Systematic Reviews
Copyright ©The Author(s) 2016.
World J Gastrointest Surg. Jul 27, 2016; 8(7): 521-532
Published online Jul 27, 2016. doi: 10.4240/wjgs.v8.i7.521
Table 1 Quality assessment tool (adapted from[6])
Items and scores
Was the assigned treatment adequately concealed prior to allocation?
2 = method did not allow disclosure of assignment
1 = small but possible chance of disclosure of assignment or states random but no description
0 = quasi-randomized
Were the outcomes of participants who withdrew described and included in the analysis (intention to treat)?
2 = intention-to-treat analysis based on all cases randomized possible or carried out
1 = states number and reasons for withdrawal but intention-to-treat analysis not possible
0 = not mentioned or not possible
Were the outcome assessors blinded to treatment status?
2 = action taken to blind assessors, or outcomes such that bias is unlikely
1 = small or moderate chance of unblinding of assessors
0 = not mentioned
Were the treatment and control group comparable at entry?
2 = good comparability of groups
1 = confounding small
0 = large potential for confounding, or not discussed
Were care programs, other than the trial options, identical?
2 = care programs clearly identical
1 = clear but unimportant differences
0 = not mentioned or clear and important differences in care programs
Were the inclusion and exclusion criteria clearly defined?
2 = clearly defined
1 = inadequately defined
0 = not defined
Were the interventions clearly defined (including estimates of nutritional value)?
2 = clearly defined interventions are applied with a standardized protocol
1 = clearly defined interventions are applied but the application protocol is not standardized
0 = intervention and/or application protocol are poorly or not defined
Were the participants blind to assignment status following allocation?
2 = effective action taken to blind participants
1 = small or moderate chance of unblinding participants
0 = not possible, or not mentioned (unless double-blind), or possible but not done
Were the treatment providers blind to assignment status?
2 = effective action taken to blind treatment providers
1 = small or moderate chance of unblinding of treatment providers
0 = not possible, or not mentioned (unless double-blind), or possible but not done
Was the overall duration of surveillance clinically appropriate?
2 = optimal (six months or more)
1 = adequate (one up to six months)
0 = not defined, or not adequate
Table 2 Outcomes of quality assessment, described for individual trials
Smedley et al[8]Saluja et al[10]Beattie et al[13]MacFie et al[9]Jensen et al[5]Keele et al[11]Rana et al[12]
Was the treatment adequately concealed prior to allocation?2020002
Were candidates who withdrew included in analysis?0No withdrawals00001
Were the assessors blinded?000020
Were treatment and control groups comparable at entry?2202122
Specific mention of “lack of detail on patients at entry”Specific mention of error “in the randomisation process”
Were care programmes otherwise identical?2222222
Were the inclusion and exclusion criteria clearly defined?2222222
Were the interventions clearly defined?2221122
Were the participants blind to assignment after allocation?0000000
Were the treatment providers blinded to allocation status?0000000
Was duration of surveillance appropriate?1122110
Table 3 Summary details of eligible trials
Ref.MethodParticipantsInterventionOutcomesConclusions/Notes
Smedley et al[8]RCTUndergoing 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 groupIncluded 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 energyWeight 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 mealsQuality 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]PRCTn = 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 dietAdverse events: ONS well toleratedSeverely 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 yrTotal 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-operativelyWeight loss: TG = 2.15 kg vs CG = 4.6 kg (P < 0.01)
Assessment was done on admission, day 3 and at dischargeOverall 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]PRCTPatients 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 mealsWeight 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: 18-80Mean body weight loss = 9.8% in CG and 5.6% in treatment groupPost-operative oral nutritional supplementation improved nutritional status, quality of life and morbidity
n = 101, intervention = 52; control = 49Triceps 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]PRCTMajor GI surgery patients n = 52; 27 had intervention of some kind. TG n = 27 (post op supplements), CG n = 25Pre and post-operative phases. For this review, only the control group and post-operative supplementation group were looked atNutritional 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 dietMorbidity: No differenceAlso 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 hMortality: No differencePossible 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 dietEffect 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 moElective and acute n = 87: 47 in CG and 40 in TGControl group: Discharged without adviceBody 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 stageInitially 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 daySerum albumin: No difference was seen at any timeRecommendation: 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 interventionn = 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 groupInpatient phasePhase 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 surgerySupplement consumption was “ad libitum”No significant difference in intake of energy or protein from ward dietBoth 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 TGBy 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 dischargen = 40; 20 control and 20 supplementedAd libitum supplementation with oral nutritional sip feed in addition to control dietNutritional 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 surgery7.8 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 boardSignificant weight loss in CG but not TG at day 3 and discharge5-6 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 snacksGrip strength difference at day 3 and discharge (P < 0.03) in favor of treatment groupWithin 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 groupsObserved 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