3.3.1 Indications for PN

Parenteral nutrition (PN) is a life-sustaining therapy for adults and children when oral and enteral nutrition are contraindicated or inadequate

• PN refers to the IV infusion of nutrients directly into the bloodstream, bypassing digestion in the bowel and stomach. PN solutions comprise amino acids, glucose (dextrose), and lipids, and should also include electrolytes, vitamins, and trace elements.¹ PN solutions are preferably administered using either individually compounded all-in-one (AIO) admixtures or standardised commercial MCBs.¹
• PN is a life-sustaining therapy for patients who cannot be fed adequately and/or safely with food, oral nutritional supplements (ONS) and/or enteral tube feeding (ETF) for a long period, such as those with intestinal failure (IF);^2,3 Both European and American guidelines recommend EN over PN for patients with a functional and accessible gastrointestinal tract in need of nutritional support.⁴
• The purpose and indications for PN should be clearly established at the outset and regularly reassessed to determine if EN can be used and to ensure proper nutrition while minimising complications. PN should not be prescribed solely based on the medical diagnosis or disease state. A thorough evaluation of EN feasibility should be conducted before starting PN, ensuring that PN is reserved for cases where EN is not sufficient. Measure to optimise enteral nutrition involve several factors that must be thoughtfully evaluated, including timing of EN initiation, the type of nutritional formula, and the method of delivery, such as gastric versus duodenal routes, and intermittent versus continuous administration. In some situations, patients receiving oral or enteral nutrition may still obtain less than 60% of their required nutrition, and in these cases, supplemental PN may be necessary to meet their nutritional needs.^4,5
• Its primary role is to prevent or treat malnutrition. PN is also used in conditions where rest of the GI tract is required to aid recovery, for example, when there is inflammation, fistulae, or obstruction,^{6, 7} and perioperatively for certain patients who are malnourished or are at risk of malnutrition,⁸ to reduce the risk of preventable post-surgical nutrition-associated complications. PN may be required short term, long-term, or sometimes for the patient’s lifetime, depending on the underlying disease or condition.
• PN can be administered in children and adults through either a central or peripheral vein, depending on the duration of treatment and indication. Patients who are not severely malnourished, require PN for less than 2 weeks, and who have no other need for central venous access may be fed via a peripheral vein (PPN).^{9, 10} When used appropriately, PPN may provide benefits over centrally administered PN, such as ease in establishing peripheral access, which may prevent delays in initiating nutrition support, and avoidance of complications (e.g., sepsis) and costs associated with use of a central venous catheter.¹¹ However, PPN may not meet the energy and protein needs of all patients (e.g., patients who are fluid restricted or require long-term PN support) because the osmolarity of the solutions limits the macronutrient concentrations.^{12, 13} Peripheral vein thrombophlebitis is often the rate-limiting factor when trying to optimise peripheral PN solutions;¹⁴ ESPEN and ASPEN guidelines recommend that, to reduce the risk of thrombophlebitis, the osmolarity of peripheral solutions should not exceed 850 mOsm/L or 900 mOsm/L, respectively.^15-17 PN solutions with osmolarity below 850 mOsmol/L are available.
• Most patients receiving PN require a central line, which allows delivery of nutrients directly into the superior vena cava or the right atrium—the tip of the catheter is placed in the lower third of the superior vena cava (at the trio-caval junction, or in the upper portion of the right atrium).¹⁵ In hospital, PN can be administered through a dedicated peripherally inserted central catheter (PICC) or a non-tunnelled central venous catheter (CVC).^{15, 18} However, a tunnelled catheter or a totally implantable device is recommended for long-term use (>30 days) as these devices are associated with a lower risk of thrombosis and infection.^{15, 18-20}
• Patients who require short-term PN, which accounts for most hospitalised patients receiving PN, usually receive it as a continuous 24-hour infusion. This method reduces the need for manipulation and maintains a slower infusion rate, helping to prevent glucose and fluid overload. In contrast, home PN is often given on a cyclic (discontinuous) schedule. Cyclic administration, typically during part of the day or night, allows the patient to be free from the intravenous tubing and pump. This approach has also been used to reduce liver damage associated with PN. When using cyclic administration, glycemia should be monitored to prevent hypoglycaemia after the infusion ends and hyperglycaemia due to the increased infusion rate.⁴
• The timing of PN initiation is an important consideration, though studies provide conflicting results. Clinical guidelines generally suggest starting PN (either supplemental or full) in well-nourished patients who are unable to meet their nutritional needs after 7 days. For patients at risk of malnutrition, guidelines recommend initiating PN earlier, within 3–6 days, if they are unlikely to achieve adequate nutrition through oral intake or EN. In malnourished patients, PN should be started as soon as possible if oral nutrition or EN is insufficient or not feasible.⁴

PN can be used to supplement dietary intake, ONS, and/or ETF (supplemental PN— SPN) or may be used as the sole source of nutrition (total parenteral nutrition—TPN)

• Depending on the patient’s needs, PN may be used as the sole source of nutrition (TPN or exclusive PN) or in addition to ETF (SPN, partial PN, complementary PN).
• The primary indications for PN in adults include intestinal failure (IF) resulting from conditions or treatments such as short bowel syndrome, inflammatory bowel diseases, intestinal pseudo-obstruction, and radiation enteritis, as well as high-output fistulas, severe intestinal obstruction, or when the gastrointestinal tract is inaccessible.⁴
• In regards to TPN, it is used in conditions such as short- bowel syndrome (SBS), severe gut dysfunction, mesenteric vascular insufficiency, bowel obstruction, GI bleeding, severe diarrhoea, high-output fistula, sepsis, severe burns, and trauma associated with continuous haemodynamic instability or severe fulminant acute or chronic pancreatitis.²¹ TPN does not require a functioning GI tract or access to the gut, nutrient delivery is not affected by abdominal distension, fistula drainage, ischemia, or nausea/vomiting.²¹ TPN may be life-saving for patients with GI tract failure.^{22, 23} TPN can also be used to delay surgical intervention in patients that cannot be fed adequately via the oral or enteral routes, avoiding prolonged, progressive malnutrition which greatly increases the risk of peri- and post-operative complications.²¹
• As for SPN, is typically indicated when oral or enteral routes cannot alone achieve the patient’s energy and protein targets defined in their nutritional care plan.¹

• Children are particularly susceptible to starvation because they require nutrients for normal growth and development as well as for maintenance of body tissues, particularly during infancy and adolescence when growth is rapid.²⁴ Small preterm infants (<1 kg) can survive only 4 days’ starvation, and less than 2 days if there is underlying disease that increases energy expenditure. Withholding nutrition for just 1 day may therefore have negative consequences.²⁴ Suboptimal feeding may slow or stunt growth, resulting in long-term adverse effects such as extrauterine growth restriction and poor neurodevelopment.^{25, 26} A growing body of evidence also suggests that undernutrition during early critical periods of development is associated with significant adverse effects that may persist into adulthood, a concept known as programming.^27-30
• PN is considered to be one of the most important advances in paediatric therapeutics over the last four decades. It is lifesaving for children who cannot be adequately fed by the oral or enteral route, because, for example, severe IF or functional intestinal immaturity.²⁴
• The use of PN to provide nutrients has significantly improved the outcomes for infants and children with intestinal failure. However, prolonged PN administration can be linked to complications, including intestinal failure-associated liver disease (IFALD).³¹
• Lipids are a crucial component of PN for paediatric patients, with current guidelines recommending a maximum intake of 3 g/kg/d, providing 25%-50% of non-protein energy. Common indications for long-term PN in children include primary digestive diseases like short-bowel syndrome and neuromuscular disorders, with a risk of IFALD in these patients. ³¹
• The use of soybean lipid emulsions at doses above 1 g/kg/d increases the risk of IFALD due to mechanisms like oxidative stress and phytosterol accumulation. Lipid emulsions containing fish oil offer advantages over soybean-based emulsions, including reduced risk of cholestasis and improved liver function.³¹
• For PN-dependent children at risk for IFALD, fish-oil emulsions are recommended to prevent liver damage. In children with existing IFALD, using fish-oil containing emulsions is recommended for reversing cholestasis, with short-term use of pure fish-oil emulsions as a rescue treatment when needed.³¹

• PN can be administered in both the hospital and community settings. HPN is not a treatment in itself but allows the provision of PN outside the hospital, typically the patient’s own home or residential care/nursing home. HPN was introduced in the early 1970s, primarily for patients with benign chronic IF (i.e., with no underlying malignancy).³² Before this, effective delivery of long-term PN was not possible and patients with permanent IF due to major intestinal resection, fistulas, or immature development of the GI tract, died within a few months of diagnosis from malnutrition, dehydration, and/or electrolyte disturbances.³³ However, advances in the preparation and administration of HPN over the past four decades have led to dramatic improvements in survival for these patients (now measured in decades³⁴) and enables many to resume normal activities, including employment, within the constraints of their underlying disease.³⁵ A large proportion of patients on HPN improve over time and are able to resume normal feeding, such as those with hyperemesis gravidarum (100%), CD (70%).³⁴
• The indications for HPN have expanded beyond benign chronic IF to include appropriate patients with cancer, including certain patients with incurable disease (see Section 3.3.1.1). However, this varies across countries (see Section 3.3.1.2).
• HPN also has a key role in shortening the length of hospital stay for patients who are ready to be discharged medically but who still require IV nutrition; this may yield considerable cost savings for healthcare systems (see Section 3.3.5).³⁶
• HPN is a vital therapy for adults with chronic IF but carries the risk of IFALD. Lipid emulsions are essential for long-term home PN, and patients must receive a dose sufficient to prevent essential fatty acid (EFA) deficiency. Adults requiring long-term PN are at risk for IFALD, particularly due to factors like catheter-related infections, excessive glucose intake, and the use of soybean oil emulsions above 1 g/kg/d. To reduce the risk of liver complications, lipid emulsions containing fish oil are preferred over soybean oil emulsions, as they provide benefits like reduced ω-6 polyunsaturated fatty acid (PUFA) and phytosterol content and increased ω-3 PUFA.³¹
• One study examined the use of ready-to-use multichamber bags (MCBs) for home HPN in patients with advanced cancer. The study finds that MCBs were non-inferior to individual compounded bags regarding infectious complications for patients with advanced cancer who were at home.³⁷

• Long-term TPN or SPN is indicated to preserve nutritional status and facilitate normal growth and development in children when oral or enteral feeding is not sufficient to meet nutritional needs.²⁴ SBS, mostly congenital, accounts for at least 30% of cases of IF in children. Other diseases that impair digestive function include intractable diarrhoea of infancy, chronic intestinal pseudo-obstruction, and inflammatory bowel disease (IBD), particularly Crohn’s disease (CD). The main non-digestive indications for long-term PN in children are HIV/AIDS, cancer, metabolic diseases, and end-stage liver disease prior to transplantation, which account for about 20% of all patients. However, the need for HPN is typically shorter for these non-digestive conditions than for primary digestive diseases. HPN provides an alternative to prolonged hospitalisation for children requiring long-term PN and is recognised as the best option for improving the QOL for both the child and their family, within the constraints of the underlying disease.²⁴