ΘΕΡΑΠΕΥΤΙΚΗ ΥΠΟΘΕΡΜΙΑ. Νικόλαος Νικολάου ΚΩΝΣΤΑΝΤΟΠΟΥΛΕΙΟ ΝΟΣΟΚΟΜΕΙΟ

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1 ΘΕΡΑΠΕΥΤΙΚΗ ΥΠΟΘΕΡΜΙΑ Νικόλαος Νικολάου ΚΩΝΣΤΑΝΤΟΠΟΥΛΕΙΟ ΝΟΣΟΚΟΜΕΙΟ

Survival (%) Επιβίωση μετά από ανακοπή εκτός νοσοκομείου 45 40 35 30 25 20 15 10 5 0 67

2 Survival (%) Επιβίωση μετά από ανακοπή εκτός νοσοκομείου prospective studies EMS treated CA USA Australia Europe Asia Berdowsky et al. Resuscitation 2010

% of deaths Αίτια θανάτου στη ΜΕΘ 70 60 50 40 30

3 % of deaths Αίτια θανάτου στη ΜΕΘ Brain Cardiac MOF Olasveegen n=129 Laver n=126

4 Θεραπευτική υποθερμία, μηχανισμός δράσης Astroglial cells macrophages Increased calcium influx Apoptosis Ischemia-reperfusion injury González-Ibarra et al Frontiers in Neurology

5 Θεραπευτική υποθερμία. Ασθενείς κωματώδεις μετά ανακοπή εκτός νοσοκομείου 7 centers-5 European countries Ν=273 (TH Ν=136) Age: Randomized External cooling Ο C,24 h, Passive rewarming N Engl J Med 2002;346:549-56

6 Θεραπευτική υποθερμία. Ασθενείς κωματώδεις μετά ανακοπή εκτός νοσοκομείου N Engl J Med 2002;346:549-56

7 N Engl J Med 2002;346:549-56

8 Ποιά είναι η καλύτερη θερμοκρασία;

9 Targeted Temperature management trial N=939 pts (36 ICUs Europe/Australia) OHCA, presumed cardiac cause All rhythms included 33 C N= C N=466

10 Inclusion Age>18 GCS<8 Arrest of cardiac cause All initial rhythms Exclusion ROSC-screening time>240 min Unwitnessed arrest+ asystole Suspected/known ICH/stroke Temp<30 C

11 Targeted Temperature Management

12 Targeted Temperature Management

13 ..rigorous guidelines for neurologic prognostication and end-of-life decisions

14 Το τέλος της υποθερμίας;

15 did not allow the natural trajectory of temperature evolution in either group aimed to prevent fever during the first 3 days after cardiac arrest. it is important to acknowledge that there may be a clinically relevant benefit of controlling the body temperature at 36 C, instead of allowing fever to develop in patients

16 Oddo: Crit Care Med 2006

17 TTM HACA Oddo: Crit Care Med 2006

18 Nielsen, Resuscitation 2015

20 Θεραπευτική υποθερμία. Κατάλληλη για όλους;

21 Υποθερμία-μη απινιδώσιμοι ρυθμοί

22 Υποθερμία-μη απινιδώσιμοι ρυθμοί

23 Υποθερμία-μη απινιδώσιμοι ρυθμοί use of therapeutic hypothermia to include comatose survivors of cardiac arrest associated initially with non-shockable rhythms as well shockable rhythms. The lower level of evidence for use after cardiac arrest from nonshockable rhythms is acknowledged. NCT Effect of TH: PEA vs. Asystole NCT Non shockable rhythms: vs ERC guidelines

24 Neurologic deficit score Πότε ξεκινάμε; P=NS P<0.01 Control TH immediately post ROSC TH delayed 15 min Kuboyama Crit Care Med 1993

27 ROSC Inclusion Tracheal intubation IV access Successful placement of esophageal probes unconsciousness Exclusion Traumatic CA Age<18 Awake Following commands T<34 C

28 Field cooling reduced time to achieve target temperature of <34for more than 1h 4.2 ( ) vs 5.5 (5 to 6)

31 Abella B S et al. Circulation. 2004;109:

32 Castrén M et al. Circulation. 2010;122:

33 Castrén M et al. Circulation. 2010;122:

34 Castrén M et al. Circulation. 2010;122:

36 ΥΠΟΘΕΡΜΙΑ+PCI Grasner et al. Crit Care 2011re 2011

37 ΥΠΟΘΕΡΜΙΑ+PCI Dumas et al. JACC

38 No of patients Thrombosis % Ibrahim Eur Heart J Panela JACC

39 ΥΠΟΘΕΡΜΙΑ+PCI

40 ΥΠΟΘΕΡΜΙΑ+PCI No of patients Thrombosis % Maze Resuscitation Rossilo JACC Chisholm Eur Heart J-ACC

42 Maintain a constant, target temperature between 32 C and 36 C for those patients in whom temperature control is used (strong recommendation, moderate-quality evidence). Whether certain subpopulations of cardiac arrest patients may benefit from lower (32 34 C) or higher (36 C) temperatures remains unknown, and further research may help elucidate this. TTM is recommended for adults after OHCA with an initial shockable rhythm who remain unresponsive after ROSC (strong recommendation, low-quality evidence). TTM is suggested for adults after OHCA with an initial non- shockable rhythm who remain unresponsive after ROSC (weak recommendation, very low-quality evidence). TTM is suggested for adults after IHCA with any initial rhythm who remain unresponsive after ROSC (weak recommendation, very low-quality evidence). If targeted temperature management is used, it is suggested that the duration is at least 24h (as undertaken in the two largest previous RCTs ) (weak recommendation, very low-quality evidence).

43 Ongoing trials of hypothermia Initial rhythm All rhythms, non-shockable 2 Optimal temperature TH+ other medication Duration of hypothermia Cooling methods Time to start cooling TH+ other interventions during CPR Complications Mild vs. moderate, time differentiated Sedation, neuromuscular blocking agent, antibiotics, Xenon, rocuronium, MgSO4 Prolonged TH Brain cooling, Internal vs. external, intravascular, intranasal Pre-hospital vs. in-hospital, intra-arrest Mechanical CPR, ECMO Intestinal ischemia, pancreatitis, hemostasis

Therapy Modulating neuronal cell death MK-801 Lamotrigine Xenon Argon Ischemic post-conditioning Caspase 3 inhibitor ZDEVD-FMK Fluoexetine Matrix metalloproteinase-9 inhibitor Proposed

44 Therapy Modulating neuronal cell death MK-801 Lamotrigine Xenon Argon Ischemic post-conditioning Caspase 3 inhibitor ZDEVD-FMK Fluoexetine Matrix metalloproteinase-9 inhibitor Proposed mechanism NMDA antagonist-ameliorate glutamate excitoxicity ameliorate glutamate excitoxicity NMDA antagonist Anti-apoptosis Anti-apoptosis Anti-apoptosis Anti-inflammatory Anti-inflammatory

45 Who to cool? When to start? Optimal temperature? TH+ PCI? TH+ other interventions

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