Implications for critical care of a new in vivo human vascular microdosing technique for giving noradrenaline and nitroglycerine by microdialysis

• Introduction: Skin has a large dynamic capacity for alterations in blood flow, and is therefore often used for recruitment of blood during states of hypoperfusion. Little is known, however, about the metabolic consequences seen in skin secondary to hyporperfusion, particularly when the effects of vasoactive drugs are involved. The aims of this study were: to develop an in vivo, human microdosing model based on microdialysis in skin; and to investigate the effects on blood flow and metabolism of administering noradrenaline and nitroglycerine locally. Method: Nine healthy volunteers each had two or three microdialysis catheters placed intradermally in the volar surface of the lower arm. After a stabilisation period, the catheters were perfused with buffers containing noradrenaline 0.5 or 5 μg/ml for 60 minutes, and after a second period of equilibrium of 60 minutes, all catheters were perfused with buffer containing nitroglycerine (0.5mg/ml). Changes in the blood flow in the skin were measured by laser Doppler imaging urea and ethanol clearance. Simultaneous changes in tissue glucose, lactate, and pyruvate concentrations were recorded. Results: Perfusing skin with noradrenaline and nitroglycerine induced appreciable changes in all variables studied, depending on time and dose. The changes in glucose and lactate concentrations correlated with the change in blood flow assessed by either laser Doppler imaging or urea clearance. The changes in glucose and lactate that were induced by vasoconstriction (noradrenaline) continued until vasodilatation was induced by nitroglycerine. Conclusion: Noradrenaline given by microdialysis in healthy volunteers induced reproducible and dose-dependent hypoperfusion and ischaemia with simultaneous metabolic consequences. Among these, we particularly note that: tissue glucose concentrations responded rapidly to hypoperfusion but remained considerably higher than zero, which suggests an energy-dependent deficiency in cellular uptake; and vasoconstriction remained after cessation of the noradrenaline perfusion, implicating vasospasm and a lack of autoregulatory (recovery) capacity in skin. These findings are particularly interesting from the critical care perspective, where noradrenaline is used extensively for circulatory support. The metabolic consequences may be underestimated and our results suggest that further investigations are warranted.

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MEDICIN

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