title: Implications for burn shock resuscitation of a new in vivo human vascular microdosing technique (microdialysis) for dermal administration of noradrenaline.
abstract: BACKGROUND
  Skin has a large dynamic capacity for alterations in blood flow, and is therefore often used for recruitment of blood during states of hypoperfusion such as during burn shock resuscitation. However, little is known about the blood flow and metabolic consequences seen in the dermis secondary to the use vasoactive drugs (i.e. noradrenaline) for circulatory support. The aims of this study were therefore: to develop an in vivo, human microdosing model based on dermal microdialysis; and in this model to investigate effects on blood flow and metabolism by local application of noradrenaline and nitroglycerin by the microdialysis system simulating drug induced circulatory support.
  
  
  METHODS
  Nine healthy volunteers had microdialysis catheters placed intradermally in the volar surface of the lower arm. The catheters were perfused with noradrenaline 3 or 30 mmol/L and after an equilibrium period all catheters were perfused with nitroglycerine (2.2 mmol/L). Dermal blood flow was measured by the urea clearance technique and by laser Doppler imaging. Simultaneously changes in dermal glucose, lactate, and pyruvate concentrations were recorded.
  
  
  RESULTS
  Noradrenaline and nitroglycerine delivered to the dermis by the microdialysis probes induced large time- and dose-dependent changes in all variables. We particularly noted that tissue glucose concentrations responded rapidly to hypoperfusion but remained higher than zero. Furthermore, vasoconstriction remained after the noradrenaline administration implicating vasospasm and an attenuated dermal autoregulatory capacity. The changes in glucose and lactate by vasoconstriction (noradrenaline) remained until vasodilatation was actively induced by nitroglycerine.
  
  
  CONCLUSIONS
  These findings, i.e., compromised dermal blood flow and metabolism are particularly interesting from the burn shock resuscitation perspective where noradrenaline is commonly used for circulatory support. The importance and clinical value of the results obtained in this in vivo dermal model in healthy volunteers needs to be further explored in burn-injured patients.
authors: Department of Anaesthesia and Intensive Care, County Council of Östergötland, Linköping, Sweden.
authors: Anders
authors: A
authors: Samuelsson
authors: Simon
authors: S
authors: Farnebo
authors: Beatrice
authors: B
authors: Magnusson
authors: Chris
authors: C
authors: Anderson
authors: Erik
authors: E
authors: Tesselaar
authors: Erik
authors: E
authors: Zettersten
authors: Folke
authors: F
authors: Sjöberg
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D002056:Burns / Q000150:complications; D020405:Dermis / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D017551:Microdialysis; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D019289:Pyruvic Acid / Q000378:metabolism; D012769:Shock / Q000188:drug therapy / Q000209:etiology; D013566:Sympathomimetics / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D013566:Sympathomimetics; D014665:Vasodilator Agents; D019344:Lactic Acid; D019289:Pyruvic Acid; D005996:Nitroglycerin; D005947:Glucose; D009638:Norepinephrine