Hypothermic Resuscitation Sombat Muengtaweepongsa M D Muengtaweepongsa, M.D. Division of Neurology Faculty of Medicine Thammasat University
Scope• Therapeutic hypothermia after cardiac arrest• Therapeutic hypothermia in ischemic stroke• Fever control in critical care neurology
2005 ILCOR• There seems to be good evidence (level 1) to recommend the use of induced ) mild hypothermia in comatose survivors of out hospital cardiac arrest of-out-hospital caused by VF.Level 1 evidence indicates one or more randomized clinical trials in whichbenefit was shown
Therapeutic Hypothermia after Cardiac Arrest (N Engl J Med 2002;346:557-63.)
The Th RCT of TH after cardiac arrest f ft di t HACA (European) Bernard trial (Australia)Sample N=275 N=77Cooled verses 137 cooled 43 coolednormothermia 138 normothermia 34 normothermiaIntervention Cooling blankets Ice packs and ice packsTarget temperature 32-34 degrees 33 degreesInitiation Prehospital p ERDuration 24 hours 12 hoursFollow up 6 months 30 days
Benefit• NNT of 7 to prevent 1 death with TH• NNT of 6 to reduce neurologic impairment with TH The NNT is the number of patients who need to be treated in order to prevent one additional bad outcome
HACA study group, 2002. New England Journal of Medicine 346(8). Adverse E Ad Events t• Bleeding, pneumonia, sepsis, pancreatitis, renal failure, pulmonary edema, seizures, ,p y , , arrhythmias and pressure sores were g recorded in both trials with no significant adverse events.“ Sepsis was more likely to develop in the patients with h pothermia than those in normothermia ith hypothermia normothermia, although this difference was not statistically significant significant” (HACA study group 2002) group,
Side ff t f Sid effects of moderate hypothermia on d t h th i various organ systemsVariable Normothermia Hypothermia After-rewarmingPlt count t 183 (145-310) 110 (20-180) 160 (50-210)aPTT 27 (20-45) 34 (25-50) 30 (20-55)lipase 140 (60-190) 250 (140-1200) 200 (135-1000)K+ 4.1 (3.5-4.7) (3.5 4.7) 3.4 (3.1-3.9) (3.1 3.9) 4.4 (4.0-5.2) (4.0 5.2)Na+ 139 (134-145) 140 (138-150) 145 (139-155)Cr ClearanceC Cl 81 (60-100) 65 (45-90) 70 (45-95)Norepinephrine 0 0.32 (0.0-0.45) 0.08 (0.0-0.24)
What is the purpose of TH?• Aimed at minimizing the effects of anoxic neurologic injury following g j y g cardiac arrest• Other than supportive care TH it is the only identified measure to improve quality of life post resuscitation f f
So why is TH not done more often?Both of these studies involved a highly selected group ofpatients, excluding up to 92% of patients with out-of-hospitalcardiac arrest initially assessed for eligibility
Suggested Inclusion Criteria gg• TH is indicated if the patient meets all of the following criteria:1. Witnessed arrest2. Initial rhythm VF or pulseless VT…. But3. Time to ACLS was less than 15 minutes and total of ACLS time less than 60 minutes4. GCS of 8 or below5. SBP of > 90 with or without vasopressors6.6 Less than 8 hours have elapsed since return of spontaneous circulation (ROSC)
Suggested Exclusion Criteria gg1. Pregnancy2. GCS 10 and improving3. Down time of > 30 minutes4. ACLS preformed for > 60 minutes5.5 Known terminal illness6. Comatose state prior to cardiac arrest7.7 Prolonged hypotension (ie MAP < 60 f >30 P l dh t i (i for 30 minutes)8. Evidence of hypoxemia for > 15 min following ROSC9. Known coagulopathy that cannot be reversed
Mechanisms of neuroprotection by M h i f t ti b hypothermia• counteract ischemic brain damage by several mechanisms – prevention of the blood–brain-barrier disruption – oxygen-based free-radical production – excitotoxicneurotransmitter release – anti-inflammatory action – delayed apoptosis
Historical Observations• Not Dead till Warm and Dead – Cold patients would wake up in the Morgue p p g• Kids / Hockey Players- fall through ice, long rescue times but good recovery times,• Hibernation: state of low oxygen, acidosis, yg low energy supply
Ideal temperature curve Induction erature RewarmingTempe Sustainment Time e
Methods to Control Brain Temperature in Stroke Patients
Methods of Cooling• Selective head cooling – Cooling helmet: ineffective in adult g• Internal cooling by intravenous and intraarterial ice-cold saline ice cold – Need large volume• Surface cooling• Endovascular cooling
Thermoregulatory Defenses Against Hypothermia• Vasoconstriction – Primary autonomic defenses y – Threshold: 36.5o C• Shivering – “last resort” response – Threshold: 35.5o C
Introduction of thermoregulatory tolerance• Nonpharmacological treatments – Whole body surface warming y g• Pharmacological treatments –AAnesthetics and M th ti d Muscle relaxants l l t – Meperidine – Drug combination • Meperidine and Buspirone p p • Meperidine and Dexmedetomidine
Rewarming• Th most critical period of risk related t The t iti l i d f i k l t d to therapeutic hypothermia• Vasodilation• Hypermetabolic response – Systemic inflammatory response syndrome (SIRS)• Passive controlled rewarming Stepwise rewarming rate: 0 1 0 5 oC per h – St i i t 0.1-0.5 hr
Rewarming• C b l side effects Cerebral id ff t – Rebound edema and ICP elevation• E Extracerebral side effects b l id ff – Infection • P Pneumonia i • Sepsis – Cardiopulmonary • Elevation of catecholamines: arrhythmia – Hematologic • Induced thrombosis
A case scenario69 y/o woman presented to an outside hospital with sudden onset of right sided h it l ith dd t f i ht id d weakness and speech impairment. She arrived at the OSH at 20 minutes after onset. CT brain was negative. TPA was CT-brain started at 90 minutes after the onset before she was transferred to SLUH SLUH.
A case scenario (cont ) (cont.)SheSh was alert and awake, b t aphasic. l t d k but h iNIHSS was 8 with: LOCb 2, partial hemianopia hemianopia, right arm drifting, some effort against gravity on right leg leg, partial sensory loss on the left side moderate aphasia. aphasia
A case scenario (cont ) (cont.)Without ith i t b tiWith t either intubation or sedation, d ti therapeutic hypothermia with endovascular cooling technique was started at 5 hours after onset. Target core temperature of 33oC was reached within 3 hrs. Shivering was under control with combination of surface warming and meperidine p p plus buspirone. Gradual p rewarming was applied after target temperature was maintained for 24 hrs.
For each 1 degrees C increase inbody temperature the relative riskof poor outcome rose by 2.2 (95percent CI 1.4-3.5) (p less than0.002).
She was discharged to a rehab after 5 days of admission with NIHSS of 5 and mRS of 3.At day 30 She walked by herself to follow 30, up at DOB. NIHSS was only 3 including hemianopia and partial sensory loss. mRSS was 2.
Fever-related Brain Injury in theNeuro-ICU • C b l I f ti Cerebral Infarction • Elevated temperature is associated with poor outcome after stroke t ft t k Hajat et al, Stroke 2000;31:410 • Subarachnoid Hemorrhage • Fever burden independently associated with mortality & poor functional outcome. y p Mayer et al, Crit Care Med 2003 (Suppl);30:A5 • Intracerebral Hemorrhage • D ti of f Duration f fever (>37.5° C) within th fi t ( 37 5° ithi the first 72 hours is independently associated with poor outcome Schwarz et al, Neurology 2000;54:354
Treatment of fever in the neurologic intensive care unit with acatheter-based heat exchange system th t b dh t h tDiringer MN, CCM 2204;32:559• 296 patients with T ≥38° C for at least 2 occasions i – SAH, TBI, ICH and cerebral infarction• Alsius Cool Line endovascular heat exchange catheter plus standard surface cooling• Fever Burden >38 °C 38 C – 7.92 °C-hours 64% relative reduction (P<0.01) – 2.87 °C-hours• Shivering “of concern” in four patients (3.7%)
Clinical Trial of a Novel Surface Cooling Systemfor Fever Control in Neurocritical Care PatientsMayer, et al, Crit Care Med 2004 • 47 patients with T ≥38.3° C for >2 consecutive hours after receiving acetaminophen – Median GCS 8 0 8.0 – SAH, ICH, infarction, TBI – Mean 42 hours >38 3° C prior to >38.3 randomization • Interventions – Standard SubZero cooling blanket – Medivance Artcic Sun surface cooling system • Main outcome measure – 24 h hour f fever b d burden
Clinical Trial of a Novel Surface Cooling Systemfor Fever Control in Neurocritical Care Patients P=0.001
Change in Glasgow Coma Scale P=.038, GEE model
Conclusion• TH is a standard treatment in selected patients after cardiac arrest. p• TH should be benefit for penumbra salvaging in acute ischemic stroke stroke.• TH is one of treatments for increase ICP.• Fever control is essential, particularly in conditions. such a bad neurological conditions
Take home message “ No evidence” doesn t doesn’t mean“Evidence does not exist”.