Skin ischaemia

Docebenone has shown anti-inflammatory effects in several animal models following local dosing phorbol ester-induced oedema and neutrophil influx in mouse skin [208,209], arachidonate-induced plasma extravasation in rabbit skin [210], the pleural reversed passive Arthus reaction in rats [211], and GPB [212], An oral dose of 80 mg/kg reduced infarct size, LTB4 levels and neutrophil infiltration in a rat myocardial infarction model [213,214], and in a rat brain ischaemia-reperfusion model oedema and LTC4 levels were reduced at 200 mg/kg [107]. Significant, but not dramatic, improvement in nasal symptoms was seen in humans following 150 mg of docebenone twice daily for 8 weeks [215], but there was no effect on bronchial hyperresponsiveness to acetylcholine in asthmatics [216]. 

When used in high doses for long periods to treat life-threatening conditions, e.g. SIRS, it may result in peripheral ischaemia or even gangrene. Extravascular leakage my result in skin necrosis. If used in late pregnancy it may induce uterine contractions and/or reduce placental blood flow. 

Isoprenaline stimulates pi and 32 adrenoceptors (pi>32) resulting in increased myocardial contractility and reduced peripheral vascular resistance. It does not act on a adrenoceptors. Cardiac output increases partly due to reduced afterload and an increase in heart rate. There is a diversion of blood to non-essential tissues, e.g. skeletal muscle and skin. Because of the decrease in peripheral vascular resistance arterial blood pressure and coronary perfusion pressure may decrease, which may predispose to myocardial ischaemia. 

Sundriyal D, Kumar N, Patnaik I, Kamble U. Terlipressin induced ischaemia of skin. BMJ Case Rep 2013 2013. 

Further debridement and irrigation may be necessary 24-72 hours after presentation. Soft-tissue cover should be achieved within 3-5 days. Closure of wounds imder tension should be avoided as this leads to tissue ischaemia and predisposes to infection. When wounds cannot be closed without tension, and skin grafting or other procedure is necessary, antibiotic prophylaxis should be continued. 

---