3.3.2.2 NUTRITIONAL STATUS

• ESPEN oncology guidelines^{168, 182} highlight that that PN has been shown to maintain nutritional status in patients with severe intestinal insufficiency caused by radiation enteritis, chronic bowel obstruction, SBS, peritoneal carcinomatosis, or chylothorax.^{182,185,269,270}

CRITICAL ILLNESS AND SURGERY

• In the large, multicentre, single-blind RCT conducted by Doig and colleagues (2013)¹⁴⁶ to evaluate the nutritional and clinical benefits of early PN in critically ill adults with a short-term relative contradiction to early ETF,132 patients randomised to receive standard care (usual clinical practice in individual ICUs), experienced significantly greater muscle wasting (0.43 vs 0.27 increase in subjective global assessment [SGA] score per week (mean difference, 0.16; 95% CI 0.038–0.28; p = 0.01)) and significantly greater fat loss (0.44 vs 0.31 increase in SGA score per week; mean difference, 0.13; 95% CI 0.01–0.25; p = 0.04) during their ICU stay than patients receiving PN within 24 hours of admission. This suggests that early administration of PN may protect against both muscle wasting and fat loss. In addition, mid-arm circumference was significantly reduced by day 2 in patients receiving standard care (0.2 cm loss) whereas patients receiving early PN did not experience any reduction (0.0 cm loss; p = 0.04); however, these differences did not remain significant for the whole of the ICU stay (0.8 vs 0.4 cm loss per week; p = 0.28).
• An open-label single-centre RCT conducted by Wu and colleagues (2016) evaluated the efficacy and safety of early SPN (within 24 hours of surgery) in 80 patients undergoing oesophagectomy. Patients receiving SPN to meet caloric targets, but not those receiving ETF alone, had preserved fat free mass (1.46 ± 2.97 vs −2.08 ± 4.16 kg) and body weight (0.18 ± 3.38 vs −2.15 ± 3.19 kg; p < .05) relative to preoperative measurements.²⁷¹
• Bauer and colleagues carried out a double-blind RCT to determine whether early SPN (ETF + PN) improves nutrition status and clinical outcomes compared with ETF alone.²⁷² This study included 120 critically ill adults (60 in each group) who were admitted to the ICU for at least 3 days and were expected to survive for at least 3 days; patients must have consumed <20 kcal/kg daily. Patients with a contraindication to ETF or PN were excluded. Patients received their assigned therapy for 4–7 days after initiation of nutritional support. Overall, 32% of patients were moderately malnourished and 9% were severely malnourished. Nutritional status, measured using levels of retinol-binding protein (RBP) and prealbumin, was significantly higher in patients receiving SPN; RBP and prealbumin corrected more rapidly from day 0 to day 7 in the SPN group than in the ETF group (p = 0.0496 and p = 0.0369, respectively), as did levels of Vitamin E (p = 0.031).
• A retrospective analysis of data from 90 consecutive patients who underwent total gastrectomy for malignancy found that post-operative nutrition support with TPN reduced in-hospital weight loss and attenuated weight loss post discharge.²⁷³ In this study, 42% of patients received postoperative TPN and 53% received IV fluids alone. At preoperative assessment, patients receiving TPN were significantly more malnourished than those who received IV fluids. However, the latter patients lost significantly more weight during their hospital stay (5.2 kg, vs 3.1 kg in those on TPN; p = 0.008). Furthermore, 69% of patients receiving only IV fluids lost a severe amount of weight (measured using Blackburn criteria) compared with 34% of the TPN group (p = 0.01). Patients who received only IV fluids continued to lose significantly more weight after discharge (7.5 kg, vs 2.9 kg in TPN patients; p = 0.01). From pre-surgery to outpatient follow-up (3 months), patients who received IV fluids lost an average of 17.8 kg, compared with 9.6 kg in TPN patients (p < 0.01).
• Liebau and colleagues evaluated the effects of supplementing EN with parenteral amino acids (equivalent to 1 g/kg per day), infused over 3 hours, on whole-body protein turnover in critically ill patients during their first week in theICU.²⁷⁴ Patients were assessed at baseline during ongoing nutrition (n = 13) and then during amino acid supplementation if they were still in the ICE 2–4 days later (n = 7). Parenteral amino acid supplementation significantly improved protein balance at both timepoints (p = 0.001 and p = 0.0018, respectively), attributed to increased protein synthesis, which attained significance during the first measurement (p = 0.007). Importantly, amino acid oxidation did not increase during the 3-hour amino acid infusion. There was also a positive correlation (r = 0.80; p < 0.0001) between total amino acids and/or protein administered and whole-body protein balance.

Use of PN (TPN and SPN) in critically ill patients may promote the recovery of immune function and improve nutritional status

• Yao and colleagues (2005) evaluated the effect of perioperative PN on nutritional status and postoperative outcome in 32 severely malnourished patients with CD who underwent bowel surgery for obstruction; 16 patients received perioperative PN and 16 received IV fluids alone (isocaloric diet).²⁷⁵ PN was started 1 week before surgery and continued for 2 weeks after. BMI increased significantly in the PN group (from 13.9 ± 0.6 to 15.3 ± 0.7 kg/m², p = 0.02) but not in the IV fluids group. In addition, serum immunoglobulin M levels, which had increased significantly in both groups before surgery (p = 0.04), returned to normal 3 weeks after surgery in patients receiving PN (p = 0.02) but not for those receiving IV fluids only, suggesting that PN had a positive effect on humoral immunity.²⁴⁴ The rate of postoperative complications was similar in both groups, but at 6 months’ follow up, more patients in the PN group had returned to work, suggesting that perioperative PN had a long-lasting effect on recovery.²⁷⁵
• A prospective RCT in China reported by Fan and colleagues compared the effects of SPN (ETF + PN), ETF alone, and PN alone on immune function, nutritional status, complications, and clinical outcomes in 120 patients with undergoing surgery for severe traumatic brain injury (40 patients in each group). Measures of immune function (certain T-lymphocyte subsets and plasma immunoglobulin) were significantly increased from baseline after 20 days of treatment in patients receiving SPN (p < 0.01) and were significantly higher than for patients receiving PN or ETF alone (p < 0.05 and p < 0.01). Nutritional status (Nutritional Risk Screening tool) was also significantly higher in the SPN group and the EN alone group (both, p < 0.01) except for serum prealbumin which was higher in the SPN group.²⁷⁶
• Jin and colleagues examined the impact of post-operative parenteral nutrition in patients with gastric cancer. In this randomised study, 80 patients were assigned to either the intervention group, which received 1 litre of peripheral intravenous nutrition (700 kcal), or the control group, which was given 1 litre of isotonic electrolyte solution. The parenteral nutrition began on the first day after surgery and continued for 4 to 8 days. Results showed that levels of albumin, prealbumin, and haemoglobin were significantly higher in the intervention group compared to the control group. Additionally, patients in the intervention group reported improved Quality of life and higher scores on the Self-rating Scale of Life Quality, along with lower scores on the Hospital Anxiety and Depression Scale and the Patient Health Questionnaire-9. Immunological markers also improved, with significantly higher percentages of CD3+ and CD4+ cells and an increased CD4+/CD8+ ratio, while CD8+ cell levels remained unchanged.²⁷⁷
• A randomised controlled trial enrolled 23 critically ill ICU patients on day 3 of admission who were receiving less than 60% of their energy target through enteral nutrition (EN) alone. Patients were randomised to either continue EN or receive SPN. Over the five-day intervention, the SPN group (n = 11) had significantly higher energy (median 24.3 vs. 17.8 kcal/kg/day, p < 0.001) and protein intake (1.11 vs. 0.69 g/kg/day, p < 0.001) than the control group, resulting in a significantly less negative energy balance by day 9 (p = 0.0027). The SPN group also showed signs of improved immune response, including lower serum IL-6 (p = 0.024), IL-1β, IL-10 levels, and reduced TNF-α secretion by PBMCs (p = 0.018). Muscle mass loss from day 4 to day 15 tended to be lower in the SPN group (−16% vs. −23%, p = 0.06).²⁷⁸

PAEDIATRIC PATIENTS

Timely protein and energy intake is associated with improved developmental outcomes

• A systematic review and meta-analysis by Moyses and colleagues (2013) showed that early administration of PN improves short-term growth outcomes in preterm infants.²⁷⁹ Eight RCTs (n = 533) and 13 observational studies (n = 1,796) met the inclusion criteria. The analysis showed that early PN reduced the time to regain birth weight by 2.2 days (1.1–3.2 days) in RCTs and 3.2 days (2.0–4.4 days) in observational studies (both p < 0.001). Furthermore, maximum percentage weight loss was lower with early PN by (1.7–4.5) percentage points in RCTs and by 3.5 (2.6–4.3) in observational studies (both p < 0.001). Early PN also improved weight at discharge or 36 weeks postmenstrual age by 14.9 g (5.3–24.5 g) in the observational studies (p = 0.002); however, no benefit was shown for length or head circumference.
• An open-label randomised controlled multi-intervention trial found that supplementing the enteral supply of energy, protein, essential fatty acids, and vitamin A with PN in very low birthweight (VLBW) infants (<1,500 g) resulted in postnatal growth in-line with birth percentiles for weight and head circumference.²⁸⁰ The SPN group had a lower mean birth weight (p = 0.03) and contained a higher proportion of infants who were small for gestational age (p = 0.04) than the group who received EN alone. Mean energy and protein delivered in the SPN group over the first 4 weeks of life were significantly higher in the SPN group (139 vs 126 kcal/kg per day [p < 0.001] and 4.0 vs 3.2 g/kg/day [p < 0.001], respectively). Infants receiving SPN regained birth weight significantly faster (p = 0.001) and maintained their z-scores for weight and head circumference from birth to 36 weeks’ postmenstrual age (both p < 0.001). Median growth velocity was also significantly higher in the SPN group (17.4 [interquartile range 16.3–18.6] vs 13.8 [13.2–15.5]] g/kg per day; p 0.001). The proportion of growth-restricted infants at this time point did not differ from baseline in the SPN group (11 of 23 infants) but increased in the control group from 4 to 13 infants (n = 21).
• An open-label, multicentre, non-comparative Phase 3 trial by Rigo and colleagues in preterm infants evaluated PN (administered for 5–10 consecutive days) containing amino acids and energy intake within the range of “aggressive” nutrition recommendations for VLBW infants,²⁸¹ Mean nutrient intake and mean weight gain were within the range recommended by guidelines²⁸² for preterm infants.
• A chart review of daily protein and energy intakes during the first 4 weeks of life in 148 extremely LBW infants showed that, after adjusting for confounding variables, week 1 energy and protein intakes were both independently associated with improvement in score on the Mental Development Index (MDI),²⁸³ such that every 42 kJ (10 kcal)/kg per day was associated with a 4.6-point increase in the MDI and each g/kg per day in protein intake was associated with an 8.2-point increase. Furthermore, higher protein intake was associated with a lower likelihood of body length <10th percentile.²⁸³

• Morisaki and colleagues (2014) analysed registry data 4,005 hospitalised Very LBW preterm infants from the Neonatal Research Network of Japan to determine whether PN had any benefits on growth in infants who reached full enteral feeding by day 14.²⁸⁴ PN was administered to 40% of infants. After adjusting for maternal, infant and institutional characteristics, infants who received PN had greater weight gain (0.09 SD; 95% CI 0.02–0.16) and head growth (0.16 SD; 95% CI 0.05–0.28), and lower odds of extra-uterine growth restriction by head circumference (OR 0.66, 95% CI: 0.49, 0.88), suggesting that even infants who can be enterally fed within 2 weeks may benefit from SPN.

• A Cochrane review evaluated whether higher versus lower parenteral amino acid intake improves growth and disability-free survival in newborns receiving parenteral nutrition. Higher amino acid intake was linked to a reduced risk of postnatal growth failure (<10th percentile at discharge), though the quality of evidence was very low. It also reduced the time needed to regain birth weight (MD –1.14 days, 95% CI –1.73 to –0.56; n = 950) and increased head circumference growth at discharge (MD 0.09 cm/week, 95% CI 0.06 to 0.13; n = 315). However, effects on other growth parameters and anthropometric z-scores were inconsistent. Higher amino acid intake was also associated with improved protein and nitrogen balance.²⁸⁵
• A Cochrane review conducted by Trivedi and colleagues (2013) evaluated the impact of early versus late administration of amino acid solution, with or without other PN components, on various outcomes in preterm infants. Evidence for improved nitrogen balance with amino acid supplementation was seen in four of the seven studies included.²⁸⁶ One of these studies (Tang et al. 2009²⁸⁷) found that infants who received amino acids with 24 hours of birth had shorter PICU stay (by 5.5 days), fewer days to enteral nutrition (by 4.2 days), shorter duration of admission (p < 0.05) and fewer days to regain birth weight (11.7 vs 14.1 days).
• In contrast, a 2018 Cochrane review by Osborn and colleagues examined the efficacy and safety of early versus late intravenous amino acid administration in preterm infants (<37 weeks gestation) receiving PN. The review found low-certainty evidence suggesting little to no difference in growth or neurodevelopmental outcomes between early and late amino acid administration. However, early amino acid (within 24 hours of birth) was associated with a notable increase in positive nitrogen balance. The authors noted that the included RCTs had small sample sizes and significant clinical heterogeneity.²⁸⁸

CANCER

• Cachexia (skeletal muscle loss with or without fat loss) is common in patients with upper GI cancer.²⁸⁹ Pelzer and colleagues (2010) showed a positive effect of PN on measures of nutritional status in patients with advanced cancer and progressive cachexia. In this Phase 2 study, 32 patients with advanced pancreatic cancer and progressive cachexia who were experiencing ongoing weight loss despite ETF received additional overnight HPN for 5 out of 7 days. Nutritional status was measured using bioelectrical impedance analysis (BIA) including phase angle, which is a potential predictor of survival in cancer patients,²⁹⁰ the ratio of extracellular mass (ECM) to body cell mass (BCM) index, and BMI. Median treatment duration was 18 weeks (8–35 weeks). Nearly half of patients had a temporarily improved phase angle (the main parameter). Median BMI increased from 19.7 to 20.5 kg/m2 during nutrition therapy, median ECM/BCM index decreased from 1.7 to 1.5, and phase angle increased by 10% (from 3.6 to 3.9). A follow-on study involving a larger patient cohort is currently being conducted to correlate the level of nutritional improvement with overall survival and QOL.²⁸⁹
• Richter and colleagues (2012) prospectively evaluated the addition of PN during chemotherapy in patients with advanced pancreatic cancer in Germany.²⁵⁶ Two groups of patients were retrospectively defined based on survival following initiation of PN: Group 1, ≥5–>37 months (n = 10) and Group 2, 1–4 months (n = 7). Eighty percent of patients in Group 1 showed an increase in body weight with initial PN and the other patients after dose adaption. This positive effect of PN was also confirmed at the cellular level using BIA (i.e., phase angle), BCM, ECM, cell content, and the ECM/BCM index. Moreover, results were reproducible in two patients who received two or three episodes of PN: when PN was interrupted, all BIA parameters worsened before improving when PN was restarted. In Group 2, PN was started in the late stage of the disease (i.e., after failure of final chemotherapy). Importantly, the results indicated that weight loss could be reversed, even if the effects on body weight and BIA parameters were less pronounced than in patients in Group 1.²⁹¹
• A bicentric single-arm clinical trial assessed the impact of early 7-day SPN on bioimpedance vectorial analysis derived body composition, handgrip strength, and serum prealbumin in 131 hypophagic, hospitalised cancer patients at nutritional risk. SPN significantly improved body composition (phase angle +0.25, p = 0.001; standardised phase angle +0.33, p = 0.002), handgrip strength (+2.1 kg, p < 0.001), and serum prealbumin levels (+3.8 mg/dL, p < 0.001). Multivariable analysis showed that improvements in bioimpedance vectorial analysis parameters were more pronounced in the 76.3% of patients who met both protein and energy requirements.²⁹²

• In a randomised controlled trial by Obling and colleagues (2019), patients with incurable gastrointestinal cancer and nutritional risk were assigned to either standard nutritional care with dietetic counselling (non-sHPN) or to counselling plus supplemental home parenteral nutrition (sHPN). Over 24 weeks, the sHPN group showed greater gains in FFM and fat-free mass index. By week 12, 69% of the sHPN group had increased FFM compared to 40% in the non-sHPN group (p < 0.01). Quality of life was also significantly better in the sHPN group at 12 weeks (p < 0.05).²⁹³
• A prospective single-arm study involving 65 patients evaluated the effects of HPN in individuals with advanced cancer undergoing chemotherapy. Over the 90-day period, significant increases were observed in body weight, BMI, and oral intake of calories and protein (p < 0.01). The percentage of patients with a BMI below 18.5% declined from 33.8% at baseline to 30.7%. By day 90, there were notable improvements in the proportion of well-nourished patients, Karnofsky performance status, and the modified Glasgow prognostic score (p < 0.01). Additionally, total body water decreased (p = 0.04), while fat mass increased (p = 0.04). The percentage of patients with a Karnofsky score above 70 rose from 66.2% to 77%. Reactance, resistance, and phase angle showed consistent associations with survival across all timepoints. Furthermore, PG-SGA category A at 90 days was a strong predictor of survival (p < 0.0001).²⁹⁴
• Culine and colleagues (2014) reported a prospective observational study in 767 patients with cancer (65.3% with metastatic disease) to evaluate the benefit of HPN.²⁹⁵ After 28 days of HPN, mean body weight had increased by 2.5% (p < 0.001), with most patients (67%) gaining weight. The nutrition status (measured using the Nutrition Risk Index and serum albumin) also increased significantly (p < 0.001), as did glycaemia and serum haemoglobin (both p < 0.05).²⁹⁵
• A longitudinal study reported by Vashi and colleagues (2014) of patients with advanced cancer (various tumour types) found significant improvements in nutritional status, measured by increased body weight from baseline at 1 month (from 61.5 to 63.1 kg; p = 0.03), 2 months (from 57.6 to 60 kg; p = 0.04), and 3 months (from 61.1 to 65.9 kg; p = 0.04) and in SGA scores (p < 0.05 for all time points), irrespective of tumour type.²⁹⁶ Each month of HPN was associated with 1.3 kg increase in body weight (p = 0.009).
• Lundholm and colleagues conducted a randomised prospective study in 309 cancer patients with progressive cachexia (primarily due to GI tumours), to evaluate whether specialised nutrition-focused care (including HPN) improved integrated whole-body metabolism and functional outcome; patients were receiving systemic anti-inflammatory treatment and erythropoietin.²⁹⁷ Approximately, 50% of patients received HPN; the other half were dependent on spontaneous oral intake alone. The intent-to-treat analysis showed an improvement in energy balance for HPN patients (p < 0.03). Furthermore, the as-treated analysis showed an improved energy balance (p < 0.001), an increase in body fat (p < 0.05; which was lower in the HPN group than in the control group at baseline), a greater maximum exercise capacity (p < 0.04), and a trend toward increased metabolic efficiency at maximum exercise capacity (p < 0.06) for patients receiving HPN, suggesting that nutritional support may protect both integrated metabolism and metabolic function in patients with progressive cancer-related cachexia.²⁹⁷
• Senesse and colleagues (2015) conducted a prospective observational study in 370 patients with GI cancer (71% with metastatic disease), to evaluate the impact of HPN on QOL and nutritional status.²⁹⁸ HPN was used to supplement oral intake in 84% of patients. After 28 days of HPN, body weight improved by 2.7% from baseline (p < 0.001) while nutrition risk decreased (NRI scores, 3.2 ± 1.1 vs 2.8 ± 1.3, p = 0.003).
• Drissi and colleagues conducted a large retrospective analysis of data from 53 oncology centres in Germany, to determine current PN practice in the outpatient setting, with a view to improving patient-centred nutritional care. Two patient cohorts were analysed: all oncology patients treated during the fourth quarter of 2004, and all patients administered PN during the whole study period (July 2010–March 2011). In the first cohort, 2.46% (n = 626) of 25,424 cancer patients received PN; the most frequent diagnosis was gastric cancer. In the second cohort (n = 1,137), impaired GI motility was a frequent indication for PN—60.3% of patients received SPN and 37.3% received TPN (2.4% missing data). Patients in the second cohort showed a stable or slowly increasing BMI (from 21.6 ± 3.8 to 21.8 ± 3.5 kg/m2): patients on TPN had a mean increase in BMI points of 0.4 ± 1.6 (range −6.0 to 6.1) during the observation period whereas patients on SPN had an increase of 0.3 ±1.5 (−6.9 to 7.0).²⁹⁹

A number of early paediatric RCTs examined the impact of PN on nutritional status in children with cancer.¹⁹² These studies show that in primarily well-nourished cancer patients, administration of PN for 17–104 days significantly increases body weight, nitrogen balance, and anthropometric measures of nutrition status, such as arm-muscle circumference and triceps skinfold measurement. PN also promoted maintenance of total leukocyte and absolute granulocyte counts compared with those of control groups.^300-302 Similarly, early non-randomised studies in which PN was administered for approximately 4 weeks showed a significant increase from baseline in anthropometric measures (e.g., arm muscle area, triceps and subscapular skinfold measurements, and percentage of diagnosis weight) as well as serum transferrin, albumin, prealbumin, and RBP levels.^{192; 303-307}

Initiating TPN in the early post-transplant period in paediatric patients undergoing autologous HSCT may improve nutritional status and contribute to recovery of haematopoiesis. Wędrychowicz and colleagues (2010) evaluated the impact of TPN on nutritional status in 22 children and adolescents (median age 5.4 years) undergoing high-dose chemotherapy followed by autologous HSCT.³⁰⁸ Patients received isoenergetic and isonitrogenous TPN with electrolytes (based on individual requirements). Mucositis was observed in 82% of patients. Assessment of nutrition parameters showed an increase in serum albumin levels after TPN (p 0.0005). Additionally, TPN duration correlated with recovery of leukocytes (p = 0.05) and platelets (p = 0.04).

KIDNEY DISEASE

• PEW is a significant cause of morbidity and mortality in patients on maintenance HD.³⁰⁹ A multicentre open-label Phase 4 RCT conducted by the German IDPN-Trial group showed that IDPN, administered three times weekly in a 16-week intervention resulted in a statistically significant and clinically relevant increase in mean serum prealbumin (a surrogate marker for outcome and survival in HD patients with PEW) and was superior to nutritional counselling.³¹⁰ IDPN significantly increased serum prealbumin (p < 0.05) compared with nutritional counselling, with rapid increases during the first 16 weeks of therapy and stabilising thereafter. Analysis of the full dataset (n = 83) showed that 40.0% of 39 patients receiving IDPN had a relevant (i.e., ≥15%) increase in prealbumin from baseline at week 4, compared with 20.5% of 44 patients in the control group, and more patients on IDPN achieved an increase in prealbumin >30 mg/L at week 16 (48.7% vs 31.8%). Furthermore, prealbumin response to IDPN was greater for patients with moderate malnutrition (SGA score B) than with severe malnutrition (SGA score C).
• Cano and colleagues (1990) conducted a non-randomised study to evaluate the impact of nutrition delivered by peridialytic PN (PDPN) in 26 malnourished patients on HD.³¹¹ Compared with control patients, patients receiving PDPN showed increases in body weight (p < 0.01), arm-muscle circumference (p < 0.02), serum transthyretin and albumin concentrations (p < 0.05), interdialytic creatinine appearance (p < 0.01), skin-test reactivity (p < 0.02), plasma leucine (p < 0.05) without modifications of other amino acids, and plasma apolipoprotein A-I (p < 0.01) but without significant changes in levels of apolipoprotein B, cholesterol, triglyceride, or phospholipid.
• Navarro and colleagues (2000) investigated the effects of intradialytic amino acid supplementation on nutritional status in a randomised study of 17 stable HD patients; 10 were randomised to receive amino acid supplementation.³¹² After 3 months, patients receiving amino acid supplementation had a significant improvement from baseline in protein catabolic rate and serum albumin and transferrin (all p < 0.05) whereas significant changes in these measures were not observed in control patients. Furthermore, these improvements occurred without any change in the dialysis dose.
• A prospective randomised controlled trial investigated the impact of IDPN in 38 haemodialysis patients with protein-energy wasting. Participants were assigned to either an IDPN group, receiving a concentrated fish-oil-based 3-in-1 parenteral nutrition formula during dialysis for 3 months, or a control group that received intensive dietary counselling once weekly over the same period. After 3 months, the IDPN group showed a significant increase in serum albumin levels compared to the control group (from 3.5 ± 0.3 to 3.8 ± 0.2 vs. 3.6 ± 0.3 to 3.5 ± 0.3 g/dL, respectively; p = 0.01). Additionally, the IDPN group demonstrated improvements in spontaneous dietary intake (p = 0.04), body weight (p = 0.01), and malnutrition inflammation score (p = 0.01), while no such changes were observed in the control group. Although muscle mass, strength, serum prealbumin, interleukin-6, high-sensitivity C-reactive protein, and acylated ghrelin did not differ significantly between groups, leptin levels increased in the control group after 3 months (p = 0.03). At 6 months, serum albumin in the IDPN group remained significantly higher than baseline (p = 0.04).³¹³
• A multicentre retrospective study assessed the effectiveness and safety of IDPN on various nutritional outcomes in 56 patients. The malnutrition inflammation score significantly decreased from a baseline average of 16.4 (95% CI: 15.3–17.65) to 14.3 (95% CI: 12.8–15.8) at the final follow-up during IDPN treatment (p = 0.0019). Additionally, IDPN led to a significant reduction in the prevalence of PEW, from 89.3% at baseline to 66.1% (p = 0.0023). Laboratory parameters also showed improvement, with significant increases in serum albumin (p = 0.0003) and total protein levels (p = 0.0024). Importantly, patients who received IDPN for longer than three months experienced greater improvements in nutritional status, as measured by the malnutrition inflammation score.³¹⁴

• Orellana and colleagues (2005) evaluated the benefit of providing supplementary nutrition via IDPN to adolescent patients on maintenance HD with PEM.³⁰⁹ IDPN was administered to all patients with >10% weight loss and who were at <90th percentile of ideal body weight. Nine patients received IDPN three times weekly for 3–22 months. Six of these patients experienced significant increases in both weight and BMI (both p < 0.01) and one patient stopped losing weight. The other two patients continued to lose weight during the initial 5 months of IDPN. Normalised protein catabolic rate also increased significantly in patients who responded to IDPN (p = 0.03) but there was no change in serum albumin. Cohort analysis determined that all patients with organic PEM responded to IDPN therapy, whereas patients with psychosocial causes of PEM did not.