illness in the intensive care unit is defined not by pathologic changes in a particular tissue or by structural changes in a specific organ , but by a constellation of quantifiable changes in physiological and biochemical measures .
to round in an intensive care unit is to be exposed to a cacophony of numbers  the ph , the glasgow coma scale , the fibrinogen level . to be an intensivist means to take this chaotic melange of digits and to transform them into a clinical profile that will support a therapeutic decision . an uninitiated visitor to a contemporary intensive care unit
could be forgiven for concluding that the intensivity of intensive care referred to the zeal with which its practitioners measure things : the continuous recording of the pulse , the blood pressure and the transcutaneous oxygen saturation , and the frequent assay of circulating factors whose function is familiar ( e.g. potassium or hemoglobin ) as well as those factors whose biologic significance is less so . high on the list of those less significant factors is procalcitonin . in the present issue of critical care , level and colleagues
report the results of a carefully conducted cohort study of 15 patients undergoing continuous venovenous hemodialysis .
they show that procalcitonin ( pct ) is cleared by continuous venovenous hemodialysis at conventional filtration rates and that the protein adsorbs to the filter , so as much as 20% of pct is removed through the membrane .
the consequences of this removal are modest , however , and are probably not clinically significant .
what message should the beleaguered intensivist , struggling to maintain a focus in the face of an onslaught of new measures and new sources of uncertainty , take from this report ?
i believe there are two : one message regarding the utility of pct as a diagnostic marker , and the second message addressing the more fundamental question of how to interpret the masses of numeric information generated within the intensive care unit .
a report by assicot and colleagues a decade ago , evaluating 79 children suspected of being infected , suggested that elevated levels of pct could reliably discriminate patients who were truly infected from those patients in whom clinical signs of acute inflammation were initiated by noninfectious stimuli . since that report , and driven in no small part by the development of a reliable assay for pct , a medline search using the keyword ' procalcitonin ' currently identifies 483 publications
these studies suggest that , although pct levels can be elevated in noninfectious conditions such as the treatment of transplant rejection with antibodies to cd3 , elevated levels of pct are a reliable and specific marker of invasive infection [ 4 - 6 ] , and that adequate treatment of such infection results in a reduction in the levels of circulating pct .
the utility of pct as a diagnostic marker appears to be less in its sensitivity to detect infection than in its specificity to rule it out . in particular ,
a low level of pct permits the clinician to be confident that infection is not present with greater than 90% certainty .
but if pct is a promising marker that permits us to conclude that a critically ill patient is not infected ( and so to avoid noninformative diagnostic investigations or exposure to unnecessary antibiotics ) , how confident can we be that the information it provides can be applied in all critically ill patients ?
clinicians must make categorical , yes / no decisions based on data that are continuous in character .
a culture of a venous catheter tip is considered positive if more than 15 colonies of bacteria are present following a standardized method of culture , or transfusion is administered if the hemoglobin level is less than 70
the validity of each of these thresholds has been established empirically , but their successful application depends on the reliability of the measure that is used .
can that reliability be significantly jeopardized by an artifact resulting from the confounding effects of the underlying disease or its treatment ?
this is the question that level and colleagues sought to address , and a question of practical importance to the interpretation of diagnostic tests in the intensive care unit .
the circulating level of a given molecule depends on three factors : the rate of production and release of the molecule , the rate of its removal , and the volume within which it is diluted .
when rates of production and removal are equal , a steady - state constant level results .
however , the actual measured level of that steady state will depend on the volume of distribution .
although the kinetics of the synthesis and release of pct are not well understood , its synthesis and release appear to be triggered by invasive infection , with the result that levels in the circulation increase .
the magnitude of this increase is clearly large enough to offset the reduction in concentration that might result from the presence of a larger volume of redistribution in the resuscitated , septic patient .
is it , therefore , either artefactually increased in renal failure or reduced by hemodialysis ?
herget - rosenthal and colleagues studied pct levels in 68 patients with acute or chronic renal failure treated by intermittent hemodialysis .
they found that elevated pct levels had an 84% positive predictive value and an 87% negative predictive value for the diagnosis of infection .
low flux membranes did not alter these figures after the start of dialysis , while high flux membranes did result in a significant reduction in the negative predictive value to 54% .
in contrast , in a study of 26 patients undergoing continuous venovenous hemofiltration , meisner showed that although pct was adsorbed to the membrane , and removed in the ultrafiltrate , plasma levels remained constant .
it thus appears that continuous venovenous hemodialysis at conventional flow rates does not jeopardize the diagnostic utility of pct ; whether high - volume hemofiltration has an effect remains to be determined . from a broader perspective
, the evolving literature on pct underlines the conceptual quandaries that confront the contemporary intensivist . why is the pro form of a calcium - regulating hormone released during bacterial infection
? is its release a marker of an appropriate host response to that infection , or is it a marker of a maladaptive response that might contribute to the morbidity of sepsis ? is pct simply a convenient diagnostic marker , or is it an appropriate target for therapy ?
are the diagnostic criteria of infection used to evaluate pct performance indicative of a disease process ( infection ) whose timely and appropriate treatment might improve outcome ? or , rather , are the criteria surrogate markers of an alternate disease ( hyperprocalcitonemia ) that merits therapy in its own right ?
the emergence of the intensive care unit as a locus for providing supportive care for critically ill patients has confronted us with challenges that are unprecedented in medical history .
intensive care units care for a population of patients who , if nature were permitted to take her course , would die a rapid death . in the absence of fluid replacement and circulatory support with exogenous catecholamines and vasoactive agents ,
the end result of shock is a quiet death from circulatory insufficiency ; without the mechanical ventilator , hypoxemia similarly leads inevitably to a rapid demise .
but if survival under these circumstances is unprecedented , how should we interpret the biochemical and physiologic events that occur in patients who remain alive only because of the intervention of the intensivist ?
there is no compelling evolutionary argument to support the advantages of one physiologic state over another : those who in an earlier era would have died do not contribute to the gene pool , and even in our own brave new age reproduction while on the ventilator is distinctly uncommon . under these circumstances ,
what is normal may not be what is optimal , and what is abnormal may not be reliable .
 intensivists depend upon a large number of measurements to make daily decisions in the icu . 
 however , the reliability of these measures may be jeopardized by the effects of therapy . moreover , in critical illness , what is normal is not necessarily optimal . 
 procalcitonin , a putative marker of occult infection , is emerging as a valuable diagnostic marker in the icu . 
 although questions remain regarding its specificity , an increasing body of work suggests that it is reliably elevated in the setting of infection . 
 as demonstrated by level and colleagues in this issue of critical care , its utility as a diagnostic marker is not affected by concomitant hemodialysis . 