Therapeutic Hypothermia

1. <?xml version="1.0"?><AllQuestions /> <?xml version="1.0"?><Settings><answerBulletFormat>Numeric</answerBulletFormat><answerNowAutoInsert>No</answerNowAutoInsert><answerNowStyle>Explosion</answerNowStyle><answerNowText>Answer Now</answerNowText><chartColors>Use PowerPoint Color Scheme</chartColors><chartType>Vertical</chartType><correctAnswerIndicator>Checkmark</correctAnswerIndicator><countdownAutoInsert>No</countdownAutoInsert><countdownSeconds>10</countdownSeconds><countdownSound>TicToc.wav</countdownSound><countdownStyle>Box</countdownStyle><gridAutoInsert>No</gridAutoInsert><gridFillStyle>Answered</gridFillStyle><gridFillColor>255,255,0</gridFillColor><gridOpacity>100%</gridOpacity><gridTextStyle>Keypad #</gridTextStyle><inputSource>Response Devices</inputSource><multipleResponseDivisor># of Responses</multipleResponseDivisor><participantsLeaderBoard>5</participantsLeaderBoard><percentageDecimalPlaces>0</percentageDecimalPlaces><responseCounterAutoInsert>No</responseCounterAutoInsert><responseCounterStyle>Oval</responseCounterStyle><responseCounterDisplayValue># of Votes Received</responseCounterDisplayValue><insertObjectUsingColor>Blue</insertObjectUsingColor><showResults>Yes</showResults><teamColors>User Defined</teamColors><teamIdentificationType>None</teamIdentificationType><teamScoringType>Voting pads only</teamScoringType><teamScoringDecimalPlaces>1</teamScoringDecimalPlaces><teamIdentificationItem></teamIdentificationItem><teamsLeaderBoard>5</teamsLeaderBoard><teamName1></teamName1><teamName2></teamName2><teamName3></teamName3><teamName4></teamName4><teamName5></teamName5><teamName6></teamName6><teamName7></teamName7><teamName8></teamName8><teamName9></teamName9><teamName10></teamName10><showControlBar>Slides with Get Feedback Objects</showControlBar><defaultCorrectPointValue>100</defaultCorrectPointValue><defaultIncorrectPointValue>0</defaultIncorrectPointValue><chartColor1>187,224,227</chartColor1><chartColor2>51,51,153</chartColor2><chartColor3>0,153,153</chartColor3><chartColor4>153,204,0</chartColor4><chartColor5>128,128,128</chartColor5><chartColor6>0,0,0</chartColor6><chartColor7>0,102,204</chartColor7><chartColor8>204,204,255</chartColor8><chartColor9>255,0,0</chartColor9><chartColor10>255,255,0</chartColor10><teamColor1>187,224,227</teamColor1><teamColor2>51,51,153</teamColor2><teamColor3>0,153,153</teamColor3><teamColor4>153,204,0</teamColor4><teamColor5>128,128,128</teamColor5><teamColor6>0,0,0</teamColor6><teamColor7>0,102,204</teamColor7><teamColor8>204,204,255</teamColor8><teamColor9>255,0,0</teamColor9><teamColor10>255,255,0</teamColor10><displayAnswerImagesDuringVote>Yes</displayAnswerImagesDuringVote><displayAnswerImagesWithResponses>Yes</displayAnswerImagesWithResponses><displayAnswerTextDuringVote>Yes</displayAnswerTextDuringVote><displayAnswerTextWithResponses>Yes</displayAnswerTextWithResponses><questionSlideID></questionSlideID><controlBarState>Expanded</controlBarState><isGridColorKnownColor>True</isGridColorKnownColor><gridColorName>Yellow</gridColorName><AutoRec></AutoRec><AutoRecTimeIntrvl></AutoRecTimeIntrvl><chartVotesView>Percentage</chartVotesView><chartLabelsColor>0,0,0</chartLabelsColor><isChartLabelColorKnownColor>True</isChartLabelColorKnownColor><chartLabelColorName>Black</chartLabelColorName><chartXAxisLabelType>Answer Bullets</chartXAxisLabelType></Settings> <?xml version="1.0"?><AllAnswers /> Therapeutic Hypothermia John S. Burr, MD, FCCP Illinois Heart and Lung Associates Advocate Medical Group

2. Therapeutic Hypothermia • No relevant disclosures

3. Therapeutic Hypothermia • Mild hypothermia by definition • Also known as Targeted Temperature Management (TTM) • What we originally knew about hypothermia came from cases of accidental hypothermia • Mammalian diving reflex is an example of prolonged brain survival in hypothermia

4. Accidental Hypothermia • Unintentional decline in core temperature below 35°C Mild Hypothermia 90-95 F 32.2-35 C Moderate Hypothermia 82.4-90 F 28-32.2 C Severe Hypothermia <82.4 F <28 C • Mild Hypothermia is used therapeutically to decrease risk, increase benefits Danzl D and Pozos R. NEJM, 1994;331:1756-1760

5. Accidental Hypothermia Danzl D and Pozos R. N Engl J Med 1994;331:1756-1760

6. Therapeutic Hypothermia • Post Cardiac Arrest: VF/VT • Ischemic and Hemorrhagic Stroke • Traumatic Brain Injury • Spinal Cord Injury • Acute Liver Failure: cerebral edema • Newborn hypoxic /ischemic encephalopathy • Limiting infarct size in MI in non arrest patient • Miscellaneous: CO poisoning, hanging, near drowning, choking.

7. Therapeutic Hypothermia • Randomized trials supporting therapeutic hypothermia in cardiac arrest • Bernard, SA et al., NEJM, Vol 346, No. 8, pp 557-563, Feb 21, 2002. Australian Study (smaller) • Holzer, M et al., NEJM, Vol. 346, No. 8, pp 549-556, Feb 21, 2002. Austrian Study (larger)

8. Therapeutic Hypothermia • Melbourne, Australia- Bernard, et al. • N=77 patient recruited with strict inclusion criteria over 33 months. Men>18, Women>50, VF arrest, coma from other than circulatory arrest excluded • Persistent shock after resuscitation excluded • Cold packs to head/chest to cool within 2 hours from arrest and maintained for 12 hours • 49% Hypothermia and 26% Normothermia group with good neurological outcome. NEJM, Vol. 346, No. 8, 557-563

9. Therapeutic Hypothermia • Melbourne, Australia- Bernard, et al. • Differences in sex between groups: 58% male in Hypothermia and 79% male in Normothermia • Bystander CPR: 49% Hypothermia 71% Normothermia (might skew to diminish effect) • Lidocaine IV used in all and SG catheter • No mortality difference in this study, just improved neurological outcome • NEJM, Vol. 346, No. 8, 557-563

10. Therapeutic Hypothermia • NEJM, Vol. 346, No. 8, 557-563

11. Therapeutic Hypothermia • Vienna, Austria- Holzer et. al. • N=275, recruitment criteria more strict, recruitment time period not mentioned • 92% screened not eligible: generalizable? • VF/pulseless VT, Witnessed arrest, Down < 15 min • ROSC (return of spontaneous circulation) < 1 hour • Age 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 549-556

12. Therapeutic Hypothermia • Vienna, Austria- Holzer et. al. • Cooling different: cold air mattress • Time average to target temp 8 hours • 19/136 patients target not reached (14%) • Hypothermia 75/136 (55%) good neuro outcome • Normothermia 54/137 (39%) good outcome • Mortality (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 549-556

13. Therapeutic Hypothermia • Both studies ROSC < 60 min- average 20-25 • Australian study cooled at beginning with cold packs to head and torso • Austrian trial ROSC to cooling 105 minutes with IQR (65-192) • Similar target temperature, 12 hr vs 24 hr • VF/VT arrest with reasonable parameters for ROSC and reduced presenting mental status

14. Therapeutic Hypothermia • Miracle Max (Billy Crystal) summarizes: • Efforts at cerebral salvage- appropriate patient

15. Therapeutic Hypothermia • Who to cool? • Adults resuscitated with ROSC from witnessed arrest of presumed cardiac etiology • Initial rhythm VF/pulseless VT • May also benefit but more study needed: ROSC from other initial rhythms: asystole, PEA, ?resuscitation from in-hospital cardiac arrest • Patients who do not have absolute criteria for avoiding hypothermia

16. Therapeutic Hypothermia • Who NOT to Cool: Absolute • Patients with TM temp <30 C (all dead) • Patients who already have coma prior to arrest • Patients with Glascow coma score > 7 (mostly alive with relatively preserved neurological function) • Terminally ill or have advanced malignancy • Obviously DNR excluded

17. Therapeutic Hypothermia

18. Therapeutic Hypothermia • Who NOT to Cool: Relative • > 15 min to initiation of BLS • Time to ROSC of > 60 minutes • Time from arrest to initiation of cooling > 6 hrs • Hemodynamic instability SBP > 90 without pressor • Intracranial pathology until assessment/imaging • Inappropriate for ICU: multi-organ dysfunction, severe sepsis, comorbidity decreasing survival • Traumatic full arrest: coagulopathy, hemorrhage

19. Therapeutic Hypothermia • Who NOT to Cool: Relative • Pregnancy: risks/benefits discussed with OB • Extremes of age • Bleeding ongoing or inherited coagulopathy • Surgery < 48 hrs before or major trauma to spleen or liver • Sepsis is reason for arrest • QT prolongation • Prolonged hypoxemia, SaO2 < 85% for > 15 minutes after ROSC • Thrombocytopenia < 50K, initial asystole, coma (med)

20. Therapeutic Hypothermia • Physiologic changes during hypothermia • Brain injury during arrest and salvage by cooling • Cardiovascular effects • Respiratory effects • Renal effects • Musculoskeletal • Immune system and infection • Endocrine/Metabolic/Hematologic

21. Therapeutic Hypothermia • After BLS and ACLS to ROSC: BE COOL

22. Therapeutic Hypothermia

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

24. Therapeutic Hypothermia Overall goal of post-resuscitation cooling

25. Therapeutic Hypothermia • Cardiovascular effects: • Decreased HR and increased BP (increased SVR) • Cardiac output decreased (SV decreased, diuresis) • CVP maintained by venocontriction • Increased 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

26. Therapeutic Hypothermia • Electrical changes during decreased temp: • Increased PR, QRS, QTc but Osborn waves rare at mild hypothermia. AF, VF, Asystole more common when <30 C but most common <28 C

27. Therapeutic Hypothermia • Respiratory Effects • Decreased RR and Minute Ventilation (but on ventilator is whatever you set) • Increased serum gas solubility for O2/CO2 so if ABG not temp corrected overestimate PaCO2 by about 10 mm and O2 by about 20 mm Hg (shoot for PaO2 85-100 mm Hg if not temp corrected) • Left shift of O2/Hemoglobin dissociation so less O2 delivery but again, less cellular respiration unless shivering starts to increase metabolism

28. Therapeutic Hypothermia • Renal and electrolyte changes • Volume loss due to cold diuresis: venocontriction then increased ANP, decreased ADH leading to polyuria. Also decreased concentration capability from decreased ion pump activity in Loop of Henle • Decreased serum levels of electrolytes: K, Mg, P • Increased urine flow with renal tubular dysfunction • Intracellular movement of K, Mg, P • Electrolytes move back out during re-warming

29. Therapeutic Hypothermia • Musculoskeletal effects: • Shivering leads to increased oxygen consumption which lead to increased temperature, increased work of breathing, HR, increased myocardial O2 demand • Antagonizes efforts to maintain cooling so must be controlled by counter-warming or pharmacy including sedation with or without paralytics

30. Therapeutic Hypothermia • Immune and infectious problems: • Immune/inflammatory suppression two-edged sword in that cerebral complication reduced while increased susceptibility to infection • Increased pneumonia risk with cooling >> 24 hrs • Increased wound infection with decreased WBC function, skin vasoconstriction, and pressure and irritation from cooling pad contact

31. Therapeutic Hypothermia • Endocrine/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 secretion • Hematologic: • Hct (concentration), Plt function, coag function, but the risk of spontaneous bleeding is low

32. Therapeutic Hypothermia • Selection of candidate: evidence covered as above: out of hospital arrest VF/VT with GCS 7 or less and no contraindications • Physiologic consideration in hypothermia, most importantly brain salvage, covered • We will now turn toward practical considerations in implementing hypothermia as therapy in ICU

33. Therapeutic Hypothermia • Team Approach to management • MD: ER, Cardiology, Neurology, Critical Care • Nursing: ER, Cath Lab, CC nurses, clinical nurse specialists/educators, nurse managers • Respiratory Therapy • Pharmacy and Laboratory support • Pre-hospital care by EMS personnel

34. Therapeutic Hypothermia • Pre-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 arrival Reindeer nasal cooling Post arrest cool dry air Circulation. 2010;122:737-742

35. Therapeutic Hypothermia • General Care on Arrival: • Communication between ER, Cardiology/Cath Lab, Critical Care • Head CT, 12 Lead EKG, Labs: CBC/BMP/Troponin, Lactate, coags • If STEMI, cath lab if deemed appropriate • Three phased hypothermia protocol: complex longitudinal care so ICU bundle/caremap

36. Therapeutic Hypothermia • Initiation of Cooling • Patient assessment for protocol and start in ED or cath lab. If not comatose, decide if appropriate. • Maintenance • Decrease and maintain temperature at goal with ongoing supportive care: manage shivering • Re-Warming • 24 hours after cooling initiated with slow controlled rise in temperature and monitoring

37. Therapeutic Hypothermia Numerous methods to maintain hypothermia: surface and catheter based common Polderman, KH, Intensive Care Medicine, 2004

38. Therapeutic Hypothermia Core Cooling

39. Therapeutic Hypothermia Blanket Cooler

40. Therapeutic Hypothermia Surface Cooling

41. Therapeutic Hypothermia Overview of Process

42. Therapeutic Hypothermia • Equipment as above and- • Arterial line important with hemodynamic change • Central line for drug and pressor delivery. Australian study used PA catheters but most studies did not uniformly insert • Temperature monitoring by PA cath, esophageal probe, caution with bladder temp only if patient oliguric/anuric, rectal temp • Sedation, Treat shivering, paralysis vs skin counter-warming, EEG if available

43. Therapeutic Hypothermia • Continuous assessment • Metabolic disturbances, arrhythmias, Glucose level, Sedation and Pain level, Shivering, Seizure, Skin Breakdown, Infection/fever, Bleeding • Temperature by core method with back up • IVF to replace diuretic losses, sedation and analgesia, NM blocker vs counter-warming • Vasopressor may be needed MAP >80 preferred for CPP • IV insulin if needed for hyperglycemia

44. Therapeutic Hypothermia • Sedation deeper if NM blockade, consider BIS monitoring although accuracy based on evidence is questioned at < 35 C • The importance of shivering is the increased metabolic heat production slows/impairs target temp acquisition • Shivering early signs decreased SvO2, increased RR, facial tensing, noise on EKG, palpable muscle fasciculation of face or chest

45. Therapeutic Hypothermia • Shivering: • Optimize sedation and analgesia • Bair Hugger Device for counter warming can decrease shivering • Paralytic IVP if above ineffective • Paralytic infusion only if above ineffective • Deep sedation for paralysis if needed and periodic assessment of TOF (train of four) which is assessed prior and during infusion

46. Therapeutic Hypothermia • Fever can be commonly secondary to aspiration pneumonia/itis from arrest • Cultures, WBC with diff, empiric coverage for source • Add Tylenol to antibiotics to prevent hyperthermia from undoing your hard work

47. Therapeutic Hypothermia • Skin breakdown is higher risk with peripheral vasoconstriction and pressure from cooling pads if used • Every 2 hours with turning do skin survey • Care in applying cooling device on areas of fragile skin or wound

48. Therapeutic Hypothermia • Slow 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 hrs • Goal 36.5 to 37 C with temperature (clamping) maintained normo-thermic for 48 hours.

49. Therapeutic Hypothermia • While cool replace K, Mg, P to LLN as needed and discontinue replacement while rewarming • If using paralytic, discontinue when 36 C • Watch for hypotension secondary to peripheral vasodilation and replace intravascular volume with additional crystalloid as need

50. Therapeutic Hypothermia • Careful selection of appropriate candidate • Mindfulness of physiologic changes of hypothermia • Reach goal temperature as soon as possible and maintain 24 h with slow rewarming • Shivering and Fever need to be controlled to help protect the brain • After arrest, hypothermia allows more people to go back to independent living with good cognitive function