Oxygen-ozone autohaemotherapy in fibromyalgia: safety profile and adverse events. A scoping review

Oxygen-ozone autohaemotherapy (O2-O3-AHT) has gained clinical interest as an adjunctive treatment for fibromyalgia (FM) based on its anti-inflammatory and anti-oxidative properties. However, comprehensive data on safety and adverse events remain limited. This scoping review aimed to systematically evaluate documented adverse events associated with O2-O3-AHT and assess risk stratification.

Following PRISMA-ScR guidelines, we searched Medline, EMBASE, AMED, Cochrane Library, CINAHL, Web of Science, TRIP, Clinical Evidence, and ROAD databases for relevant articles published in the last decade. Search terms included "ozone autohaemotherapy," "GAET," "autologous blood transfusion," "systemic ozone therapy," combined with "adverse effects," "side effects," "contraindications," and "iatrogenic complications." Studies involving local injections, hyperbaric oxygen therapy, veterinary applications, or non-systemic routes were excluded.

The literature search identified predominantly case reports documenting rare but potentially serious adverse events. Major categories included: haemolysis and renal failure (associated with excessive ozone concentrations >60 μg/mL), hyperkalaemia in patients with complex comorbidities (hypertension, diabetes, chronic kidney disease), myocardial infarction and ischaemic events (attributed to vasoconstrictive and pro-thrombotic effects), cerebral gas embolism in patients with patent foramen ovale, autonomic reactions related to rapid reinfusion rates, anaphylactic reactions (linked to equipment materials), and infectious complications due to protocol breaches. The overall incidence of serious adverse events cannot be reliably quantified given the absence of prospective registries and reliable denominator data: A frequent cited historical low estimation of uncertain methodology should be interpreted with considerable caution. Most safety data were derived from mixed clinical populations and not specifically from fibromyalgia cohorts, although they are relevant for clinical decision-making in this setting.

Current evidence does not identify a pattern of frequent serious unexpected harm when standardised protocol is followed. Key safety measures include mandatory glucose-6-phosphate dehydrogenase screening, adherence to recommended ozone concentrations (10-40 μg/mL), controlled reinfusion rates (<50 drops/minute), pre-treatment cardiovascular evaluation in selected cases, and strict aseptic technique. The estimated incidence of serious complications derived from historical global data on O2-O3 autohaemotherapy may be only inferred in a fibromyalgia population. Standardisation of treatment protocols and prospective adverse event registries are needed to further optimise safety.