Benefits of post-operative oral protein supplementation in gastrointestinal surgery patients: A systematic review of clinical trials

Table 3 Summary details of eligible trials

Ref.	Method	Participants	Intervention	Outcomes	Conclusions/Notes
Smedley et al[8]	RCT	Undergoing elective moderate-major lower GI surgery n = 89; 39 patients were controls in the pre-op phase and in the TG in phase 2 making them the treatment group for this analysis. Fifty patients were controls throughout making them the control group	Included multiple groups with patients receiving pre and post-operative supplementation. This review focused on the group that received no supplements pre- and post-op, as well as the group that received no supplement pre-op and supplements post-operation (CG = Group 4, TG = Group 3)	Complications: Fewer minor complications in TG (P < 0.05)	The patients in this study had a baseline of good nutritional intake
			Supplementation began when patients allowed light diet or free fluids post-operation.	Length of stay: No difference
			Fortisip, nutricia used as supplement: 0.05 g/mL protein, 1.5 kcal/mL energy	Weight loss: Significant reduction in patients given ONS before and after surgery and in patients given postoperative ONS only
			TG asked to drink as they desired in addition to meals	Quality of life: No difference (Short Form 36, EuroQol instruments were used)
				Cost: Reduced by GBP£300 (15%) per patient, however not statistically significant
				Post-surgery oral nutritional supplements were of benefit independently of nutritional status
Saluja et al[10]	PRCT	n = 60 (30/30) divided into BM, MM and SM using the NRI[26]	0.033 g/mL of protein or 16.66 g/500 mL drink and 500 kcal energy, in addition to ward diet. Ward diet only was provided to control group. Trial started once surgical team allowed fluids or light diet	Adverse events: ONS well tolerated	Severely malnourished patients have increased energy requirements and less oral intake, and will therefore lose lean body mass as a substrate for energy
		Age: Between 20-60 yr		Total protein intake: Increased in TG (P < 0.01)	Albumin half-life is 20 d - early post-op period is too short to demonstrate a difference due to supplementation
		Elective and emergency abdominal procedures (not just GI)		Voluntary protein intake higher though not significant
		Treatment started from day-1 post-operatively		Weight loss: TG = 2.15 kg vs CG = 4.6 kg (P < 0.01)
		Assessment was done on admission, day 3 and at discharge		Overall weight loss: TG = 5.6%, CG = 6.4%
				Severely Malnourished Patients: TG = 6.3%, CG = 10% (P < 0.01)
				No significant change in lymphocyte count
				Complications: No significant difference
				Length of stay: Statistically significant reduction in severely malnourished patients. No difference in other categories in length of stay
				No change in mid arm circumference
				No change in hand grip strength
				Treatment group felt better than control group (subjective assessment)
				No difference in voluntary intake in group consuming supplements
Beattie et al[13]	PRCT	Patients had a BMI < 20 or > 5% weight loss between hospital admission and trial inclusion, and other anthropometric criteria.	Oral nutritional supplement containing 0.06 g/mL protein, 1.5 kcal/mL energy. Patients encouraged to consume 400 mL/d postoperatively. In practice, patients had between 200 and 400 mL/d in addition to normal meals	Weight loss: CG lost an average maximum of 5.96 kg at 8 wk after admission, while TG lost a maximum of 3.4 kg on average in the first 4 wk and then gained weight (P < 0.001)	Support for nutritional intervention in patients with malnutrition:
		Age: 18-80		Mean body weight loss = 9.8% in CG and 5.6% in treatment group	Post-operative oral nutritional supplementation improved nutritional status, quality of life and morbidity
		n = 101, intervention = 52; control = 49		Triceps skin fold and MAMC were higher in TG than CG (P < 0.001)
				Function: Improved grip strength at 10 wk (P < 0.001)
				Quality of life (UK SF-36): Statistically significant improvement in mental and physical health (P < 0.001)
				Complications: Reduced (P < 0.05)
				No difference in infection rates
				Length of stay: No difference
MacFie et al[9]	PRCT	Major GI surgery patients n = 52; 27 had intervention of some kind. TG n = 27 (post op supplements), CG n = 25	Pre and post-operative phases. For this review, only the control group and post-operative supplementation group were looked at	Nutritional intake: Increased protein and energy seen (but no benefits could be seen)	Similar intakes of supplements as previous trials (Rana, Keele) that showed benefit
			Fortisip, Nutricia given - 0.05 g/mL protein and 1.5 kcal energy/mL or an alternative Fortijuice, Nutricia containing 0.025 g/mL protein and 1.25 kcal/mL energy. Patients encouraged to consume 400 mL/d in addition to normal ward diet	Morbidity: No difference	Also concluded: No difference in benefit when looked at the 17 malnourished patients in the study
			Supplementation commenced as soon as permitted fluids post-surgery, usually within 24 h	Mortality: No difference	Possible lack of difference due to small study numbers in each group, or in general, early return to eating post-surgery in practice along with dietician support normally at the hospital
			CG was provided standard ward diet	Effect on voluntary food intake: No difference
				Nutritional status: No difference
				Functional status: No difference
				Hospital stay: No difference
				Weight Loss: No significant difference
				Serum albumin: No significant difference
				Psychological Status: No significant differences
				Return to normal activities at 6 mo: No difference
				No evidence that increased supplements decreased amount of ward diet eaten
Jensen and Hessov[5]	RCT - Supplements given after discharge from colorectal surgery for 4 mo	Elective and acute n = 87: 47 in CG and 40 in TG	Control group: Discharged without advice	Body mass: (50 d after discharge) lean body mass increase seen in TG of 1.3 kg (P = 0.009) and in overall body mass 2.0 kg (P = 0.005). 110 d after discharge: Total mass difference was +2.7 kg for TG relative to CG (P = 0.014), and lean body mass +1.4 kg for TG (P = 0.029) No significant difference in fat mass was seen at either stage	Initially patients in the intervention group gained LBM without fat mass; later there were gains in both types of mass
			TG: Dietetic advice and a variety of supplements including protein only - aiming for 1.5 g protein/kg per day	Serum albumin: No difference was seen at any time	Recommendation: Patients should increase protein intake to 1.5 g/kg per day for 2 mo post-surgery
Keele et al[11]	Short and long term (4 mo after discharge) benefits of intervention	n = 100 moderate-major elective GI surgery; n = 53 in CG and n = 47 in TG.	TG was given oral nutritional supplement post-operatively in addition to ward diet, which was given to the control group	Inpatient phase	Phase 1 assessment was at day 3 and discharge
			In-patient and out-patient phases (to 4 mo after discharge)	Nutrient intake: Significant increase in protein and energy intake increase at days 1 and 2 (P < 0.001) and 3 (energy P < 0.01, protein P < 0.001), day 4 (P < 0.05) and day 7 - protein only (P < 0.05)	Clinically significant benefits with short term supplementation but not long term supplementation
	(There were four groups in this study: C/C had no supplementation before/after surgery; C/S had none before and supplementation after; S/C had supplementation before and none after; S/S had supplementation before and after surgery		Supplement consumption was “ad libitum”	No significant difference in intake of energy or protein from ward diet	Both CG and TG had below requirement levels of protein as in-patients
	For the purposes of the review C/C were taken as CG and C/S were taken as TG)		Supplements - 200 mL cartons of Fortisip with 1.5 kcal and 0.05 g/mL (10 g protein/carton)	Energy intake 1 m after discharge: Significantly higher in TG	By 1 mo, patients in both groups were eating well so supplements had little effect on well-being
				Weight loss: Less in treatment group at day 3 and discharge (P < 0.001)	The rapidity of the effects of protein supplementation suggests that its effect is due to a direct action of key nutrients rather than repletion of tissue stores
				Serious complications: Less in treatment group (P < 0.05)
				Handgrip: Significant reduction in CG at days 3 and 7; strength lost at day 3 in treatment group but regained by discharge
				Subjective fatigue: Increased fatigue in CG at day 3 and discharge (P < 0.001), no significant increase in fatigue in TG
				Complications: More in control group (P < 0.05)
				Giving food did not reduce voluntary food intake
				Outpatient phase
				Nutrient Intake: No significant difference in protein intake in the out-patient phase. Significantly higher energy intake was seen (P < 0.05) in groups consuming supplements post-discharge compared to controls
				No benefit was seen with supplementation post-discharge
Rana et al[12]	Short term only: Started on day patients could receive free fluids until discharge	n = 40; 20 control and 20 supplemented	Ad libitum supplementation with oral nutritional sip feed in addition to control diet	Nutritional intake: significantly higher energy intake in the treatment group P < 0.004 (as well as the nutritional value of the supplements, more energy was consumed from ward diet by these patients) and protein intake (due solely to supplements)	In the CG there is a significant protein deficit by day 3 which persisted to day 7 (often the day of discharge)
		Major G-I surgery	7.8 g/L unhydrolysed protein. 1.5 kcal/mL energy density. 1.4 L is needed to provide all required nutrient as defined by United Kingdom health board	Significant weight loss in CG but not TG at day 3 and discharge	5-6 d on average elapsed between day of operation and day 1 of study period where diet was allowed. Study period began when surgical team allowed “free-fluids or light diet”
			Controls and given ward diet and allowed snacks	Grip strength difference at day 3 and discharge (P < 0.03) in favor of treatment group	Within 3 d of “free fluids/light diet” treatment patients were consuming 70 g protein/d and about 2000 kcal
				No difference in mid-arm circumference/triceps skin folds changes between groups	Observed increased number of calories (not protein) being eaten from ward diet in the treatment group - inference that supplementation helped to maintain appetite
				Serious complications (pneumonia, wound infection) significantly higher in CG
				No difference in length of stay
				Complications: Pneumonia and wound infection seen. P < 0.02 in favor of treatment group
				Blood proteins: No difference in serum albumin, retinol binding albumin, prealbumin. Significant difference in retinol binding protein as CG declined while TG levels remained same. P < 0.05
				Hospital stay length: No statistically significant difference

TG: Treatment group; CG: Control group; RCT: Randomised controlled trial; PRCT: Prospective randomised controlled trial; ONS: Oral nutritional supplement; MAMC: Mid-arm muscle circumference; LBM: Lean body mass; BM: Borderline malnourished; MM: Moderately malnourished; SM: Severely malnourished; NRI: Nutritional risk index.