Appendix

First author
Year / Patient population / Restrictive intervention / Findings
Oxygen
Girardis 2016[1] / General critical illness / Target Pao2 between 70 and 100 mm Hg and SpO2 94-98% vs. usual care of PaO2 150 mmHg and SpO2 of 97-100% / Restricting oxygen therapy is associated with better survival
Feeding
Arabi 2015[2] / General critical illness / Permissive underfeeding (40-60% of calculated caloric requirements) vs. standard enteral feeding (70-100%) with similar protein intake / Restricting non-protein calories does not result in worse outcomes
Rice 2012[3] / Acute lung injury / Trophic vs. full enteral feeding for 6 days / Restricting enteral feeding for 6 days does not result in worse outcomes but reduces gastrointestival intolerance
Mechanical ventilation
ARDSNet 2000[4] / Acute respiratory distress syndrome / Tidal volumes of 6 mL per kilogram of predicted body weight and a plateau pressure of 30 cmH2O vs. 12 mL per kilogram of predicted body weight and a plateau pressure of 50 cmH2O / Low tidal volumes associated with worse gas exchange but better survival
Intravenous fluids
Bickell 1994[5] / Penetrating trauma and hypotension / Delayed administration of intravenous fluids until reaching the operating room vs. standard fluid resuscitation before reaching the hospital / Delayed fluid therapy and permissive hypotension is associated with better survival
Maitland 2011[6] / Severe pediatric febrile illness and malperfusion in Africa / No intravenous fluid boluses vs. intravenous boluses / Maintenance intravenous fluid therapy without boluses is associated with better survival
Blood transfusion
Hebert 1999[7] / General critical illness / Transfusion target hemoglobin value of 7.0 vs. 9.0 g per deciliter / Restricting blood transfusions does not result in worse outcomes
Villanueva 2013[8] / Severe acute upper gastrointestinal bleeding / Transfusion target hemoglobin value of 7.0 vs. 9.0 g per deciliter / Restricting blood transfusions is associated with better survival
Carson 2011[9] / High-risk surgery hip fracture surgery / Transfusion target hemoglobin value of 8.0 vs. 10.0 g per deciliter / Restricting blood transfusions does not result in worse outcomes
Holst[10] / Septic shock / Transfusion target hemoglobin value of 9.0 vs. 7.0 g per deciliter / Restricting blood transfusions does not result in worse outcomes
Insulin
Finfer 2009[11] / General critical illness / Target blood glucose value of 10.0 mmol per liter or less vs. 4.5 to 6.0 mmol per liter / Restricting insulin therapy is associated with worse blood glucose values but better survival

References of selected trials of lower intensity vs higher intensity interventions for critically ill patients

1. Girardis M, Busani S, Damiani E et al (2016) Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial. JAMA 316: 1583-1589. DOI 10.1001/jama.2016.11993

2. Arabi YM, Aldawood AS, Haddad SH et al (2015) Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults. The New England journal of medicine 372: 2398-2408. DOI 10.1056/NEJMoa1502826

3. National Heart L, Blood Institute Acute Respiratory Distress Syndrome Clinical Trials N, Rice TW et al (2012) Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA 307: 795-803. DOI 10.1001/jama.2012.137

4. (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. The New England journal of medicine 342: 1301-1308. DOI

5. Bickell WH, Wall MJ, Jr., Pepe PE et al (1994) Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. The New England journal of medicine 331: 1105-1109. DOI 10.1056/NEJM199410273311701

6. Maitland K, Kiguli S, Opoka RO et al (2011) Mortality after fluid bolus in African children with severe infection. The New England journal of medicine 364: 2483-2495. DOI 10.1056/NEJMoa1101549

7. Hebert PC, Wells G, Blajchman MA et al (1999) A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. The New England journal of medicine 340: 409-417. DOI

8. Villanueva C, Colomo A, Bosch A et al (2013) Transfusion strategies for acute upper gastrointestinal bleeding. The New England journal of medicine 368: 11-21. DOI 10.1056/NEJMoa1211801

9. Carson JL, Terrin ML, Noveck H et al (2011) Liberal or restrictive transfusion in high-risk patients after hip surgery. The New England journal of medicine 365: 2453-2462. DOI 10.1056/NEJMoa1012452

10. Holst LB, Haase N, Wetterslev J et al (2014) Lower versus higher hemoglobin threshold for transfusion in septic shock. The New England journal of medicine 371: 1381-1391. DOI 10.1056/NEJMoa1406617

11. Investigators N-SS, Finfer S, Chittock DR et al (2009) Intensive versus conventional glucose control in critically ill patients.[see comment]. New England Journal of Medicine 360: 1283-1297. DOI