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the hypothesis that a systemic or a regional reduction of sympathetic activity  for example , induced by thoracic epidural anesthesia  might have positive effects on the perfusion and oxygenation ( that is , increase them ) of splanchnic organs like the liver and gut and that reduction of pain improves pulmonary function sounds profound .
although interest in this field of research has been increasing over the past years , detailed knowledge about the effects of increased or reduced sympathetic activity on organ perfusion and oxygenation and the mechanisms involved , as well as how these change or sympathetic activity changes immunomodulation during pathophysiological conditions , is still lacking . in recent issues of critical care , freise and
colleagues   and lauer and colleagues   presented studies that provide interesting information concerning this subject .
sprague - dawley rats that were fitted with thoracic epidural catheters and treated with cecal ligation and puncture .
intravital microscopy was used to investigate sinusoidal diameters , loss of sinusoidal perfusion , sinusoidal blood flow , and permanent leukocyte adhesion to sinusoidal and venolar endothelium . in their experiments ,
cardiac output  measured in an additional group of animals , which were not investigated with intravital microscopy  remained constant in animals with induced sepsis with and without epidural anesthesia . from their intravital microscopy results they concluded that sinusoidal blood flow increased in the sepsis group and was normalized in the group with sepsis and thoracic epidural anesthesia
however , sinusoidal vasoconstriction was not ameliorated by thoracic epidural anesthesia and nor was liver tissue injury affected .
while there is broad agreement that thoracic epidural anesthesia improves postoperative pulmonary function , the underlying mechanisms  for example , via reduction of abdominal pain after general abdominal surgery  still remain unclear .
thoracic epidural anesthesia modulated the nitric oxide ( no ) pathway and exerted positive  that is , lower levels of exhaled no  effects on pulmonary endothelial integrity in hyperdynamic septic rats , but not in hypodynamic septic rats . in the latter ,
this study shows the importance of distinguishing between different phases of disease , especially during early ( hyperdynamic ) and late ( hypodynamic ) sepsis .
one has to keep in mind that the authors did not describe any differences in volume management within their experimental groups and , thus , intravascular normovolemia could not be proven in either .
in general , both studies add interesting results to the necessary discussion about the usefulness of epidural anesthesia during sepsis .
why is this so ? increased sympathetic activity plays an important role in the development of different pathophysiological conditions  for example , during endotoxemia [ 4 - 7 ] , hemorrhagic shock   and even during and after routine abdominal surgical procedures .
thus , epidural anesthesia might decrease mortality during sepsis , especially as splanchnic hypoperfusion and hypoxia are said to be key factors in the development of systemic inflammatory response syndrome , sepsis and multiple organ failure .
diverse studies , however , have presented contradictory results concerning this , with some reporting decreased mortality in older animal studies   and newer meta - analyses   and others reporting increased mortality in an animal model .
the main problem with all the published studies is that hardly any are comparable with each other .
humans and different animals ( for example , pigs , rats , mice , rabbits ) have been used , either systemic or regional reduction of sympathetic activity has been investigated ( effects of clonidine , spinal anesthesia , epidural anesthesia ) , and the method of epidural anesthesia has differed , from lumbar epidural anesthesia in older studies to thoracic epidural anesthesia in recent studies , including or not the nervi accelerantes . however
, to prove an effective reduction in sympathetic activity , and especially that the epidural anesthetic is working , is very difficult , especially in clinical situations .
hence , the most important considerations for future studies on the effect of epidural anesthesia on sepsis or endotoxemia are normovolaemia at any point of the experiment , a clear definition and timeline of hypodynamic and hyperdynamic circulation in sepsis , the proven spread of the epidural anesthesia , which includes or excludes the nervi accelerantes ( thereby reducing or maintaining cardiac output , respectively ) , and the continuous , proven reduction of sympathetic activity  including or excluding the adrenal glands  during the different phases of the developing pathophysiological conditions .
surrogate parameters like sinusoidal width or the number of perfused sinusoids should be used with care to judge sinusoidal perfusion , as laboratory findings should be treated cautiously if not accompanied by definitive  and relevant  physiological changes .
although studies like those from freise and colleagues and lauer and colleagues have increased our understanding of how reduction of regional sympathetic activity can influence different organ functions during sepsis , we still largely lack understanding of the underlying mechanisms , and this will persist as long as there are no standardized , or at least fairly definitive , studies on reduced sympathetic activity during sepsis . only with these studies
research interest in epidural anesthesia during sepsis has grown over the past years and studies have tried to determine its mechanisms , which should , theoretically , protect organs and reduce morbidity and mortality . 
 however , different experimental approaches in different animal models have provided conflicting results over whether epidural anesthesia has protective or harmful effects and whether these alter depending on the phase of sepsis , the spread of epidural anesthesia or additional supportive therapies . in the future , more standardized research is necessary to integrate the results of all studies , which have been published .