3.3.1.1 INDICATIONS FOR PN IN SPECIFIC PATIENT GROUPS

PN is used to provide nutritional support to adults and children with a variety of diseases and conditions. This section provides a summary of the main indications for PN in specific patient groups and a comparison of ASPEN and ESPEN guideline recommendations for each condition. Please refer to tables in Section 4.3 for recommendations and guidance from other international and internationally recognised guidelines.

GASTROINTESTINAL DISEASE

• Diseases and conditions that involve the digestive system (oesophagus, stomach, small and large intestines, rectum, liver, gallbladder, and pancreas) can make it challenging to achieve adequate nutrition using the oral or enteral routes.³⁸ PN may be required short term (see Table 3.11) when the gut is temporarily unavailable (known as transient intestinal insufficiency).³⁹ In such cases, when gut function begins to recover, food, ONS or ETF can be carefully reintroduced whilst PN is slowly reduced, ensuring that total nutritional requirements continue to be met.³ However, PN may be required long term, or even permanently, for conditions that result in chronic IF, such as SBS (see Table 3.11).³⁹ SBS results from an inadequate length of intestine after surgical resection (<200 cm).⁴⁰ The prevalence of SBS is estimated to be 3 to 4 cases per million population, depending on geographical region.⁴¹

Abbreviations: ETF, enteral tube feeding; GI, gastrointestinal; SBS, short bowel syndrome

PN (TPN or SPN) is typically used to maintain nutritional status in patients with acute intestinal failure (AIF) and enterocutaneous fistula (ECF)

• ESPEN defines IF as reduction in GI function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that IV supplementation is required to maintain health and/or growth.⁴⁰ IF is an umbrella term that includes surgical SBS due to intestinal resection for congenital or acquired GI diseases and disorders of gut motility. IF is functionally classified as Types I, II, and III, based on onset, metabolic, and expected outcome criteria.⁴² Types I and II IF are considered acute conditions. Type I is considered short term and is typically self-limiting, whereas Type II is prolonged and may require PN over weeks or months.
• Patients with Type II AIF usually have a high output fistula or enterostomy, sepsis, and complications associated with SBS.^{43, 44} Optimisation of nutritional status is a key aspect of therapy alongside treatment of the underlying condition.⁴³ In patients with AIF who develop sepsis it is important to minimise negative energy and protein balance and muscle loss (by preventing starvation) and maintain tissue function, particularly in the liver, immune system, skeletal muscles, and respiratory muscles.^{43, 45}
• ESPEN guidelines note that although ETF is the route of choice for nutritional support in patients with AIF and ECF, it is unlikely to be sufficient because of the extent of injury to the GI tract.⁴³ Therefore, PN is typically used, either alone (TPN) or in combination with ETF (SPN). Additionally, guidelines jointly published by ASPEN and the Federación Latino Americana de Terapia Nutricional, Nutrición Clínica y Metabolismo (FELANPE) state that PN (TPN or SPN) may be required for patients with high-output ECF (>500 mL/day) to meet fluid, electrolyte, and nutrient requirements to support spontaneous (or surgical closure) of the ECF.⁶

• Although ASPEN has not published specific guidance relating to type II AIF, these patients often require admission to an ICU. Therefore, ASPEN–SCCM guidelines on nutrition support therapy in adults with critically illness apply (see subsection CRITICAL ILLNESS), as do ASPEN consensus recommendations on appropriate PN use.¹⁷ These guidelines state that PN should be used in patients who are malnourished or at risk for malnutrition when there is a contraindication to ETF (or the patient cannot tolerate adequate ETF) or if gut function is not sufficient to preserve or restore nutrition status.¹⁷

• Type III IF is a chronic condition that requires PN over months or years.
• Five main pathophysiological conditions underlie CIF: SBS, intestinal fistula, intestinal dysmotility, mechanical obstruction, and extensive small bowel mucosal disease,⁴⁰ which may occur as a result of various GI or systemic diseases.⁴⁰ In patients with SBS, intestinal fistula, or extensive small bowel disease, IF is caused by surgical (or disease- related) reduction or bypass of the absorptive mucosal surface, resulting in malabsorption of ingested food. In patients with intestinal dysmotility or intestinal mechanical obstruction, IF is caused by feed-related digestive symptoms or episodes of mechanical or non-mechanical intestinal obstruction, resulting in limited tolerance of ONS or ETF.⁴⁰ CIF is the rarest form of organ failure and may be caused by severe benign GI or systemic disease or the end stage of intra-abdominal or pelvic cancer.³⁵
• Regardless of the underlying aetiology, PN is a life-saving therapy for children and adults with CIF and may be needed for the patient’s lifetime unless the condition can be reversed surgically.⁴⁰ ASPEN guidelines on nutrition support therapy in critically ill adults note that PN should be continued in patients with SBS upon admission to the intensive care unit (ICU) unless bacteraemia is suspected.⁴⁶

• HPN allows the provision of nutrients for individuals with CIF; it is associated with 5-year survival rates of about 80% for adults and 90% for children.⁴⁷ HPN enables many patients to live a normal life within the constraints of their condition. About two-thirds of adults are able to partly or fully resume normal social and working activities while on HPN.⁴⁸
• US and European guidelines recommend that HPN be considered for adults with IF who are clinically stable and able to receive therapy outside of the acute care setting.^{17, 32} ESPEN guidelines recommend that HPN should be administered without delay in malnourished patients with chronic GI motility dysfunction resulting from chronic intestinal pseudo-obstruction and in malnourished patients with radiation enteritis if ONS/ETF is not adequate.⁴⁰ Additionally, ETF or ONS may be used alongside PN in adults with SBS and a low-level of HPN dependence, if the expected gain with ETF could enable the patient to be weaned off HPN.⁴⁰
• ESPGHAN guidelines recommend that all children who need long-term PN should be discharged on HPN as long as social and familial requirements are met.²⁴ Similarly, ASPEN consensus recommendations state that HPN should be considered in carefully selected clinically stable paediatric patients who are expected to require PN for a prolonged period; however, PN should be initiated in the hospital setting.¹⁷
• Updated ESPEN guidelines further confirm the need for PN in adults with CIF .⁴⁹ Among the additions, these guidelines expanded the definition of CIF to include a number of conditions that can lead to IF and highlighted the importance of quality of life .⁴⁹ Importantly, while the majority of recommendations were graded as Good Practice Points (GPP), nearly all achieved strong consensus among experts.

PN is lifesaving in patients with Crohn’s disease (CD) who have prolonged gastrointestinal failure

• IBD comprises Crohn’s disease (CD) and ulcerative colitis (UC). CD can involve any section of the GI tract from the mouth to the rectum whereas UC is restricted to the colon. Therefore, malnutrition is more common in patients with CD (20–85% of patients) and is particularly prevalent in patients with IF resulting from SBS due to CD.^50-52 Malnourished patients with IBD are at increased risk for hospitalisation following emergency department attendance⁵³ and are more likely to be admitted to hospital with infection (27.5% of all IBD hospitalisations).⁵⁴ Infections account for significant morbidity and mortality in patients with IBD.⁵⁴
• Patients with IBD are at risk of protein–energy malnutrition as a result of poor oral intake, malabsorption due to active disease or bowel surgery, high protein catabolism due to systemic inflammation, and the adverse effects of treatment.⁵⁵ Protein requirements are therefore increased in patients with active IBD (1.2–1.5 g/kg per day).⁷
• Malnutrition is frequent in children and adults with CD and may result in impaired muscle function and growth retardation in up to 40% of children and adolescents.⁵⁶ Two-thirds of hospitalised paediatric patients with CD have negative nitrogen balance at presentation.⁵⁷ Therefore, nutrition support has become an important adjunctive therapy for these patients.⁵⁶
• In patients with IBD who are unable to maintain or recover nutrition status because of an impaired GI function, PN is essential to prevent further nutritional loss, restore homeostasis, and prevent long-term sequalae of malnutrition.⁵⁷
• ESPEN guidelines on clinical nutrition in IBD, published in 2023, recommend PN in patients with IBD when ONS or ETF is not sufficient (e.g., when the GI tract is dysfunctional or in CD patients with SBS) and for patients with an obstructed bowel when there is no possibility of placing a feeding tube beyond the obstruction, or this has failed, or other complications arise such as an anastomotic leak or a high-output intestinal fistula.^7,58 PN is also indicated in surgical patients with the aforementioned conditions and in patients who cannot tolerate ETF or in whom nutrition cannot be maintained with ETF.
• The ESPEN IBD guidelines⁷ highlight that published guidance by ESPEN on nutrition in the surgical patient⁸ (see subsection on SURGERY) also applies to patients with IBD undergoing surgery, namely, if energy and nutrient needs cannot be met by oral and enteral intake (<50% of caloric requirement) for more than 7 days, combined EN and PN is recommended. Moreover, PN should be administered as soon as possible if nutrition therapy is indicated and there is a contraindication for EN (e.g., intestinal obstruction). ESPEN IBD guidelines recommend that patients admitted for emergency surgery should receive ETF or PN if they are malnourished or oral diet cannot be resumed within 7 days after surgery. Furthermore, non-emergency surgery for IBD should be delayed for 7–14 days, if possible, if the patient is malnourished to allow intensive artificial feeding⁷—studies in patients undergoing GI surgery (non-IBD) ^59-64 show that malnutrition has a negative impact on clinical outcomes, rate of postoperative complications, and mortality. ETF should be used in preference to PN in the perioperative phase; however, SPN should be considered in patients requiring nutrition support if >60% of their energy needs cannot be met with ETF.⁷ TPN should only be used if ETF is not possible or contraindicated. However, ESPEN recommends that patients with CD undergoing surgery should receive early nutritional support (independently of the route of administration),⁷ as it reduces the risk for postoperative complications.^{65, 66}
• For patients with active CD undergoing surgery, ESPEN guidelines⁶⁷ recommend that preoperative PN is used to improve nutritional status only when other modes of nutrition are not possible;⁶⁸ however, patients with a proximal and/or very-high-output fistula should receive SPN or TPN,⁶⁷ as preoperative optimisation of nutritional support increases the likelihood of successful surgical correction of this condition.⁶⁹
• CD is one of the most common reasons for SBS in adults (along with mesenteric artery thrombosis and irradiation damage),⁵⁶ resulting from frequent surgery and bowel resection;^{70, 71} younger patients with CD who have undergone multiple small-bowel resections are at particularly increased risk for SBS.⁷² ESPEN guidelines state that PN is a mandatory and life-saving therapy in patients with CD and prolonged GI failure, such as those with SBS, at least in the early stages of IF.⁷ Patients with UC are less likely to require PN because they are typically well-nourished when in remission.⁵⁶ ESPEN guidelines recommend PN in patients with UC only if they have IF.⁷
• ASPEN has not published any recent guidance specifically addressing the use of PN in patients with IBD. Consensus recommendations published by ASPEN in 2017 state that use of PN in adults should not be based solely on disease state but should be used in patients who are malnourished or at risk for malnutrition when ETF is contraindicated or not tolerated or the patient has inadequate bowel function to maintain or restore nutrition status.¹⁷ Similarly, TPN or SPN should be initiated in paediatric patients, when indicated, if ETF is not feasible or sufficient to meet total nutrient needs.¹⁷ ASPEN–SCCM guidelines on nutrition in patients with critical illness (discussed in the subsection CRITICAL ILLNESS) will also apply to patients with IBD who are admitted to the ICU.⁴⁶

CRITICAL ILLNESS

Many critically ill patients are malnourished or will become malnourished while in the ICU, leading to poor clinical outcomes and higher healthcare costs

• Critically ill patients are often malnourished when admitted into the ICU.⁷³ Rates of malnutrition at admission of 20–68% have been reported for acutely ill patients,^74-78 and rates of about 50% for critically ill patients admitted to the ICU.^79-81 Furthermore, failure to provide optimal calories and protein during critical illness can result in deterioration of nutritional status in patients who are not malnourished and can promote further nutritional decline in patients with existing malnutrition.⁸²
• Critical illness typically induces a state of catabolism46 which promotes a systemic inflammatory response and nutritional deterioration. Systemic inflammation has been shown to alter both the structure and function of the GI tract,⁴⁶ leading to inadequate nutritional intake.⁸³ Studies suggest that up to 60% of patients in the ICU experience impairments in GI motility, digestion, or absorption, which can result in an energy deficit and loss of skeletal muscle.^84-86 Critical illness is also associated with increased energy expenditure, the magnitude of which is positively related to the severity of injury.⁸² Insufficient energy provision in patients with critical illness leads to the breakdown of protein tissues such as muscles and organs.^{82, 87} Thus, energy requirements should be accurately assessed in critically ill patients, and balanced nutrition provided in order to avoid the adverse effects of under-or overfeeding.⁸²
• Malnutrition and loss of muscle tissue in critically ill patients, whatever the cause, is associated with worse outcomes, such as weakness, respiratory failure, increasing dependency on ventilatory support, increased risk of pressure ulcers, delayed wound healing, insulin resistance, compromised immune function, resistance to infections, higher healthcare costs, and increased mortality.^88-100 Patients who have lost skeletal muscle also require longer rehabilitation to resume normal life.101 The cost of treating a malnourished patient is estimated to be 2–3 times higher than for a non-malnourished patient.¹⁰² By contrast, sufficient energy and protein provision during critical illness is associated with fewer infectious complications,¹⁰³ shorter duration of mechanical ventilation,98 faster recovery,¹⁰⁴ and reduced mortality,^{98, 99, 104, 105} especially in patients with poor nutritional status. Provision of nutrition support in patients who are malnourished or at high nutritional risk is also cost saving by reducing requirements for healthcare resources.¹⁰⁶
• Worldwide, most adults in the ICU, including those at high nutritional risk, do not achieve protein and energy targets, even though clinical guidelines highlight the importance of adequate nutrition during critical illness.^107-109 Data from the 2013 International Nutrition Survey (INS) of clinical practice in 201 ICUs from 26 countries, involving some 4,000 patients, showed that, on average, critically patients received approximately 60% of prescribed calories and 58% of prescribed protein.¹⁰⁷ It is estimated that 43–88% of critically ill patients have a protein-energy deficit.^{110, 111}
• Underfeeding is common in the ICU because of prolonged periods nil by mouth, feeding intolerance, interruptions to feeding and inappropriate use of nutrition support. Appropriate and timely nutrition support may also be avoided because of traditional concerns about the safety of feeding during critical illness.¹⁰⁸ Studies have been carried out to identify the reasons for feeding interruptions in the ICU. One prospective observational study conducted in three ICUs found that presumed feeding intolerance (gastric residual cutoff 120–200 mL across the three centres) was the primary reason for interruption of feeding, followed by intubation/extubation and tests/procedures. Another prospective observational study conducted over 3 months in a medical ICU reported an average of 5 hours’ feeding interruption per day.¹¹² As a result, patients received only about 64% of their daily energy requirements. Interruptions for tests and procedures accounted for approximately 36% of the total interruption in feeding time, followed by changes in body position (15%), unstable clinical conditions (13.5%), high gastric residual volume (11.5%), and nausea and vomiting (9.2%). Similar findings have been reported in other observational studies.^113-116
• To prevent muscle loss in critically ill patients,⁹¹ sufficient protein and non-protein energy is required.¹¹⁷ Nutrition guidelines therefore recommend that critically ill patients who are malnourished or at nutritional risk receive adequate nutritional support to prevent the significant morbidity and mortality that is associated with starvation or underfeeding.⁹⁷
• ESPEN and ASPEN-SCCM guidelines^{46, 97} and expert opinion¹¹⁸ recommend that sufficient (high-dose) protein should be provided to critically ill patients. Protein requirements in critically illness are expected to be 1.2–2.0 g/kg actual body weight per day and are likely to be higher in patients with burns or multiple traumas.^{46, 97, 118, 119, 120}
• ESPEN guidelines recommend that, during acute illness, isocaloric nutrition (70% or greater of estimated needs) can be gradually applied. In the absence of indirect calorimetry, patients should receive 20-25 kcal/kg per day. In addition, if predictive equations are used to estimate energy requirements, providing hypocaloric nutrition (less than 70% of estimated needs) is recommended over isocaloric feeding during the first week of ICU stay.¹¹⁹ According to the ASPEN guidelines, it is recommended that patients receive between 12 and 25 kcal/kg during the first 7–10 days of ICU stay.¹²⁰
• In stable, critically ill adult patients requiring PN, intravenous lipid emulsions (ILEs) are an essential component of PN.¹²¹
• There is sufficient scientific evidence to support the use of fish-oil-based ILEs in critically ill adult surgical patients requiring PN.¹²¹
• The use of fish-oil-based ILEs should be considered within the first week of admission in adult ICU patients requiring PN, including those who are critically ill or surgical.¹²¹
• In stable, critically ill adult patients, the total lipid dose should not exceed 1.5 g lipids/kg/d, including non-nutritive lipid sources. A minimum dose should be provided to prevent essential fatty acid (EFA) deficiency.¹²¹
• Based on available clinical data, it is recommended to administer 0.1–0.2 g fish oil/kg/d from fish-oil-based lipid emulsions for stable, critically ill adult patients requiring PN.¹²¹
• ASPEN guidelines recommend a non-protein calories to nitrogen ratio of 70:1 to 100:1 for critically ill patients, which should be reduced to 30:1 to 50:1 for obese critically ill patients.⁴
• In a systematic review and meta-analysis of 20 RCTs, the outcomes of supplemental parenteral nutrition (SPN) and EN alone were compared in critically ill adult patients. The study found that adding SPN to EN significantly reduced ICU mortality and the risk of nosocomial infections but had no significant effect on ICU stay duration or mechanical ventilation time. These findings suggest that combining SPN with EN can improve clinical outcomes in critically ill patients.¹²²

• Underfeeding in critically ill children is common during the initial days of ICU admission, and nutrition support is often delayed until patients are clinically stable, which may be several days.^{123, 124} However, adequate nutrition and restoration of energy balance are crucial to ensure a good clinical outcome and survival in critically ill children,¹²⁵ especially because of their intrinsically high anabolic drive and lower nutrient reserves compared with adults.¹²⁶
• Children admitted to the ICU are at risk of deterioration of nutritional status because energy and protein intake is often less than recommended.¹²⁷ A prospective observational study that assessed daily nutritional intake in a mixed population of 261 critically ill children admitted to a tertiary PICU in the Netherlands reported substantial cumulative energy and protein deficits during the first 14 days of admission.¹²⁸ Moreover, these deficits had significant negative effects on growth parameters, such as mid-upper arm circumference (energy: p = 0.025 for term neonates and older children; protein: p = 0.033 for cumulative deficit of 10 g/kg) and weight (energy and protein both p < 0.001).
• Many studies have shown that infants and children who have impaired nutrition status and nutrient delivery during critical illness are more likely to experience adverse clinical outcomes, such as longer periods of ventilation, infectious complications, longer PICU and hospital stay, and increased risk of dying.^{80, 129-132}

Guidelines agree that in critically ill patients who are malnourished or at nutrition risk, TPN should be started within 24–48 hours of ICU admission if ETF is not feasible or is contraindicated

• ESPEN recommends that TPN should be administered within 24–48 hours if ETF is contraindicated and the patient is not expected to resume oral nutrition within 3 days of ICU admission.⁹⁷ Similarly, ASPEN–SCCM guidelines recommend that TPN is administered as soon as possible following admission to the ICU in patients who are severely malnourished or at high risk for malnutrition if ETF is not possible.⁴⁶

Whilst there is no consensus on when to start SPN in the ICU, many experts suggest timely initiation where nutritional intake from other routes is inadequate

• International guidelines differ regarding the timing of SPN in patients with critical illness. ESPEN intensive care guidelines recommend that SPN should be considered after 2 days if ETF is not providing adequate nutrition.⁹⁷ By contrast ASPEN–SCCM guidelines recommend that in patients at low or high nutrition risk, SPN should be considered after 7–10 days if at least 60% of energy and protein requirements cannot be met by ETF alone⁴⁶ whereas PN should be initiated as soon as possible after ICU admission in patients at high nutrition risk who are unable to receive nutrition through the enteral route.
• The ASPEN–SCCM recommendation on the timing of SPN in the ICU was informed by studies showing that provision of SPN within 48 hours of admission to the ICU had little or no benefit.^133-136 However, it has been highlighted.^{108, 137, 138} that these studies have methodological limitations that result in a high risk of bias which may confound the results. For instance, many patients included in large studies evaluating different levels of nutrition provision are not considered to be at high nutritional risk and therefore may not respond to optimal nutrition intake.¹³⁷ By contrast, a meta-analysis of studies that enrolled patients with short-term relative contraindications to EN found that patients randomised to receive PN within the first 24 hours of ICU admission had a significantly reduced risk of mortality compared with patients receiving standard care (i.e., no nutrition support for 2–5 days).¹³⁹ Recently published studies have also provided evidence to support timely initiation of SPN in critically ill patients with relative contraindications to ETF, ^140-142 such as improved nutrition intake^{140, 141, 143} and nutrition status (i.e., less muscle wasting),¹⁴⁴ shorter duration of mechanical ventilation (Early PN Trial),¹⁴² and fewer hospital-acquired infections (The Swiss SPN study).¹⁴⁰ Reducing the incidence of hospital-acquired infections¹⁴⁵ and dependence on mechanical ventilation with SPN are also likely to yield economic benefits.¹⁴⁶ Results from a recently published randomised controlled pilot study (TOP-UP trial)143 in mechanically ventilated adult ICU patients (BMI <25 or ≥35 kg/m2) who received SPN to reach 100% of their prescribed nutrition goal showed significantly increased energy and protein delivery over the first week of ICU admission, with no increased infection risk and non-significant trends in reduced hospital mortality and improved QOL and functional outcomes; these findings may warrant investigation in a suitably powered large-scale trial.
• It has also been suggested that RCTs in which many patients spend only a short time in the ICU may be too short to demonstrate a benefit with early SPN.¹⁴⁷ Indeed, a prospective multicentre multinational cohort study demonstrated that greater nutritional intake in high-risk longer-stay patients is associated with both lower mortality and shorter time to discharge alive—every 10% increase in protein intake relative to goal was associated with a significant 6.6% decrease in mortality for high-risk patients who remained in the ICU for at least 4 days, and 10.1% for those remaining in the ICU for at least 12 days (both p = 0.003).¹⁴⁸ The authors concluded that, as it is not possible to predict which patients are likely to have longer ICU stays, best clinical practice would be to feed all critically ill patients at target protein and calorie levels, while accepting that patients with less severe disease or at lower nutritional risk may not receive additional benefit from this approach. The decision to start SPN timely in ICU patients is also supported by other medical nutrition experts.¹⁴⁹
• ASPEN guidelines on nutrition support in the critically ill paediatric patient (i.e., age>1 month and <18 years) recommend that protein is provided early in the course of critical illness, to meet protein targets and promote positive nitrogen balance.¹²⁷ PN should be considered when ETF is not feasible or is contraindicated and may be used to supplement ETF in the first week of hospitalisation if the patient is severely malnourished or at risk of nutrition deterioration or if the patient is unable to advance on low volumes of ETF. The time when PN should be initiated to supplement insufficient EN is also unknown. The threshold for and timing of PN initiation should be individualised. On the basis of a single RCT (PEPaNIC),¹⁵⁰ ASPEN guidelines do not recommend initiation of PN within the first day of PICU admission. Current European guidelines on paediatric PN recommend that the decision to initiate PN depends on individual circumstances and the age and size of the infant or child. In the small preterm infant starvation for just one day may be detrimental and where it is clear that enteral feeds will not be tolerated soon PN must be instituted shortly after birth. However older children and adolescents may tolerate up to 7 days of inadequate nutrition depending on age, nutritional status, underlying disease, surgery, and medical intervention.²⁴ This document was however prepared before the completion of the new European (ESPGHAN) PN guidelines and the reader should refer to these new guidelines for the latest recommendations when published.

SURGERY

Patients undergoing surgery have a high risk of developing malnutrition and severe protein loss due to catabolism and prolonged periods nil by mouth

• Full recovery after surgery can take weeks or months, even after ambulatory surgery,¹⁵¹ and may be hindered by preoperative organ dysfunction, surgical stress and catabolism, pain, postoperative nausea and vomiting, ileus, fluid excess, semistarvation and immobilisation.^{151, 152} Interventions to reduce surgical stress and improve recovery include afferent neural blockade, medication, fluid and temperature management, nutrition, and exercise.¹⁵³
• Patients undergoing major surgery are at heightened risk for malnutrition due to hypermetabolism, inflammation, and protein catabolism.¹⁵⁴ Resting energy expenditure in surgical patients can increase by up to 40% within the first week of hospital admission, and exceeds 100% during the second week.^{155, 156} Furthermore, surgical patients often require periods of starvation before procedures and in the event of perioperative complications such as ileus and inability to tolerate oral or enteral feeding,^{155, 157} further increasing the risk for malnutrition. Nutritional status in patients undergoing abdominal surgery is also influenced by the presence of cancer or chronic diseases that affect nutrient metabolism.¹⁵¹ Malnutrition in surgical patients is an independent risk factor for postoperative complications such as infections and delayed healing, as well as increased mortality, length of hospital stay, and healthcare costs. ¹⁵⁵ Development of malnutrition during the hospital stay confers an even greater risk for negative outcomes, especially if the patient is already malnourished, has chronic disease, or is elderly.¹⁵⁵ A large evidence base shows that targeted nutrition therapy is associated with fewer infectious complications, reduced requirement for mechanical ventilation, decreased length of hospital stay, and lower mortality in surgical patients admitted to the ICU.¹⁵⁵

PN is an important modality for patients undergoing surgery to maintain nutrition status and prevent postoperative complications when nutritional targets cannot be met with oral and/or enteral nutrition

• ESPEN surgery guidelines state that nutritional support is indicated in surgical patients who are malnourished or at nutritional risk, in order to prevent and treat catabolism and malnutrition, and reducing the risk for postoperative complications.¹⁵⁸ ONS and ETF are preferred; however, PN should be administered as soon as possible if nutrition therapy is indicated and there is a contraindication for EN. When indicated, nutrition therapy is typically administered perioperatively to maintain nutritional status and should start as soon as nutritional risk is identified, in order to reduce the risk of postoperative complications. ^{158, 159} ESPEN recommends that perioperative nutritional support should also be initiated without delay in patients who are not expected to be able to eat for more than 5 days perioperatively and in patients who are expected to have low oral intake and who are not able to maintain more than 50% of recommended intake for more than 7 days.;¹⁵⁸ Furthermore, SPN is recommended if energy and nutrient requirements cannot be met by oral and enteral intake alone (<50% of caloric requirement) for more than 7 days. ESPEN considers improvement in nutritional status and functional recovery (including QOL) to be the most important nutritional goals in the late postoperative period.¹⁵⁸ ASPEN–SCCM critical care guidelines suggest that PN should be initiated in patients who have undergone major upper-GI surgery if ETF is not possible and the duration of therapy is anticipated to be ≥7 days.⁴⁶ However, unless the patient is at high nutrition risk, PN should not be started in the immediate postoperative period but should be delayed for 5–7 days.
• In adult surgical patients requiring PN, intravenous lipid emulsions (ILEs) are an integral part of the therapy. There is sufficient scientific evidence from clinical trials, systematic reviews, and meta-analyses to demonstrate that fish-oil containing ILEs offer advantages over standard ILEs (without fish oil). When PN is necessary, fish-oil containing ILEs should be considered, where possible. The intravenous lipid dose should not exceed 1.5g/kg/d, including non-nutritional lipid sources, and a minimum dose of ILEs should be provided to prevent essential fatty acid (EFA) deficiency. Based on available clinical data, it is recommended to provide 0.1–0.2 g fish oil/kg/d from lipid emulsions containing fish oil. Early initiation of PN should be considered in low-risk patients if it is anticipated that they will be unable to achieve 50–60% of their goal energy and protein intake within the first 5-7 days. For malnourished or high-risk patients, PN should be considered early if enteral or oral nutrition is contraindicated or insufficient.¹²¹
• In a multicentre randomised clinical trial involving 230 patients undergoing abdominal surgery, the effect of early versus late SPN was examined. The study found that early initiation of SPN (day 3 after surgery) seems to be a favourable strategy to reduce nosocomial infections among patients with high nutritional risk and poor tolerance to EN after major abdominal surgery. In addition, those in the early SPN group were found to have higher serum albumin and prealbumin levels, and fewer therapeutic antibiotic days.¹⁶⁰

Enhanced Recovery After Surgery (ERAS) protocols support the use of PN for certain patients undergoing surgery

• The ERAS protocol, introduced in 2001, was developed by academic surgeons in Europe to optimise outcomes in patients undergoing surgery.¹⁶¹ ERAS protocols have been (or are being developed) for many surgical procedures, including colonic/rectal resection, pancreaticoduodenectomy, gastric resection, bariatric surgery, liver resection, head and neck cancer surgery, and oesophageal resection (complete list available from http://www.erassociety.org). Each protocol lists the actions to be performed by different professionals and disciplines at different phases of the surgical patient’s journey(pre-admission, pre-, intra-, and post-operative).¹⁶¹
• ERAS guidelines on perioperative care following pancreaticoduodenectomy recommend that PN should be used preoperatively in patients who are significantly malnourished,if the enteral route is not feasible, and postoperatively in patients who cannot eat and drink normally and who are unable to tolerate EN.¹⁶² ERAS guidelines for head and neck cancer surgery state that PN is indicated in patients with a non-functioning gut and when enteral access is not possible.¹⁶³ For patients undergoing liver surgery, perioperative PN is indicated in severely undernourished patients who cannot be fed adequately through the oral or enteral routes; postoperative enteral EN or PN is indicated in malnourished patients and those with prolonged fasting due to complications (e.g., ileus >5 days or delayed gastric emptying).¹⁶⁴ The ERAS protocol for patients undergoing gastrectomy recommends that significantly malnourished patients should receive preoperative oral or enteral nutritional support and that PN may be warranted if the tumour prevents access to the duodenum. The guidelines highlight that patients undergoing total gastrectomy are likely to be at higher risk of malnutrition and cachexia during surgery than other groups of patients with abdominal cancer. Thus, it is expected that total calorie intake will be low for the first few days following surgery and that some patients with need additional nutrition support. Therefore, in patients who are clearly malnourished or are unable to meet 60% of daily requirements by postoperative day 6, nutrition support with ETF is indicated when oral intake is not possible and with PN if the gut is not functional or cannot be accessed.¹⁶⁵

CANCER

• As described in Section 1.1 (Identifying malnutrition), malnutrition is highly prevalent in patients with cancer and occurs in up to 70% of patients with solid tumours (e.g., pancreas, lung, gastric, colorectal, head and neck).¹⁶⁶ Weight loss is often the first presenting symptom in patients with cancer^{96, 167} and results from reduced food intake and metabolic derangements that promote the loss of lean muscle mass.¹⁶⁸ Cancer- associated weight loss impairs patients’ ability to receive, tolerate, and respond to anticancer therapy and predicts poor clinical outcomes independently of other risk factors.^169-173 Studies suggest that malnourished patients have a 2–5-fold higher risk of dying than patients with little or no evidence of malnutrition.^174-176 Two multivariate analyses have shown that undernutrition is an independent risk factor for complications in patients undergoing surgery for cancer, as well as increased mortality, length of hospital stay, and healthcare costs.^{8, 177, 178} Moreover, even minimal weight loss during chemotherapy and/or radiotherapy is associated with significantly shorter survival.¹⁷⁹
• In a narrative review on cancer-related malnutrition, the role of PN was examined in cancer patients with advanced disease or gastrointestinal complications. The review found that PN is a crucial therapeutic option for managing malnutrition in these patients, particularly when enteral nutrition is not feasible. It highlighted the benefits of PN in improving nutritional status, supporting recovery, and enhancing quality of life and survival outcomes.¹⁸⁰

• The aim of nutrition therapy in patients undergoing cancer treatment is to maintain or improve nutritional intake and reduce metabolic dysfunction in order to preserve skeletal muscle mass, physical function, and QOL, to prevent treatment-related complications, and to enable completion of planned treatment.¹⁶⁸ ESPEN and ASPEN guidelines highlight that their recommendations for nutrition therapy in patients undergoing surgery are equally applicable to patients with cancer who are undergoing tumour resection.^58,120 Moreover, the ESPEN surgery guidelines¹⁵⁸ highlight that management of nutrition in the preoperative period may be critical for long-term outcomes in patients with cancer.
• ESPEN and ASPEN have also published cancer-specific guidelines.^{181, 182} ESPEN cancer guidelines recommend that PN should be administered when ETF is not sufficient or feasible in cancer patients who are unable to eat adequately (who are likely to achieve <50% of their nutritional target for more than 1weeks or only 50-75% of their nutritional target for more than 2 weeks).¹⁸² According to the ASPEN cancer guidelines, nutrition therapy is recommended during active anticancer treatment for patients who are malnourished and who are unlikely to achieve adequate nutritional intake for 7–14 days; the enteral route is recommended for patients with a functioning gut.¹⁸¹
• Nutrition support is also indicated in patients undergoing cancer-related surgery, radiation therapy, or chemotherapy who experience complications or chronic adverse effects, such as severe radiation enteritis, malabsorption, mucositis, intractable vomiting, ileus, protracted diarrhoea, or GI graft versus host disease following haematopoietic stem cell transplantation (HSCT).^{182, 183} ESPEN guidelines on CIF in adults recommend that HPN should not be delayed in patients with radiation enteritis who are malnourished if oral or enteral nutrition is inadequate, noting that most patients requiring HPN because of radiation enteritis have type III IF^{42, 44} due to structuring and/or fistulising disease (often associated with surgical complications). Up to 20% of patients receiving pelvic radiotherapy are estimated to have chronic radiation enteritis,¹⁸⁴ 5% of whom develop CIF;¹⁸⁵ ESPEN guidelines note that HPN may be superior to surgical intervention for these patients.^{186, 187} Likewise, ESPEN cancer guidelines highlight that when PN is indicated in patients undergoing intensive chemotherapy and HSCT, it should be administered early in order to prevent or minimise further loss of weight and body cell mass.¹⁸² Patients undergoing HSCT are typically malnourished at admission, particularly those receiving allogeneic HSCT.¹⁸² Nutrition status may be further compromised because of the GI adverse effects associated with high-dose radiotherapy/chemotherapy (e.g., nausea, vomiting, mucositis, diarrhoea, and infections) which lead to weight loss, particularly in the first 40 days after admission, compromising clinical outcomes.^{188, 189}
• The ESPEN and ASPEN guidelines agree that PN may improve QOL and prolong survival in patients with incurable cancer (including cachectic patients) who are unable to receive nutrition via the oral or enteral routes.^{181, 182} It is noted that some cancer patients may survive many months or even years on TPN.^{182, 185, 190} However, both guidelines caution that the decision to implement PN in patients with incurable cancer should be taken in consultation with the patient (and close relatives or partners) and should consider both the expected benefit on QOL, and potentially survival, as well as the burden associated with nutritional therapy.^{181, 182} Ethical considerations for PN in patients with cancer relate to its use during the terminal phase of the disease. In general, the risks of PN are considered likely to outweigh the benefits in patients who are near the end of life (i.e., life expectancy of weeks rather than months).^{181, 182} However, it is important to note that provision of nutrition and hydration, whether by natural or artificial means, is considered essential in certain cultures.

• HPN is generally recommended in patients with CIF due to end-stage cancer if predicted life expectancy is greater than 2–3 months.^{32, 182, 191} Patients with incurable cancer may also enter a HPN program if they are unable to achieve nutritional targets with oral in take or EN and are at risk of dying from malnutrition. HPN is not contraindicated in patients with cancer who are no longer receiving anticancer treatment but should not be initiated if the patient is likely to die from the underlying disease rather than from malnutrition.
• ASPEN and ESPEN have not published PN guidelines specifically for paediatric patients with cancer, although the ASPEN Nutrition Support Practice Manual states that indications for PN in children with cancer are similar to those for adults.¹⁹²

KIDNEY DISEASE

Malnutrition is common in hospital patients with acute kidney injury (AKI) and is associated with an increased risk of in-hospital morbidity and mortality

• Malnutrition is frequent in hospital patients with AKI180 and is associated with increased morbidity (e.g., infection, poor wound healing, longer dependence on mechanical ventilation, and increased length of hospital stay) and mortality.^{126, 193-196} Together, ARF and critical illness result in intense and prolonged catabolism and sustained inflammation.^{126, 197} Continuous renal replacement therapy (CRRT), used to support critically ill patients with AKI, is associated with significant amino acid loss (10–15 g per day).¹⁹⁸

The goals of nutrition support for patients with AKI are the same as those for other critically ill patients

• ESPEN guidelines highlight that the primary goals of PN in adults with AKI are the same as for patients for other catabolic conditions in the ICU: to prevent protein-energy wasting (PEW) and further metabolic dysfunction, maintain skeletal muscle mass and nutritional status, enhance wound healing, support immune function, and reduce mortality.¹⁹⁹ Additional goals are to reduce systemic inflammation and oxidative stress and to improve endothelial function.¹⁹⁹ Thus, ESPEN¹¹⁹ and ASPEN–SCCM⁴⁶ recommendations for PN in critically ill patients (see subsection CRITICAL ILLNESS) apply to patients with AKI. Specifically, ESPEN guidelines state that PN is appropriate in AKI when ETF is not possible or not sufficient to meet nutritional targets.¹⁹⁹ PN should be slowly withdrawn when GI function returns, and ETF or oral nutrition introduced.

The goals of PN in patients with chronic kidney disease (CKD) are to prevent and treat PEW, provide optimum nutrition support, and attenuate disease progression

• Patients with CKD who are not on haemodialysis (HD) are unlikely to require PN outside of the ICU unless they have severe PEW or GI (or other) complications.¹⁹⁹ However, PEW has been reported in up to 70% of adults with CKD who are on HD and is an independent predictor of morbidity and mortality in these patients.^{199, 200} The actual prevalence of PEW may be even higher, as published studies typically include only clinically stable patients.²⁰⁰ The risk and severity of PEW increase the longer a patient remains on HD,²⁰¹ due to declining nutritional intake and metabolic dysfunction associated with renal failure.^{202, 203} GI symptoms such as constipation, impaired gastric emptying, and motility disorders, which occur frequently in patients with CKD, also contribute to PEW.²⁰⁰
• The indications for PN in patients with CKD are similar to those for patients without kidney disease, such that PN should only be considered in malnourished patients requiring nutritional support if oral or enteral intake are not feasible or insufficient to meet nutritional targets.²⁰⁴ ESPEN considers PN to be a “desired choice” in patients with conservatively treated CKD who cannot achieve adequate nutrition through oral intake or ETF or who have severe GI complications that preclude enteral access.¹⁹⁹ However, PN should be slowly withdrawn when GI function returns and ETF or normal nutritional intake resumed. ESPEN guidelines note that special attention should be given to surgical patients with CKD who require PN during the perioperative period.²⁰⁴ The goals of PN in patients with CKD are to prevent/treat PEW in order to prevent cachexia, provide optimum nutrition support, and attenuate disease progression through protein or phosphate restriction.¹⁹⁹
• ESPEN states that the decision to initiate PN in acutely ill patients with CKD on HD should be based on the same criteria as for patients with ARF.²⁰⁴ Intradialytic PN (IDPN), which provides nutrition support directly via the venous access for HD, is recommended for non-acutely ill patients who are exhibiting severe PEW and are unable to comply with ONS.¹⁹⁹ Many studies, including RCTs, have demonstrated improvements in nutritional parameters with IDPN¹⁹⁹ and it is considered a safe and convenient treatment for patients who cannot meet their nutritional needs orally.²⁰⁰ However, EN can be necessary if ONS or IDPN do not improve nutritional status.²⁰⁴ Indeed, ESPEN guidelines point out that ONS and IDPN are unlikely to be sufficient in patients with severe PEW in whom spontaneous intake is <20 kcal/day (or in stress conditions) and are therefore not recommended. ESPEN recommends central venous PN in these patients when ETF is not possible or sufficient to meet nutritional targets. ASPEN guidelines on adult renal failure state that IDPN should not be used as a nutritional supplement in malnourished patients with stage V CKD (i.e., kidney failure, dialysis or kidney transplant needed). The 2017 ASPEN consensus recommendation on the appropriate use of PN recommend that IDPN should not be used as the sole source of nutrition support in malnourished patients with CKD¹⁴ but should be considered for adult and paediatric patients who are unable to tolerate adequate oral intake or ETF.¹⁷
• ESPEN guidelines note that the prevalence and consequences of PEW are similar for patients on continuous ambulatory peritoneal dialysis (CAPD) and HD. For patients on CAPD, ESPEN guidelines highlight that, based on current data, PN should be limited to those who are malnourished and stressed, or with severe encapsulating peritonitis, when nutritional requirements cannot be ensured by ONS or ETF.¹⁹⁹
• Finally, ESPEN guidelines recommend that, in patients undergoing kidney transplantation, early intake of normal food or ETF should occur within 24 hours of surgery, and, if necessary PN should be combined with ETF (SPN).⁸

LIVER DISEASE

In patients with acute liver failure, PN ensures provision of sufficient energy and optimises protein synthesis when ETF is inadequate

• Acute liver failure results in severe metabolic dysfunction and is almost always accompanied by multiple organ failure.²⁰⁵ Resting energy expenditure in patients with acute liver failure is increased 1.2–1.3-fold compared with healthy individuals. Nutritional therapy in these patients therefore aims to ensure adequate provision of energy and optimal rates of protein synthesis by providing sufficient intake of protein or amino acids.²⁰⁵ ESPEN guidelines state that artificial nutrition is indicated in patients with acute liver failure, irrespective of nutritional status, when normal oral nutrition is not likely to be resumed within 5–7 days, and that PN is a safe second-line option to adequately feed patients in whom ETF is not possible or sufficient.²⁰⁶ ASPEN–SCCM critical care guidelines state that ETF should be used in preference to PN in ICU patients with acute and/or chronic liver disease.⁴⁶

Malnutrition is highly prevalent in patients with chronic liver disease, due to decreased nutrient intake, metabolic derangement, and malabsorption, and is associated with a poor prognosis

• Patients with chronic liver disease are particularly susceptible to malnutrition because of central role of the liver in maintaining normal nutrition and energy balance and the synthesis and degradation of key proteins.²⁰⁷ Chronic liver disease is also associated with poor appetite, leading to a reduction in nutritional intake and further compromising nutrition status.²⁰⁷ Up to 90% of patients with cirrhosis, which is the most common indication for transplantation, are malnourished.^207-209 Protein malnutrition in patients with liver disease is associated with higher rates of complications, mortality, and reduced survival following liver transplantation.^{206, 210, 211}

PN should be administered in patients with cirrhosis who are moderately or severely malnourished and who cannot be fed adequately with oral or enteral nutrition

• ESPEN guidelines highlight that PN is safe for patients with cirrhosis and improves mental recovery in those with hepatic encephalopathy.²⁰⁶ PN should be started immediately in moderately or severely malnourished patients with cirrhosis who cannot be adequately fed by diet and ONS or ETF and when fasting exceeds 72 hours.²⁰⁶ Furthermore, PN should be considered in patients with unprotected airways and hepatic encephalopathy if cough and swallow reflexes are impaired. Early postoperative PN is indicated for patients with cirrhosis who are undergoing surgery if they cannot be adequately nourished by diet and ONS or ETF.²⁰⁶
• ESPEN guidelines highlight that PN improves nutrition status and liver function in patients with alcoholic steatohepatitis (ASH) and should be started immediately in moderately or severely malnourished patients who cannot be fed sufficiently with diet and ONS or ETF²⁰⁶ and should also be initiated when fasting exceeds 72 hours.

PN is safe and effective for patients undergoing liver transplantation

• The ESPEN liver disease guidelines state that perioperative PN (including during liver transplantation) is safe and reduces the rate of postoperative complications.²⁰⁶ In these guidelines ESPEN recommends that postoperative nutrition should be provided early after liver transplantation, and that PN is a secondary option to ETF. ²⁰⁶

PANCREATITIS

PN should be administered early in patients with severe pancreatitis when ETF is not feasible or sufficient

• Metabolic derangements in patients with acute pancreatitis (or an acute episode of chronic pancreatitis) can promote hypermetabolism and negative nitrogen and energy balance, leading to progressive nutritional decline.²¹² Although the impact of nutrition status on the prognosis for patients with acute pancreatitis is not completely understood, it is expected to be same as in other critical illnesses.^{213, 214} Patients with severe pancreatitis, which is characterised by the development of major organ failure, are more likely to require nutrition support than patients with mild disease.²¹²
• ESPEN pancreatitis guidelines state that nutritional support is indicated in acute pancreatitis if the patient is unable to feed orally; EN is preferred to PN and should be initiated early (within 24-72 h). ²¹⁵ PN or ETF are unlikely to be required in patients with mild acute pancreatitis unless malnutrition is evident. In these cases, PN is indicated if ETF is not feasible—because of intestinal failure, prolonged ileus, complex pancreatic fistulae, abdominal compartment syndrome, for example—or is not tolerated.²¹⁵However, If it is anticipated that ETF cannot be started early or will not be fully tolerated, PN (preferably SPN) should be started as soon as possible and decreased as ETF tolerance increases.²¹⁵ ESPEN guidelines²¹⁵ note that PN does not significantly stimulate pancreatic secretion or impair pancreatic function.^216-218
• ASPEN–SCCM critical care guidelines suggest that, based on expert consensus, PN should be considered in patients with severe acute pancreatitis after 1 week from the onset of the attack when ETF is not feasible.⁴⁶ Similarly, International Consensus Guidelines on pancreatitis²¹⁹ recommend that if nutrition support is indicated, such as in mild-to-moderate disease with complications, severe disease, or fasting >5–7 days, PN should be used when ETF is contraindicated or not tolerated. The guidelines also note that PN does not have any complications specific to patients with pancreatitis.²¹⁹ Nutrition support should be started early in patients with severe pancreatitis.

Preoperative PN is indicated in patients with chronic pancreatitis who are malnourished and is also indicated in those patients with gastrointestinal obstruction or complex fistulating disease

• Chronic pancreatitis is a serious disease that can have long-term and life-threatening consequences, such as diabetes and pancreatic cancer, and can severely impair QOL.²²⁰ The incidence in Europe is around 5–10 cases per 100,000, and prevalence approximately 120 per 100,000 population.²²¹ Alcohol is the causal factor in 60–70% of cases.²²² PEW is common in these patients, particularly during the terminal phase, and is partly due to pain-induced anorexia and ongoing alcohol misuse.²²³ Furthermore, resting energy expenditure is increased in up to half of all patients with chronic pancreatitis.²²²
• ESPEN guidelines²¹⁵ and United European Gastroenterology guidelines²²⁰ state that in patients with chronic pancreatitis, PN is indicated for gastric outlet obstruction secondary to duodenal stenosis and in patients with complex fistulating disease. The United European Gastroenterology guidelines also state that PN is also indicated in patients with apparent severe malnutrition prior to pancreatic surgery if ETF is not possible.²²⁰