises per 1000 ml of the amino acid solution, at least one constituent, selected from the group consisting of:

   approximately 5 g of isoleucine, approximately 7.4 g of leucine, approximately 9.31 g of lysine acetate (corresponding to approximately 6.6 g of lysine), approximately 4.3 g of methionine, approximately 5.1 g of phenylalanine, approximately 4.4 g of threonine, approximately 2 g of tryptophan, approximately 6.2 g of valine, approximately 12 g of arginine, approximately 3 g of histidine, approximately 14 g of alanine, approximately 11 g of glycine, approximately 11.2 g of proline, approximately 6.5 g of serine, approximately 0.4 g of tyrosine 25 and approximately 1 g of taurine or a combination thereof, and/or

   wherein the lipid emulsion comprises, per 1000 ml of the lipid emulsion, at least one constituent, selected from the group consisting of: approximately 60 g of soya oil, approximately 60 g of MCTs, approximately 50 g of olive oil and approximately 30 g of fish oil or 30 of a combination thereof.
4. The parenteral nutrition solution for the use according to one of the preceding claims, wherein the parenteral nutrition solution further comprises at least one constituent, selected from the group consisting of: electrolytes, dipeptides, trace elements, vitamins or a combination thereof.
5. The parenteral nutrition solution for the use according to claim 4, wherein the parenteral nutrition solution comprises, per 1000 ml of the nutrition solution, electrolytes selected from the group consisting of approximately 32.8 mmol of sodium to approximately 48 mmol of sodium, approximately 24 mmol of potassium to approximately 36 mmol of potassium, approximately 4.1 mmol of magnesium to approximately 6.1 mmol of magnesium, approximately 2 mmol of calcium to approximately 3 mmol of calcium, approximately 8.2 mmol of phosphate to approximately 15.6 mmol of phosphate, approximately 0.032 mmol of zinc to approximately 0.048 mmol of zinc, approximately 4.1 mmol of sulphate to approximately 6.1 mmol of sulphate, approximately 28.8 mmol of chloride to approximately 43.2 mmol of chloride, approximately 84.8 mmol of acetate to approximately 127.2 mmol of acetate or a combination thereof, wherein preferably the parenteral nutrition solution comprises, per 1000 ml of the nutrition solution, electrolytes, selected from the group consisting of approximately 41 mmol of sodium, approximately 30 mmol of potassium, approximately 5.1 mmol of magnesium, approximately 2.5 mmol of calcium, approximately 13 mmol of phosphate, approximately 0.04 mmol of zinc, approximately 5.1 mmol of sulphate, approximately 36 mmol of chloride, approximately 106 mmol of acetate or a combination thereof.
6. The parenteral nutrition solution for the use according to one of the preceding claims, wherein the nutrition solution comprises, per 100% of energy, 25 to 35% of energy from amino acids, 40 to 45% of energy from glucose and 22 to 30% of energy from lipids, wherein preferably the nutrition solution comprises, per 100% of energy, 28 to 34% of energy from amino acids, 41 to 44% of energy from glucose and 25 to 27% of energy from lipids, wherein most preferably the nutrition solution comprises, per 100% of energy, 32% of energy from amino acids, 42% of energy from glucose and 26% of energy from lipids.
7. The parenteral nutrition solution for the use according to one of the preceding claims, wherein the nutrition solution has an energy content of 700 kcal to 975 kcal per 1000 ml, wherein preferably the nutrition solution has an energy content of 800 kcal to 880 kcal per 1000 ml, wherein most preferably the nutrition solution has an energy content of 820 kcal to 860 kcal per 1000 ml.
8. The parenteral nutrition solution for the use according to one of the preceding claims, wherein the parenteral nutrition solution is contained in a three-chamber pouch comprising a first chamber, a second chamber and a third chamber, with (i) the first chamber comprising the amino acid solution, (ii) the second chamber comprising the glucose solution, and (iii) the third chamber comprising the lipid emulsion, wherein the amino acid solution, the glucose solution and the lipid emulsion are combined and mixed prior to use.
9. The parenteral nutrition solution for the use according to one of the preceding claims, wherein the intensive-care patient is a patient in a hypercatabolic state and/or hypermetabolic state, wherein preferably the intensive-care patient is a patient, who is critically ill and/or is a patient, who has a condition, selected from the group consisting of: trauma, burn, infection, sepsis and surgical operation or a combination thereof.
10. The parenteral nutrition solution for the use according to one of the preceding claims, the obesity is selected from the group consisting of: class I obesity, class II obesity and class III obesity.
11. The parenteral nutrition solution for the use according to one of the preceding claims, wherein the amount of the parenteral nutrition solution to be administered daily is determined by a parameter, selected from the group consisting of: height of the patient, gender of the patient, degree of obesity or a combination thereof.
12. The parenteral nutrition solution for the use according to one of the preceding claims, wherein, if the patient is female and suffers from class I or class II obesity, approximately 2100 ml of the parenteral nutrition solution in the case of a height of 180 cm, approximately 1950 ml in the case of a height of 174 cm, approximately 1800 ml in the case of a height of 168 cm, approximately 1650 ml in the case of a height of 163 cm or approximately 1500 ml in the case of a height of 157 cm are to be administered to the patient per day, or wherein, if the patient is female and suffers from class III obesity, approximately 2590 ml of the parenteral nutrition solution in the case of a height of 180 cm, approximately 2405 ml in the case of a height of 174 cm, approximately 2220 ml in the case of a height of 168 cm, approximately 2035 ml in the case of a height of 163 cm or approximately 1850 ml in the case of a height of 157 cm are to be administered to the patient per day, or wherein, if the patient is male and suffers from class I or class II obesity, approximately 2550 ml of the parenteral nutrition solution in the case of a height of 187 cm, approximately 2400 ml in the case of a height of 182 cm, approximately 2250 ml in the case of a height of 178 cm, approximately 2100 ml in the case of a height of 173 cm, approximately 1950 ml in the case of a height of 168 cm or approximately 1800 ml in the case of a height of 163 cm are to be administered to the patient per day, or wherein, if the patient is male and suffers from class III obesity, approximately 3145 ml of the parenteral nutrition solution in the case of a height of 187 cm, approximately 2960 ml in the case of a height of 182 cm, approximately 2775 ml in the case of a height of 178 cm, approximately 2590 ml in the case of a height of 173 cm, approximately 2405 ml in the case of a height of 168 cm or approximately 2220 ml in the case of a height of 163 cm are to be administered to the patient per day.
13. A three-chamber pouch comprising a first chamber, a second chamber and a third chamber, the first chamber comprising 750 ml to 2250 ml of an amino acid solution comprising 56.3 g to 281.3 g of amino acids, the second chamber comprising 250 ml to 750 ml of a glucose solution comprising 75 g to 375 g of glucose, and third chamber comprising 125 ml to 375 ml of a lipid emulsion comprising 18.8 g to 93.8 g of lipids, wherein the three-chamber pouch, based on the total volume of the first, the second chamber and the third chamber, comprises at least 50 g of amino acids per 1000 ml, wherein preferably the three-chamber pouch, based on the total volume of the first, the second chamber and the third chamber, comprises at least 60 g of amino acids per 1000 ml, particularly preferably at least 63 g of amino acids.
14. The three-chamber pouch according to claim 13, wherein the first chamber comprises 1500 ml of an amino acid solution comprising 135 g to 187.5 g of amino acids, preferably 150 g of amino acids, the second chamber comprises 500 ml of a glucose solution comprising 150 g to 250 g of glucose, preferably 200 g of glucose, and the third chamber comprises 250 ml of a lipid emulsion comprising 37.5 g to 62.5 g of lipids, preferably 50 g of lipids, or wherein the first chamber comprises 750 ml of an amino acid solution comprising 67.5 g to 93.8 g of amino acids, preferably 75 g of amino acids, the second chamber comprises 250 ml of a glucose solution comprising 75 g to 125 g of glucose, preferably 100 g of glucose, and the third chamber comprises 125 ml of a lipid emulsion comprising 18.8 g to 31.3 g of lipids, preferably 25 g of lipids, or the first chamber comprises 2250 ml of an amino acid solution comprising 202.5 g to 281 g of amino acids, preferably 225 g of amino acids, the second chamber comprises 750 ml of a glucose solution comprising 225 g to 375 g of glucose, preferably 300 g of glucose, and the third chamber comprises 375 ml of a lipid emulsion comprising 56.3 g to 93.8 g of lipids, preferably 75 g of lipids.