Therapeutic Hypothermia

Therapeutic Hypothermia
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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

Accidental Hypothermia
Unintentional decline in core temperature below 35°C Mild Hypothermia F C Moderate Hypothermia F 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:

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

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.

Randomized trials supporting therapeutic hypothermia in cardiac arrest Bernard, SA et al., NEJM, Vol 346, No. 8, pp , Feb 21, Australian Study (smaller) Holzer, M et al., NEJM, Vol. 346, No. 8, pp , Feb 21, Austrian Study (larger)

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,

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,

NEJM, Vol. 346, No. 8,

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

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

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

Miracle Max (Billy Crystal) summarizes: Efforts at cerebral salvage- appropriate patient

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

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

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

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)

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

After BLS and ACLS to ROSC: BE COOL

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:

Overall goal of post-resuscitation cooling

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

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

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 PaO 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

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

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

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

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

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

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

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:

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

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

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

Core Cooling

Blanket Cooler

Surface Cooling

Overview of Process

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

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

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

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

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

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

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.

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

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

Case of VF Arrest 53 yo female went to work with vague CP
Arrest 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 ER At the time critical care called patient was unresponsive on propofol drip Should she be chilled or continue current care?

Thank You The Importance of Bedside Assessment

Therapeutic Hypothermia

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