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

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1 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, Division of Stroke and Critical Car Director, Neuro-Intensive Care Unit Rutgers, The State University of New Jersey Robert Wood Johnson Medical School Disclosure Has been consultant for Bard, Chiesi Educational Objectives State indication of targeted temperature management (TTM) in post cardiac arrest List potential neurological indications of TTM State TTM s role in intracranial hypertension 1

2 Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest 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) Does the different levels of hypothermia matter? 2

3 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. Nielsen N et al. N Engl J Med 2013;369:

4 Probability of Survival through the End of the Trial. 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 36 C. (Funded by the Swedish Heart Lung Foundation and others; TTM ClinicalTrials.gov number We see many gunshot injuries to the head: ICP in TBI 4

5 Medical management of intracranial hypertension 1. Adequate sedation 2. Osmotic agents 3. Hypothermia 4. Barbiturate coma 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) 5

6 387 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 Andrews PJ et al. N Engl J Med 2015;373:

7 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 Conclusions of Eurotherm 3235 TBI with ICP>20mmHg, hypothermia plus standard care vs standard care alone does not result in outcomes benefits 7

8 Critiques and lessons: 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 now 30 hours out from onset 8

9 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 9

10 Ischemic Stroke 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 SAH 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 10

11 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. 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. These mechanisms may counteract neuroprotective effects oftherapeutic hypothermia..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. 11