McCowen 2000.

Methods	Study design: prospective, randomized, controlled non‐blinded trial Study dates: Not stated Setting: single‐centre, university‐affiliated teaching hospital with a dedicated total parenteral nutrition (TPN) service. Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts Country: USA
Participants	Inclusion criteria Sequential participants requiring TPN according to standard hospital criteria Exclusion criteria Severely underweight (< 50 kg) Home TPN Malnutrition requiring specific pre‐operative TPN Reinstitution of TPN for a setback of the current illness Sample size 48 participants were initially included, but 4 in each group were excluded from the analysis because of PN duration ≤ 4 days, leaving 21 participants in the hypocaloric group and 19 in the control group Age (years; mean ± SD). Group 1 hypocaloric: 57.5 ± 14.9; Group 2 control: 56.6 ± 20.4 Sex (% male): Group 1: 57; Group: 53 Primary disease of the participants. Mainly surgical participants with different types of complications. Major differences between groups: Group 1 acute pancreatitis and bowel surgery/postoperative ileus: n = 6 and 3 participants respectively; Group 2 n = 1 and 6 respectively. Mechanically‐ventilated participants (n). Hypocaloric group: 11; Control group: 6 Comorbidities. Diabetes (n). Group 1: 5 participants; Group 2: 2 participants. Obesity: 4 participants in each group Nutrition status. BMI (mean ± SD). Group 1: 27.6 ± 8.1; Group 2: 25.7 ± 6.2
Interventions	Group 1 hypocaloric (n = 21) Administration of 1 litre of fat‐free TPN, providing 70 grams protein, 210 grams of dextrose and ˜ 1000 kcal when maximally concentrated Group 2 control (n = 19) Standard TPN regimen with a maximum of 25 total kcal/kg actual weight/day (adjusted weight in obese participants). Goal of 20 to 25 kcal/kg/day with 1.5 gr protein/kg/day. Fat could account for up to ⅓ of the calories. Co‐interventions After 10 days the participants were removed from the experimental protocol and fed in the traditional manner.
Outcomes	Reduction of hyperglycaemia: frequency rate of glycaemia > 220 mg/d (measured by fingerstick and confirmed in the laboratory), average capillary glycaemia during the TPN administration Incidence of in‐hospital infections: pneumonia, venous catheter infection, wound infection, abdominal collection/abscess. Infection diagnoses were done by well‐defined common clinical objective methods Nitrogen balance at day 5 of TPN (difference of measured 24‐hr urinary urea nitrogen plus 4 gr/day and TPN nitrogen) Time points of measurements The outcomes were evaluated during the time of TPN. Nitrogen balance was measured in only 12 participants (57%) in the hypocaloric and 10 (53%) of the control group, usually because of an error during collection.
Funding sources	Not available
Declarations of interest	Not available
Notes	Due to a protocol violation, fat was given to 1 participant in the hypocaloric group. Some results associated with hospital rules to avoid iatrogenic hyperglycaemia by gradual increase of nutrients to avoid complications.The hypocaloric group also received less protein than the control group. More participants in the hypocaloric group had acute pancreatitis and mechanical ventilatory support than in the control group. The hypocaloric group received 14 ± 3 kcal/kg/day and the control group 18 ± 4 kcal/kg/day (also hypocaloric). The hypocaloric group not only received significantly fewer calories than the control group (due to fewer dextrose and fat calories), but also less protein (1.1 ± 0.2 versus 1.3 ± 0.2 in the control group). If the infection rate trend observed were to persist, they calculated the study would have required ˜174 participants to see a statistical difference between the 2 groups.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not mentioned
Allocation concealment (selection bias)	Unclear risk	Not mentioned
Blinding of participants and personnel (performance bias) All outcomes	High risk	No blinding: the standard group received parenteral nutrition as 3‐in‐1 bags, and the hypocaloric group received 1 litre of fat‐free parenteral nutrition. Outcomes could have been influenced by different performance of clinical personnel.
Blinding of outcome assessment (detection bias) All outcomes	High risk	No blinding and not clearly‐defined and objective outcomes that would warrant a low risk of detection bias
Incomplete outcome data (attrition bias) All outcomes	High risk	4 participants in each group were excluded from the data analysis because of a TPN duration of ≤ 4 days (not prespecified exclusion criteria).
Selective reporting (reporting bias)	High risk	Nitrogen balance was only measured in 12 participants (57%) in the hypocaloric and 10 (53%) of the control group, usually because of an error during collection.
Other bias	Unclear risk	The lack of detail in the description of the Methods section could not warrant a low risk of other sources of bias.