Ibrahim 2002.

Methods	Study design: prospective, randomized controlled trial Study dates: May 1999 to December 2000 Setting: Medical ICU, Barnes‐Jewish Hospital, affiliated to Washington University School of Medicine. St. Louis, Missouri Country: USA.
Participants	Inclusion criteria ICU participants > 18 years, expected to require mechanical ventilation for > 24 hrs Exclusion criteria Transferred to the medical ICU for lack of beds in the other hospital ICUs Expected to die or extubated within 24 hours of ICU admission With prior mechanical ventilation during the same hospitalization With contraindication of enteral feeding (e.g. pancreatitis, short gut, malabsorption) Classified as malnourished at hospital admission With enteral or parenteral nutrition prior to admission to the medical ICU Different strategy of nutrition support according to the prescription of the attending physician Refusal to give informed consent to participate in the study Without tolerance of the placement of oral or naso‐gastric tube (e.g. severe coagulopathy, oesophageal varices) Sample size 189 consecutive participants were evaluated for enrolment, with 39 not included for different reasons, and 150 finally included and analysed. 75 participants were randomized to each study group. The estimated sample size for a significant reduction of the incidence of pneumonia (primary outcome) was 82 participants in each study group. Age (years, mean ± SD). Group 1: 59.1 ± 19.0; Group 2: 56.5 ± 15.6 Sex (% of male). Group 1: 46.7; Group 2: 37.3 Primary reason for ICU admission. Respiratory diseases (%). Group 1: 58.7; Group 2: 64.0 Disease severity: APACHE II score. Group 1: 25.6 ± 8.3; Group 2: 24.7 ± 8.4 PaO2/FiO2 (mean ± SD). Group 1: 204 ± 108; Group 2: 207 ± 126 Predicted mortality based on APACHE II score (%, mean ± SD). Group 1: 48.7 ± 24.9; Group 2: 49.6 ± 23.9 Process of care variables: with 2 exceptions, all of them had statistically non‐significant differences between the study groups: Duration of enteral nutrition and of mechanical ventilation (days, mean ± SD respectively). Group 1: 5.2 ± 5.9 and 8.1 ± 7.4; Group 2: 9.9 ± 12.3 and 12.9 ± 15.7 respectively. Comorbidities, nutrition status and level of inflammation: not reported
Interventions	Group 1 late feeding‐hypocaloric (n = 75) Participants scheduled to receive 20% of their estimated daily requirements for the first 4 days of mechanical ventilation (to prevent atrophy of the intestinal mucosa) and full requirements beginning at day 5 of mechanical ventilation. Group 2 early feeding‐normocaloric (n = 75) Participants scheduled to receive their estimated total daily enteral nutrition requirements starting on day 1 of mechanical ventilation. Co‐interventions The goal for enteral nutrition daily requirements were defined as 25 kcal/kg ideal body weight/day and 1 to 1.3 grams of protein/kg ideal body weight/day. The enteral nutrition, with a polymeric iso‐osmolar formula, was administered in the stomach by bolus feeding, through an orogastric tube inserted on day 1 of mechanical ventilation. In case of 3 consecutive gastric residual volumes > 150 ml, a post‐pyloric enteral tube was inserted for continuous drop enteral nutrition.
Outcomes	Primary outcome Occurrence of ventilator‐associated pneumonia. Diagnosis of pneumonia done by one of the investigators blinded to the group assignment, based on predetermined and well‐defined clinical diagnostic criteria of pneumonia; they also registered several described potential risk factors for the development of ventilator‐associated pneumonia. Secondary outcomes Hospital mortality Length of stay in ICU Length of stay in hospital Length of mechanical ventilation Diarrhoea associated with clostridium difficile infection (rectal swab for culture of the clostridium difficile) 6. Need for a gastrostomy tube Total number of antibiotic days in the ICU How measured or defined The authors defined most of the study items. Time of measurements During the first 5 days of mechanical ventilation Subgroups No subgroups were analysed in the study.
Funding sources	Supported in part by a grant from the Barnes‐Jewish‐Christian Health Care Innovations Program
Declarations of interest	Information not available
Notes	The total calories and protein received by the participants showed a statistically significant difference between the study groups, but participants in each group only received a percentage of the defined goals during the first 5 days of mechanical ventilation: in the hypocaloric group the participants received 7% of their estimated caloric requirements and 7.7% of the estimated protein requirements, and in the control group they received 27.9% and 26.9% respectively.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	The study allocated participants to treatment groups based on the date of their ICU admission using a quasi‐randomized design (odd/even‐numbered days).
Allocation concealment (selection bias)	High risk	The study allocated participants to treatment groups based on the date of their ICU admission using a quasi‐randomized design.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Unblinded study. Details on healthcare processes to be followed by personnel (e.g. co‐interventions) were not described in order to make an appropriate judgement on possible performance bias.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Not blinded but main and secondary outcomes well‐defined. We judge that the outcome measurement was probably not influenced by lack of blinding.
Incomplete outcome data (attrition bias) All outcomes	Low risk	All outcomes: outcome data were available for all participants.
Selective reporting (reporting bias)	High risk	Some prespecified secondary outcomes (duration of mechanical ventilation, need for gastrostomy tube) not reported
Other bias	Low risk	No evidence of other bias