procalcitonina y pcr en politrauma

7/25/2019 Procalcitonina y PCR en Politrauma

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Correlation of Procalcitonin and C-Reactive Protein to Inflammation,

Complications, and Outcome During the Intensive Care Unit Course of

Multiple-Trauma Patients

Michael Meisner; Heie !ina; "oachi# $ch#itrit are. !""5#1"$1% &!""5 'io(ed entral, )td.op*right to this article is held b* the a+thor$s%, licensee 'io(ed entral )td. This is an pen -ccess article: verbatimcop*ing and redistrib+tion o this article are permitted in all media or an* p+rpose, provided this notice is preserved

along with the articles original citation.0osted 1!/"7/!""5

!bstract an Introuction

!bstract

%ack&roun:- comparison o the amo+nt o and the inetics o ind+ction o procalcitonin $0T% with that o 2reactiveprotein $0% d+ring vario+s t*pes o and severities o m+ltiple tra+ma, and their relation to tra+ma2relatedcomplications, was perormed.Methos:4inet* ad+lt tra+ma patients admitted to the intensive care +nit o o+r tertiar* care hospital were eval+ated in

a prospective case st+d*. +ring the initial !6 ho+rs ater tra+ma the n+r* everit* core, the epsis2related rganail+re -ssessment score, and the -c+te 0h*siolog* and hronic ;ealth +ito+sl*increased and its inetics were m+ch slower. omplications s+ch as sepsis, inection, blood trans+sion, prolongedintensive care +nit treatment, and poor o+tcome were more re>+ent in patients with initiall* high 0T $? 1 ng/ml%,whereas increases o 0 showed no positive correlation.Conclusion:n patients with m+ltiple tra+ma d+e to an accident, the 0T level provides more inormation than the0 level since onl* moderate amo+nts o 0T are ind+ced, and higher concentrations correlate with more severetra+ma and a higher re>+enc* o vario+s complications, incl+ding sepsis and inection. (ost importantl*, the moderate

tra+ma2related increase o 0T and the rapidl* declining concentrations provide a baseline val+e near to the normalrange at an earlier time rame than or 0, th+s allowing a aster and more valid prediction o sepsis d+ring the earl*period ater tra+ma.

Introuction

(+ltiple2tra+ma patients are especiall* prone to develop complications s+ch as inections and sepsis. ince clinicals*mptoms and conventional marers are not alwa*s reliable signs or the diagnosis o sepsis and inection, biomarerss+ch as procalcitonin $0T% or 2reactive protein $0% are oten +sed as a diagnostic tool in these patients. (+ltiple2tra+ma patients, however, similar to patients +ndergoing elective s+rger*, ma* show an increase o 0T, 0, andother biomolec+les, indicating inlammation, d+ring the earl* postoperative or post2tra+matic period independent o thediagnosis o sepsis or inection. @126A

everal st+dies previo+sl* described the inetics and the amo+nt o 0T ind+ced ater elective s+rger* and tra+ma. @1,38AThe ind+ction o 0T and 0 ater s+rger* has been described >+ite well in the meantime: 0T levels increase ar
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less than 0 levels, and the period o +nspeciic ind+ction is m+ch shorter. @1,7AThe 0T parameter is thereore thebetter choice to diagnose sepsis and inection earl* ater s+rger*. ata on 0 ind+ction ater m+ltiple tra+ma arescarce, however, and provide no detailed data on the ind+ction o this protein at vario+s severit* levels and t*pes otra+ma as compared with 0T.@3,9A

The aim o this st+d* was to describe the amo+nt o and the time co+rse o 0T and 0 ind+ction in patients withvario+s t*pes o and severities o high2velocit* tra+ma. We +rther registered tra+ma2related complications $oreBample, sepsis, inection, blood trans+sion, organ d*s+nction%, as described b* the epsis2related rgan ail+re-ssessment $-% score, the -c+te 0h*siolog* and hronic ;ealth +are o the highest points in each o the three mostseverel* in+red areasM. The ollowing regions are scored according to a scale o " $no in+r*% to D $maor in+r*%:head/nec, ace, thoraB, abdomen, eBtremities, and eBternal wo+nds.

$tatistical !nalysis

tatistical eval+ation was carried o+t +sing the program 0 1"." or Windows. Nariables were deined as the medianand +pper and lower >+artiles. When Or+sal=Wallis anal*sis indicated a signiicant dierence among gro+ps, the(ann=Whitne* Utest was +sed to compare the gro+ps. orrelations were calc+lated b* the pearman rancorrelation. ncreased ris was calc+lated b* the odds ratio, and signiicance was tested b* the chi2s>+are test. Thearea +nder the c+rve o the receiver operating characteristic was calc+lated and plotted b* 0 1".". tatistical

comparison between the area +nder the c+rve o the vario+s parameters was calc+lated +sing the method developedb* ;anle* and (c4eil,@1DAin which z? 1.9D indicates a level o signiicance or an alpha error less than 5P. The


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(c4emar test was +sed or comparison o sensitivit* and speciicit* among parameters and scores at a given c+topoint. tatistical signiicance was accepted or PI "."5. - 'onerroni correction was calc+lated or each gro+p ocomparisons.

Results

Patient Characteristics

+t o 1"! patients with accidental high2velocit* m+ltiple tra+ma, 9" met the incl+sion criteria d+ring the st+d* period.Twelve o the initiall* eval+ated patients co+ld not be ollowed +p beca+se o a atal o+tcome within 1! ho+rs. Themedian age was 36 *ears $range, 1D=86 *ears# !9 emale patients, D1 male patients%.


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(i&ure ).

;istogram o the da* o maBim+m concentrations o procalcitonin $0T% and 2reactive protein $0% in m+ltiple2tra+ma patients

0T concentrations declined more rapidl* than those o 0 $ig+re !%. n da* 7 ater tra+ma, the 0T level waswithin the normal range in 88P o the patients while the 0 level was within the normal range in onl* DP o thepatients.


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(i&ure *.

er+m levels o procalcitonin $0T% and 2reactive protein $0% in patients with m+ltiple tra+ma

Inluence o Ty+e o an $e,erity o Trau#a

The maorit* o the patients presented with m+ltiple tra+ma o vario+s regions o the bod*. even patients were in+redin onl* one or two regions, !5 patients in three regions, 35 patients in o+r regions, and !3 patients in ive or moreregions. 0T and 0 concentrations according to the region o in+r* are s+mmariEed in Table !. There was nostatistical dierence in 0T levels between the speciic tra+ma patterns# however, patients with abdominal tra+maobvio+sl* presented with somewhat higher 0T levels $PQ ".""6, corresponding to an ad+sted alpha error o D.5P orm+ltiple comparisons%.


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with those with maor blood loss $? ! +nits trans+sed, 0T Q 3."5 ng/ml, median# PI ".""1%.

When patients were categoriEed into those with moderate or severe tra+ma $ I !" or F !"%, the initial 0T b+t not0 was signiicantl* higher in patients with severe tra+ma $PI ".""1 and P


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(i&ure /.

o+rse o procalcitonin $0T% $median, >+artiles% d+ring the irst wee ater tra+ma in nons+rvivors $n Q 15% and ins+rvivors $n Q 75%


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(i&ure 0.

o+rse o 2reactive protein $0% $median, >+artiles% d+ring the irst wee ater tra+ma in nons+rvivors $n Q 15% and ins+rvivors $n Q 75%

Role o Inection

n the present st+d*, inection was s+spected in 69 o the 9" patients and was proven in 6" patients d+ring the !12da*observation period. 0ositive microbial indings were derived rom pne+monia in 31 cases, rom positive blood c+lt+resin 1" patients, rom colitis in 1" patients, and rom wo+nd and +ngal inections in o+r patients. ive patients had+rinar* tract inections $m+ltiple microbiological indings%. n average, inections occ+rred D S 3 da*s $mean S standarddeviation% ater the tra+ma. nitial 0T levels $da*s 1 and ! ater tra+ma% were signiicantl* higher in patients whos+bse>+entl* developed inections: !.D9 ng/ml vers+s ".56 ng/ml $median, PI ".""1% or s+spected inection vers+s nos+spected inection, and 3."1 ng/ml vers+s ".57 ng/ml or proven inection vers+s no proven inection $ PI ".""1%. nitial0 concentrations $da*s 1=3% did not signiicantl* dier in patients developing a proven inection $1"9 mg/l vers+s13D mg/l, PQ "."!8# not signiicant according to m+ltiple comparisons% or in patients in whom inection was s+spected$1"9 mg/l vers+s 1!! mg/l, PQ ".1D3# not signiicant according to m+ltiple comparisons%. or a 0T val+e F 1 ng/ml the


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odds ratio or the development o an inection was D.1 $95P conidence interval, !.6=15.7%.

The d+ration o treatment on the C was also dierent in patients with diagnosis o inection as compared with in thosewitho+t. n average, patients witho+t an inection were treated in the C or D S 6 da*s $mean S standard deviation%,as compared with !" S 1! da*s or those who had an inection $PI "."5%. -mong patients witho+t an inection onl* 1D

o+t o 5" patients $3"P% were treated on the C or more than 7 da*s, as compared with 38 o+t o 6" patients $95P% inwhom an inection had developed. imilarl*, 0T concentrations on da* 7 were signiicantl* higher in patients who hadan inection, compared with those witho+t an inection: ".D6 ng/ml $median, >+artiles ".1=8.35% vers+s I ".3 ng/ml$median, >+artiles ".1=".57% $PI ".""1, (ann=Whitne* Utest%. 0 concentrations did not signiicantl* dier at thistime point $13! mg/l and 9" mg/l, PQ "."5!%.

-e,elo+#ent o $e+sis

epsis, severe sepsis, or septic shoc was also more re>+entl* diagnosed d+ring the observation period in patientswho initiall* developed higher 0T levels. n the contrar*, the level o the initial 0 concentration was not related tothis diagnosis $ig+re 5%. or eBample, the initial 0T median $>+artiles% concentration in patients who did not develops*stemic inlammator* response s*ndrome $% or sepsis d+ring their whole co+rse was ".53 ng/ml $I ".3 to ".98

ng/ml%, compared with those who did develop $".77 ng/ml, I ".3 to !.53# not signiicant%, sepsis $!.!1 ng/ml,1."3=5.1D# PQ ".""3%, severe sepsis $5.D8 ng/ml, 1.8!=9.5D# PI ".""5% or septic shoc $D."D ng/ml, !.D9=13.6# PI".""5%. 0T levels o patients who had either or sepsis were not signiicantl* dierent $PQ "."!1# not signiicantor m+ltiple comparisons%. 0T concentrations remained elevated in patients with sepsis, severe sepsis, or septicshoc, b+t rapidl* dropped bac to near2normal val+es in patients witho+t sepsis $ig+re D%.


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(i&ure 1.

nitial ser+m concentrations o procalcitonin $0T% $"=68 ho+rs% and 2reactive protein $0% $"=7! ho+rs% ater

mechanical tra+ma, and the development o septic complications d+ring a !12da* ollow2+p


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(i&ure 2.

o+rse o procalcitonin $0T% in patients who developed vario+s stages o sepsis, s*stemic inlammator* responses*ndrome $%, or no sepsis $median and >+artiles%

The odds ratio or the development o sepsis/severe sepsis or septic shoc was increased or 0T $F 1 ng/ml%, or $F !"%, and or - score $F 1!%, b+t not or the other parameters $PI ".""!, chi2s>+are test% $ Table 3%.

-e,elo+#ent o Co#+lications: Or&an -ysunction

-ltho+gh high 0T levels related to a higher re>+enc* o developing sepsis, the initial 0T and 0 concentrationsdid not correlate with the severit* o organ d*s+nction, meas+red as maBim+m - score val+es d+ring the st+d*period $rQ ".638, PI "."1# not signiicant or m+ltiple comparisons%. (oreover, 0T levels meas+red dail* onl* weal*correlated with the corresponding - score at this time point $ rQ ".5"=".73 rom da* 1 to da* 16, PI "."5%.imilarl*, the initial 0T val+es did not correlate with the -0-;< score, meas+red 1 da* ater the tra+ma had
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occ+rred $rQ ".395, PQ "."1%.

-iscussion

The present st+d* was designed to anal*Ee the amo+nt o and the inetics o ind+ction o 0T and 0 earl* atertra+ma depending on the t*pe and the severit* o the tra+ma and its related complication. 0T and 0 were ind+cedin vario+s amo+nts in patients with mechanical tra+ma. 'oth parameters showed dierent time co+rses o ind+ction.0 ind+ction ater tra+ma showed a +niorm response with no signiicant relation to tra+ma severit*, development othe vario+s stages o sepsis, as well as the d+ration o C treatment and o+tcome. +rthermore, concentrations wereelevated or several da*s ater the tra+ma. 0T ind+ction was moderate, b+t diered according to the severit* otra+ma. 0atients with high 0T plasma levels more re>+entl* developed vario+s complications, incl+ding theprolongation o treatment in the C and a worse o+tcome. nterestingl*, compared with the inetics seen or 0,plasma levels o 0T declined more rapidl* in patients witho+t complications.

0T and 0 are increasingl* +sed as marers or the diagnosis o sepsis and inection. ;owever, both parametersare also ind+ced independent rom inection $or eBample ollowing cardiogenic shoc, maor s+rger*, or mechanicaltra+ma%. @1,3,17,18An cardiac s+rger*, 0T is elevated in patients with p+lmonar* d*s+nction and noninectio+s . @!,192!!A

ncreased plasma levels are related to circ+lator* ail+re, the need or high doses o catecholamines, bloodtrans+sions, and s+rgical re2interventions.@!A-lso, ater elective general s+rger*, high posts+rgical plasma levels wererelated with a higher rate o complications. 0atients +ndergoing colon s+rger* or aortic s+rger* more re>+entl*developed inections or ins+icienc* o the anastomosis when 0T concentrations were increased ater s+rger*. @!3A

T*picall*, a c+to 0T2level o 1.5=! ng/ml has been described as an indicator o increased ris ater vario+s t*pes oelective s+rger* $or eBample, colon s+rger*, aortic s+rger*, and cardiothoracic s+rger*%. @!,!3,!6A

To compare the increase o 0T in this st+d* in patients who later developed complications with the data o previo+sst+dies, we calc+lated a c+to val+e or the diagnosis o sepsis. ontrar* to the previo+s st+dies, however, this c+toval+e onl* indicates the ris or the development o s+ch complications d+ring the +rther co+rse o the disease, b+t notthe act+al sensitivit* or speciicit* or the diagnosis o sepsis or the respective complications at this speciic time point.4evertheless, 0T with a c+to val+e o 1.5 ng/ml had a speciicit* o 7"P or the diagnosis o sepsis in this st+d*.These data were similar to the res+lts o 0T meas+rements o a st+d* p+blished previo+sl* b* Wanner andcolleag+es. The* reported a c+to val+e o 1.5 ng/ml 0T on da* 1 or da* 3 ater tra+ma and a sensitivit* andspeciicit* o 75.DP and 77.3P, respectivel*, or the diagnosis o sepsis as compared with the noninection2relatedsevere .@3A

-lso in o+r st+d* the amo+nt o 0T and 0 t*picall* ind+ced ater accidental tra+ma did not s+bstantiall* eBceedthose concentrations reported previo+sl* ater elective s+rger*, especiall* i maor s+rgical proced+res were compared.@1,!,7,!"2!!A

0T concentrations o approBimatel* 1=1.5 ng/ml are also reported in vario+s st+dies to be the best c+to level or thediagnosis o sepsis as compared with . @!52!8ANer* high 0T concentrations ater tra+ma thereore indicate as+bstantiall* increased ris o complications, incl+ding sepsis, organ d*s+nction, or lethal o+tcome, whereas

moderatel* increased 0T concentrations $below 1.5=! ng/ml% are +s+all* not o maor concern.

n the present st+d*, 0T levels were not dierent in patients who +nderwent s+rgical proced+res earl* ater tra+ma ascompared with those witho+t s+rger*. We o+nd a tendenc* to higher 0T levels ollowing abdominal tra+ma. This is inagreement with ormer observations in patients +ndergoing elective s+rgical proced+res at dierent regions o theorganism, where we o+nd higher 0T and 0 levels ater s+rger* o the intestine $0T: median, 1.5" ng/ml# 9"Ppercentile, 3." ng/ml# 0: median, 131 mg/l# 9"P percentile, !3" mg/l% than ater minor and less elective tra+matics+rger* $0T: median, ".38 ng/ml# 9"P percentile, ".73 ng/ml# 0: median, D1 mg/l# 9"P percentile, 181 mg/l%. @1A

The ca+se o the ind+ction o 0T ater tra+ma is not completel* +nderstood.


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cell+lar activation, and dierent cell+lar behavior when cells are native or pre2eBposed to proinlammator* stim+li. nshort, onl* adherent monoc*tes prod+ce a signiicant amo+nt o 0T. irc+lating monoc*tic cells do not prod+ce a>+antitative amo+nt o 0T. This is the irst e* or the +nderstanding o 0T ind+ction ater tra+ma, since theeBpression o adhesion molec+les and receptors also occ+rs in tra+matiEed tiss+e.

nce ind+ced, 0T acts as a chemoine in this area, attracting +rther monoc*tes# however, this propert* is lost ater aew ho+rs, when cells are preinc+bated or are in contact with 0T, th+s limiting the local action to the ac+te phaseresponse.@3!A+rthermore, prod+ction o 0T in adherent monoc*tes is also limited to a period o onl* a ew ho+rs. )ateron, parench*mato+s cells are a maor so+rce or 0T d+ring sepsis,@33Ab+t these cells $as investigated presentl* onl* oradipoc*tes% prod+ce maor amo+nts o 0T onl* when the* become directl* in contact with activated monoc*tes. @36AThisis another e* or the +nderstanding o 0T ind+ction ater tra+ma.

ho+ld s*stemic inlammation, sepsis, or organ d*s+nction occ+r, there is a contin+o+s and s*stemic stim+l+s or theprod+ction o 0T, whereas the tra+ma2related local ind+ction o 0T soon declines, i the inlammation in thetra+matiEed tiss+e disappears. onse>+entl*, local tiss+e in+r* in combination with the activation o the imm+nes*stem is a maor ca+se or the ind+ction o 0T ater tra+ma. +ring a s*stemic inlammator* response s+ch assepsis there eBist additional maor so+rces or 0T $or eBample, the liver%. ncreased levels o 0T, compared with

lower circ+lating plasma levels, have been meas+red in hepatic veno+s blood,

@35A

and a signiicant 0T prod+ction wasabsent in an anhepatic baboon d+ring endotoBin shoc.@3DA

ther complications o tra+ma that are associated with severe tiss+e tra+ma $or eBample, malper+sion d+e tohemorrhagic shoc or tra+ma2associated blood loss% and trans+sion o allogeno+s blood cells ma* also contrib+te tothe ind+ction o 0T and ma* promote the development o organ d*s+nction and poor o+tcome in these patients. 0Tind+ction occ+rred d+ring hemorrhagic shoc in a baboon shoc model, b+t it was weaer than 0T ind+ction d+ringendotoBin shoc.@37A

The biological action o 0T obvio+sl* has a signiicant inl+ence on the co+rse o the s*stemic inlammation andsepsis. The mortalit* rate o hamsters decreased when calcitonin prec+rsors where ne+traliEed,@38Aand the mean arterialpress+re and +rine o+tp+t increased ater the in+sion o ne+traliEing antibodies against calcitonin prec+rsor molec+lesin a porcine model.@39AIn vitro, 0T a+gmented the ind+ction o ind+cible nitric oBide s*nthase in c+lt+red smooth

m+scle cells preinc+bated with proinlammator* stim+li. @6"A- negative eect o high 0T levels in m+ltiple2tra+mapatients in the +rther co+rse o inlammation and the development o complications s+ch as organ d*s+nction cannotbe eBcl+ded at present.

Conclusion

0T and 0 levels meas+red earl* ater tra+ma increase in patients with severe tra+ma. n addition to previo+sst+dies, we have anal*Eed the vario+s t*pes o tra+ma and have compared 0T with 0 and vario+s clinical scores*stems. Cnlie 0, 0T val+es t*picall* declined rapidl* ater tra+ma. The rapid decline o the tra+ma2ind+cedresponse o 0T towards its normal range compared with the long2lasting increase o 0 promises an earlierdiagnostic +se o 0T as a marer o sepsis and inection than o 0, since sepsis and inection can be diagnosedwith high speciicit* onl* i there is no or onl* minor +nspeciic ind+ction.@!D,61A+r data demonstrate that the 0 level in

tra+ma patients is not a valid parameter to gather more inormation abo+t the severit* o s*stemic inlammation,complications, and prognosis o the patient. 0T and clinical score s*stems are e>+all* s+perior to 0 or ris2stratiication o the patient. ;owever, since 0T can additionall* be +sed as a marer or the diagnosis o sepsis soonater the initial tra+ma2related increase has again declined, the meas+rement o 0T is the s+perior parameter ochoice to diagnose sepsis in these patients. n the contrar*, the diagnostic +se o 0 ater tra+ma is limited sincesigniicant ind+ction occ+rs in almost all patients, and its inetics are slow.

O+en !ccess

This research article is open access, which means it is +niversall* and reel* accessible via the ritical are website,deposited in at least one widel* and internationall* recogniEed open access repositor* $s+ch as 0+b(ed entral%, andthe cop*right rests with the a+thors.

To access research articles on related topics, visit http://ccor+m.com/researcharticles.
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Table ). Patient Characteristics an Inection Markers Early !ter Minor or Ma3or $e,ereMechanical Trau#a

Table *. Inuction o Procalcitonin 4PCT5 an C6reacti,e Protein 4CRP5 !ccorin& to the Re&iono In3ury7 -eine by the In3ury $e,erity $core

Table /. $ensiti,ity an $+eciicity or the Preiction o 8arious Co#+lications in Multi+le6

trau#a Patients


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Reerences

1. (eisner (, Tschaiows* O, ;+tEler -, chic , ch+ttler : 0ostoperative plasma concentrations oprocalcitonin ater dierent t*pes o s+rger*. ntensive are (ed 1998, !6:D8"2D86.

!. (eisner (, a+schma*er , chmidt , e*rer , esnevar , 'redle , Tschaiows* O:


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procalcitonin and neopterin in m+ltiple tra+ma patients with or witho+t brain in+r*. 4e+rotra+ma !""3,!":95329D".

D. ;ensler T, a+erland , )eering , 4agelschmidt (, 'o+illon ', -ndermahr , 4e+geba+er ',


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$0roT% and opioid peptides co+rse d+ring a model o . hoc 1997, 8:67268.3". 4isten (W, linga 0, ;oestra ;: n vitro and in vivo stim+lation o procalcitonin b* T4UV and )2D.

-nasthes ntensiv Ther !""1, !:582D".31. berhoer (, tonans , +ssw+rm , tonane


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Michael Meisner,1Heie !ina,!and "oachi# $ch#it3

1epartment o -naesthesiolog* and ntensive are (edicine, ;ospital resden 4e+stadt, nd+striestrasse 6", 2"11!9 resden, Lerman*!epartment o -naesthesiolog* and ntensive are Therap*, riedrich chiller Cniversit* ena,

procalcitonina y pcr en politrauma

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