INOX-ICU Project

INsufficient OXygen supply in ICU patients


In the Netherlands, as in other western countries, about 20% of all red blood cell units are transfused in the ICU, with a low serum haemoglobin concentration serving as the most common indication for transfusion. According to the ABC-study, 63% of intensive care unit (ICU) patients had a mean haemoglobin concentration of less than 12 g/dl and 29% less than 10 g/dl.1

In the anaemic patient, oxygen delivery is maintained by compensatory mechanisms in response to the reduced arterial O2 content. However, at low enough haemoglobin concentrations, the compensatory mechanisms are overwhelmed and O2 supply becomes inadequate, leading to a high risk of tissue hypoxia. This critical haemoglobin concentration is not likely a fixed value as it varies for different organs and depends on multiple factors such as age, admission diagnosis, severity of illness, co-morbidities and medication use. The aim of red blood cell transfusion is to restore adequate oxygen delivery  in patients at risk for tissue hypoxia or organ-specific ischaemia as far as this is due  to a very low haemoglobin concentration.


Current practice guidelines are mostly based on the results of the randomized controlled TRICC trial. This large prospective randomized study showed that a restrictive strategy (transfusion)trigger of 7 g/dl) is at least as effective as a liberal transfusion strategy (trigger of 10 g/dl) in critically ill patients.2 This result is consistent with the systematic review of observational studies carried out by Marik and colleagues who reported the association between red blood cell transfusion and increased morbidity and mortality.3 As a result, fewer and fewer patients receive red cell transfusions despite overt anaemia. Some suggest this trend is leading to under-treatment of anaemic, critically ill patients and consequently to potentially avoidable deleterious clinical outcomes.4
The major concern about these studies is their reporting of an overall effect of red blood cell transfusion. This effect on the heterogeneous ICU population does not likely hold for an individual patient due to confounding factors. Before deciding to transfuse, a clinician needs to estimate an individual patient’s probability of anaemia-related complications both with and in the absence of red cell transfusion. It is difficult for a clinician to make a reliable estimate. To support clinicians in their daily practice, guidelines are developed by experts in the field, notwithstanding the paucity of quantitative evidence on the effect of red blood cell transfusion. Despite clear transfusion triggers, the guidelines are not conclusive. They all emphasize that haemoglobin concentration is not sufficient as a stand-alone parameter for a transfusion decision. Other individual patient characteristics should be considered when making transfusion decisions.5-7 The challenge is therefore to identify these characteristics and investigate the characteristics of patients in which transfusions do more good than harm.


To develop an electronic clinical decision tool that can be used in intensive care departments to optimize transfusion decisions in critically ill patients with anaemia.
To examine the effect of implementation of this electronic tool on clinical outcomes in future critically ill patients with anaemia.

Study Design

Multicentre cohort study

Study population

All non-bleeding, critically ill patients with serious anaemia

Main study endpoint

An efficacy-prognostic function of red blood cell transfusion

Research Staff

  • FJ Kranenburg MD (PhD student and coordinating investigator)1
  • JG van der Bom MD PhD1
  • MS Arbous MD PhD2
  1. Center for Clinical Transfusion Research, Sanquin Research, Leiden
    Department of Clinical Epidemiology, Leiden University Medical Center, Leiden
    Jon J van Rood Center for Clinical Transfusion Research, Sanquin-Leiden University
    Medical Center, Leiden
  2. Department of Critical Care Medicine, Leiden University Medical Center, Leiden


  1. Vincent JL, Baron JF, Reinhart K, Gattinoni L, Thijs L, Webb A et al. Anemia and blood transfusion in critically ill patients. JAMA 2002; 288(12):1499-1507.
  2. Hebert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999; 340(6):409-17.
  3. Marik PE, Corwin HL. Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature. Crit Care Med 2008; 36(9):2667-74.
  4. Vincent JL. Indications for blood transfusions: too complex to base on a single number? Ann Intern Med 2012; 157(1):71-2.
  5. Carson JL, Grossman BJ, Kleinman S, Tinmouth AT, Marques MB, Fung MK et al. Red blood cell transfusion: a clinical practice guideline from the AABB*. Ann Intern Med 2012; 157(1):49-58.
  6. Napolitano LM, Kurek S, Luchette FA, Corwin HL, Barie PS, Tisherman SA et al. Clinical practice guideline: red blood cell transfusion in adult trauma and critical care. Crit Care Med 2009; 37(12):3124-57.
  7. Retter A, Wyncoll D, Pearse R, Carson D, McKechnie S, Stanworth S et al. Guidelines on the management of anaemia and red cell transfusion in adult critically ill patients. Br J Haematol 2013; 160(4):445-64.