3.3.3 Functional benefits of PN

CRITICAL ILLNESS AND SURGERY

• Ferrie and colleagues (2016) compared standard amino acid intake versus the higher level recommended amino acid intake (0.8 vs 1.2 g/kg) in a double-blind RCT involving 120 critically ill (mostly surgical) patients requiring PN; all patients had received mechanical ventilation.³¹⁵ Data were available for 59 patients who received high protein and 60 who received standard protein. Actual amino acid delivery from PN was 0.9 and 1.1 g/kg in the two groups, respectively. The primary endpoint of handgrip strength at discharge did not quite meet statistical significance (p = 0.54); however, the high-protein group showed a significant improvement in handgrip strength at day 7 (secondary endpoint; p = 0.025). These patients also experienced less fatigue, measured using the Chalder score (mean [SD]: 5.4 [2.2] vs 6.2 [2.2]; p = 0.045) and greater forearm-muscle thickness (3.2 [0.4] vs 2.8 [0.4] cm; p < 0.0001).

• In an open-label single-centre RCT reported by Wu et al. (2016), timely (within 24 hours) initiation of SPN (ETF + PN) following surgical resection of oesophageal cancer resulted in significant improvements at 90 days post-surgery in physical functioning (Medical Outcomes Survey Short-Form versus ETF [MOS-SF 36] scores 71.5 ± 24.3 vs 60.4 ± 27.4 [p = 0.0387])) and energy/fatigue (62.9 ± 19.5 vs 54.2 ± 23.5 [p = 0.0482]).²⁷¹ Furthermore, multivariate regression analysis showed that changes in body weight (p = 0.015; 95% CI 1.544–2.808 kg) and fat-free mass (p = 0.048; 95% CI 0.761–2.612 kg) were independent predictors for improvement in physical functioning score, while change in fat-free mass (p < 0.001; 95% CI 3.006–4.018 kg) was an independent predictor for improvement in energy/fatigue score.

• Yao and colleagues (2005) evaluated the effect of perioperative PN on nutritional status and postoperative outcome in 32 severely malnourished patients with CD who had undergone bowel surgery for obstruction. Patients who received preoperative PN for 3 weeks were more likely return to work within 6 months than those who did not (p value not reported).²⁷⁵

CANCER

• A randomised prospective study that investigated the impact of specialised nutrition- focused patient care (including PN) in 309 cancer patients with progressive cachexia (primarily due to GI tumours) showed that those receiving PN had greater maximum exercise capacity (measured by treadmill walking test that progressively increased speed and incline) than control patients who did not receive nutrition support (p < 0.04).²⁹⁷
• Culine and colleagues (2014) reported a prospective observational study that assessed the impact of HPN on QOL in cancer patients (n = 767). Functional capacity (evaluated using performance status [PS] score) improved in 22% of patients and was stable in 58% after 28 days of HPN (p values not reported).²⁹⁵ Moreover, there was a significant association between functional capacity and measures of nutritional status, including body mass index (BMI) (p = 0.006), serum albumin (p = 0.005), Nutrition Risk Index (p = 0.01), and weight loss (p < 0.0001). Decline in PS correlated with deterioration in nutritional status (p value not reported), suggesting that poor nutritional status may compromise functional capacity.
• A longitudinal study by Vashi and colleagues (2014) in 52 patients with advanced cancer (various diagnoses) receiving HPN reported significant improvements from baseline in key PS after 1 month (61.6 to 67.3; p = 0.01), 2 months (63.2 to 73.2; p = 0.01), and 3 months (63.2 to 73.2; p = 0.01), irrespective of tumour type.²⁹⁶ Furthermore, every 1 month of HPN was associated with an increase of in Karnofsky Performance Status (KPS) of 5.8 points (p < 0.001).
• Analysis of data from 618 patients with advanced cancer who received HAN (53.9% HPN) in Italy between 1990 and 2012 showed that key PS was related to survival (p < 0.0001).³¹⁶ One month after starting HAN, KPS remained unchanged in 67% of patients and was increased in 21% of patients, with no significant difference between ETF versus PN. KPS was also significantly increased (p < 0.05) in the patients with head and neck cancer.

• A prospective, longitudinal, observational study reported by Cotogni and colleagues (2017) assessed the QOL (measured using the European Organisation for Research and Treatment of Cancer [EORTC) Core Quality of Life questionnaire [QLQ-C30]) in 111 patients with advanced cancer. All patients had a residual but insufficient oral food intake and required supplemental HPN.²³⁷ Significant improvements were seen in global QOL (p < 0.001), physical functioning (p < 0.001), role functioning (p < 0.007), emotional functioning (p < 0.001), appetite (p = 0.004) and fatigue (p = 0.022) while patients were receiving HPN, even in patients with advanced cancer who were receiving chemotherapy.
• Senesse and colleagues (2015) reported a prospective observational study that evaluated the effect of HPN on QOL and nutritional status in 370 patients with GI cancer, 71% of whom had metastatic disease. Global QOL increased significantly after 28 days of HPN (from 48.9 at inclusion to 50.3, p = 0.007).²⁹⁸
• Aeberhard and colleagues (2015) reported a multicentre observational benchmarking study of adult HPN in Switzerland.³¹⁷ Data on personal characteristics, demographics, and social activities were collected through interviews and QOL data using the MOS SF-36 (version 2). The analysis was based on 33 patients, mostly with cancer, radiation enteritis, or requiring PN following bariatric surgery. Before the disease, 52% of patients were very active whereas 58% were not active at all during the disease but before HPN. Activity levels improved during HPN, with 52% reporting that they were now “a little active”. During the 3-month observation period, nearly all patients showed improved mental and physical QOL: physical component scores improved from 34.0 2 to 39.7 and mental component scores improved from 41.91 to 46.35.³¹⁷
• In a prospective observational study by Culine and colleagues (2014) to assess the impact of HPN on QOL in cancer patients (n = 767), significant improvement from baseline were seen in QOL (Functional Assessment of Cancer Treatment – General [FACT-G] questionnaire) after 28 days of HPN (from 48.35 ± 5.01 at baseline to 49.95 ± 5.82; improvement of 3.2%; n = 412; p < 0.0001).²⁹⁵ Mean physical wellbeing improved by 13% at day 28, and familial/social, emotional and functional wellbeing improved by , 4.1 and 6.6%, respectively. Overall, QOL was improved in 60% of patients, and 15% had stable QOL, after 28 days of HPN. Furthermore, almost 80% of patients perceived a positive impact of HPN (i.e., >5 on a 0–10 visual analogue scale).
• In a longitudinal study conducted by Vashi and colleagues (2014) in 52 patients with advanced cancer (various diagnoses) receiving HPN, significant improvements from baseline in global QOL (EORTC QLQ-C30) were reported after 2 months (from 37.1 to 49.2; p = 0.02), and 3 months (from 30.6 to 54.4; p = 0.02), irrespective of tumour type.²⁹⁶ Every 1 month of HPN was associated with an increase of 6.3 points in global QOL (p < 0.001).
• Several older studies provide further evidence that in patients with incurable cancer who survive for more than 3 months, QOL remains stable in those receiving HPN.^318-321