Arabi 2011.

Methods	Study design: prospective, randomized controlled trial Study dates: April 2006 to January 2008 Setting: 1 tertiary care academic hospital Country: Saudi Arabia
Participants	Inclusion criteria Participants aged 18 to 80 years, admitted to an ICU, blood glucose concentration of > 110 mg/dl, expected to remain in ICU ≥ 48 hours Exclusion criteria Type 1 diabetes Diabetic ketoacidosis Hypoglycaemia Brain death Do‐not‐resuscitate status Terminal illness Pregnancy Postcardiac arrest Burns Seizures within the past 6 months Liver transplant Readmission to the ICU within the same hospitalization Enrollment in a competing trial Oral feeding Total parenteral nutrition Sample size: authors estimated a relative difference of 50% in ICU mortality between participants receiving .90% of caloric requirements and those receiving 60% to70% of caloric requirements (28% compared with 14%). Quote: “on the basis of an estimated 28‐d mortality rate of 25%, a power of 0.8, and an α of 0.05, the number of subjects needed to show a reduction in mortality was 120 in each group.” Age (years): intervention group: 50.3 ± 21.3; Control group: 51.9 ± 22.1 Sex (male, %): intervention group: 71.1; Control group: 65 Primary disease of the participants Intervention; Control group Admission category (n (%)) Nonoperative 95 (79.2); 103 (85.8) Postoperative 25 (20.8); 17 (14.2) Traumatic brain injury 35 (29.2); 31 (25.8) Disease severity score: APACHE II Intervention group: 25.2 ± 7.5; Control group: 25.3 ± 8.2 Mechanical ventilation n (%) Intervention group: 119 (99.2); Control group: 119 (99.2) Comorbidities: not available Nutrition status: intervention group; Control group: Not available Level of inflammation: not available
Interventions	Intervention Group 1 (n = 120) Permissive‐underfeeding group: caloric goal 60% to 70% of caloric requirements Control Group 2 (n = 120) Target‐feeding group: 90% to 100% of caloric requirements Quote: “for both groups, caloric requirement was estimated by the dietitian using the Harris‐Benedict equations and adjusting for stress factors. The selection of formula was left to discretion of the attending physician as long as it satisfied the total caloric intake criteria and was not enriched with immunonutrients. Calculation of caloric intake took into account intravenous dextrose and propofol infusions.” Quote: “the patients were followed until discharge from the ICU, except if the patient tolerated oral feeding, had a do‐not‐resuscitate order written (after enrolment), or became brain dead (after enrolment). In the latter situations, the intervention was stopped but the outcome data were collected.” Co‐interventions Quote:“The protein requirement was calculated as 0.8–1.5 g/kg on the basis of patient condition and underlying diseases. To avoid protein malnutrition in the permissive underfeeding group, additional protein (Resource Beneprotein; Nestle Healthcare Nutrition Inc, Minneapolis, MN) was added to maintain the full protein requirement without affecting the assigned caloric intake.”
Outcomes	Primary outcome 28‐day all‐cause mortality Secondary outcomes 180‐day mortality ICU mortality Hospital mortality ICU length of stay Hospital length of stay Mechanical ventilation duration Hypoglycaemic episodes Packed red blood cell transfusion Renal replacement therapy Hypokalaemic episodes Health care–associated infections: bacteraemia, catheter‐related bloodstream infection, urinary tract infection, ventilator‐associated pneumonia, and skin and soft tissue How measured or definition and time point measured 28‐day mortality: mortality rate at 28 days of ICU admission 180‐day all‐cause mortality: mortality rate at 180 days of ICU admission ICU mortality: mortality rate at ICU discharge Hospital mortality: mortality rate at hospital discharge Health care–associated infections:according to the National Nosocomial Infection Surveillance (NNIS) System (Emori 1991) Hypoglycaemia: defined as a blood glucose concentration ≤ 2.2 mmol/L or 40 mg/dL Hypokalaemia: defined as a potassium concentration < 2.8 mmol/L Health care–associated infections: according to Nosocomial Infection Surveillance (NNIS) System Subgroups Not available/not performed
Funding sources	Funded by King Abdulaziz City for Science and Technology (LG 10‐30).
Declarations of interest	No potential conflict of interest relevant to this article was reported.
Notes	As it was a 2 x 2 factorial trial, the enrolled participants were randomly assigned by using concealed envelops to 1 of the 4 study groups: 1‐permissive underfeeding with intensive insulin therapy (IIT), 2‐permissive underfeeding with conventional insulin therapy (CIT), 3‐target feeding with IIT, and 4‐target feeding with CIT. We grouped 1 and 2; 3 and 4. Blood glucose concentration target was 4.4 – 6.1 mmol/L (80 – 110 mg/dL) in the IIT group and 10 – 11.1 mmol/L (180 – 200 mg/dL) in the CIT group. The frequency of blood glucose monitoring increased to every 20 mins when blood glucose concentrations decreased to > 3.2 mmol/L (58 mg/dL) and reduced to every 2 – 4 hrs when measurements were stable.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	On the basis of (quote:) "computer‐generated random permuted blocks"
Allocation concealment (selection bias)	Low risk	The enrolled participants were randomly assigned by using concealed envelopes.
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)	Low risk	All outcomes reported
Other bias	Low risk	No evidence of other bias