Hemoglobin spray as adjunct therapy in complex wounds: Meta-analysis versus standard care alone in pooled data by wound type across three retrospective cohort controlled evaluations

Objectives: Low tissue oxygenation is a predictor of healing outcomes in complex wounds. Adjunct hemoglobin to aid oxygen diffusion has been demonstrated to achieve superior healing outcomes; however, the relative healing benefit across different wound types and evaluations has not yet been estimated. This article does this for the first time. Methods: Data were pooled from previously published real world controlled evaluations, three retrospective cohort controlled studies of a variety of wounds within standard care across hospital and primary care in the North of England in patients with diabetic foot ulcers (n = 40), chronic wounds (n = 100), and sloughy wounds (n = 200). Wounds were equally distributed between adjunct hemoglobin and control and the hemoglobin spray was used as per instructions for use and applied twice weekly, mostly for the duration of the wounds in all three evaluations. Wound healing over 26 weeks was the primary outcome in each of the evaluations, with additional healing and quality of life indicators including pain, wound size, slough coverage, wound exudate levels, adverse events, and dressing regimen used, over time. Each wound type with 10 or more patients in both the standard care alone and adjunctive hemoglobin groups (n = 257/73% of patients) was evaluated. Results: Cox proportional hazards log-rank regressions demonstrated significantly higher weekly chance of healing in each wound type (beta, 95% range, sample, p): trauma 1.55 (1.23-1.96, n = 110, p < 0.001), diabetic foot ulcers 2.39 (1.52-3.75, n = 60, p = 0.01), venous leg ulcers 4.98 (1.69-14.7, n = 33, p = 0.04), burns 1.82 (1.11-2.99, n = 30, p = 0.02), and post-surgical wounds 2.75 (1.53-4.96, n = 24, p = 0.001). Results on additional healing indicators were consistent with the main findings. Notably, controlling for ischemia in diabetic foot ulcers resulted in an increased beta of 5.68 (2.33-13.86, n = 29, p < 0.001). Conclusion: Adjunct hemoglobin spray, when implemented within standard care, is likely to achieve substantial healing benefits to patients, in particular for diabetic foot ulcers, venous leg ulcers, and post-surgical wounds.