Targeted temperture management

Targeted temperture management (Therapeutic hypothermia)

1. THERPEUTIC HYPOTHERMIA DR. ASWIN R. M.

2. TARGETED TEMPERATURE MANAGEMENT Previously known as Therapeutic hypothermia or Protective hypothermia Specific body temperature x specific duration of time To prevent Ischemia related injury to brain After a cardiac arrest or other causes of ischemia Concept very old But accepted treatment only since last 15 years

3. MECHANISM OF TTM Cardiact arrest f/b ROSC - 2 types of brain injury

4. EFFECTS OF HYPOTHERMIA Decreases metabolic demand - 1 degree fall in temperature decreases O2 consumption by 6% Attenuation and/or reversibility of ischemic depolarization of the central nervous system (CNS) leading to membrane stabilization, electrolyte redistribution, and normalization of intracellular water concentration and intracellular pH (stabilization of the blood-brain barrier) Reduces release of excitatory amino acids Attenuation of lipid peroxidation & oxygen free radical production Restoration of calcium modulation Inhibition of deleterious signaling mechanisms, such as apoptotic signaling Inhibition of deleterious inflammatory products ( ie , cytokines, interleukins, arachidonic acid cascade end products) Inhibition of cytoskeletal breakdown Decreases ICP.

5. HISTORY First description of cold as treatment modality -Edwin Smith Papyrus, an ancient Egyptian treatise on medicine and surgery ,5000 years ago Hippocrates advised snow and ice packing to reduce hemorrhage in the wounded Total body cooling was used for tetanus treatment in the fourth- and fifth-century Late 1700s, Dr James Currie Scottish physician - first systematic experiments on humans to determine the effects of various methods of cooling upon body temperature, pulse, and respiration. 1803 - Russian method of packing in ice Baron de Larrey , Napoleon’s chief surgeon observed that wounded soldiers kept closer to a fire died faster than those who were neglected.

6. HISTORY Dr Temple Fay -credited with reintroducing therapeutic hypothermia to modern day medicine In his famous experiment in 1938 Used induced hypothermia to relieve pain from metastatic breast cancer (32°C for 24 hours). Invented one of the earliest “cooling blankets” Advised the same for traumatic brain injury 1950s - Bigelow and colleagues documented positive physiological effects of hypothermia on the brain during cardiac surgery in animals Late 1950s to 1960 was common practice in neurosurgical procedures

7. HISTORY 1958 - The first clinical trial of hypothermia in the treatment of comatose patients following cardiac arrest was published 50% survival for patients (6 of 12) managed with hypothermia at 33°C compared to 14% (1 of 7) of patients in the normothermic group 1964 - became a part of the first published algorithm on heart–lung resuscitation Advocated cooling patients within 30 minutes of the return of spontaneous circulation if there were no signs of central nervous system recovery. Further interests declined due to side effects until it became evident that even mild hypothermia has potential benefits 1990s - again became common practice

8. 2002 – 2 RCTS In 2002 - 2 landmark RCTs were published in NEJM by independent researchers in Europe & Australia.

9. BERNARD et al Melbourne 77 Patients randomized to Hypothermia (33°C for 12 h) & Normothermia group Demonstrated that 49% of hypothermia-treated patients survived versus 26% of control patients, with odds ratio (OR) = 5.25 in benefit of hypothermia . THE HYPOTHERMIA AFTER CARDIAC ARREST STUDY GROUP TRIAL (HACA TRIAL) 9 centres in five European countries Demonstrated better neurological outcomes in the treated group 275 were randomly assigned to the hypothermia (32–34°C for 24 h) & normothermia group Observed Increased recovery (55% vs 39% in the control) as well as lower 6-month mortality (41% vs 55%).

10. In 2003 ILCOR (International Liaison Committee on Resuscitation ) endorsed the use of targeted temperature management following cardiac arrest.

11. AHA GUIDELINES Recommendations 2005 2010 2015 OHCA-VF/p-VT IIa Class I, LOE B Class I, LOE B Non VF OHCA IIb Class IIb , LOE B Class I, LOE C IHCA IIb Class IIb , LOE B Class I, LOE C Temperature & Duration Strength of evidence 32- 34°C 12-24 hrs Poor 32- 34°C 12-24 hrs Poor 32- 36°C 24 hrs Class I LOE B Active rewarming of spontaneous mild hypothermia ( > 33°C) Class III, LOE C Class III, LOE C Class III, LOE C

12. 2015 AHA ACLS Comatose ( ie , lack of meaningful response to verbal commands) adult patients with ROSC after cardiac arrest have TTM Class I, LOE B for VF/ pVT OHCA Class I, LOE C for non-VF/ pVT ( ie , “ nonshockable ”) & in-hospital cardiac arrest). Selecting and maintaining a constant temperature between 32ºC and 36ºC during TTM. (Class I, LOE B) Specific Feature of individual patient will determine the target tempertaure It is reasonable that TTM be maintained for at least 24 hours after achieving target temperature. (Class IIa , LOE C)

13. 2015 AHA ACLS Recommends against the routine prehospital cooling of patients after ROSC with rapid infusion of cold intravenous fluids . (Class III: No Benefit, LOE A) It may be reasonable to actively prevent fever in comatose patients after TTM. (Class IIb, LOE C) Hemodynamically stable patients with spontaneous mild hypothermia (>33°C) after resuscitation from cardiac arrest should not be actively rewarmed

14. AAN RECOMMENDATIONS “ Reducing brain injury after cardiopulmonary resuscitation,” American Academy of Neurology (AAN) guideline May 10, 2017

15. IDEAL TEMPERATURE 34 VS 36 ° C ILCOR , 2005 & 2010 AHA guielines recommended a target temperature of 32 – 34 °C The 2015 guideline revised the target temperatures of 32-36 °C, which only some institutions have adopted so far This was following a large RCT in 2013 & a subsequent meta analysis in 2015 which confirmed the results In 2015 ILCOR adopted the term targeted temperature management (TTM).

16. 2013 950 OHCA patients Randomised to 33 & 36 °C Primary outcome – all cause mortality Secondary outcome - composite of poor neurologic function or death at 180 days Hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with 36°C

17. COOLING METHODS

18. SURFACE COOLING WITH ICE PACKS Inexpensive but messy Appropriate way to initiate cooling. Less than optimal in the rate of cooling and temperature maintenance. Ice packs placed in anatomic areas with large heat-exchange capability (the head, neck, axillae, and groin) Replaced when the ice packs have substantially melted. In addition to ice packs  evaporative cooling with fans also used. Average temperature drop - moderately slow and highly variable 0.03°0.98°Celcius per hour.

19. NEWER SURFACE COOLING SYSTEMS Works by circulating cold fluid or cold air through blankets or pads that are wrapped around the patient The temperature of the circulating fluids can be adjusted Cooling blankets Surface cooling pads Many of them has auto feed back mechanism to adjust the temperature of the circulating fluids.

20. COOLING BLANKETS Curewrap ™ with CritiCool by MTRE, Yavne , Israel Kool -Kit® with Blanketrol III by Cincinnati Sub-Zero, Cincinnati Conventional surface cooling blankets are also suboptimal because of poor surface contact with the patient’s skin. Combination with ice packs are effective at rapidly cooling patients and are fair at maintaining target temperature Once target temperature is achieved , ice packs removed & blanket used for maintenance

21. SURFACE COOLING PADS Better heat exchange due to conducting gels Superior cooling rate than cooling blankets. InnerCool STX Philips ,Netherlands (non adhesive surface pads) Artic Sun® by Medivance , Louisville (adhesive pads) EMCOOLS cooling system Vienna, Austria – adhesive non-invasive HypoCarbon ® pads with a carbon-based cooling gel and provides cooling rates of 3.5°C/h.

22. Artic Sun® Cooling system

23. SURFACE COOLING ADVANTAGES Ease of application and rapid initiation of treatment. Most devices has computerized auto-feedback mechanisms -Set target temperature and the system modifies the coolant temperature using the feedback from patient’s skin and core temperature sensors. DISADVANTAGES Rare risk of skin burns and skin irritation The initiation of hypothermia varies between different devices and can range from 2–8 hours. Shivering is more commonly seen with surface systems than with other systems which may necessitate the use of muscle relaxants & sedatives

24. SURFACE COOLING HELMET Contains a solution of aqueous glycerol that facilitates heat exchange. Although this method works, it may be slower than other methods.

25. INTERNAL(CORE) COOLING COLD INFUSIONS CATHETER BASED TECHNIQUES TRANSNASAL EVAPOARTIVE COOLING

26. COLD INFUSIONS 4°Celcius Saline or Ringer Lactate 30 mL/KG (2 L) Given over 30-60 mins Temperature reduction upto 2.5°C Given through peripheral line or femoral Vein. Not to be given by subclavian or internal jugular vein

27. CATHETER BASED CORE COOLING Uses endovascular heat-exchange catheters. Placed into central vein (Femoral , IJV , Subclavian ) Heat exchange occurs between cooled saline that passes through the heat-exchange portion of the catheter and the blood that flows over the outer surface of the catheter. 2 devices currently available on the market: Thermoguard XP temperature management system ( Zoll ) InnerCool RTx with Accutrol catheter (Philips).

28. Thermogaurd XP

29. CATHETER BASED CORE COOLING ADVANTAGES Has computerized temperature control with an auto-feedback mechanism. Faster cooling (1.46 -1.59°C/h ) and precise temperature control during all 3 stages Fewer incidences of failure to reach target temperature than other systems Less overcooling than other systems. Less shivering compared to surface devices. Sedation & paralysis not required DISADVANTAGES There was no difference in outcome when compared to surface cooling systems Added risk of catheter-related bloodstream infection, venous thrombosis and complications related to insertion of intravascular lines

30. TRANS NASAL EVAPORATIVE COOLING RhinoChill device –battery-operated device composed of a control unit, coolant bottle and a transnasal cooling catheter Two 10 cm long nasal catheter prongs inserted Perfluro carbon coolant mixture in sprayed into the nasal cavity. Cerebral hypothermia is induced by Evaporation of coolant into skull cavity Conduction - Rapid cooling of skull base Convection - Cooling of blood in adjacent blood vessels The coolant that is expelled by the lungs in gas form is inert and nontoxic.

31. TRANS NASAL EVAPORATIVE COOLING ADVANTAGES Portable & simple -Can be used by nonmedical personnel in the field Rapid intiation of therapeutic hypothermia Continue maintaining the temperature while the patient is actively resuscitated transported. Enables brain cooling even in the absence of blood circulation. DISADVANTAGES Minor – Epistaxis , Cold injury nose

32. OTHER METHODS CRRT Some positive reports for continuous renal replacement therapy (CRRT) for induction and maintenance of hypothermia Selective brain cooling by hypothermic retrograde jugular vein flush Relevant in conditions where whole body hypothermia may be detrimental. Intrapulmonary perflurochemical fluids For induction and maintenance of hypothermia and also to support gas exchange The esophageal route Also being investigated, Because of the close proximity of the esophagus to blood flow from the heart and great vessels

33. TTM

34. INCLUDED PATIENTS Post cardiac arrest ROSC within 60 mins Duration of arrest <6 hrs Maximum down time 15 mins Able to maintain a systolic blood pressure >90 mm Hg (with or without pressors ) Patient with GCS < 3

35. CONTRAINDICATIONS Not maintaining MAP 65 mmHg 30 mins after ROSC Recent major surgery within 14 days - Hypothermia may increase the risk of infection and bleeding . Systemic infection/sepsis - Hypothermia may inhibit immune function and is associated with a small increase in risk of infection. Coma from other causes (drug intoxication, preexisting coma prior to arrest) Known bleeding diathesis or with active ongoing bleeding - Inappropriate for patients with DNR order Not recommended for an isolated respiratory arrest. Reccurrent arrhythmia Intrcranial Haemorrhage Frank pulmonary edema

36. 3 STAGES

37. TREATMENT GOAL 24 hours X 32ºC-36ºC. Intiate at the earliest. Each 1 hr delay - increases mortality by 20 %. Achieve the target temperature as quickly as possible. Most cases - achieved within 3-4 hours of initiating cooling. Rewarming - 24 hours after the time of initiation of cooling (not from the time the target temperature is achieved). More evidence is needed to define the optimal duration of hypothermia treatment in humans

38. PATIENT PREPERATION Should be initiated in the emergency department. Can be continued while doing PCI. Continuous core Temperature measurement is done Foleys Catheter with probe commonly used (but adequate urine output required) . Otherwise esophageal or rectal. Most ideal - PA probe. Place an early arterial line - Vasoconstriction will make placing the line later difficult Surface cooling methods- sedation , analgesia and chemical paralysis is usually necessary. Use of endovascular cooling can negate the need for paralysis Buspirone and meperidine - lower the shivering threshold DVT prophylaxis

39. INTIATION

40. MAINTENANCE & SUPPORTIVE TREATMENT Feedback mechanisms used to modulate the amount of cooling provided. MAP goal > 80 mm Hg is preferred Norepinephrine at 0.01 mcg/kg/min starting dose and titrated to a MAP greater than 80 mm Hg. Practice standard neuroprotective strategies such as placing the head of the bed at 30º Monitor the patient for arrhythmias Osborn waves often seen. Heart rate < 40 bpm is frequent Arrhythmia & bleeding – rewarming to be intiated . Investigations CBC RFT LFT Blood sugar electrolytes troponin level, ABG, APTT PT-INR at baseline Glucose, K+, and ABG every 6 hours

41. MAINTENANCE & SUPPORTIVE TREATMENT Cooling – Decreases K+ , Increases Blood sugar K+ < 3.5 mEq /L should be treated Hyperglycemia delitirous – no guideline but strict control recommended Normocarbia advised (35-45 mm Hg for PaCO2) Avoid hypoxia & hyperoxia (SPO2> 94% recommended) Skin checked every 2-6 hours for thermal injury Regularly temperature check with a secondary temperature monitoring device . No nutrition during all 3 phases. Avoid fever

42. CONTROLLED REWARMING Most critical Peripheral Vasodilatation - hypotension. Recommended speed -0.3ºC-0.5ºC every hour. Approximately 8-12 hours required . Remove cooling blankets (and ice if still in use). Cooling Pads & Catheter based devices may be set at 35°C Increase the water temperature by 0.5°C every 1-2 hours until a stable core body temperature of 36°C has been reached for 1 hour.

43. CONTROLLED REWARMING Maintain the paralytic agent and sedation until the patient’s temperature reaches 36°C. Discontinue the paralytic agent first. The sedation may be discontinued at the practitioner’s discretion. Monitor the patient for hypotension secondary to vasodilatation related to rewarming. Discontinue potassium infusions. The goal after rewarming is normothermia ( ie , avoidance of hyperthermia)

44. PHYSIOLOGIC EFFECTS AND COMPLICATIONS All complications infrequent Shivering Arrhythmias Hyperglycemia Electrolyte disorders Coagulopathy Alterations in drug metabolism Risk of Infections Cold diuresis

45. Shivering management Shivering - body’s attempt at maintaining temperature Major concern when trying to achieve a hypothermic state. Shivering is uncomfortable, and generates heat and is therefore counterproductive to targeted temperature management. Meperidine (50 mg IV q 6 hrs) Buspirone (30 mg po q 8 hrs) Sedation (midazolam, fentanyl, propofol , lorazepam) Neuromuscular blocker ( vecuronium 0.1 mg/kg bolus; cisatracurium infusion 0.15 mg/kg bolus followed by 1-10 mcg/kg/min infusion) N euromuscular blocker can hide seizure activity, Rapid on off sedation medications are preferable to permit serial neurological assessment.

46. More experience needed… OTHER INDICATIONS TBI -Shown to be effective in traumatic brain injury with high ICP. Refractory intracranial hypertension in new born Acute stroke PREHOSPITAL COOLING Originally thought to improve outcomes, To date, no cooling manoeuvres begun in the prehospital period have improved neurologic recovery or mortality in several trials     One study noted - increased pulmonary oedema and repeat cardiac arrest with 2 L of cold intravenous fluids.   COOLING VARIABLES Timing of the initiation of cooling, cooling technique, rate, depth, and length of cooling and rewarming all have some effect on mortality and morbidity These variables are not well studied & no head to head comparisons Might be having different levels of importance on the basis of clinical indications.

47. SUMMARY Cool early (in the emergency department). Use any cooling method but temperature strictly monitored & for induction combination of methods required. Patients can continue to be cooled during percutaneous coronary intervention (PCI). Tight glycemic control, vigilance for signs of infection, maintain perfusion, and use pressors if necessary Practice standard neuroprotective strategies Rewarming should be slow. Predict and be proactive regarding management of complications from ROSC and hypothermia

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