12/1/2017. Disclosure. When I was invited to give a talk in Tokyo 2011 at the 4 th International. Hypothermia Symposium

Size: px

Start display at page:

Download "12/1/2017. Disclosure. When I was invited to give a talk in Tokyo 2011 at the 4 th International. Hypothermia Symposium"

Arnold Green
5 years ago
Views:

1 Disclosure Different Levels of Hypothermia: Is Cooler Better? Nothing to disclose (wish I did) Absolutely no conflict of interest for this lecture Kiwon Lee, MD, FACP, FAHA, FCCM Vice Chairman of Neurology and Neurosurgery for Critical Care Associate Professor of Neurology and Neurosurgery Chief, Division of Critical Care Director, NS-ICU and Neurotrauma ICU Director, Neurocritical Care Fellowship The University of Texas Medical School at Houston Memorial Hermann Texas Medical Center Houston, Texas, U.S.A. When I was invited to give a talk in Tokyo 2011 at the 4 th International Hypothermia Symposium 1

Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest Kiwon Lee, MD, FACP, FAHA Assistant Professor of Neurology and

and mortality 32-34C for 24h, OOHCA Neonatal Hypoxic Ischemic Encephalopathy (HIE) First RCT of Cooling for perinatal asphyxia: Selective head cooling with

2 Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest Kiwon Lee, MD, FACP, FAHA Assistant Professor of Neurology and Neurosurgery Columbia University College of Physicians and Surgeons Neurological Intensive Care Unit The New York Presbyterian Columbia University Medical Center New York, New York, U.S.A. The Hypothermia after Cardiac Arrest Study Group * N EnglJ Med 2002; 346: February 21, 2002 hypothermia did better both in favorable neurologic outcome and mortality 32-34C for 24h, OOHCA Neonatal Hypoxic Ischemic Encephalopathy (HIE) First RCT of Cooling for perinatal asphyxia: Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Gluckman, Lancet full term infants with moderate to severe injury randomized (clinical and EEG amplitude) Selective head cooling improve survival in less severe encephalopathy (not effective in severe) 2

Matrix metallopeptidase-9 MMP9 has been found to be associated with

Child Revived Almost 2 Hours After "Drowning" - But How?

childfell into an icy tributary of Buffalo Creek, Pennsylvania.

pulse and was not breathing at the time of discovery and may have been in

3 Matrix metallopeptidase-9 MMP9 has been found to be associated with numerous pathological processes, including cancer, immunologic and vascular diseases. Reduction in MMP 9, Attenuates BBB disruption in animal models 2-year-old Child Revived Almost 2 Hours After "Drowning" - But How? March 20, 2015 by Justine Alford Last Wednesday evening, a 2-year-old childfell into an icy tributary of Buffalo Creek, Pennsylvania. The boy was quickly swept downstream for about a quarter of a mile, had no pulse and was not breathing at the time of discovery and may have been in the 1 o C (34 o F) water for as long as 30 minutes. CPR/ACLS was performed total of 1 hour and 40 minutes and the infant had ROSC 6 days later went home with noneurological deficits 3

Does hypothermia buy some time? How long do you do CPR/ACLS for?

with cardiac arrest and hypothermia: Dutch nationwideretrospective

and hypothermia after drowning Downed children with ROSC not achieved

function among survivors So there seems to be a favorable response to

Perinatal asphyxia with hypoxic-ischemic encephalopathy Drowning in

4 Does hypothermia buy some time? How long do you do CPR/ACLS for? Outcome after resuscitation beyond 30 minutes in drowned children with cardiac arrest and hypothermia: Dutch nationwideretrospective cohort study BMJ N=160 children with cardiac arrest and hypothermia after drowning Downed children with ROSC not achieved within 30min did extremely poorly with high mortality 89% dead, poor function among survivors So there seems to be a favorable response to hypothermia in Out of hospital cardiac arrest due to v-tach and v-fib Perinatal asphyxia with hypoxic-ischemic encephalopathy Drowning in cold water (young boys) Does it help with Heart Attack? Stroke (AIS/ICH/SAH)? TBI? 4

Rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction.

5 Rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. The CHILL-MI trial The trial: : a randomized controlled study of the use of central venous catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction. CHILL-MI take-home messages: David Erlinge et al. J. Am College of Cardiology Hypothermia induced by cold saline and endovascular cooling was feasible and safe, and it rapidly reduced coretemperature with minor reperfusion delay. The primary end point of Infarct Size was not significantly reduced. Lower incidence of heart failure and a possible effect in patients with early anterior ST-segment elevation myocardial infarctions need confirmation. Trial tests adjunctive hypothermia before, during primary PCI for STEMI Cooling does NOT reduce infarct size but decreases heart failure at 45 days Exploratory analysis suggests treatment more effective for early anterior STEMI THERAPEUTIC HYPOTHERMIA FOR THE TREATMENT OF ACUTE MYOCARDIAL INFARCTION: POOLED ANALYSIS OF THE RAPID MI-ICE AND THE CHILL-MI TRIALS Does the different levels of hypothermia matter? David Erlinge(Lund University of Sweden) J Am CollCardiol2014 Cooled to 33C before PCI and maintained for 1-3h after reperfusion Looking at infarct size on cardiac MR The pooled analysis of RAPID MI-ICE (N=20) and CHILL-MI (N=120) demonstrates the feasibilityof cooling STEMI patients, and indicates opportunities for reduction of infarct size and incidence of heart failure. 5

6 Targeted Temperature Management at 33 C versus 36 C after Cardiac Arrest Niklas Nielsen and TTM Trial Investigators N EnglJ Med 2013; 369: December 5, C versus 36 C 36 ICUs in Europe and Australia Age 18 or older Unconscious (GCS <8), OOHCA presumed cardiac, regardless of rhythm ROSC>20min, excluded ROSC>240min, unknown period of asystole, body temp<30c. 33C vs 36C for 36 hours Body Temperature during the Intervention Period. Probability of Survival through the End of the Trial. Nielsen N et al. N Engl J Med 2013;369: Nielsen N et al. N Engl J Med 2013;369:

In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33 C did not confer a benefit as compared with a targeted temperature of

7 In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33 C did not confer a benefit as compared with a targeted temperature of 36 C. (Funded by the Swedish Heart Lung Foundation and others; TTM ClinicalTrials.gov number We see many gunshot to the head: ICP in TBI Hypothermia for Intracranial Hypertension after Traumatic Brain Injury Peter J.D. Andrews, Eurotherm3235Trial Collaborators N EnglJ Med 2015; 373: December 17, 2015 Adult TBI with ICP>20mmHg AFTER stage 1 therapy (sedation+ventilation) Hypothermia (32-35C) vs. Standard N=387, 47 centers in Europe Stopped due to safety concerns (ran from 11/ /2014) 387 randomized (18 countries) 195 hypothermia, 192 control Stage1: intubated, sedated, head elevated, MAP>80, EVD/surgery if needed Stage2: mannitol, HTS Control got: mannitol/hts Hypothermia got: hypothermia and mannitol/hts if needed 7

Andrews PJ et al. N Engl J Med 2015;373:2403-2412. 2412.

alone Stopped early due to safety concerns Cooling to normothermia was allowed for control group

8 Andrews PJ et al. N Engl J Med 2015;373: Results: EUROTHERM months later: worse outcomes with hypothermia than with standard care alone Stopped early due to safety concerns Cooling to normothermia was allowed for control group (so they were cooled in a way if fever occurred) Suggest possible harm of hypothermia Andrews PJ et al. N Engl J Med 2015;373:

Conclusions of Eurotherm 3235 Critiques and lessons: TBI with ICP>20mmHg, hypothermia plus standard care vs standard care alone does not result in outcomes benefits 1.

9 Conclusions of Eurotherm 3235 Critiques and lessons: TBI with ICP>20mmHg, hypothermia plus standard care vs standard care alone does not result in outcomes benefits 1. this is not how we normally use cooling for high ICP (we do stage1, stage2 then consider cooling). But this is a lesson for those HYPOTHERMIA LOVERS that cooling before stage 2 (osmotics) is not wise Study did not test benefits and risks of TBI patients with severe ICP crisis that is refractory to all stage 2 (osmotic) treatments before initiating hypothermia 2. Both groups had same ICP, CPP, MAP no wonder no differences in 6 months outcomes 3. Control group were cooled to normothermia(so they did use temperature modulation) 27 year old with malignant R MCA infarct Somnolent but arousable Left hemiplegic R forced gaze deviation Would you do hemicraniectomy? It is not 30 hours out 9

Well, I didn t Hypertonic saline: Na target

33C or 36C, and 36C preferred if serious

10 Well, I didn t Hypertonic saline: Na target 150 Mild hypothermia: Temp target 36C He did not herniate! Future of therapeutic hypothermia: Summary OOHCA 33 vs. 36 vs. nothing is being planned Until then: either 33C or 36C, and 36C preferred if serious adverse events are observed hypotension, severe electrolyte disturbances, coagulopathy, sepsis and septic shock 10

$HTS) without jeopardizing CPP may be reasonable High grade SAH with refractory ICP crisis May need more monitoring than just ICP/CPP PbtO2?$ Understand that if cooling is used during spasm, then remember hypothermia may reduce ICP but also may reduce PbtO2 likely due to reduction in flow-may be

Understand that if cooling is used during spasm, then remember hypothermia may reduce ICP but also may reduce PbtO2 likely due to reduction in flow-may be

outcome byhypothermia-some even indicated worse outcome TBI patients may suffer fromhypothermia-inducedpulmonary and coagulation side effects, from side

11 Ischemic Stroke SAH NO strong data yet May have a role in reducing cerebral edema prior to malignant MCA infarction combined approach (hypothermia plus HTS) without jeopardizing CPP may be reasonable High grade SAH with refractory ICP crisis May need more monitoring than just ICP/CPP PbtO2? Understand that if cooling is used during spasm, then remember hypothermia may reduce ICP but also may reduce PbtO2 likely due to reduction in flow-may be harmful TBI quote from Sandestiq (Ther Hypothermia Temp Management 2014 Mar 1;4(1):10-20 The best-performed randomized studies showed no improvement in outcome byhypothermia-some even indicated worse outcome TBI patients may suffer fromhypothermia-inducedpulmonary and coagulation side effects, from side effects of vasopressors when reestablishing thehypothermia-inducedlowered blood pressure, and from a rebound increase in intracranial pressure (ICP) during and after rewarming. 11

12 The difference between body temperature and temperature set by the biological thermostat may cause stress-induced worsening of the circulation and oxygenation in injured areas of thebrain..we conclude that we still lack scientific support as a first-tier therapy for the use oftherapeutic hypothermiain TBI patients for bothadultsandchildren, but it may still be an option as a second-tier therapy for refractory intracranial hypertension. These mechanisms may counteract neuroprotective effects oftherapeutic hypothermia. 12

12/4/2017. Disclosure. Educational Objectives. Has been consultant for Bard, Chiesi

12/4/2017. Disclosure. Educational Objectives. Has been consultant for Bard, Chiesi Temperature Management in Neuro ICU Kiwon Lee, MD, FACP, FAHA, FCCM Professor of Neurology, RWJ Medical School Chief of Neurology, RWJ University Hospital Director, RWJ Comprehensive Stroke Center Director,