What is the first-line treatment for anemia in critically ill patients?

Treatment of Anemia in Critically Ill Patients

The first-line treatment for anemia in critically ill patients is a restrictive red blood cell transfusion strategy with a hemoglobin threshold of 7.0 g/dL, combined with minimizing iatrogenic blood loss from diagnostic phlebotomy. 1

Primary Treatment Approach

Restrictive Transfusion Strategy

• Transfuse at hemoglobin <7.0 g/dL in most critically ill patients, targeting a post-transfusion hemoglobin of 7.0-9.0 g/dL 1
• This threshold is supported by landmark trials including TRICC and TRISS, which demonstrated no mortality difference compared to liberal strategies (transfusing at 10.0 g/dL), while significantly reducing transfusion requirements 1
• The TRISS trial specifically showed in septic shock patients that restrictive (7.0 g/dL) versus liberal (9.0 g/dL) strategies resulted in similar 90-day mortality (43% vs 44.9%) with median transfusion of 1 unit versus 4 units 1
• Administer single units sequentially, reassessing hemoglobin and clinical status after each unit rather than transfusing multiple units simultaneously 2, 3

Non-Pharmacological Prevention

• Implement a diagnostic phlebotomy reduction strategy to decrease both volume and frequency of blood draws 1
• Mean daily phlebotomy volume in ICU patients is 40-80 mL, which significantly contributes to iatrogenic anemia 1, 2
• This expert opinion recommendation has strong agreement despite limited direct evidence on mortality outcomes 1

Special Population Considerations

Patients with Cardiovascular Disease

• Consider a slightly higher threshold of 8.0 g/dL for patients with known coronary artery disease or acute coronary syndrome 1, 2, 3
• However, the optimal transfusion threshold in critically ill patients with chronic cardiovascular disease remains uncertain, and no formal recommendation could be made by guideline panels 1
• Avoid liberal transfusion strategies (>10.0 g/dL) even in cardiac patients, as these increase transfusion-related complications without improving outcomes 2, 3

Septic Shock Patients

• Use the standard restrictive threshold of 7.0 g/dL in septic shock, as the TRISS trial demonstrated safety and efficacy 1
• No difference in ischemic events was observed between restrictive and liberal strategies 1
• One-year mortality analysis also showed no significant difference (53.3% vs 54.6%) 1

ARDS and Mechanically Ventilated Patients

• Apply the restrictive threshold of 7.0 g/dL in patients with ARDS and those requiring mechanical ventilation 1, 3
• This population was specifically studied and showed no adverse outcomes with restrictive strategies 1

Pharmacological Interventions: Limited Role

Erythropoietin and Iron Therapy

• Available evidence does not support routine use of erythropoietin or iron therapy to treat anemia in critically ill patients 1
• While these agents can increase hemoglobin levels, they have not demonstrated improvements in mortality, ICU length of stay, or duration of organ support 1
• The guidelines prioritized clinical outcomes (mortality, morbidity, quality of life) over hemoglobin increases alone 1

Vitamin B12 and Folic Acid

• No recommendation could be formulated regarding vitamin B12 or folic acid supplementation in critical care patients due to insufficient evidence 1

Critical Pitfalls to Avoid

Do Not Use Liberal Transfusion Strategies

• Avoid transfusing to hemoglobin targets >10.0 g/dL, as this increases transfusion requirements without improving outcomes and may increase complications 1, 2, 3
• The TRICC trial showed restrictive strategies reduced transfusion from 5.6 ± 5.3 to 2.6 ± 4.1 units without increasing mortality 1

Do Not Rely on Hemoglobin Alone

• Always assess clinical context including hemodynamic stability, active bleeding, signs of tissue hypoxia, and patient comorbidities when making transfusion decisions 3, 4
• Hemoglobin is not an objective per se; the focus should be on mortality, organ support needs, and ICU length of stay 1

Recognize Transfusion Risks

• Blood transfusion carries risks including transfusion reactions, infections, immunosuppression, and potentially increased mortality in some populations 3, 4
• These risks must be weighed against benefits, particularly when hemoglobin is in the 7.0-9.0 g/dL range 4, 5

Evidence Quality and Consensus

The restrictive transfusion strategy recommendations have high-level evidence (GRADE 1) based on multiple large randomized controlled trials 1. The phlebotomy reduction strategy, while having strong expert consensus, is based on expert opinion due to limited direct outcome data 1. The 2025 Association of Anaesthetists guidelines and 2020 French Society guidelines are in complete agreement on these core principles 1.