What is the most appropriate threshold to transfuse packed red cells in critically ill patients?

Duncan Chambler

The World Health Organisation have given blood transfusion practice, and the availability of blood products by donation, a high priority. The Blood Safety Health Topic (1) defines the
worldwide aim of global access to safe products, at a reasonable cost through a sustainable programme within existing health systems, to meet the needs of each patient with transfusion only when necessary. The UK is fortunate to have adequate resources to meet these aims, and is one of 106 countries to have in place a national blood transfusion policy to guide use and transfusion (2).

With regard to anaemia and transfusion practice in critically ill patients, Timothy Walsh at Edinburgh’s Royal Infirmary published a definitive review (3) of the relevant literature in 2006.

Where specific references have not been given for smaller studies, please see this review for summaries and references.

Summarising the European ABC study (4), the CRIT study (5) from the USA, and a smaller cohort study from Scottish ICUs, the prevalence at the time of admission to ICU of mild anaemia (Hb < 12 g/dl) is 60-70% and moderate anaemia (Hb < 9 g/dl) is 20-30%. This highlights how common anaemia is in the critically ill. Pre-existing chronic anaemia could be found in only 13% of admissions, suggesting it relates to acute changes more often than not.

Haemoglobin concentrations are not only low on admission, but have been shown to fall rapidly in the initial 72 hours. Nguyen (6) demonstrated a mean fall of 0.66 g/dl each day for three days, followed by a slower 0.12 g/dl fall per day thereafter. The case described here featured an initial Hb fall at a rate of 1.9 g/dl per day. This greater rate of fall may be attributed to post-operative bleeding and acute fluid retention, secondary to the patient’s kidney injury and stress response.

Advice on when to transfuse, in both the UK guidance and Walsh’s review, is based upon two papers: Rivers et al’s study (7) of goal directed therapy for septic shock; and the TRICC study (8) that compared a high and low trigger and target Hb. Rivers demonstrated improved outcome in sepsis through a goal directed package of care, with the aim of increasing oxygen delivery to tissues. This included maintaining a haematocrit > 30% or haemoglobin > 10 g/dl. Two years earlier, the TRICC study demonstrated that a restrictive strategy (trigger for transfusion of < 7 g/dl and target of 7-9 g/dl) was at least as effective and possibly superior to a liberal strategy (trigger of < 10 g/dl and target 10-12 g/dl), especially in those under 55 years of age or with an APACHE-II score < 20, of which this particular case is neither.

The difference between these two landmark papers is whether the clinician targets an arbitrary Hb concentration or an end-point of tissue oxygen delivery. Considering the latter briefly, lab studies in both animals and humans have demonstrated no evidence of inadequate oxygen delivery or utilisation, or organ function in healthy subjects until the Hb is < 6 g/dl. The exception within these lab data, and within the TRICC study, is if there is acute or chronic significant ischaemic heart disease, where an target Hb of 8-9 g/dl is advocated by experts for chronic disease and >9 g/dl for acute disease. This is based on trends in data and expert opinion rather than robust trial outcomes.

Relating these studies and opinions to this particular case, an important factor in the decision making progress relates to his possible diagnosis of an acute cardiac event. Prior to the cardiology review, it would seem reasonable to transfuse to maintain his Hb > 9 g/dl, and to anticipate a further fall in the next 24 hours at least. After the review, which excluded acute cardiac disease, a lower threshold of 7-9 g/dl should have been set. If he demonstrated evidence of inadequate oxygenation (ischaemic ECG changes, ScvO2 < 70% or lactate > 4 mmol/l), then a target of > 10 g/dl may have been appropriate.

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References

1 World Health Organisation. Blood Safety Health Topic. http://www.who.int/topics/blood_safety/. (Accessed 7 May 2013)
2 United Kingdom Blood Services. Handbook of Transfusion Medicine, 4th Edition. 2007 http:// www.transfusionguidelines.org.uk/docs/pdfs/htm_edition-4_all-pages.pdf (accessed 7 May 2013)
3 Walsh TS, and Saleh E. Anaemia during critical illness. BJA 2006; 97(3): 278-91.
4 Vincent JL, et al. Anemia and blood transfusion in critically ill patients. JAMA 2002; 288: 1499-507.
5 Corwin HL, et al. The CRIT Study: Anemia and blood transfusion in the critically ill—current clinical practice
in the United States. Crit Care Med 2004; 32: 39-52.
6 Nguyen BV, et al. Time course of hemoglobin concentration in non-bleeding intensive care unit patients. Crit Care Med 2003; 31: 406-10.
7 Rivers E, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001: 345; 1368-77.
8 Herbert PC, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators (TRICC), Canadian Critical Care Trials Group. N Engl J Med 1999; 340: 409-17.