Sepsis needs follow-up studies in intensive care units : another avenue for translational research

Mini Re iew Volume 1 Issue 1 - May 2017 No App o D ug Des De Copy igh © All igh s a e ese ed by Ca lo a Saldanha Sepsis Needs Follow-Up S udies in In ensi e Ca e Uni s- Ano he A enue o T ansla ional Resea ch Ca lo a Saldanha* and An ónio Messias** *Ins i u e o Molecula Medicine, Ins i u e o Biochemis y, Facul y o Medicine, Uni e si y o Lisbon, Po ugal **Di ec o o In ensi e Ca e Uni in Hospi al Bea iz Ângelo. Lou es, Po ugal Submission: Ma ch 28, 2017; Published: May 02, 2017 *Co esponding au ho : Ca lo a Saldanha, Ins i u e o Molecula Medicine, Ins i u e o Biochemis y, Facul y o Medicine, Uni e si y o Lisbon, Po ugal, Email: Mini Re iew The high mo ali y e i ied wo ldwide in pa ien s wi h sepsis in in ensi e ca e uni s (ICU) is a sad social p oblem ha needs o be sol ed. Sepsis is s ill a a al condi ion besides he epo e o many bioma ke s o diagnos ic and p ognos ic. “In he Uni ed S a es was es ima ed he occu ence o 751,000 cases o se e e sepsis pe yea (3.0 cases pe 1,000 popula ion and 2.26 cases pe 100 hospi al discha ges), o whom 383,000 (51.1%) ecei ed in ensi e ca e and an addi ional 130,000 (17.3%) we e en ila ed in an in e media e ca e uni o ca ed o in a co ona y ca e uni . Mo ali y was 28.6% o 215,000 dea hs na ionally. The a e age cos s pe case we e $22,100, wi h annual o al cos s o $16.7 billion na ionally. The Incidence was p ojec ed o inc ease by 1.5%pe annum [1] om he onse o sepsis synd ome, an imbalance be ween p o-in lamma o y and an i-in lamma o y mechanisms occu s. The in ensi y and du a ion o he in lamma o y esponse has been closely ela ed wi h mo ali y, since once ou o con ol in lamma ion leads o massi e p oduc ion o p o-in lamma o y cy okines, which in u n leads o coagula ion diso de , issue inju y, mul iple o gan dys unc ion, and ul ima ely o dea h. All s udies conduc ed un il now highligh di icul ies and inabili y o add ess he he e ogenei y ha cha ac e izes sepsis. Simul aneously in lamma o y esponse is igge ed as well o he s molecula mechanism in ol ing ho monal me abolic con ol, mac o and mic oci cula ion con ols a e call o eac changing hei homeos asis [2]. A mic oci cula ion blood low h ough small essels a o gas exchanges such as oxygen and ni ic oxide (NO) wi h ca bon dioxide, deli e nu ien s and emo e me aboli es and was e p oduc s [3]. E y h ocy es deli e O2 and NO in lowe oxygen pa ial p essu e (Pa O2) and sca enge hem a high PaO2 [3]. The abili y o e y h ocy e o deli e o e ain NO depends on he memb ane AChE enzyme ac i i y and p o ein con o ma ions [4]. Mic oci cula ion hemodynamic in luences blood p essu e, hemo heology and mic o ascula cells wall pa icipa e in in lamma ion. When mic oci cula ion s a s o be comp omised se e e uncon olled ou comes appea . Impai ed sensi i i y o endo helial cell (EC) in mic o ascula u e o asocons ic ion/ asodila ing subs ance is a signal o endo helium dys unc ion [5]. This is wo sening by he dec ease in blood low a e consequen ly o dec eased e y h ocy e de o mabili y and inc ease e y h ocy e agg ega ion [5]. So, he e a e c ea ed condi ions o a high pe manence o whi e blood cells (WBC) in he EC su ace [5]. Unde in lamma o y s imuli he WBC dec ease i s olling eloci y, inc easing adhe ence and ansmig a ion un il he ocus o issue inju y [6]. Neu ophils ec ui men o si es o in ec ion is a c i ical elemen o he inna e immune esponse, being he cells ha mig a e i s o an in ec ious si e esponding o chemo a ac an s ac o s and cy okines. Neu ophils a e able o kill mic oo ganisms by eleasing bac e icidal agen s like oxygen and ni ogen eac i e species. The neu ophils, in addi ion also elease, cy okines and chemokines which enhance he ec ui men and ac i a ion o immune cells. Du ing he p o- No App o D ug Des De 1(1): NAPDD.MS.ID.555555 (2017) 001 Abs ac Sepsis cha ac e is ics we e highligh in his mini e iew in o de o call a en ion o a complex, age- independen , acu e disease aced suddenly by he human body unde in ec ion o auma ic s imuli. I may ollow su gical in e en ion, auma ic acciden o exposu e o an in ec ious agen . Timely diagnosis and accu a e s a i ica ion o he se e i y o sepsis a e needed o unde s and he molecula mechanisms in ol ed in his pa hophysiology and educe mo ali y. In o de o ob ain hese achie emen s ollow-up s udies need o be conduc ed in in ensi e ca e uni s unde ansla ional esea ch. Keywo ds: Sepsis, In ensi e ca e uni , In lamma ion, Ni ic oxide, Ace ylcholines e ase How o ci e his a icle: C Saldanha, A Messias. Sepsis Needs Follow-Up S udies in In ensi e Ca e Uni s- Ano he A enue o T ansla ional Resea ch. No App o D ug Des De . 2017; 1(1) : 555555. 002 No el App oaches in D ug Designing & De elopmen in lamma o y phase, cy okines eleased om inna e immune sys em cells con ibu e o endo helial dys unc ion by di e en ways, including he in e e ence wi h he exp ession o iNOS ha o igina es ni ic oxide (NO) inc ease. The cu en knowledge on he mechanism by which NO modula es ascula unc ion/ dys unc ion in sepsis is limi ed. In sepsis, he ini ia ing s imuli o sys emic in lamma ion a e o en bac e ial componen s which induce he sec e ion o p o-in lamma o y cy okines om cells o he immune sys em [2]. The elease o hose p o-in lamma o y media o s in he cen al ne ous sys em a he onse o sepsis leads o neu onal loss [7]. This inding is on he base o cogni i e impai men wi h elec oencephalog aphic changes obse ed in some sepsis su i o s [7]. Sepsis p esen s an acu e pa e n o esponse o he immune sys em o he inju y wi h a my iad o changes in media o s o in lamma ion, hemos asis and me abolism [8]. Insulin esis ance in sepsis is la gely a ibu ed o he highe le els o TNF- alpha, IL-1, and IL-6 [8]. Insulin, glucose and lac a e le els a e associa ed wi h he clinical sepsis sco e APACHE-II alues [9]. In esponse o endo oxin, he body exhibi s ansien sys emic insulin esis ance, in an a emp o spa e glucose o u iliza ion by immune cells [10]. Pe sis en insulin esis ance appea s in sepsis because o he ni osyla ion o ni a ion o i s ecep o [10]. Insulin esis ance can be elimina ed in some pa ien s wi h sepsis by con inuous in a enous in usion o insulin in he o m o glucose-insulin-po assium (GIP) egimen ha imp o es su i al [11]. This is p esumably ela ed wi h dec eased exp ession o NF-kB, IL-1 and IL-6 [11]. Howe e , he deg ee o cell dys unc ion esul ing om he hype glycaemia ( ela ed o insulin esis ance) gene a es a mul i ude o changes in me abolic, hemos asis, and mic oci cula o y blood low in pa ien s unable hem o su i e [12]. Hype glycemia gene a es imbalanced oxidan and an i- oxidan pa hways, gene a ing high le els o oxygen and eac i e ni ogen species accompanied by abolished plasma an ioxidan capaci y [13]. This inc eased oxida i e s a e con ibu es o he endo helial dys unc ion wi h o e exp ession o inducible ni ic oxide syn heses (iNOS) and high elease o NO o he lumen [14]. NO sca enged by e y h ocy e impai ed he de o mabili y ha clogs capilla ies in he mic oci cula ion [15]. Mic oci cula ion issues gained inc eased impo ance in sepsis. The in oduc ion o bedside echniques in o clinical p ac ice allow unc ional hemodynamic moni o ing showing mic oci cula o y ailu e associa e o ad e se ou comes in pa ien ’s sepsis a in ensi e ca e uni (ICU) [16]. The complexi y o he sys emic in lamma o y esponse in di e en phases o sepsis, he lack o p og ess in ea men and also in pa ien s’ diagnosis and s a i ica ion demons a e he lack in knowledge o sepsis pa hophysiology. The app oach o measu ing a simple in lamma o y ma ke is no enough o assess pa ien s’ s a us. To di ec app op ia e he apy o indi idual pa ien and o imp o e diagnosis and s a i ica ion o pa ien s i is necessa y o iden i y he in lamma o y esponse p o ile o di e en pa ien s using mul iple ma ke s, and o un eil he ela ion o hose p o iles wi h he disease se e i y. To achie e ha an accompanying ollow-up e alua ion o in lamma o y, hemos a ics, bio heological and mic oci cula o y ma ke s is needed. In his pe spec i e, he p obabili y o an indi idualized ea men based on clinical and labo a o y e alua ions will be highe . Re e ences 1. Angus DC, Linde-ZWT, Lidicke J, Cle mon G, Ca cillo J, e al. (2001) Epidemiology o se e e sepsis in he Uni ed S a es: analysis o incidence, ou come, and associa ed cos s o ca e. C i Ca e Med 29(7): 1303-1310. 2. Ho chkiss RS, Ka l IE (2003) The pa hophysiology and ea men o sepsis. N Engl J Med 348(2): 138-150. 3. Ellswo h M, Ellis CG, Goldman D, S ephenson AH, Die ich HH, e al. (2009) E y h ocy es: Oxygen senso s and modula o s o ascula one. Physiology (Be hesda) 24: 107-116. 4. de Almeida Lopes JP, F ei as-San os, Saldanha C (2009) Fib inogen- Dependen Signaling in Mic o ascula E y h ocy e Func ion: Implica ions on Ni ic Oxide E lux. J Memb Biol 231(1): 47-53. 5. Ba i enko NN, Aslam M, Filosa J, Ma eucci E, Nikinmaa M, e al. (2013) Tissue oxygen demand in egula ion o he beha iou o he cells in he ascula u e. Mic oci cula ion 20(6): 484-501. 6. Tousoulis D, Simopoulou C, Papageo giou N, Oikonomou E, Ha zis G, e al. (2014) Endo helial dys unc ion in condui a e ies and in mic oci cula ion. No el he apeu ic app oaches. Pha macol The 144(3): 253-267. 7. Semmle A, F isch C, Debei T, Ramana han M, Okulla T, e al. (2007) Long- e m cogni i e impai men , neu onal loss and educed co ical choline gic inne a ion a e eco e y om sepsis in a oden model. Exp Neu ol 204(2): 733-740. 8. Ri i sch D, Flie l MA, Wa d PA (2008) Ha m ul molecula mechanisms in sepsis. Na Re Immunol 8(10): 776-787. 9. Nakamu a M, Oda S, Sadahi o T, Wa anabe E, Abe R, e al. (2012) Co ela ion be ween high blood IL-6 le el, hype glycemia, and glucose con ol in sep ic pa ien s. C i Ca e 16(2): R58. 10. Mo ei a APB, Al enas RCG (2012) The in luence o endo oxemia on he molecula mechanisms o insulin esis ance. Nu Hosp 27(2): 382- 390. 11. an den Be ghe G, Wou e s P, Weeke s F, Ve waes C, B uyninckx F, e al. (2001) In ensi e insulin he apy in C i ically ill pa ien s. N Engl J Med 345(19): 1359-1367. 12. Das UN (2002) Insulin and in lamma ion: u he e idence and discussion. Nu i ion 18(6) 526-527. 13. Cowley HC, Bacon PJ, Webs e NR, Jones JG, Menon DK ( 1996) Plasma an ioxidan po en ial in se e e sepsis: a compa ison o su i o s and non-su i o s. C i Ca e Med 24(7): 1179-1183. 14. Han YJ, Kwon YG, Chung HT, Lee SK, Simmons RL, e al. (2001) An ioxidan enzymes supp ess ni ic oxide p oduc ion h ough he inhibi ion o NF-kappa B ac i a ion: ole o H(2)O(2) and ni ic oxide in inducible ni icoxide syn hase exp ession in mac ophages. Ni ic Oxide 5(5): 504 - 513. 15. Ba eman RM, Jagge JE, Sha pe MD, Ellswo h ML, Meh a S, e al. (2001) E y h ocy e de o mabili y is a ni ic oxide-media ed ac o in dec eased capilla y densi y du ing sepsis. Am J Physiol Hea Ci c Physiol 280(6): H2848-H2856. 16. G ua mone G, Mesquida J, Ince C (2017) Mic oci cula o y moni o ing in sep ic pa ien s: Whe e do we s and? Med In ensi a 41(1): 44-52. How o ci e his a icle: C Saldanha, A Messias. Sepsis Needs Follow-Up S udies in In ensi e Ca e Uni s- Ano he A enue o T ansla ional Resea ch. No App o D ug Des De . 2017; 1(1) : 555555. 003 No el App oaches in D ug Designing & De elopmen You nex submission wi h Junipe Publishe s will each you he below asse s • Quali y Edi o ial se ice • Swi Pee Re iew • Rep in s a ailabili y • E-p in s Se ice • Manusc ip Podcas o con enien unde s anding • Global a ainmen o you esea ch • Manusc ip accessibili y in di e en o ma s ( Pd , E-pub, Full Tex , Audio) • Unceasing cus ome se ice T ack he below URL o one-s ep submission h ps://junipe publishe s.com/online-submission.php This wo k is licensed unde C ea i e Commons A ibu ion 4.0 License