Hypotermiav intenzvnej medicneMUDr Peter SklienkaARK FN Ostrava

Hypotermia- TT < 35 Cspontnna vs terapeutick

Terapeutick hypotermia:- prv zmienky: Hippocrates - pozitvny efekt u poranen hlavy- prv pouitie: Fay 1938 (27 C) u pacientov v terminlnom tdiu ndorovch onemocnen pozoroval redukciu tumorznej masy

sasn indikcie: neuroprotektvny efekt

HypotermiaTerapeutick hypotermia:

mild 32-34 Cmoderate 28-32 Cdeep 15-27 Cprofound

Terapeutick hypotermia- neurochirurgick operatva- kardiochirurgick operatva- neonatolgia- ischemick postihnutie CNS - globlne- stp KPCR - foklne- CMP- kraniocerebrlne poranenia- traumat, vojnov chirurgia /experimentlne/- status epilepticus, hepatick ecefalopatia, disseminovan encefalopatie /raritn zmienky/

Neuroprotektvne inky1. Inhibcia excitotoxickej kaskdy - inhibcia presynaptickho uvoovania neuroexcitanch aminokyseln (glutamt)

inhibcia konformanch zmien Glu- aktivovanch inovch kanlov

stabilizcia bunkovch membrn znenie intracelulrneho influxu Ca, Na, K

Neuroprotektvne inky2. Inhibcia produkcie vonch radiklov

3. Inhibcia koagulcie

4. Inhibcia apoptzy

5. Inhibcia syntzy proinflamatrnych cytoknov

6. Inhibcia cerebrlneho termopoolingu

Neuroprotektvne inky7. Zlepenie energetickej bilancie buniek CNS- pokles TT o 1 C- redukcia nrokov na kyslk (CMRO2) a glukzu (CMRglc) o 5-7% - inhibcia glykolzy i Krebsovho cyklu

ALE - vzostup PCr/Pi i ATP/Pi - vzostup intra- i extracelulrneho pH

Neuroprotektvne inky7. Zlepenie energetickej bilancie buniek CNS- pri zachovan adekvtnej perfzie a oxygencie je inhibcia tvorby ATP slabia ne inhibcia metabolickch dejov spotrebovvajcich energiu

tvorba ATPCMRO2, CMRglcdegradcia ATPpozitvna energetick bilancia

Zauner A et al, Neurosurgery 2002Hypotermia ovplyvuje vetky rovne neurotoxickej kaskdy

Indikcie hypotermie1. Novorodeneck ischemick a hypoxick pokodenie- dta nedostatonLevel of evidence: Class III

2. KPCR- pediatria- dta nedostatonLevel of evidence- Class III

3. Subarachnoidlne a intraparenchymatzne krvcanie- dta nedostatonLevel of evidence- Class IV

Kraniocerebrlne poranenieMcIntyre LA et al, JAMA 2003- metaanalza 12 tdi:

19% redukcia rizika mrtia 95% CI 0,69-0,96 22% redukcia rizika poor neurologic outcome 0,63-0,98Hypotermia- benefit na mortalitu pi t > 48hRR 0,65, 95% CI 0,48-0,97

Kraniocerebrlne poranenieMcIntyre LA et al, JAMA 2003- metaanalza 12 tdi: Hypotermia- benefit na neurologick outcome pri t > 48h a TT 32-33 C

Alderson P et al, Cochrane Library 2008metaanalza 14 RCT, 1094 pacientovbez efektu na mortalitu

Alderson P et al, Cochrane Library 2008metaanalza 14 RCT, 1094 pacientovbez efektu na neurologick outcome

Alderson P et al, Cochrane Library 2008metaanalza 14 RCT, 1094 pacientovale signifikantne vyia incidencia pneumni

Kraniocerebrlne poranenieEBM 2007:

- hypotermia je efektvna pri zniovan ICPale redukcia ICP nie je spojen so znenm mortalityLevel of evidence: Class I

- rutinn pouitie hypotermie nie je doporuenLevel of evidence: Class III

- kontrola febrili moe by prospenLevel of evidence: Class IIa

Zstava obehuKa Wai Cheung et al, Can J Emerg Med 2006

- metaanalza 4 RCT, 436 pacientov:hypotermia tatisticky signifikantne:- zniuje nemocnin mortalitu- zniuje incidenciu poor neurologic outcome- na zchranu 1 ivota 7 aplikci hypotermie - na zlepenie neurologickho outcome 5 aplikci- neboli zisten signifikantn rozdiely v incidencii zvanch komplikci

Zstava obehuEBM 2007:

Hypotermia moe by pouit u pacientov po zstave obehu z kardilnych prin, s inicilnym rytmom komorovej fibrilcie, bez znmok hypoxmie a refraktrneho oku

Level of evidence: Class I

Ischemick CMPReith J et al, Lancet 1996Kammersgaard LP et al, Stroke 2002

prospektvna observan tdia, 390 pacientov (1991-3)Zver: vodn telesn teplota je nezvislm, tatisticky signifikantnm prediktoromzvanosti CMP a rozsahu infarktumortality- 3 mesiace: 80,4% < 37,5C > 62,5%, p=0.001mortalita- 5 rokov: 40,2% < 37,5 C > 26,1%, p= 0,006neurologickho outcome u preivchvzsotup TT o 1C = vzostup rizika mortality o 30%!

Ischemick CMPBoysen G et al, Stroke 2001

- prospektvna tdia, 725 pacientov (584 ischemia, 141 ICH)- vzostup teploty pozorovan po 4-6h len u pacientov s akou CMP /SSS

Ischemick CMPSchwab S et al, Stroke 1998

25 pacientov s akou ischemickou CMP (malgny MCA infarkt) v povod MCA k liebe postischemickho edmu- 33C po dobu 48-72 hodn Zver- hypotermia:- efektvna v liebe ICP 20,9 vs 13,4 mmHg p < 0.05- u zomrelch bola prinou smrti hernicia pri vzostupe ICP po rewarmingu (rchlos neuveden)- akceptabiln bezpenostn profil

zlepen prevanie v porovnan s dostupnmi dtami

Schwab S et al, Stroke 1998

Ischemick CMPSchwab S et al, Stroke 2001

Multicentrick tdia, 50 pacientov s mozgovm infarktomCie- pouitie a bezpenos hypotermie (TT < 33 C)Z vsledkov:- 30% pacientov zomrelo poas rewarmingu na nsledky vzostupu ICP !!!- 8% zomrelo poas hypotermie na jej komplikcie- vek rozptyl v timingu zahjenia hypotermie, dobe dosiahnutia cieovej TT, dke rewarmingu

ICP zvisl na dobe rewarminguSchwab S et al, Stroke 2001

Ischemick CMPGeorgiadis D et al, Stroke 2002

randomizovan tdia, 36 pacientov s akou ischmiou v povod MCA (viac ne 2/3 povodia)- 17 hemikraniektomia (CE)- isch.nondominantn hemisfra- 19 hypotermia (MH)- ischemick dominantn hemisframortalita: CE 12% (2/17) vs MH 47% (9/19) p = 0.02dta ako interpretovaten- vstupn parametre: NIHSS score: CE 17 vs MH 20 p = 0.002NIHSS- podhodnocuje postihnutie nondominantnej hemisfry

Ischemick CMPEls T et al, Cerebrovascular Dis 2006

prospektvna randomizovan tdia, 25 pacientov s malgnym mozgovm infarktom- 13 hemikraniektomia (HA)- 12 hemikraniektomia + moderate hypotermia (HH)

mortalita- 3m: 15% (2/13) HA vs 8% (1/12) HH NSNIHSS 6m: 11 HA vs 10 HH- p < 0.08

Ischemick CMPKrieger DW et al, Stroke 2001

19 pacientov s inicilnym NIHSS > 15 a pretrvvjcim NIHSS > 8 po 6h ( = po trombolze), randomizcia:10 pacientov moderate hypotermia (MH) 12 72 hodn 9 kontroln skupina (C)

mortalita- 3 mesiace: 30% MH vs 22,2% C- NS.mRS score 3 mes,: 3,1 MH vs 4,2 C- NS

- akceptabiln bezpenostn profil hypotermie

Ischemick CMPLyden PD et al, J Stroke Cerebrovasc Dis 2005ICTuS trial

- prospektvna tdia, 19 pacientov, sledovan bezpenos a tolerancia intravaskulrneho navodenia hypotermie u bdelch pacientov, paralelne podvan antipyretik- zisten akceptabiln bezpenostn profil metdy

Guluma KZ et al, Neurocrit Care 2008ICTuS Trial- udvan efekt hypotermie na redukciu edmu(CAVE- dta sporn!)

Ischemick CMPPublikovan tdie:

- mal sbory pacientov- nehomognne sbory pacientov- problematick metodolgia - typ tdie - sposob navodenia, hbka a doba hypotermie - rewarming- doba, sposob- problematick interpretcia dt

Ischemick CMP

There is currently no evidence from randomised trials to support the routine use of physical or chemical cooling therapy in acute stroke. Since experimental studies showed a neuroprotective effect of hypothermia in cerebral ischaemia, and hypothermia appears to improve the outcome in patients with severe closed head injury, trials with cooling therapy in acute stroke are warranted.

Correia M et al, The Cochrane Databasis of Systematic Reviews 2000

Ischemick CMPEBM 2007

Animal studies and preliminary clinical studies have shown that hypothermia may be helpful to reduce infarct size and improve neurological outcome, however the implementation of hypothermia as treatment for stroke still holds aClass III Level of evidence

Hachimi-Idrissi S, ICU management 2007

Ischemick CMPGuideliness 2007

Neuroprotektvna terapia:Class III Recommendation At present, no intervention with putative neuroprotective actions has been established as effective in improving outcomes after stroke, and therefore none currently can be recommended (Class III, Level of Evidence A). This recommendation has not changed from previous guidelines.

Ischemick CMPZdroj:Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists.

Stroke 2007Circulation 2007

Navodenie hypotermie1. Kondukcia= chladenie cirkulujcou tekutinou- cirkulan vodn madrace alebo helmy- celotelov kpe

2. Konvekcia= chladenie cirkulujcim vzduchom- celotelov blankety, vzduchov postele

3. Intravaskulrne chladenie- intravaskulrn katetre s nastavitenou teplotou- chladen infzie

2 C/ hod

Navodenie hypotermie4. Extrakorporlne ochladzovanie- eliminan metdy- extrakorporlna cirkulcia

5. ochladzovanie nasofaryngu perfluoro- zleninami- prietok 0,1-1 l/min a kg- flow-dependentn inok- vhoda selektvne a rchle ochladenie CNS- nevhoda - cena

Wolfson MR 2006Pozn.- T mozgu tesn korelcia s tympanickou teplotou

Navodenie hypotermie6. farmakologick znenie TT- akkovek dostupn antipyretikum

CAVE: Navodenie hypotermie neznamen tolerova perifernu malperfziu a ok!

Cost-effectivenesshypotermia u KPCR:cena na zchranu 1 ivota: 6000 euroQALY: 900 euro

vemi priazniv ekonomick profil!QALY: airbag (1 vs 2) 28 000 vs 72 000 USD DrotAA 27 400 USD IDF 40 000 USD Tx pc 44 000 USD KPCR (celk.nklady) 215 000 USD

Komplikcie1. Hemodynamick- dysrytmie riziko fibrilcie komor!- pokles srdenho vdaja- perifrna vazokonstrikciaCAVE- zmeny variabiln vo vzahu k aktivite sympatiku

2. Ventilan- pri miernej hypotermii dochdza hyperventilcii, pi alom poklese pokles MV a zstava dychu

Komplikcie3. Koagulopatia- znenie funkcie trombocytov- hypokoagulcia pi znen fce enzmov regulujcich koagulan kaskdu

4. Ladvinn- v inicilnej fze vzostup, potom ale pokles GF- riziko myoglobinmie !!!

Komplikcie5. Imunitn a metabolick- inhibcia inntnej i pecifickej imunitnej odpovede= zven incidencia infekci- zhoren hojenie rn - iontov dysbalancie a zmeny pH- posun disocianej krivky Hb doava

6. Loklne kon nekrzy- pri nesprvne aplikovanej hypotermii

Hypotermia ???- efektvny postup ktor nevieme pouva ???

Indikcie- diagnza vs klinick stav ( edm- ICP, rozsah penumbry, znmky tkanivovej hypoxie-SjO2, tPO2, znmky aktivovanej neurotoxickej kaskdy - NSE, S-100B) ???Timing ???Rchlos a metda navodenia ???Hbka hypotermie ???Doba trvania ???Kombincia s inmi postupmi ???Rewarming- sposob, rchlos ???Ako monitorova efektivitu ???

5200 rokov ultrahlbok hypotermianezniuje mortalitu muov postrelench pom

5200 rokov ultrahlbok hypotermia pravdepodobne nezniuje mortalitu muov postrelench pom Level of evidence: Class IVCAVE:- sbor prli mal !- gender-ratio v rozpore s ISO EU- neprebehla fza rewarmingu !!!

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