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COMBIKLAS: The Most Versatile TPN To Reduce Complication And Negative Outcome In Patients At Nutritional Risk During COVID-19 Treatment

Author: Dr. Shailaja Shankar Behera

MBBS, MD (IMS BHU), PDCC Cri􀆟cal Care Medicine (IMS BHU), Post Doctoral Fellowship in Neuro Critcal Care (NIMHANS, Bengaluru), DM (Critical Care), AIIMS New Delhi" Apex Super specialty Hospitals, Varanasi.

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Malnutrition among critically ill patients is very prevalent. The metabolic response to stress, injury, surgery, or inflammation cannot be accurately predicted and these metabolic alterations may change during the course of illness. Underfeeding and overfeeding both are very common in Intensive Care Unit (ICU), and this resulting in large energy and other nutritional imbalances. Better understanding of human nutrition and metabolic process has led to formulation of scientific parenteral solutions to suit specific situations. This article shows the negative consequences due to lack of nutrition and how Total Parenteral Nutrition can be helpful for the critically ill patients.     

Keywords: Parenteral Nutrition, Total Parenteral Nutrition



The feeding of nutritional product to a person intravenously, bypassing the usual process of eating and digestion is known as Parenteral nutrition. When no significant nutrition is obtained by other routes then the person will receive a nutritional formula that contain nutrients including glucose, salts, amino acids, lipids and added vitamins and dietary minerals. It is called total parenteral nutrition (TPN). Total parenteral nutrition (TPN) supplies all daily nutritional requirements.

The interruption in the continuity of gastrointestinal tract or the impairment in the absorptive capacity of gastrointestinal tract can be treated by total parenteral nutrition (TPN). TPN is also used to prevent malnutrition in patients who are unable to obtain adequate nutrients by oral or enteral route.

JW Lifesciences is a Korea-based company, primarily engaged in manufacture and distribution of Intravenous(IV) fluid products and infusion solutions. The Company offers product that contents amino acids, lipids, proteins, vitamins, and minerals which is used in special cases. The company is also engaged in manufacture of total parenteral nutrition (TPN) products and others. COMBIKLAS is unique “Three-in-One” formulation, scientifically designed by JW Lifesciences.


Negative Consequences Regarding Lack of Nutrition

According to WHO, Nutrition is the pillar of human life, health and development across the entire life span. The body requires many different vitamins and minerals that are crucial for both body development and preventing disease. Nutrients aren’t produce naturally in the body, so you have to get them from your diet.  An unhealthy diet increases the risk of many diet-related diseases. Basic nutrients for all life activities are carbohydrates, fats, and proteins. These constitute the carbon skeleton of numerous useful molecules, and deliver energy through oxidative decomposition. The main aim of nutrition is to prevent and treat nutritional deficiencies.

  1. In Critically Ill Patient

The critical ill patients are at high risk of malnutrition because of stress catabolism and inadequate or delayed nutrition intake.

Catabolic hormones (such as glucagon, cortisol, and catecholamines) are secreted in the early stage of critical illness to mobilize body nutrition reserves (muscle and adipose tissue) for the generation of endogenous energy substrate (glucose, amino acids, and free-fatty acids) and to prioritize the delivery of these energy substrates to vital organs (such as the brain or the heart). Proinflammatory cytokines such as Interleukin (IL)-1, IL-6 and tumor necrosis factor-α are also secreted at the same time in response to the body’s acute insult and further exaggerate the catabolism process [1]. During such inflammatory states, the provision of nutrition is not able to completely reverse the loss of body cell mass [2]. Such conditions make critically ill patients more prone to develop a risk of malnutrition (loss of body cell mass to a critical level), and the risk of complications is significantly increased if malnutrition develops [3]. At this stage, the priority is to provide nutrition support to support vital organ system functions and preserve appropriate host responses while the underlying disease is treated [4].

Depending on the patient’s history, the patients may already have features of malnutrition with a reduced or restricted food intake long before intensive care unit (ICU) admission the reason behind could be either underlying chronic conditions (such as chronic obstructive pulmonary disease, cancer, or chronic renal failure) or have reduced intake from a hospital stay prior to ICU admission [4,5].

Moreover, in the ICU, the patients may continue to have restricted nutrition intake and thus they may experience prolonged fasting or frequent feeding interruptions due to various ICU procedures [5].

These two factors, preexisting malnutrition and iatrogenic underfeeding, may further complicated the nutrition status and worsen clinical outcomes.  


  1. In Bacterial Infected Patients

Infection and malnutrition have always been intricately linked. Malnutrition is the primary cause of immunodeficiency worldwide, with infants, children, adolescents, and the elderly most affected. Malnutrition and infection shows a strong relationship, because poor nutrition leaves individual underweight, weakened, and vulnerable to infections, primarily because of epithelial integrity and inflammation (figure 1) [6].


Figure 1: Interactions between malnutrition and infection


Malnutrition can make a person more susceptible to infection, and infection also contributes to malnutrition, which causes a vicious cycle (figure 2). An inadequate dietary intake leads to weight loss, lowered immunity, mucosal damage, invasion by pathogens, and impaired growth and development in children. A sick person’s nutrition is further aggravated by diarrhea, malabsorption, loss of appetite, diversion of nutrients for the immune response, and urinary nitrogen loss, all of which lead to nutrient losses and further damage to defense mechanisms. This results in the reduction of dietary intake. In addition, fever increases both energy and micronutrient requirements. Malaria and influenza, for example, have mortality rates proportionate to the degree of malnutrition [7].


Figure 2:  The “vicious cycle” of malnutrition and infection


  1. In GI tract disease

Nutrition and intestinal function are intimately interrelated. The chief purpose of the gut is to digest and absorb nutrients so as to take care of life. Consequently, chronic gastrointestinal (GI) disease commonly leads to malnutrition and increased morbidity and mortality.


Practical Guidance for Nutritional Treatment

  1. All the critically ill patients should undergo nutrition assessment, on admission [8].
  2. Observation of signs of malnutrition (e.g., cachexia, edema, muscle atrophy, BMI <20 kg/m2) is critical [9].
  3. EN should be started early, preferably within first 24–48 h [8].
  4. In case the nutrition requirement is not met adequately with EN even after 7 days of ICU admission, then usage of parenteral nutrition (PN) may be considered [8].
  5. Nutritional support should to be considered as of therapeutic benefits and not just supportive or adjunctive [8].
  6. Electrolytes should be strictly monitored in the patient on nutrition therapy [10].
  7. Assessment of drug–nutrient interaction to be done on daily basis [11].
  8. Tube feeding to be considered if even 50%–60% of nutrition targets are not met adequately within 72 h of oral nutrition support.



Combiklas is the most versatile TPN designed by JW Lifesciences. It is a sterile hypertonic emulsion, for central venous administration, in a three chamber bag with no added sulfites (table 1).


Table 1: Three chambers of COMBIKLAS




Chamber 1

Dextrose solution

It is for fluid replenishment and caloric supply

Chamber 2

Amino acids solution with Electrolytes

It comprises essential and nonessential amino acids provided with electrolytes

Chamber 3

Intralipid® 20% (a 20% Lipid Injectable Emulsion)

It is prepared for intravenous administration as a credit of calories and essential fatty acid


Route of Administration (Peripheral and Central)

JW Lifesciences, introduced Combiklas in both variants peripheral parenteral nutrition (Peri) and total parenteral nutrition (Central). Depending on which vein to be used, this procedure is often referred to as either total parenteral nutrition (TPN) or peripheral parenteral nutrition (PPN) [12]. Total Parenteral Nutrition (TPN) and Peripheral Parenteral Nutrition (PPN) are provided to patients who do not have any other source of nutrition. Both the TPN and the PPN are provided through IV route (figure 3). Though the two are used to provide the required nutrition to a patient, they are different various ways (table 2).


Figure 3: Routes of Feeding


When a patient is on Total Parenteral Nutrition, he relies on it completely. On the other hand, Peripheral Parenteral Nutrition, or PPN, is only partial. This means that the patient may be getting nutrition from other sources along with the PPN.

Another difference that can be seen is that Total Parenteral Nutrition comes in a higher concentration, and can only be administered through a larger vein. On the contrary, Peripheral Parenteral Nutrition comes in a lesser concentration, and can be delivered through a peripheral vein. Generally, the TPN is administered in the larger vein in the chest or neck.

PPN is not a preferred nutritional supplement for a long time. This is because it is not safe to use hyperosmolar solutions in peripheral veins for a very long time. However, the TPN can be used for a longer duration as it is delivered through a central vein.

Total Parenteral Nutrition is given to patients who are suffering from digestive disorders, or who are having any extended consequences of surgery or accident. The Peripheral Parenteral Nutrition is prescribed if a person’s digestive system has been blocked, or if the patient is not getting enough nutrition during an extended stay in the hospital [13].


Table 2: Comparison Between TPN and PPN [14]

Parameter of Comparison

Total Parenteral Nutrition (TPN)

Peripheral Parenteral Nutrition (PPN)


It is a process in which the patient is given nutrients through veins when they do not have other nutrition sources

It is a process of providing supplements with the other source of obtaining/receiving nutrients

Time period

It is long-term therapy

It is normally a fourteen days' process. It is a short-term therapy


TPN is more caustic as it has minerals, glucose, and electrolytes

It is not very caustic as compared to TPN


TPN can only be applied in larger veins near the chest or neck of the patient

PPN can only be applied to be in a short vein in a patient body


TPN can be given to a person who has a digestive disorder, accident, or has critical surgery

PPN can be given to a person whose digestive system has been blocked or unable to take a sufficient amount of nutrients from other sources


Indication and Pack Specified Usage

Combiklas indication remains same for every variant of pack size available but the use of different pack size depends upon the patient’s medical condition. Some of the most discussed indications are mentioned below:

  1. Newborns with gastrointestinal anomalies such as tracheoesophageal fistula, massive intestinal atresia, complicated meconium ileus, massive diaphragmatic hernia, gastrochisis, omphalocele or cloacal exostrophy, and neglected pyloric stenosis.
  2. Failure to thrive in infants with short bowel syndrome, malabsorption, inflammatory bowel disease, enzyme deficiencies and chronic idiopathic diarrhea.
  3. Other paediatric indications include necrotizing enterocolitis, intestinal fistulae, severe trauma, burns, postoperative infections and malignancies.
  4. Adults with short bowel syndrome secondary to massive small-bowel resection or internal or external enteric fistulae.
  5. Malnutrition secondary to high intestinal obstruction for example achalasia, oesophageal strictures and neoplasms, pyloric obstruction and gastric neoplasms.
  6. Prolonged ileus due to medical or surgical causes (for example post-operative, following abdominal trauma or polytrauma).
  7. Malabsorption secondary to sprue, enzyme & pancreatic deficiencies, regional enteritis, ulcerative colitis, granulomatous colitis, and tuberculous enteritis.
  8. Functional gastrointestinal disorders like idiopathic diarrhoea, psychogenic vomiting, anorexia nervosa.
  9. Patients with depressed sensorium (for example, following head injury or intracranial surgery) in whom tube feeding is not possible.
  10. Hypercatabolic states secondary to severe sepsis, extensive full - thickness burns, major fractures, polytrauma, major abdominal operations etc.
  11. Patients with malignancies in whom malnutrition may jeopardize successful delivery of a therapeutic option (surgery, chemo- or radiotherapy).
  12. Paraplegics/quadriplegics with pressure sores in pelvic or perineal regions where fecal soiling is a problem [15].


Available Pack Size

  1. Combiklas 384 ml – Given to pediatric patients as well as to the patients with Fluid Restriction in cases such as:
  • Acute Kidney Failure
  • Acute Respiratory Syndrome
  • Congestive Heart Failure                                                   
  • Malnourished Patients
  1. Combiklas Peri 1440 ml – Preferred during short duration of treatment (3-5 days) where patient body weight is less than or up to 60kg
  2. Combiklas Peri 1920 ml – Preferred during short duration of treatment (3-5 days) where patient body weight is more than 60 kg
  3. Combiklas Central 1540 ml – Preferred during long duration of treatment (6-12 days) where patient body weight is less than or up to 60kg
  4. Combiklas Central 2053 ml – Preferred during long duration of treatment (6-12 days) where patient body weight is more than 60kg


Benefits of Fulfilling the Nutritional Requirement of Patient Through TPN

The development of parenteral nutrition (PN) contraindicated a long-held belief that nutritional administration entirely through the veins was impossible, impractical, or unaffordable. The ability to supply nutrients to patients lacking a functional GI tract ultimately saved lives that would have otherwise been lost due to malnutrition.

The major advantages of parenteral nutrition are:

  • Provision of adequate nutrients during gastrointestinal dysfunction
  • Useful during fluid restriction since caloric density can be increased with a central venous catheter
  • Generally indicated when patient cannot eat enough or be fed adequately by tube


Macronutrient Composition

Patient with severe symptoms needs ICU admission and also after intensified conditions by extended stay during hospitalization; consequently, leads to the demand of nutritional therapy based on their health conditions. Following recommendation are based on international guidelines for critically ill patient treatment which must be considered:

  • Carbohydrates are the primary source of energy for the human body. The brain and neural tissues, erythrocytes, leukocytes, the lens of the eyes, and the renal medulla either require glucose or use it preferentially. The base of all PN solutions is carbohydrates, most commonly dextrose monohydrate. Dextrose provides 3.4 kcal/kg and is available in concentrations from 5% to 70%, with higher concentrations used primarily for patients on fluid restrictions.
  • Protein is necessary to maintain cell structure, tissue repair, immune defense, and skeletal muscle mass. Protein is provided in the form of crystalline amino acids in concentration ranging from 3% to 20%. Amino acids provide 4 kcal/kg.
  • Amino acid solutions are usually a physiologic mixture of both essential and nonessential amino acids. Disease-specific amino acid solutions are available and are primarily used for renal and hepatic disease. Patients with declining kidney function who are not yet candidates for dialysis are at risk for urea nitrogen accumulation when infused with nonessential amino acids. These patients receive only essential amino acids. Patients with severe hepatic encephalopathy may benefit from branch-chain amino acids (BCAAs). BCAAs are oxidized primarily in the muscle, rather than the liver, preserving hepatic metabolic pathways in case of liver failure. In general, disease-specific amino acid solutions offer an incomplete amino acid profile and should not be used for more than 2 weeks.
  • Lipids in oil-in-water emulsion concentrations ranging from 10% to 30% provide fats in PN. Lipid solutions currently available in the United States contain long-chain triglycerides (LCT) in the form of soybean or safflower oil, egg phospholipids as an emulsifier, water, and glycerol to create an isotonic solution.

Inclusion of lipids in IV nutrition prevents essential fatty acid (EFA) deficiency. Solutions that provide up to 4% of total calories from linoleic acid or 10% of total calories from safflower oil-based emulsions will meet daily EFA requirements. Patients who receive PN without lipids, usually those with an egg allergy, should be monitored for EFA deficiency.

  • Fluid volume recommended requirement for stable patients is 30 mL/kg/day of fluid for adult and 28 mL/kg/day for elderly. It is of utmost importance to maintain neutral fluid balance in critically ill patients with specific consideration to renal and prerenal failure. It is recommended to control the amount of intravenous fluids in elderly patients and for large areas of pulmonary consolidation. If there is fever; for every 1°C increase in body temperature, supplement approx. 4 mL/kg fluid [16].



MALNUTRITION among hospitalized patients has been associated with increased morbidity, prolonged hospital stay, and increased costs to the health care system.

Total parenteral nutrition does not influence the overall mortality rate of surgical or critically ill patients. It may be helpful in reducing the complication rate, especially in malnourished patients, but study results are influenced by patient population, use of lipids, methodological quality, and year of publication.



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