" man is a creature composed of countless millions of cells : a microbe is composed of only one , yet throughout the ages the two have been in ceaseless conflict " septic shock remains a common cause of death in intensive care units worldwide and presents the clinician with a variety of management problems .
the surviving sepsis campaign has gone far in collating the considerable wealth of information currently available about this devastating condition and provides excellent guidelines , which are essential reading for consultant and trainee alike
. however , new insights into the management of these patients continue to accumulate , and the last few months have been no exception .
one of the basic tenets of treating septic shock is the provision of cardiovascular support through the use of catecholamines , although there is much interest in other agents as addressed in the study by russell and colleagues in the new england journal of medicine .
they examined the use of the pituitary - derived peptide hormone vasopressin in patients with septic shock through a multi - centred , randomised trial involving 778 patients given low - dose vasopressin ( 0.01 to 0.03 u / min ) in addition to noradrenaline ( norepinephrine ) compared with noradrenaline alone .
no overall differences were found between the two groups in terms of either the primary endpoint of 28-day mortality or the various secondary endpoints .
interestingly , the vasopressin - treated group had a 28-day mortality of 35% compared with 39% of the group treated with noradrenaline alone , which is clearly much less than one would expect .
the authors do suggest that this may reflect an improvement in the overall care of patients with septic shock , but equally it could reflect the selection criteria used : 6,229 patients were assessed for eligibility but more than 5,000 patients were not enrolled , a significant proportion of whom had cardiac disease .
the authors themselves do concede that the baseline mean arterial pressures observed ( 72 to 73 mmhg ) were somewhat higher than expected and therefore the trial probably reflects the use of vasopressin as a catecholamine - sparing drug rather than being an evaluation of vasopressin as an agent in shock unresponsive to catecholamines .
subgroup analysis on those " thought to be more severe " ( at least 15 g noradrenaline per minute ) , on whom vasopressin might be deemed to have a greater effect , failed to show any decrease in mortality .
it does show that , in this carefully selected patient cohort , vasopressin use is safe but does not confer any additional benefit over catecholamine use . as with many studies ,
we await the next randomised controlled trial ! the differences between everyday clinical practice and the restrictive environs of the randomised controlled trial are further highlighted in a retrospective observational study by wheeler and colleagues on the use of drotrecogin alfa ( activated ; drotaa ) .
this is an interesting study that compares drotaa use in five teaching institutions with that reported in the recombinant human activated protein c worldwide evaluation in severe sepsis ( prowess ) trial   and demonstrates that in the group observed , which reflects current practice , patients who received drotaa were younger , had more severe illness , increased comorbidities and received treatment later than those enrolled in the prowess study .
indeed , nearly 50% of those treated would have been ineligible for the prowess trial principally through delayed onset of treatment , with 33.9% of patients receiving drotaa later than 2 days after the onset of severe sepsis .
what is clear is that those patients receiving early treatment ( day 0 ) fared similarly in terms of mortality to those in the prowess study despite the disparity in the groups .
those treated later did not ; for example , patients treated at day 0 had a 33% mortality , whereas those treated at day 2 or later had a 52% mortality .
these results probably strengthen the case for drotaa use when applied appropriately and yet again emphasises the need for the early recognition and treatment of sepsis .
the evolution of the treatment of our patients with septic shock requires continuing to search for improvements in outcome through alternative agents .
relatively recently , the anti - inflammatory role of the vagus nerve has been explored in an animal model of endotoxaemia and shock , the so - called ' cholinergic anti - inflammatory pathway ' , and is a mechanism for the neural inhibition of inflammation through regulation of the inflammatory response . a recent study by hofer and colleagues in critical care medicine addresses this through assessing the role of pharmacological cholinesterase inhibition on survival in experimental sepsis . a murine model of sepsis
animals were then treated with intraperitoneal injections of nicotine , physostigmine or lipopolysaccharide - free 0.9% normal saline .
animals treated with intraperitoneal injections of nicotine ( 400 g / kg ) , physostigmine ( 80 g / kg ) and neostigmine ( 80 g / kg ) demonstrated improved survival , and treatment with physostigmine significantly reduced lethality as efficiently as direct stimulation of the cholinergic anti - inflammatory pathway with nicotine .
downregulation of the binding activity of nuclear factor-b was observed , together with a significant decrease in the concentrations of the circulating pro - inflammatory cytokines tumour necrosis factor- , interleukin-1 and interleukin-6 as well as a decrease in pulmonary neutrophil invasion .
there was no observed difference in survival between the groups treated with neostigmine and physostigmine ; interestingly , as in most things , septic delay of treatment beyond 6 hours negated any positive effects on survival .
the last 5 years has seen a small collection of studies that have demonstrated a potential role for cholinesterase inhibitors and nicotine in the management of sepsis and improved outcomes ; we await further studies with interest .
barnato and colleagues present a different slant on sepsis , performing a retrospective study on the racial variation of patients with sepsis admitted to hospitals within six us states .
this study demonstrates that the incidence of severe sepsis in blacks is significantly higher than in whites or hispanics .
the authors have made considerable efforts to negate the confounding effects of poverty and geography , although they admit that unmeasured differences in behaviour may be relevant to their results .
however , they do raise the hypothesis that biological differences in susceptibility may also have a role .
no doubt , with the rising tide of genetic studies , further information is not too far away .
finally we return to the surviving sepsis campaign guidelines , which ' recommend the protocolized resuscitation of a patient with sepsis - induced shock ... this protocol should be initiated as soon as hypoperfusion is recognized and should not be delayed pending icu admission ' .
the studies highlighted here all reinforce the need for the prompt recognition and early treatment of sepsis .
adherence to these guidelines may have more of an impact on the outcome of our patients than any new , as yet unproven , treatments .
drotaa = drotrecogin alfa ( activated ) ; prowess = recombinant human activated protein c worldwide evaluation in severe sepsis .
 the choice of inotropic agent , particularly in catecholamine - resistant septic shock , remains an area of debate . 
 here we discuss a recent trial examining the use of vasopressin in a carefully controlled trial setting . 
 yet more data on the use of drotrecogin alfa ( activated ) in septic shock are described , as are novel but as yet experimental approaches to the treatment of sepsis . 
 finally , it is important not to forget to read the latest surviving sepsis guidelines . 
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