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Skin microcirculation and vasopressin infusion: a laser Doppler study


Use of arginine vasopressin in the management of refractory vasodilatory shock has been associated with development of ischaemic skin lesions. Because of the increasing popularity of arginine vasopressin, it is important to evaluate its effects on microcirculatory blood flow. Such studies are crucial if we are to appreciate the microcirculatory consequences of our various resuscitation strategies. However, methodological issues must always be considered because they can significantly influence interpretation of the results. Some aspects of use of laser Doppler to evaluate the microcirculation are reviewed within the context of recent findings presented by Luckner and coworkers in this issue of Critical Care.


Arginine vasopressin (AVP) is increasingly used in the management of refractory vasodilatory shock. Indeed, it was recently incorporated into the recommendations (grade IIB) proposed by the American Heart Association for treatment of refractory septic shock [1] and the guidelines of the Surviving Sepsis Campaign (grade E) [2]. However, although the global haemodynamic effects of AVP are relatively well described, its effects on the microcirculation are still largely unknown.

In this issue of Critical Care, Luckner and coworkers [3] present an original study in which they evaluated skin micro-vascular blood flow, using laser Doppler fluxmetry, before and after AVP infusion in patients with refractory septic shock. They report that AVP infusion did not impair forearm skin perfusion compared with norepinephrine alone. The authors intended to explore further the results of two of their previous studies: a retrospective analysis [4], in which they reported a 30.2% rate of ischaemic skin lesions with AVP infusion; and a prospective controlled trial [5] that found no difference in the incidence of such lesions between a group of patients treated with AVP plus norepinephrine and patients treated with norepinephrine alone. Of note, it is difficult to draw conclusions regarding the safety of AVP administration on the basis of the latter study because the dose of norepinephrine received by the patients in the AVP/norepinephrine group was half that in the other group.

As mentioned by the authors, their results presented in this issue are in striking contrast to those of several published physiological experiments on the topic. Indeed, animal and human studies [69] have revealed significant dose-dependant impairment in skin blood flow with AVP. Indeed, the skin microvasculature is considered to be a vascular bed that is rather sensitive to AVP [10]. Accordingly, the results of the study presented by Luckner and coworkers are somewhat unexpected, and some methodological issues might account for the discrepancies.

Technical issues: laser Doppler fluxmetry

It is important to note the technical limitations of laser Doppler. Laser Doppler fluxmetry only provides an estimate of the average blood flow in a given volume of tissue; this volume can vary according to its intrinsic refractive properties. Multiple individual and environmental factors, including haemoglobin level and temperature, can also influence the results of laser Doppler fluxmetry [11]. Moreover, laser Doppler fluxmetry does not take into account the type of microvessels under study, their morphology, the direction of flow and, more importantly, the heterogeneity of perfusion; the latter is a key component in the study of microcirculation, especially in sepsis. More specifically, the biological zero, which can represent up to 80% of the total laser Doppler fluxmetry signal, can be modified during ischaemia/reperfusion procedures because it is influenced by vasodilatation [12]. Therefore, various authors have suggested that the biological zero should always be taken into account when red blood cell flux is measured in the skin using laser Doppler fluxmetry [12]. Finally, measurement of differential perfusion is impeded by the rather small signal and oscillatory pattern of basal cutaneous microcirculation [13]. In addition, it is worth noting that vasomotion patterns are highly dependant on probe location relative to the tissue of interest [14]. This could explain, to some extent, the considerable difference reported in baseline vasomotion between groups. These technical issues account for the substantial short-term variability in laser Doppler fluxmetry measurements [15]. Hence, it is apparent that relatively large observed changes or large sample sizes are needed to detect statistically significant differences between groups.

Statistical issues: power calculation and variance

The power of a study is a measure of its ability to detect a statistical difference when it truly exists; it is particularly important to bear this in mind when interpreting studies that return negative findings. The calculated power of the study reported by Luckner and coworkers is approximately 40%, considering the observed difference in primary outcome (area under the curve of the laser Doppler fluxmetry signal) between the two groups. This means that there is a 60% chance that a true difference will remained undetected. With only three additional patients in each group (assuming the same difference in variance between groups) the study would identify a significant difference in microvascular blood flow perfusion and lead to the conclusion that AVP has, in fact, a considerable deleterious impact on skin microcirculation. Finally, the important variance in AVP response (8.56 in the AVP group versus 3.25 in the norepinephrine group; data provided by Luckner and coworkers) suggests that AVP had rather heterogeneous effects from patient to patient and that other factors (e.g. interindividual variability in sensitivity to AVP stimulation, endogenous AVP level, relative adrenal insufficiency, among others) could have played a role.


Luckner and colleagues [3] are to be commended for their pioneering work on the microcirculatory effects of AVP. Such studies are essential if we are to understand better the micro-circulatory consequences of our resuscitation strategies. However, this work should be duplicated, and we should exercise caution interpreting these results as reassurance that AVP is devoid of adverse microcirculatory side effects. Further work examining different microcirculatory beds and using different measurement tools to assess microcirculation will improve our knowledge of the role of AVP in resuscitation.



= arginine vasopressin.


  1. European Resuscitation Council: Part 6: advanced cardiovascular life support. Section 6: pharmacology II: agents to optimize cardiac output and blood pressure. European Resuscitation Council. Resuscitation 2000, 46: 155-162. 10.1016/S0300-9572(00)00279-3

    Article  Google Scholar 

  2. Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, et al.: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004, 32: 858-873. 10.1097/01.CCM.0000117317.18092.E4

    Article  PubMed  Google Scholar 

  3. Luckner G, Dünser MW, Stadlbauer K-H, Mayr VD, Jochberger S, Wenzel V, Ulmer H, Pajk W, Hasibeder WR, Friesenecker B, et al.: Cutaneous vascular reactivity and flow motion response to vasopressin in advanced vasodilatory shock and severe postoperative multiple organ dysfunction syndrome. Crit Care 2006, 10: R40. 10.1186/cc4845

    Article  PubMed Central  PubMed  Google Scholar 

  4. Dunser MW, Mayr AJ, Tur A, Pajk W, Barbara F, Knotzer H, Ulmer H, Hasibeder WR: Ischemic skin lesions as a complication of continuous vasopressin infusion in catecholamine-resistant vasodilatory shock: incidence and risk factors. Crit Care Med 2003, 31: 1394-1398. 10.1097/01.CCM.0000059722.94182.79

    Article  PubMed  Google Scholar 

  5. Dunser MW, Mayr AJ, Ulmer H, Knotzer H, Sumann G, Pajk W, Friesenecker B, Hasibeder WR: Arginine vasopressin in advanced vasodilatory shock: a prospective, randomized, controlled study. Circulation 2003, 107: 2313-2319. 10.1161/01.CIR.0000066692.71008.BB

    Article  PubMed  Google Scholar 

  6. Liard JF, Deriaz O, Schelling P, Thibonnier M: Cardiac output distribution during vasopressin infusion or dehydration in conscious dogs. Am J Physiol 1982, 243: H663-H669.

    CAS  PubMed  Google Scholar 

  7. Friesenecker B, Tsai AG, Dunser MW, Mayr AJ, Martini J, Knotzer H, Hasibeder W, Intaglietta M: Oxygen distribution in microcirculation after arginine vasopressin-induced arteriolar vaso-constriction. Am J Physiol Heart Circ Physiol 2004, 287: H1792-H1800. 10.1152/ajpheart.00283.2004

    Article  CAS  PubMed  Google Scholar 

  8. Weber R, Pechere-Bertschi A, Hayoz D, Gerc V, Brouard R, Lahmy JP, Brunner HR, Burnier M: Effects of SR 49059, a new orally active and specific vasopressin V1 receptor antagonist, on vasopressin-induced vasoconstriction in humans. Hypertension 1997, 30: 1121-1127.

    Article  CAS  PubMed  Google Scholar 

  9. Hayoz D, Hengstler J, Noel B, Brunner HR: Vasopressin induces opposite changes in blood flow in the skin and the muscular circulation. Adv Exp Med Biol 1998, 449: 447-449.

    Article  CAS  PubMed  Google Scholar 

  10. Waeber B, Schaller MD, Nussberger J, Bussien JP, Hofbauer KG, Brunner HR: Skin blood flow reduction induced by cigarette smoking: role of vasopressin. Am J Physiol 1984, 247: H895-H901.

    CAS  PubMed  Google Scholar 

  11. Bircher A, de Boer EM, Agner T, Wahlberg JE, Serup J: Guidelines for measurement of cutaneous blood flow by laser Doppler flowmetry. A report from the Standardization Group of the European Society of Contact Dermatitis. Contact Dermatitis 1994, 30: 65-72.

    Article  CAS  PubMed  Google Scholar 

  12. Wahlberg E, Olofsson P, Swedenborg J, Fagrell B: Effects of local hyperemia and edema on the biological zero in laser Doppler fluxmetry (LD). Int J Microcirc Clin Exp 1992, 11: 157-165.

    CAS  PubMed  Google Scholar 

  13. Wilkin JK: Poiseuille, periodicity, and perfusion: rhythmic oscillatory vasomotion in the skin. J Invest Dermatol 1989, 93: 113S-118S. 10.1111/1523-1747.ep12581224

    Article  CAS  PubMed  Google Scholar 

  14. Braverman IM, Keh A, Goldminz D: Correlation of laser Doppler wave patterns with underlying microvascular anatomy. J Invest Dermatol 1990, 95: 283-286. 10.1111/1523-1747.ep12484917

    Article  CAS  PubMed  Google Scholar 

  15. Abbink EJ, Wollersheim H, Netten PM, Smits P: Reproducibility of skin microcirculatory measurements in humans, with special emphasis on capillaroscopy. Vasc Med 2001, 6: 203-210.

    Article  CAS  PubMed  Google Scholar 

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We should like to thanks Prof. Daniel G Bichet for inspiring discussions on vasopressin microvascular reactivity.

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Correspondence to Colin Verdant.

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The authors declare that they have no competing interests.

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Bernard, F., Vinet, A. & Verdant, C. Skin microcirculation and vasopressin infusion: a laser Doppler study. Crit Care 10, 135 (2006).

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