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Therapeutic HypothermiaJohn S. Burr, MD, FCCPIllinois Heart and Lung AssociatesAdvocate Medical Group

NumericNoExplosionAnswer NowUse PowerPoint Color SchemeVerticalCheckmarkNo10TicToc.wavBoxNoAnswered255,255,0100%Keypad #Response Devices# of Responses50NoOval# of Votes ReceivedBlueYesUser DefinedNoneVoting pads only15Slides with Get Feedback Objects1000187,224,22751,51,1530,153,153153,204,0128,128,1280,0,00,102,204204,204,255255,0,0255,255,0187,224,22751,51,1530,153,153153,204,0128,128,1280,0,00,102,204204,204,255255,0,0255,255,0YesYesYesYesExpandedTrueYellowPercentage0,0,0TrueBlackAnswer BulletsTherapeutic HypothermiaNo relevant disclosuresTherapeutic HypothermiaMild hypothermia by definitionAlso known as Targeted Temperature Management (TTM)What we originally knew about hypothermia came from cases of accidental hypothermiaMammalian diving reflex is an example of prolonged brain survival in hypothermiaAccidental HypothermiaUnintentional decline in core temperature below 35CMild Hypothermia90-95 F32.2-35 C

Moderate Hypothermia82.4-90 F28-32.2 C

Severe Hypothermia50, VF arrest, coma from other than circulatory arrest excludedPersistent shock after resuscitation excludedCold packs to head/chest to cool within 2 hours from arrest and maintained for 12 hours49% Hypothermia and 26% Normothermia group with good neurological outcome.NEJM, Vol. 346, No. 8, 557-563Therapeutic HypothermiaMelbourne, Australia- Bernard, et al.Differences in sex between groups: 58% male in Hypothermia and 79% male in NormothermiaBystander CPR: 49% Hypothermia 71% Normothermia (might skew to diminish effect)Lidocaine IV used in all and SG catheterNo mortality difference in this study, just improved neurological outcomeNEJM, Vol. 346, No. 8, 557-563Therapeutic Hypothermia

NEJM, Vol. 346, No. 8, 557-563Therapeutic HypothermiaVienna, Austria- Holzer et. al.N=275, recruitment criteria more strict, recruitment time period not mentioned92% screened not eligible: generalizable?VF/pulseless VT, Witnessed arrest, Down < 15 minROSC (return of spontaneous circulation) < 1 hourAge 18-75, excluded: pregnancy, TM < 30 C, pre-existing coma prior to arrest, hypotension, re-arrest after EMS arrival, response to verbal commands (GCS too high), pre-existing coag.

NEJM, Vol. 346, No. 8, p 549-556Therapeutic HypothermiaVienna, Austria- Holzer et. al.Cooling different: cold air mattressTime average to target temp 8 hours19/136 patients target not reached (14%)Hypothermia 75/136 (55%) good neuro outcomeNormothermia 54/137 (39%) good outcomeMortality (H) 41% vs (N) 55%There is consensus based on aspects of both trials to guide patient selection for therapeutic hypothermia

NEJM, Vol. 346, No. 8, p 549-556Therapeutic HypothermiaBoth studies ROSC < 60 min- average 20-25Australian study cooled at beginning with cold packs to head and torsoAustrian trial ROSC to cooling 105 minutes with IQR (65-192)Similar target temperature, 12 hr vs 24 hrVF/VT arrest with reasonable parameters for ROSC and reduced presenting mental statusTherapeutic HypothermiaMiracle Max (Billy Crystal) summarizes:

Efforts at cerebral salvage- appropriate patient

Therapeutic HypothermiaWho to cool?Adults resuscitated with ROSC from witnessed arrest of presumed cardiac etiologyInitial rhythm VF/pulseless VTMay also benefit but more study needed: ROSC from other initial rhythms: asystole, PEA, ?resuscitation from in-hospital cardiac arrestPatients who do not have absolute criteria for avoiding hypothermiaTherapeutic HypothermiaWho NOT to Cool: AbsolutePatients with TM temp 7 (mostly alive with relatively preserved neurological function)Terminally ill or have advanced malignancyObviously DNR excludedTherapeutic Hypothermia

Therapeutic HypothermiaWho NOT to Cool: Relative> 15 min to initiation of BLSTime to ROSC of > 60 minutesTime from arrest to initiation of cooling > 6 hrsHemodynamic instability SBP > 90 without pressorIntracranial pathology until assessment/imagingInappropriate for ICU: multi-organ dysfunction, severe sepsis, comorbidity decreasing survivalTraumatic full arrest: coagulopathy, hemorrhage

Therapeutic Hypothermia Who NOT to Cool: RelativePregnancy: risks/benefits discussed with OBExtremes of ageBleeding ongoing or inherited coagulopathySurgery < 48 hrs before or major trauma to spleen or liverSepsis is reason for arrestQT prolongationProlonged hypoxemia, SaO2 < 85% for > 15 minutes after ROSCThrombocytopenia < 50K, initial asystole, coma (med) Therapeutic HypothermiaPhysiologic changes during hypothermiaBrain injury during arrest and salvage by coolingCardiovascular effects Respiratory effectsRenal effectsMusculoskeletalImmune system and infectionEndocrine/Metabolic/Hematologic Therapeutic HypothermiaAfter BLS and ACLS to ROSC: BE COOL

Therapeutic Hypothermia

Therapeutic HypothermiaBy multiple mechanisms proposed above, cooling prevents spread of already existing anoxic/ischemic neural injury, limiting damage and thereby treat post-resuscitation diseaseCurrent target of 33 C, mild hypothermia, has less risk than severe hypothermia of causing other systemic side effectsThe temperature of benefit may be 36 C ?NEJM 2013; 369: 2197-2206Therapeutic Hypothermia

Overall goal of post-resuscitation coolingTherapeutic HypothermiaCardiovascular effects:Decreased HR and increased BP (increased SVR)Cardiac output decreased (SV decreased, diuresis)CVP maintained by venocontrictionIncreased SvO2 despite CO due to decreased peripheral oxygen extraction from cellular respiration. Myocardial O2 extraction also so myocardial oxygenation improves despite decreased coronary blood flow

Therapeutic HypothermiaElectrical changes during decreased temp:Increased PR, QRS, QTc but Osborn waves rare at mild hypothermia. AF, VF, Asystole more common when 24 hrsIncreased wound infection with decreased WBC function, skin vasoconstriction, and pressure and irritation from cooling pad contactTherapeutic HypothermiaEndocrine/Metabolic considerations:Decreased metabolic rate 8% per degree C Drug levels increased due to decreased hepatic clearance ( enzyme function, blood and bile flow)Hyperglycemia from decreased insulin sensitivity and secretionHematologic: Hct (concentration), Plt function, coag function, but the risk of spontaneous bleeding is low Therapeutic HypothermiaSelection of candidate: evidence covered as above: out of hospital arrest VF/VT with GCS 7 or less and no contraindicationsPhysiologic consideration in hypothermia, most importantly brain salvage, coveredWe will now turn toward practical considerations in implementing hypothermia as therapy in ICUTherapeutic HypothermiaTeam Approach to managementMD: ER, Cardiology, Neurology, Critical CareNursing: ER, Cath Lab, CC nurses, clinical nurse specialists/educators, nurse managersRespiratory TherapyPharmacy and Laboratory supportPre-hospital care by EMS personnel

Therapeutic HypothermiaPre-hospital attempts to cool in the field: ice bags (in Australian study), iced saline, cool air evaporative cooling: no convincing evidence (yet) that superior to cooling on ER arrivalCirculation. 2010;122:737-742

Reindeer nasal coolingPost arrest cool dry airTherapeutic HypothermiaGeneral Care on Arrival:Communication between ER, Cardiology/Cath Lab, Critical CareHead CT, 12 Lead EKG, Labs: CBC/BMP/Troponin, Lactate, coagsIf STEMI, cath lab if deemed appropriateThree phased hypothermia protocol: complex longitudinal care so ICU bundle/caremapTherapeutic Hypothermia Initiation of CoolingPatient assessment for protocol and start in ED or cath lab. If not comatose, decide if appropriate. MaintenanceDecrease and maintain temperature at goal with ongoing supportive care: manage shivering Re-Warming24 hours after cooling initiated with slow controlled rise in temperature and monitoringTherapeutic Hypothermia

Polderman, KH, Intensive Care Medicine, 2004Numerous methods to maintain hypothermia: surface and catheter based commonTherapeutic Hypothermia

Core CoolingTherapeutic Hypothermia

Blanket CoolerTherapeutic Hypothermia

Surface CoolingTherapeutic Hypothermia

Overview of Process41Therapeutic HypothermiaEquipment as above and-Arterial line important with hemodynamic changeCentral line for drug and pressor delivery. Australian study used PA catheters but most studies did not uniformly insertTemperature monitoring by PA cath, esophageal probe, caution with bladder temp only if patient oliguric/anuric, rectal tempSedation, Treat shivering, paralysis vs skin counter-warming, EEG if availableTherapeutic HypothermiaContinuous assessmentMetabolic disturbances, arrhythmias, Glucose level, Sedation and Pain level, Shivering, Seizure, Skin Breakdown, Infection/fever, BleedingTemperature by core method with back upIVF to replace diuretic losses, sedation and analgesia, NM blocker vs counter-warmingVasopressor may be needed MAP >80 preferred for CPPIV insulin if needed for hyperglycemiaTherapeutic HypothermiaSedation deeper if NM blockade, consider BIS monitoring although accuracy based on evidence is questioned at < 35 CThe importance of shivering is the increased metabolic heat production slows/impairs target temp acquisitionShivering early signs decreased SvO2, increased RR, facial tensing, noise on EKG, palpable muscle fasciculation of face or chestTherapeutic HypothermiaShivering:Optimize sedation and analgesiaBair Hugger Device for counter warming can decrease shiveringParalytic IVP if above ineffectiveParalytic infusion only if above ineffectiveDeep sedation for paralysis if needed and periodic assessment of TOF (train of four) which is assessed prior and during infusionTherapeutic HypothermiaFever can be commonly secondary to aspiration pneumonia/itis from arrestCultures, WBC with diff, empiric coverage for sourceAdd Tylenol to antibiotics to prevent hyperthermia from undoing your hard workTherapeutic HypothermiaSkin breakdown is higher risk with peripheral vasoconstriction and pressure from cooling pads if usedEvery 2 hours with turning do skin surveyCare in applying cooling device on areas of fragile skin or woundTherapeutic HypothermiaSlow re-warming starts 24 hours after the onset of the cooling phase (not when TT reached)Rewarming should proceed no faster than 0.25 C or 0.5 F per hour averaged over 4 hrsGoal 36.5 to 37 C with temperature (clamping) maintained normo-thermic for 48 hours.Therapeutic HypothermiaWhile cool replace K, Mg, P to LLN as needed and discontinue replacement while rewarmingIf using paralytic, discontinue when 36 CWatch for hypotension secondary to peripheral vasodilation and replace intravascular volume with additional crystalloid as needTherapeutic HypothermiaCareful selection of appropriate candidateMindfulness of physiologic changes of hypothermiaReach goal temperature as soon as possible and maintain 24 h with slow rewarmingShivering and Fever need to be controlled to help protect the brainAfter arrest, hypothermia allows more people to go back to independent living with good cognitive functionCase of VF Arrest53 yo female went to work with vague CPArrest near cafeteria at work, AED delivered shock, intubated in field, CPR for PEA (but no epinephrine given), given versed for agitation then placed on propofol drip in ERAt the time critical care called patient was unresponsive on propofol dripShould she be chilled or continue current care?Thank You

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