Although we controlled for the major factors influencing endothelial function, we cannot exclude minor influences of altered thyroid or adrenal function. Due to variations in sample processing time, we were unable to determine accurate plasma arginine values for all subjects. Thus the reported arginine values may not be fully representative of the groups as a whole. Of the subjects who had an initial measurement of RH-PAT index, 70% had a repeat measurement 2 to 4 days later. Although those who were not followed up had a similar baseline APACHE II score to those who were followed up, this may not have been a representative population, because subjects who rapidly improved and were discharged home did not have repeat measurements. Thus the observed degree of recovery in microvascular reactivity is likely to be an underestimate.The mortality rate in this cohort was low (hospital and 28-day mortality 9% overall and 21% among those with septic shock). Although this is consistent with the relatively low mortality rate in severe sepsis previously documented in our ICU [35], it does mean that the study may have been underpowered to detect associations of measured variables with mortality.ConclusionsIn summary, we have found that peripheral arterial tonometry is a feasible tool for measuring microvascular reactivity in sepsis, and that it is impaired in sepsis in proportion to disease severity, suggesting reduced endothelial function and decreased endothelial NO bioavailability. Baseline RH-PAT was useful in predicting subsequent deterioration in organ dysfunction, although this should be reproduced by other investigators before its clinical utility can be confirmed. Given the growing interest in HMG CoA reductase inhibitors [58] and other potential adjunctive therapies targeting the endothelium in sepsis [55], better tools for monitoring the response of the endothelium in clinical trials are needed. RH-PAT is an attractive option for such studies, as other current methods are user-dependent and have limited availability.Key messages? Current tools for assessing endothelial function in patients with sepsis are generally user dependant and are not widely available.? Peripheral arterial tonometry, a simple, user-independent technique for measuring endothelium-dependent microvascular reactivity is feasible in patients with sepsis.? Endothelium-dependent microvascular reactivity is impaired in sepsis, in proportion to disease severity, and may predict subsequent deterioration in organ function.