Introduction Intraosseous (IO) administration of medications and blood products is accepted practice in major trauma when intravenous access is not immediately available. However, there is a concern that the high infusion pressures required for IO transfusion may increase the risk of red cell haemolysis and its associated complications. The aim of this systematic review is to synthesise the existing evidence describing the risks of red cell haemolysis in IO blood transfusion.

Methods We undertook a systematic search of MEDLINE, CINAHL and EMBASE using the search terms: “intraosseous transfusion” and “haemolysis”. Two authors independently screened abstracts, and reviewed full-text articles against the inclusion criteria. Reference lists of included studies were reviewed and a grey literature search undertaken. Studies were assessed for risk of bias. Inclusion criteria were: all human and animal study types that reported novel data on IO-associated red cell haemolysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was used.

Results Twenty-three abstracts were identified; n=9 full papers met the inclusion criteria. No further studies were identified from reference lists or grey literature. These papers included: seven large animal translational studies, a prospective and a retrospective human study. The overall risk of bias was high. One animal study with good translatability to adult patients with trauma demonstrated haemolysis. Other animal studies had methodological constraints that limit their human applicability. No haemolysis was observed in low-density flat bones (sternum), whereas haemolysis was reported in long bones (humerus, tibia). IO infusion using a three-way tap was associated with haemolysis. Conversely, pressure bag transfusion was not associated with haemolysis, but this method may result in insufficient flow rates for effective resuscitation.

Conclusions There is a paucity of high-quality evidence surrounding the risks of red cell haemolysis in IO blood transfusion. However, evidence from one study suggests that the likelihood is increased by use of a three-way tap to administer blood transfusion to young adult male patients with trauma. Further research is needed to address this important clinical question.

PROSPERO registration number CRD42022318902.