Vasoconstriction blood substitutes

Poll de Figueiredo, L.F. Mathru, M. Solanki, D. W., M.V. Hess, J. Kramer, G.C. Pulmonary hypertension and systemic vasoconstriction may offset the benefits of acellular hemoglobin blood substitutes. J. Trauma, Inj. Infect. Crit. Care. 1997, 42, 847-856. 

Fizpatrik CM, Savage SA, Kerby JD, et al. Resuscitation with a blood substitute causes vasoconstriction without nitric oxide scavenging in a model of arterial hemorrhage. J Am Coll Surg 2004 199 693-710. 

As the anesthetic agent is absorbed and thus removed from the site of application, its local action ceases, and its systemic and toxic effects start. Because most of these drugs, especially cocaine, are rapidly destroyed in the body, the systemic toxicity increases with the rapidity of absorption. It is therefore desirable and often necessary to delay the absorption. This may be done by restricting the local circulation. Cocaine itself tends to do this by producing a local vasoconstriction, an action that is not shared by its substitutes. This vasoconstriction should be reinforced by the addition of epinephrine. More dilute solution may thus be used, and the anesthetic effect is much more prolonged. With intracutaneous infiltration, the pressure and edema also result in ischemia. In suitable situations, the circulation may be slowed by bandages, or arrested by temporarily clamping the arterial blood supply. 

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