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Serotonin kinetics in patients with burn injuries: A comparison between the local and systemic responses measured by microdialysis-A pilot study
Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Anesthesiology . Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Intensive Care UHL.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Surgery . Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
Department of Hand and Plastic Surgery Linköpings Universitet.
Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
2008 (English)In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 34, no 5, 617-622 p.Article in journal (Refereed) Published
Abstract [en]

Objectives: To investigate serotonin (5HT) locally in burned and uninjured skin (intracutaneous) by microdialysis, and simultaneously record urinary and blood values in the same subjects. For comparison, serotonin values were also measured in skin of healthy controls. Design and setting: An experimental study in burned patients with of more than 25% TBSA (total burn surface area) % in an 8-bed tertiary burns unit, serving about 3.5 million persons. Patients and methods: Six subjects with a median TBSA% of 59% (range 33.5-90), and five healthy controls were examined by intracutaneous microdialysis of the skin. Results: 5HT was increased in burned patients, compared with controls. This increase was tenfold in skin and was noted both in uninjured and burned skin. The highest values were recorded on day 1 (median 16.1 nmol in uninjured and 9.5 nmol in burned skin) and day 2 (15.6 nmol in uninjured and 13.4 nmol in burned skin). A rapid reduction was noted on day 3 (4.9 nmol in uninjured and 3.8 nmol in burned skin). The corresponding value for control subjects was 1.3 nmol. The 5HT in blood was twice normal on day 2, and gradually reduced on days 3 and 4 (3189, 3035 and 2573 nmol, respectively). Urinary 5HT concentrations were increased only on day 2 at 1755 nmol and thereafter returned to the normal range on days 3 and 4 (1248 and 1344 nmol, respectively). Conclusions: We showed that microdialysis may be used in the critical care of burns, and local skin serotonin concentrations examined continuously for several days. The findings of significantly raised tissue serotonin concentrations, compared to that in blood and urine, suggests that serotonin may be important in local vascular control and formation of oedema. © 2007 Elsevier Ltd and ISBI.

Place, publisher, year, edition, pages
2008. Vol. 34, no 5, 617-622 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-43419DOI: 10.1016/j.burns.2007.08.003Local ID: 73800OAI: oai:DiVA.org:liu-43419DiVA: diva2:264278
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
In thesis
1. Effects of burns and vasoactive drugs on human skin: Clinical and Experimental studies using microdialysis
Open this publication in new window or tab >>Effects of burns and vasoactive drugs on human skin: Clinical and Experimental studies using microdialysis
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients who require critical care, including those with burns, are affected by a systemic inflammatory reaction, which at times has consequences such as multiple organ dysfunction and failure. It has become increasingly evident that other factors important in the development of organ dysfunction are disturbances at the tissue level, in the microcirculation. Such disturbances activate cascade systems including stress hormones, all of which have local effects on organ function.

Despite this knowledge, monitoring and treatment in critical illness today relies mainly on central haemodynamics and blood sampling.

Microdialysis is a minimally invasive technique that enables us to study the chemical composition and changes in biochemistry in the extracellular, extravascular space in living tissues. Most of our current experience is from animal models, but the technique has also been used in humans and has become routine in many neurosurgical intensive care units to monitor brain biochemistry after severe injury. In skin, this experience is limited. During the first half of this thesis we studied the injured and uninjured skin of severely burned patients. The results show that there are severe local metabolic disturbances in both injured and uninjured skin. Most interesting is a sustained tissue acidosis, which is not detectable in systemic (blood) sampling. We also recorded considerable alterations in the glucose homeostasis locally in the skin, suggesting a cellular or mitochondrial dysfunction. In parallel, we noted increased tissue glycerol concentrations, which indicated appreciable traumainduced lipolysis.

We also examined serotonin kinetics in the same group of patients, as serotonin has been claimed to be a key mediator of the vasoplegia and permeability disturbances found in patients with burns. We have shown, for the first time in humans to our knowledge, that concentrations of serotonin in skin are increased tenfold, whereas blood and urine concentrations are just above normal. The findings support the need for local monitoring of substances with rapid local reabsorption, or degradation, or both. The results also indicate that serotonin may be important for the systemic response that characterises burn injuries.

In the second half of the thesis we evaluated the effects of microdosing in skin on metabolism and blood flow of vasoactive, mainly stress-response-related, drugs by the microdialysis system. The objectives were to isolate the local effects of the drugs to enable a better understanding of the complex relation between metabolic effects and effects induced by changes in local blood flow. In the first of these two studies we showed that by giving noradrenaline and nitroglycerine into the skin of healthy subjects we induced anticipated changes in skin metabolism and blood flow. The results suggest that the model may be used to examine vascular and metabolic effects induced locally by vasoactive compounds. Data from the last study indicate that conventional pharmacodynamic models (Emax) for time and dose response modelling may be successfully used to measure the vascular and metabolic response in this microdosing model.

We conclude that the microdialysis technique can be successfully used to monitor skin metabolism and iso late a mediator (serotonin) of the local skin response in burned patients. It was also feasible to develop a vascular model in skin based on microdialysis to deliver vasoactive substances locally to the skin of healthy volunteers. This model provided a framework in which the metabolic effects of hypoperfusion and reperfusion in skin tissues could be examined further.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2010. 83 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1195
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-59519 (URN)978-91-7393-342-1 (ISBN)
Public defence
2010-10-08, Berzeliussalen, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2010-09-17 Created: 2010-09-17 Last updated: 2012-05-09Bibliographically approved

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Samuelsson, AndersAbdiu, AvniSjöberg, Folke

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