THERAPEUTIC HYPOTHERMIA GAIL DELFIN MSN RN CCRN CCNS HOSPITAL OF THE UNIVERSITY OF PENNSYLVANIA May 2011 Presenter Disclosure Information Gail Delfin MSN RN Therapeutic Hypothermia FINANCIAL DISCLOSURES: No relevant financial relationships exist UNLABELED/UNAPPROVED USES: None Prevalence There are 200,000 – 300,000 deaths per year due to cardiac arrest (Nichol et al, 2008) What Happens After Successful CPR? How do we improve survival and optimize neurological outcomes? Mitochondria – Where the Action is! “Oxygen deprivation is merely the start of the cascade. Dying turns out to be almost as complicated as living.” – Lance Becker MD, Center for Resuscitation Science at Penn Mitochondria Function • Energy • “Death control” During ischemia followed by reperfusion, brain cells partially / fully recover or enter a pathway of programmed cellular death (apoptosis) The key is… Prevention of Mitochondrial Dysfunction! The Apoptotic Pathway • ATP and other high-energy metabolites breakdown, leading to increased intracellular levels of lactate, H+ ions and phosphates, resulting in intracellular acidosis • Ca+ influx induces mitochondrial dysfunction • Prolonged glutamate exposure causes neuron hyperexcitability (Polderman, 2009) Other Effects of Reperfusion Injury • Increase in pro-inflammatory mediators (tumor necrosis factor, interleukin-1, cytokines) leads to accumulation of inflammatory cells • Free radical production (i.e., superoxide, hydrogen peroxide) damages cellular components • Disruption of the blood-brain barrier leads to cerebral edema (Polderman, 2009) An Historical View of TH Hippocrates 450 BC Baron Larrey 1814 Peter Safar 1960s Packed Injured Patients in Snow Napoleonic Wars Father of CPR Landmark Studies 300 275 250 200 150 100 77 50 30 0 IDRISSI BERNARD HACA Belgium 2001 Australia 2002 Austria 2002 Outcomes of mild induced therapeutic hypothermia HYPOTHERMIA NORMOTHERMIA Alive @ hospital discharge - favorable neurological recovery HACA Study Group Bernard Hachimi-Idrissi 72/136 (53%) 21/43 (49%) 4/16 (25%) 50/137 (36%) 9/34 (26%) 1/17 (6%) Alive at 6 months - favorable neurological recovery HACA Study Group 72/136 (52%) 50/137 (36%) Recommendations from the AHA 2010 Comatose out-of-hospital VF – Class I Comatose in-hospital, other rhythms - Class IIb Decision-making after ROSC          Comatose with Glasgow Motor < 6 No alternative reason for coma No uncontrolled bleeding Hemodynamically stable; no uncontrollable dysrhythmias Absence of severe MODS or sepsis Full code status prior to event Pre-arrest cognition not meaningfully impaired ? Prolonged arrest time (> 60 minutes) ?Pregnancy – consult maternal-fetal medicine Framework for TH Induction      Apply all appropriate ICU monitoring equipment – intubate (if not already done) Immediate EKG; ECHO if indicated Blood work Guarantee that cooling equipment is ready Begin infusion of 2 liters of cold (4 degree C) NSS      Arterial line (always prior to cooling) Central line Temperaturefeedback device If paralysis is part of protocol, guarantee sedation, baseline TOF Apply continuous EEG if available Goal: To Reach Target Temp of 32–34 Degrees C Within 4 Hours   But if the EKG looks unusual? How do we incorporate catheterization? Neumar et al (2008) recommend that because CAD is present in the majority of out-of-hospital arrest victims, patients with ST segment elevation should undergo immediate cardiac intervention – If there is no clear cut EKG evidence but suspicion for ACS is high, these patients should also be considered for immediate coronary angiography – Studies have demonstrated that intervention during TH is safe and may improve outcomes (Hovdenes et al, 2007) Cardiac ECHO May reveal global hypokinesis – myocardial stunning  May reveal segmental hypo- or akinesis indicative of MI  May be helpful in directing use of vasoactive support related to the ejection fraction  What Can Bloodwork Tell Us?    HCG on all women of child-bearing age ABG with ionized calcium – pH of >7.25 to normal acceptable – Keep CO2 normal (avoid hyper– /hypoventilation) – Maintain normal calcium levels CBC, platelets, coags, fibrinogen – Baseline Hgb – Platelets may decrease with cooling – Rule out disseminated intravascular clotting Bloodwork (cont’d)  Electrolytes, magnesium, phos, glucose – Expect decrease in potassium and magnesium as cooling diuresis begins and intracellular shifts occur – Maintain phos at normal levels to support ventilator weaning – Glucose will rise during cooling and fall during warming  Amylase, lipase, liver function values may be elevated – expect to return to normal Bloodwork (cont’d)       Lactate – Abnormal lactate is to be anticipated should fall to normal; if elevates again, investigate Troponins, CK-MB Cortisol level Pan-culture Toxicology panel if appropriate Hgb/O2 sat (co-oximetry panel) Temperature Measurement  Temperature accuracy for feedback to cooling device – Gold standard - jugular venous bulb or pulmonary artery catheter; accurate, no lag time – Peripheral sites are never used – Others (bladder, esophageal) have some lag time and may be more complicated to place Sedation and Paralysis   Sedatives include propofol, lorazepam, midazolam and fentanyl – most protocols recommend both a benzodiazepine and opiate (Chamorro et al, 2009) Paralysis – Initiate prior to cooling; initiating after cooling is begun could drop temperature precipitously – prevent shivering! – Increases MVO2 40 – 100% – May use other methods other than paralysis Sedation/Paralysis  BIS Monitor to maintain sedation – small study (62 patients) demonstrated that any patient that had a BIS of 0 at any time point did not survive (Leary et al, 2010)  Train-of-four to monitor paralysis Post-resuscitation Care – A Critical Component of Advanced Life Support (Circulation, 2005)  Providers should: – Optimize hemodynamic, respiratory and neurologic support – Identify and treat reversible causes of cardiac arrest – Monitor and consider treatment for disturbances of temperature regulation and metabolism Similarity of Post–arrest Syndrome to Sepsis Syndrome (Adrie et al, 2002) Goal-Directed Therapy for Hemodynamic Optimization*     Maintain MAP 80 – 100 (may consider lower if ACS) Maintain CVP 8 – 15 Maintain ScvO2 equal to or greater than 65 Monitor lactate to determine cellular perfusion *(Gaieski et al, 2009) Determining Which Vasoactive Drugs to Use  Unknown ejection fraction or < 40% – dobutamine  Add dopamine or epinephrine  Ejection fraction is normal – norepinephrine  Severe hypotension – consider IABP  Hypertension – nitroglycerin (Gaieski et al, 2009) Normal Side Effects of TH           Tachycardia then bradycardia when temp < 35 C Vasoconstriction – increased B/P Increased CVP reading (venoconstriction) but decreased CVP due to cooling diuresis Cooling diuresis Mottling of skin Left shift of oxyhemoglobin curve Decreased metabolic rate (8% for every degree C drop) Hyperglycemia (decreased insulin sensitivity) Arrhythmias rare if temp >30 Change in drug metabolism Re-Warming Considerations         Should occur slowly - < 0.5 C/hr Discontinue all K+ containing fluids to prevent hyperkalemia Hydrate patient to maintain CVP prior to/during re-warming; consider fluid boluses for hypotension Frequent glucose monitoring to avoid hypoglycemia Observe for arrhythmias, shivering, seizures Prevention of fever for at least 48 hours Discontinue paralytics at 36 C; titrate sedation Consider treatment plan – ? cath, ? ICD, followup Adverse Effects     Stress ulcers – prophylaxis Bleeding (very low incidence) Risk of pneumonia, wound infections due to impaired immune response Atrial fibrillation progressing to VF if temp drops < 30 degrees Incidence of significant adverse effects is low Nursing Care       Skin care – observe skin, turn Q 2 hours, adjust skin wraps Assessment for shivering, seizures Eye care (paralysis) Careful documentation of IV sites; prevention of VAP, skin breakdown Consider 2:1 nursing care of the patient for first 6 hours, then 1:1 for remainder of TH course Family support Family Needs      Very difficult time – “marathon, not a sprint” Encourage support by chaplain, social services Provide information, websites, articles for laypersons Encourage family to take care by sleeping, eating, reaching out to other family members and friends, especially during 24 hours that patient remains cooled All health care providers should be on same page when communicating with the family Neuroprognostication     Published prognostic criteria are not valid for these patients (Rittenberger, 2009) CT of brain commonly shows swelling – without prognosticating value MRI of brain – poorly studied in early phase of post-arrest resuscitation EEG alone is insufficient to prognosticate futility (Abella, 2009) Neuroprognostication (cont’d)  Some indications of poor outcome: – No motor response to pain after three days – Bilaterally absent somatosensory evoked potentials after three days – Status epilepticus during the post-cardiac arrest period up to three days  Neuroprognostication should absolutely not occur before 72 hours after ROSC! (and maybe as long as 5 – 6 days) (Abella, 2009)  Hypothermia Network Registry Oct 2004-Oct 2008 986 OHCA pts > 18 yrs; 34 centers, 7 countries OHCA to ROSC:  OHCA to initiation of hypothermia:  OHCA to goal temperature (≤34 C):    – 20 (14–30) minutes – 90 (60–165) minutes – 260 (178–400) minutes (Nielsen, 2009) Results • VT/VF > 412 survivors (61%) 380 good outcome (56%) > 54 survivors (25%) 46 good outcome (21%) > 18 survivors (27%) (n = 686) • Asystole (n = 217) • PEA (n = 66) 15 good outcome (23%) Penn Data Total cooled since 2005 – 154 patients     Initial rhythm: Survival to discharge: VT/VF – 45 (29%) 27 (60%) PEA – 62 (37%) 20 (32%) Asystole – 28 (18%) 5 (18%) Other/unknown – 19 (13%) 6 (32%) Total survived: 57 (37%) Neurologically intact: 41 (72%) A Successful TH Course… TH improved survival and functional outcome for every one in six comatose survivors of cardiac arrest In experienced hands, TH is safe and highly effective References      2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2005; 12: Dec 13 Supplement. Abella BS. Prognostication and setting family expectations. Presentation, October 30 2009. Adrie C, Adib-Conquy M, Laurent I et al. Successful cardiopulmonary resuscitation after cardiac arrest as a “sepsis-like” syndrome. Circulation 2002; 106: 562-68. Chamorro C, Borrallo J, Romera M et al. Anesthesia and analgesia protocol during therapeutic hypothermia after cardiac arrest: A systematic review. Presentation, January 22 2010. Gaieski DF, Band RA, Abella BS et al. Early goal-directed hemodynamic optimization with therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest. Resuscitation 2009; 80 (4): 418-24. References (cont’d)       Hovdenes J, Laake JH, Aaberge L et al. Therapeutic hypothermia after out-of-hospital arrest: experiences with patients treated with percutaneous coronary intervention and cardiogenic shock. Acta Anaesthesiol Scand 2007; 51 (2): 137-42. Leary M, Fried D, Gaieski D et al. Neurologic prognostication and bispectral index monitoring after resuscitation from cardiac arrest. Resuscitation 2010; doi: 1016/j.resuscitation.2010.04.021. Nielsen N, Hovdenes J, Nilsson F et al. Outcome, timing and adverse effects in therapeutic hypothermia after out-of-hospital cardiac arrest. Acta Anaesthesiol Scand 2009; 53 : 926-34. Neumar RW, Nolan JP, Adrie C et al. Post cardiac arrest syndrome: Epidemiology, pathophysiology, treatment, and prognostication – A consensus statement from the International Liaison Committee on Resuscitation. Circulation 2008; 118: 245283. Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med 2009; 37 (7)(Suppl): S186-202. Rittenberger JC. Post-arrest care: Coronary catheterization, neuro monitoring. Presentation, October 30 2009.