Therapeutic Hypothermia Dr SM Lam ICU Clinical Meeting 20th October, 2006
Therapeutic hypothermia • The controlled lowering of core temperature for therapeutic reasons. Survival after out-of-hospital cardiac arrest of cardiac etiology & CPR in Germany. Heart 1999;82:674-9 Post-arrest brain damage Neuroprotection
History 1996: Review of animals studies support clinical trials in selected patients. 1950: Bigelow introduced IH for neurologic protection during cardiac surgical procedures. 1937: T. Fay first cooled a female patient with metastatic breast Ca to 32oC for 24hrs 2002 1940s: Hypothermia experiments in Dachau concentration camps. 1980s: Accidental hypothermia during prolonged cardiac arrest in dogs found to be beneficial. 1941: Fay used IH in victims with severe head injury & noted marked clinical improvement. 2000s: randomized controlled trials.
Physiologic effects of IH (1) • CNS: • Relative improvement in O2 supply to ischemic areas of brain; • - Apoptosis, free radicals & excitatory neurotransmitters, stabilize membranes; • ICP; • Anticonvulsant. • CVS: • HR & SVR. SV preserved; • Arrhythmia, more common with moderate to severe hypothermia.
Physiologic effects of IH (2) • Respiratory system: • MV in response to metabolic rate. • Renal system: • Diuresis (reabsorption of solute in ascending limb); • Serum K (shifted into cells); • PO4.
Physiologic effects of IH (3) • Gastrointestinal system: • Gut motility Delay enteral feeding; • Hyperglycemia from insulin release. • Hematologic system: • WCC numbers & function incidence of sepsis; • Platelet numbers & function; • Prolongs clotting.
Clinical applications of IH • Cerebral protection in neuro & cardiac surgeries; • Out-of-hospital cardiac arrest from VF; • Severe head trauma; • Cardiac arrest following trauma & exsanguination; • Asphyxia (near-drowning, hanging); • Ischemic stroke; • ARDS; • Newborn hypoxic-ischemic encephalopathy.
Out-of-hospital cardiac arrest • Patients randomized to hypothermia group were: • Cooled by a cooling mattress with cover + ice packs; • Aiming at a temperature between 32oC & 34oC; • Maintained for 24hrs from the start of cooling; • Followed by passive rewarming. • Included victims of : • Witnessed cardiac arrest from VF/pulseless VT; • Remained comatose after ROSC; • Stable hemodynamics & w/o hypoxemia; • Without preexisting coagulopathy.
Among patients in whom spontaneous circulation had been restored after cardiac arrest due to VF, systemic cooling to a bladder temp between 32oC & 34oC for 24hrs the chance of survival & of favourable neurologic outcome, as c/w standard normothermic life support. NNT = 6 At 6 months NNT = 7 Only 8% of 3551 patients assessed for eligibility were included!
Similar study design as HACA, except: • Cooling initiated by paramedics in field using cold packs; • Aimed at core temp of 33oC, & maintained for 12hrs after hospital arrival; • Followed by active rewarming using heated-air blanket beginning at 18hrs; • Insertion of PAC; • Neurologic function stratified according to place of discharge (home/rehab facility vs long-term nursing facility/death). NEJM 2002; 346(8):557-63
NEJM 2002; 346(8):557-63 49% 26% Before hospital discharge Induced hypothermia improves outcomes in patients who are comatose after resuscitation from out-of-hospital cardiac arrest.
ILCOR advisory statement Recommendations on therapeutic hypothermia from the International Liaison Committee on Resuscitation In October 2002, the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation recommended: Unconscious adult patients with spontaneous circulation after out-of-hospital cardiac arrest should be cooled to 32°C–34°C for 12–24 hours when the initial rhythm was ventricular fibrillation. Such cooling may also be beneficial for other rhythms or in-hospital cardiac arrest. Circulation 2003;108:118-21
Severe head injury NEJM 2001; 344(8):556-63 • Victims of non-penetrating HI with GCS 3-8; • Excluded if bleeding, life-threatening injury to another organ, hypotensive/hypoxemic after resuscitation; • Maintained at 32.5oC – 34oC for 48hrs. • Adverse effects.
Severe head injury Induced hypothermia that reaches 33oC 8hrs after injury did not prevent a poor outcome in patients with severe head injury. • Retrospective analysis: • Hypothermic patients on arrival have more severe injuries; • Patients >45 year-old fare worse from hypothermia than if normothermia was maintained; • Warming of hypothermic patients on arrival may be detrimental. NEJM 2001; 344(8):556-63
Severe head injury Retrospective analysis: Warming of hypothermic patients on arrival may be detrimental. NEJM 2001; 344(8):556-63
Severe head injury Methodological issues: • Excluded patients with persistent hypoxia or hypotension: • The very persons to benefit? • Hypothermia instituted 8hrs after injury. • Rewarmed at 48hrs regardless of ICP: • Rebound intracranial HT; • Delay rewarming until ICP controlled? • Different fluid management in different centres.
Near-drowning • Case report: • Paediatric experience: death in hypothermic group from neutropenic sepsis. 2002 World Congress on Drowning (Amsterdam): IH recommended for near-drowning victims who remained comatose after return of adequate spontaneous circulation. (Med J Aust 2004;181(9):500-1)
Ischemic stroke • Fever significantly morbidity in stroke patients; • Mild spontaneous hypothermia associated with a favorable prognosis; • Cochrane library: • A review of available uncontrolled studies concluded that clinical trials of IH after major stroke are warranted. • On-going trials: CHILI & NOCSS. • Effect on current practice.
External cooling techniques Cooling mattress & blanket Cooling helmet Ice pack
Internal cooling techniques Intravascular heat exchange device Cooled IV fluid (LVICF) Extracorporeal cooling (cardiopulmonary bypass, hemodialysis) Peritoneal, pleural or gastric lavage
An example of induced hypothermia protocol (I) • Patient selection: • Post-cardiac arrest adults with initial VF/pulseless VT who remain comatose; • Stable BP+ vasopressors. • Relative exclusion: • Major head trauma. CT brain 1st; • Recent major surgery <14days; • Known bleeding diathesis, or active ongoing bleeding; • Systemic infection or sepsis; • Coma from other causes (DO, pre-existing coma prior to arrest).
An example of induced hypothermia protocol (II) • Goal: • Target temp 32-34oC for 12-24hrs from start of cooling; • Target time to reach temp goal 6-8hrs. • Cooling: • 2 cooling blankets to “sandwich” patient; • Ice packs at sides of neck, axilla, groin; • + internal cooling techniques e.g. LVICF; • Use sedation & non-depolarizing NMB.
An example of induced hypothermia protocol (III) • Monitoring: • Continuous core temp monitoring • Thermocouple in ventriculostomy catheter; • Bladder probe, jugular bulb, PAC temp probe; • Rectal probe. • Vital signs (BP, ECG); • Urine output; • Electrolytes (K, PO42-); • ABG (RR); • Glucose; • Skin care.
An example of induced hypothermia protocol (IV) • Rewarming: • Passive / active • Aim at 0.5-1oC/hr warming; • Continue sedation and NMB till ≥36oC; • Beware of hyperk & hypotension; • Goal is normothermia. Avoid hyperthermia.
Future perspectives • IH in specific subgroups: • Out-of-hospital cardiac arrest other than VF/pulseless VT; • Other clinical conditions. • Rapid induction of hypothermia: • In ambulance, AED; • Cooling techniques; • Modulation of temp set-point (hibernation). • Temperature & duration of IH
Our own experience Case 1 • Mr Fu. M/53. • Chronic smoker. HT, hyperlipidemia. • Collapsed in public library. • Autodefibrillated at 15:16. • ROSC 15:26. • GCS 3/15. Intubated at A&E.
Case 1 Propofol infusion 1/6 2/6 3/6 4/6 5/6 6/6 7/6 17:20 Initiation of hypothermia Extubated
Case 1 • 3/6: Extubated. • E4M5V1 • Needs safety vest for mild confusion. • 12/6: MMSE 9/30. • Needs supervision on toileting & bathing. • Weak short-term memory. • 15/6: MMSE 15/30. • Poor short-term memory. • Partially disoriented to time & place.
Our own experience Case 2 • Madam Hau. F/55. • DM, HT. • Rescued from bottom of pool. • Hemodynamically stable. • GCS 3/15. Intubated at A&E. • ICU admission 26/6 09:05.
Case 2 09:05 ICU admission Temp oC Rocuronium infusion 38 36 34 32 26/6 27/6 28/6 29/6 11:20 Initiation of hypothermia 11:45 Termination of hypothermia 10:35 Extubated. GCS 15. Requested DAMA.
Take home messages • Mortality after out-of-hospital cardiac arrest mainly from post-arrest brain damage. • Induced hypothermia improves neurologic & overall outcomes. • Evidence strongest for patients with cardiac arrest with initial VF/pulseless VT who remain comatose after ROSC. • Target temp 32-34oC for 12-24hrs after initiation.
Take home messages • Clinical trials for other conditions warranted. • Different cooling techniques. • Monitoring for possible adverse effects of induced hypothermia is important.
References • NEJM 2002; 346(8):549-56. • NEJM 2002; 346(8):557-63. • NEJM 2001; 344(8):556-63. • Circulation 2003;108:118-21. • CCM 2003; 31(7):2041-51. • Neurol Clin 2006; 24:61-71. • Neurol Clin 2006; 24:73-87.
The end Thank you