Post Cardiac Arrest - Adult - Inpatient/Emergency Department Consensus Care Guideline Note: Active Table of Contents – Click each header below to jump to the section of interest Table of Contents INTRODUCTION .................................................................................................................................3 SCOPE ................................................................................................................................................3 RECOMMENDATIONS .........................................................................................................................4 1. Targeted Temperature Management (TTM) ................................................................................... 4 Patient Eligibility .............................................................................................................................................. 4 Recommended Exclusion Criteria .................................................................................................................... 4 Systemic Cooling .............................................................................................................................................. 5 Prevention of Shivering.................................................................................................................................... 5 Table 2. Bedside Shivering Assessment Scale ............................................................................................................ 6 Table 3. Antishivering Protocol .................................................................................................................................. 7 2. Identify and Treat the Etiology of the Arrest ................................................................................... 8 3. Optimize Mechanical Ventilation to Minimize Lung Injury ............................................................. 8 4. Reduce the Risk of Multi-Organ Injury & Support Organ Function ................................................. 9 Hemodynamic Support .................................................................................................................................... 9 Hypotension Treatment ................................................................................................................................. 10 Blood Glucose Control ................................................................................................................................... 10 Metabolic Considerations .............................................................................................................................. 10 Central Nervous System Support ................................................................................................................... 11 5. Rewarm Slowly ............................................................................................................................... 11 6. Prognostication of Neurological Outcome .................................................................................... 12 7. Organ Donation .............................................................................................................................. 13 TABLE 1. POST-CARDIAC ARREST SYNDROME: PATHOPHYSIOLOGY, CLINICAL MANIFESTATIONS, AND POTENTIAL TREATMENTS ................................................................................................................. 14 APPENDIX A. EVIDENCE GRADING SCHEMES ..................................................................................... 17 APPENDIX B. TTM COOLING PRODUCTS ............................................................................................ 19 APPENDIX C. POST CARDIAC ARREST ALGORITHM............................................................................. 20 REFERENCES .................................................................................................................................... 21 Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. Content Experts: Name: Brad Ternus, MD – Cardiology Phone Number: (608) 262-2935 Email Address: bwternus@medicine.wisc.edu Contact for Changes: Center for Clinical Knowledge Management (CCKM) Email Address: CCKM@uwhealth.org Guideline Author: Patti Madden, PharmD – CCKM Workgroup Members: Sarah Ahrens, MD – Medicine - Hospitalist Carin Bouchard, PharmD – Pharmacy - Drug Policy Program Paula Breihan, RT – Respiratory Therapy Gozde Demiralp, MD – Anesthesia - Critical Care Joshua Gauger, MD – Emergency Medicine Giorgio Gimelli, MD – Cardiology Josh Glazer, MD – Emergency Medicine Laura Hammel, MD – Anesthesia - General Stephanie Kraus, MS, RN, CCRN – Cardiology Brittani Reinhardt, MS, RN, CCNS, CCRN – Trauma Life Support (TLC) Jennifer Lai, PharmD, BCPS – Pharmacy- Inpatient Services Rama Maganti, MD – Neurology – General Joshua E. Medow, MD – Neurological Surgery - General Anne O’Connor, MD – Cardiology Amish Raval, MD – Medicine - Cardiology Kelly Sprague, RRT – Respiratory Therapy Andrea Stapelman, MSN, RN, CCRN, TCRN – Clinical Nurse Specialist - Emergency Medicine Jeffrey E. Wells, MD – Medicine - Pulmonary Reviewers: Ciara Barclay-Buchanan, MD – Emergency Medicine David Yang, MD – Pathology Committee Approval(s): Clinical Knowledge Management (CKM) Council (09/23/2021) Plan for Review: This guideline will be reviewed when the American Heart Association Cardiopulmonary Resuscitation and Emergency Cardiovascular Care recommendations are updated, or a minimum of every five years. Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. Introduction Cardiac arrest results in 300,000 deaths per year in North America. Out-of-hospital cardiac arrest (OHCA) is a challenging condition with approximately 10.4% of patients surviving their initial hospitalization and 8.2% surviving with good functional status. In-hospital cardiac arrest (IHCA) in the US is estimated to occur in 1.2% of adult hospital admissions, with only 25.8% of patients surviving to discharge.1 Post cardiac arrest syndrome is sequelae of cardiac arrest with systemic manifestations. The key components include post-arrest brain injury, post-arrest myocardial dysfunction, systemic ischemia/reperfusion response, and persistent acute and chronic pathology that precipitated the event (Table 1).2,3 There is increasing recognition that systematic post-cardiac arrest care after return of spontaneous circulation (ROSC) can improve the likelihood of survival with good quality of life. A comprehensive, structured, multidisciplinary system of care should be implemented in a consistent manner for the treatment of patients after ROSC.1 (AHA Class 1, LOE B-NR) The 2015 and 2020 AHA Post Cardiac Arrest Care Guidelines served as an outline to this document.1,4 The clinical trials and data in regards to the care of cardiac arrest patient is not as vigorous as other cardiovascular disease processes (e.g., Acute Coronary Syndromes and Congestive Heart Failure); thus, the guideline workgroup has chosen to include some 2a and 2b level of evidence recommendations. Scope Intended Users: Emergency Medicine, Cardiology and Critical Care Physicians, Advanced Practice Providers, Nurses, and Pharmacists caring for patients who have suffered an OHCA or IHCA. These recommendations are not intended for patients managed with extracorporeal membrane oxygenation (ECMO). See Extracorporeal Membrane Oxygenation (ECMO): Initiation and Management – Adult – Inpatient/Emergency Department Consensus Care Guideline. Objective: To provide recommendations for the care of OHCA and IHCA patients which have the potential to improve long-term patient outcomes (e.g., mortality, neurological function). Target Population: Patients ≥ 18 years of age who have suffered an OHCA or IHCA. Interventions and Practices Considered: • Targeted Temperature Management (TTM) • Optimization of hemodynamics and gas exchange • Immediate coronary reperfusion when indicated for restoration of coronary blood flow with percutaneous coronary intervention • Glycemic control • Neurologic diagnosis, management, and prognostication Major Outcomes Considered: • Sudden cardiac death • Survival • Morbidity • Neurological recovery • Quality of life Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. Recommendations 1. Targeted Temperature Management (TTM) Patient Eligibility Therapeutic hypothermia (cooled to 32°C to 36°C)1 (AHA Class 1, LOE B-R) for at least 24 hours1 (AHA Class 2a, B-NR) for neurologic protection is recommended in the following patient groups with sudden and unexpected cardiac arrest, that remain comatose (i.e. lack of meaningful response to verbal commands), and are without exclusion criteria: • Return of spontaneous circulation (ROSC) after out-of-hospital arrest with any initial rhythm.1 (AHA Class 1, LOE B-R) • ROSC after in-hospital cardiac arrest with initial non-shockable rhythm.1 (AHA Class 1, LOE B-RO) or with initial shockable rhythm.1 (AHA Class 1, LOE B-NR) Data from a recent major RCT suggests targeted normothermia confers the same benefit as targeted hypothermia in patients with OHCA, with no difference in mortality or functional outcome.5 Surface or intravascular cooling was initiated in the normothermic group to maintain a temperature of ≤ 37.5 ºC and the hypothermic group received intravascular cooling to 33ºC. Data from a previous RCT suggested that a higher temperature goal of 36ºC may confer the same neurologic benefit in some circumstances.6 Taking these data into account, the targeted goal temperature between 33°C to 37°C is a clinical decision left up to the discretion of the treating clinician on a case-by-case basis, and may be influenced by specific clinical features or the initial temperature of the patient.4,7 (UW Health Low quality evidence, C recommendation) Active or rapid rewarming should be avoided in comatose patients who spontaneously develop a mild degree of hypothermia (> 32°C) after resuscitation from cardiac arrest during the first 48 hours after ROSC. (UW Health Low quality evidence, C recommendation) Recommended Exclusion Criteria Targeted temperature management is not recommended for patients who meet any of the following exclusion criteria: • > 12 hours since return of spontaneous circulation (ROSC) • Motor component of Glasgow Coma Scale score ≥ 5 (i.e., patient completes purposeful movement) • Minimal pre-morbid functional status (e.g., advanced dementia, metastatic cancer) • Sepsis as cause of arrest • Do Not Resuscitate (DNR) status • Core body temperature < 30ºC A non-enhanced CT scan of the head can provide information about structural lesions, stroke, or intracranial hemorrhage that may have contributed to cardiac arrest. This should be obtained prior to TTM induction.2 (UW Health Moderate quality evidence, S recommendation) If intracranial process present, contact Neurosurgery for a decision of the type of cooling and goal temperature, as these patients were excluded from many of the mild hypothermia post cardiac arrest clinical trials.6,8 Pregnancy is a unique circumstance in post cardiac arrest care. A pregnancy test should be performed in all women of childbearing age. (UW Health High quality evidence, S recommendation) There are reports of TTM being used as a successful therapy in pregnant women who have Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. suffered a cardiac arrest.9,10 The decision to use TTM in a pregnant patient should be made in the context of the entire clinical picture and in consultation with Obstetrics. (UW Health Low quality evidence, C recommendation) Systemic Cooling Providers should closely monitor patient core temperature after ROSC.4 (AHA Class I, LOE C) A core body temperature should be assessed immediately following patient presentation. Two temperature sources should be evaluated (either tympanic, esophageal probe or a urinary probe).2 Throughout TTM initiation, maintenance, and rewarming, temperature should be monitored continuously via esophageal, bladder, or rectal sources.4 Systemic cooling can occur via two mechanisms (see Appendix B for available equipment): 1. Surface cooling with cooling blankets/ hypothermic wraps 2. Intravascular cooling Surface cooling should be initiated immediately following determination that a patient is a candidate for targeted temperature management (i.e., considerations of exclusion criteria and non-contrasted CT of the head has been performed). (UW Health Moderate quality evidence, C recommendation) There is a 20% increase in mortality for every hour of delay in TTM initiation.11 Therefore, early communication with the accepting Critical Care service should occur, allowing for a decision on cooling method and core temperature goal. Routine prehospital cooling of patients after ROSC with rapid infusion of cold intravenous fluids is NOT recommended.4 (AHA Class III, LOE A) However, intravascular cooling may be initiated upon arrival to the Emergency Department or inpatient admission. A prototype of the catheter used at UW Health is the Zoll Quattro® catheter. This catheter is both a triple lumen central venous access for medication and fluid delivery and contains heat exchange balloons to allow for systemic body temperature modification. The Quattro® contains 4 heat exchange balloons which increases the surface area for cooling and is the longest heat exchange catheter made by Zoll at 45 cm. However, it is imperative to consider the patient’s body size in selecting a cooling catheter, as smaller body sizes may not be amendable to Quattro® placement and use of a shorter catheter may be best. Once the intravascular cooling catheter has been placed appropriately in the femoral vein cooling can commence. For additional details, see Nursing Departmental Policy #1.42AP. In the interim while placing the catheter, it is up to the discretion of the clinician as to the concomitant use of other temporary methods of cooling, such as external ice wraps or cold saline. Prevention of Shivering TTM is associated with shivering, which occurs in up to 40% of patients undergoing TTM.12 Shivering may cause cerebral metabolic stress by decreasing brain tissue oxygen tension (PbtO2).13 Pharmacologic and nonpharmacologic14 treatments are available to control shiver. Various pharmacologic protocols have been created to mitigate the effects of shivering.15-17 A protocolized approach can effectively manage shivering and minimize the potential sedative and paralytic effects associated with some antishivering medications.16,18 Prophylactic antishivering medications should be administered before starting temperature management.16,18 (UW Health Moderate quality evidence, C recommendation) The Bedside Shivering Assessment Scale (BSAS)19 should be performed to objectively document the degree of shivering (Table 2). (UW Health Moderate quality evidence, C recommendation) Pharmacologic therapy should follow a tiered protocol based on the degree of shivering (Table 3). (UW Health Moderate quality evidence, C recommendation) Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. Acetaminophen has been shown to lower hypothalmic set point.20,21 Buspirone and meperidine can synergistically reduce the shivering threshold as well.22-24 Magnesium peripherally vasodialates and improves comfort and cooling rates during hypothermia.25 Analagosedation, which is often already being utilized in cardiac arrest, has the added benefit of aiding in shivering control and therefore should be optimized. Dexmedetomidine in combination with meperedine or buspirone, have been shown to reduce shivering threshold.26,27 Neuromuscular blockade (NMB) is an option for shivering, however, NMBs may mask appropriate sedation or seizure, lead to polyneuropathy, interfere with neurologic exam and additionally, NMBs fail to shut down central shivering mechanisms. Therefore, NMBs should be utilized after other modalities have been attempted.16,28,29 (UW Health Moderate quality evidence, C recommendation) Neuromuscular blocking agents should initially be ordered as boluses, as needed to prevent shivering, with consideration given to an infusion only if shivering cannot be adequately controlled with boluses. Atracurium may be used as the first line agent for post- cardiac arrest patients due to the high incidence of renal dysfunction in this patient population. (UW Health High quality evidence, C recommendation) Venous thromboembolism (VTE) prophylaxis (UW Health High quality evidence, S recommendation) and scheduled eye lubrication (UW Health High quality evidence, S recommendation) are recommended for patients who receive a neuromuscular blocking agent. For complete recommendations including dosing, refer to the UW Health Continuous Infusion Neuromuscular Blocking Agents – Adult – Inpatient Guideline. Table 2. Bedside Shivering Assessment Scale19 Score Shivering Patient Behavior 0 None No shivering 1 Mild Shivering localized to the neck/thorax, may be seen only as an artifact on ECG or felt by palpation 2 Moderate Intermittent involvement of the upper extremities ± thorax 3 Severe Generalized shivering or sustained upper/lower-extremity shivering Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. Table 3. Antishivering Protocol16,18 Typical BSAS Score at Initiation Intervention Dose Additional Information BSAS: 0 Initiate before starting TTM Acetaminophen and Buspirone and Magnesium Sulfate and Skin Counterwarming Acetaminophen 650 mg NGT q6hrs Continue throughout TTM Buspirone 30 mg NGT q8hr Continue throughout TTM Magnesium Sulfate 4 g IV infused over 4 hours followed by infusion per titration table Obtain serum magnesium level at baseline and q 4-6hrs during TTM Magnesium Titration Table Serum Mg Level (mg/dL) Intervention 2.0 - 2.5 Increase infusion by 0.5 g/hr 2.6 - 3.0 Increase infusion by 0.25 g/hr 3.1 - 4.0 Continue current infusion rate 4.1 - 4.5 Decrease infusion by 0.25 g/hr > 4.5 Hold infusion and recheck serum Mg in 4 hours. When serum Mg ≤ 4 mg/dL restart infusion at 0.5 g/hr less than previous rate. Skin Counterwarming: Bair Hugger (43°C MAX temp) Can be used when intravascular cooling methods are utilized. Apply to hands and feet. BSAS: 1 Opioid or Dexmedetomidine Meperidine 12.5-50 mg IV q 4 hrs prn Use with caution in elderly patients and those with impaired renal function; in these populations initial dose 12.5mg. Fentanyl IV 25-200 mcg/hr Transition if not already being used as primary pain control medication. May bolus and increase infusion rate. BSAS: 2 Opioid and Dexmedetomidine Dexmedetomidine IV 0.2-1.5 mcg/kg/hr Add to baseline sedative BSAS: 3 Propofol Propofol IV 10-70 mcg/kg/min Transition if not already being used as primary sedative BSAS: 3 Use only if all other medications unable to control shivering Neuromuscular Blocking Agent (NMBA) Vecuronium 0.1 mg/kg IV bolus q 60 min PRN Rocuronium 0.6 mg/kg IV bolus q 60 min PRN Cisatracurium 0.2 mg/kg IV bolus q 60 min PRN Neuromuscular blockade last resort after inability to control shivering despite all other medications. Check TOF (placement on face preferred) every hour and consider additional dose if > 2 out of 4 twitches. Continuous infusion of NMBA for shivering only if bolus dosing is inadequate to keep BSAS < 2. Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. 2. Identify and Treat the Etiology of the Arrest Acute coronary syndrome (ACS) is a common cause of cardiac arrest. A 12-lead electrocardiogram (ECG) should be obtained as soon as possible after ROSC to determine whether acute ST segment elevation is present.1 (AHA Class 1, LOE B-NR) Patients with ST-segment elevation myocardial infarction (STEMI) Because it is impossible to determine the final neurological status of comatose patients in the first hours after ROSC, aggressive treatment of ST-segment elevation myocardial infarction (STEMI) should begin as in non–cardiac arrest patients, regardless of coma or induced hypothermia.1,2 (AHA Class 2a, LOE C-LD) Patients with suspected cardiac etiology Emergent coronary angiography should be strongly considered for all OHCA patients with suspected cardiac etiology of arrest and ST elevation on ECG.1 (AHA Class 1, LOE B-NR) The decision to proceed with coronary angiography should be made with discussion with the interventional cardiologist, and after weighing the potential risks and benefits of the procedure. Because of the high incidence of acute coronary ischemia, consideration of emergent coronary angiography may be reasonable in select patients (e.g., electrically or hemodynamically unstable) even in the absence of STEMI.1 (AHA Class 2a, LOE B-NR) Patients with ventricular fibrillation (VF) or ventricular tachycardia (VT) arrest and shockable rhythm on presentation should be strongly considered due to the benefits demonstrated in the Parisian Registry.30 (UW Health Moderate quality evidence, C recommendation) TTM can be safely combined with primary percutaneous coronary intervention (PCI) after cardiac arrest caused by acute myocardial infarction (AMI).31 Continuous telemetric monitoring should take place to detect and treat arrhythmias.1 (UW Health High quality evidence, S recommendation) Post cardiac arrest myocardial dysfunction is sequelae of OHCA and a transthoracic echocardiogram should be obtained within 24 hours of presentation; in order ensure there is no reversible etiology behind the cardiac arrest and to guide ongoing management.32 (UW Health Moderate quality evidence, C recommendation) In post cardiac arrest patients with arrest due to confirmed pulmonary embolism, thrombolysis, surgical embolectomy, and mechanical embolectomy are reasonable emergency treatment options.1 (AHA Class 2a, LOE C-LD) In patients with arrest presumed due to pulmonary embolus, fibrinolytics may be considered.1 (AHA Class 2b, LOE C-LD) 3. Optimize Mechanical Ventilation to Minimize Lung Injury Pulmonary dysfunction after cardiac arrest is common. Etiologies include hydrostatic pulmonary edema from left ventricular dysfunction; noncardiogenic edema from inflammatory, infective, or physical injuries; severe pulmonary atelectasis; or aspiration occurring during cardiac arrest or resuscitation. During postresuscitation care, both hyperoxemia and hypoxemia have been associated with worse outcomes.33 Hyperoxemia may increase oxidative stress and organ damage after reperfusion and hypoxemia may increase ischemic injury to the brain and other organs. It is important to optimize mechanical ventilation in the post arrest setting to minimize further pulmonary compromise. The well-established ventilation management strategies for patients at risk for acute lung injury and adult respiratory distress syndrome (ARDS)34 are also appropriate strategies in the post cardiac arrest population. Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. Aggressive ventilator management should be performed to avoid both hypoxia and hyperoxia, using the following strategies: 1. Hypoxemia should be avoided in all patients who remain comatose after ROSC.1 (AHA 1, LOE B-NR) It is reasonable to use the highest available oxygen concentration until the arterial oxyhemoglobin saturation or the partial pressure of arterial oxygen can be measured.1 2. Avoid hyperoxemia by titrating the FiO2 to target an oxygen saturation of 92-98% once reliable measure of peripheral blood oxygen saturation is available.1 (AHA Class 2b, LOE B-R) 3. Maintain the PaCO2 within a normal physiological range (generally 35-45 mmHg).1 (AHA Class 2b, LOE B-R) Note: Hypothermia can affect the accuracy of the PaO2 measurement because the process of measuring PaO2 involves pre-heating specimens to 37ᵒC. At this time, the UW Health Laboratory does not adjust for the patient’s body temperature at the time the sample was obtained; therefore, the PaO2 may be artificially elevated. 4. A chest radiograph should be obtained to ensure proper endotracheal tube placement. (UW Health High quality evidence, S recommendation) 5. It is reasonable to consider the titrated use of sedation and analgesia in critically ill patients who require mechanical ventilation or shivering suppression during induced hypothermia after cardiac arrest. (UW Health Moderate quality evidence, C recommendation) Note: Hypothermia can reduce the clearance of sedatives and analgesics; initiate treatment with bolus dosing of these agents as needed rather than continuous infusions to facilitate assessment after normothermia. Continuous infusions are recommended for patients receiving neuromuscular blocking agents (see UW Health Continuous Infusion Neuromuscular Blocking Agents – Adult – Inpatient Guideline). 4. Reduce the Risk of Multi-Organ Injury & Support Organ Function During the cooling process the patient should have a systemic evaluation to ensure that each system is maximally supported. Hemodynamic Support Hemodynamic instability is common after cardiac arrest.2,35 Death due to multi-organ failure is associated with a persistently low cardiac index during the first 24 hours after resuscitation. Early goal directed hemodynamic optimization is hypothesized to decrease the systemic inflammatory syndrome and reduce the post cardiac arrest brain injury.36,37 Bleeding Risk TTM induces coagulative abnormalities which can make the patient more prone to bleeding.38 Therefore, any concern for bleeding should be investigated thoroughly. If no active bleeding is detected, consider starting venous thromboembolism (VTE) prophylaxis as patients are at an increased risk for deep venous thrombosis or pulmonary embolism given immobility. (UW Health Moderate level of evidence, C recommendation) For detailed recommendations, refer to the UW Health Venous Thromboembolism Prophylaxis Guideline. Mean Arterial Pressure Goals Following cardiac arrest, cerebral auto regulation is significantly modified, and in some cases absent. These changes mean that cerebral perfusion pressure becomes even more dependent Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. upon mean arterial pressure (MAP).8,31,33,39-44 A systolic blood pressure of ≥ 90 mmHg and a MAP of ≥ 65 mmHg should be maintained to avoid hypotension.1 (AHA Class 2a, LOE B) Continuous arterial blood pressure monitoring should be undertaken with placement of an intra- arterial catheter to constantly follow these values. Use of central venous oxygen saturation to guide therapy is reasonable and clinicians can consider further treatment when central venous oxygenation levels are < 70%. Hypotension Treatment Fluid administration in the absence of contraindications is typically the first line treatment of hypotension.38 (UW Health High quality evidence, S recommendation) Vasodilation may occur from loss of sympathetic tone and from metabolic acidosis. In addition, the ischemia/reperfusion of cardiac arrest and electric defibrillation both can cause transient myocardial stunning and dysfunction that can last many hours, but may improve with use of vasoactive drugs.38 If hypotension is persistent, pharmacotherapeutic agents can be employed. Vasoactive (e.g., norepinephrine), inotropic (e.g., dobutamine), and inodilator (e.g., milrinone) agents should be titrated as needed to optimize blood pressure, cardiac output, and systemic perfusion. (UW Health High quality evidence, C recommendation) There is no evidence supporting one pharmacotherapeutic agent over another. For detailed recommendations on vasoactive medications, refer to the UW Health Vasoactive Continuous Infusions in Adult Patients - Adult - Inpatient Guideline. Blood Glucose Control The benefit of any specific target glucose range is uncertain in adults with ROSC after cardiac arrest.1 (AHA Class 2b, LOE B-R) Strategies to target moderate glycemic control (140-180 mg/dL) may be considered.1 (UW Health Low quality evidence, C recommendation) Attempts to control glucose concentration within a lower range (80 to 110 mg/dL [4.4 to 6.1 mmol/L]) should NOT be implemented after cardiac arrest due to the increased risk of hypoglycemia. (UW Health Low quality evidence, C recommendation) Targeted arterial glucose levels of 140-180 mg/dL or current insulin infusion algorithm goal of 110-150 mg/dL in intensive care unit patients are recommended per UW Health Wisconsin Insulin Infusion Practice Protocol and are supported by an American Association of Clinical Endocrinologists/American Diabetes Association (AACE/ADA) consensus statement on inpatient glycemic control.45 These ranges are consistent with the American Heart Association (AHA) guideline recommendations to target moderate glycemic control in adult patients with ROSC after cardiac arrest.1,2 (UW Health Moderate quality evidence, C recommendation) Hyperglycemia is common2,38 and serial whole blood glucose samples should be obtained through a Basic Metabolic Panel (BMP) at least every 6 hours in addition to POC glucose testing every hour throughout cooling and rewarming. (UW Health Moderate quality evidence, C recommendation) Metabolic Considerations Following presentation to the hospital (likely via the Emergency Department), the following labs should be assessed: CBC with differential, magnesium, phosphate, liver function tests (ALT, AST, albumin), troponin, prothrombin time/INR, PTT, lactate, electrolytes, BUN, calcium, and creatinine. (UW Health Moderate quality evidence, C recommendation) Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. Hypothermia induces many metabolic effects, which need to be carefully monitored throughout the cooling period. These patients are critically ill with changing volume status. Hypothermia induces an intracellular shift and diuresis46,47 which will result in low potassium, magnesium, and phosphate levels which could be a trigger for cardiac arrhythmias or respiratory complications. Therefore, serial electrolyte, calcium, magnesium, BUN, creatinine, and phosphate labs should be measured at least every 6 hours. Potassium should be replaced to maintain serum levels within a normal range, magnesium to ≥ 2.0 mg/dL, and phosphate to ≥ 2.5 mg/dL. It is important to note that rewarming reverses the potassium flux and increases serum levels,47 so repletion should be held 4 hours before rewarming begins.46 Serial lactate labs47 will allow the clinician to ensure adequate tissue oxygenation and are helpful in modifying vasoactive medications. Central Nervous System Support Brain injury is a common cause of morbidity and mortality in post–cardiac arrest patients. Brain injury is the cause of death in 68% of patients after out-of-hospital cardiac arrest and in 23% after in-hospital cardiac arrest.48 The pathophysiology of post–cardiac arrest brain injury involves a complex cascade of molecular events that are triggered by ischemia and reperfusion and then executed over hours to days after ROSC. Events and conditions in the post–cardiac arrest period have the potential to exacerbate or attenuate these injury pathways and impact ultimate outcomes.38 An electroencephalogram (EEG) should be performed, with prompt interpretation as soon as possible, and should be monitored frequently or continuously in comatose patients after ROSC.4 (AHA Class I, LOE C-LD) Continuous EEG monitoring will allow for early detection and treatment of seizures which may be masked due to the use of neuromuscular blockades, and pose a risk of further neurologic injury if not treated. The Neurology resident on call should be notified of the patient to initiate the continuous EEG process. Clinical manifestations of post–cardiac arrest brain injury include coma, seizures, myoclonus, various degrees of neurocognitive dysfunction (ranging from memory deficits to persistent vegetative state), and brain death.3 The same anticonvulsant regimens for the treatment of seizures (including myoclonic status epilepticus) used for status epilepticus caused by other etiologies may be considered after cardiac arrest.4 (AHA Class IIb, LOE C-LD) 5. Rewarm Slowly If the patient tolerates TTM to goal temperature for 24 hours, rewarming should subsequently ensue. It is important that rewarming occurs slowly. While the optimal re-warming rate is not known, literature suggests rates between 0.2 to 0.5º C/hour.49 Rewarming should occur at 0.25º C per hour.46 (UW Health Moderate quality evidence, C recommendation) Pyrexia Risk It may be reasonable to actively prevent fever in comatose patients after TTM.1 (AHA Class 2b, LOE C-LD) Rebound hyperthermia is a recognized complication of OHCA. There is as an association of poor neurological outcome in patients with fever after ROSC who have not been treated with TTM; however this finding is not consistently reported in patients treated with TTM.1 Current guidelines recommend intervening to prevent pyrexia; however, there is a lack of randomized controlled data on methods of treatment (anti-pyretics or cooling techniques). Post rewarming core body temperature should be maintained at 37º C with surface cooling devices for the next 48 hours. To facilitate this, anti-pyretic pharmacotherapy with acetaminophen may be used in the absence of hepatic dysfunction. Carefully consider the contribution of nosocomial infectious processes during this time period. Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. 6. Prognostication of Neurological Outcome In patients who remain comatose after cardiac arrest, decisions to withdraw life sustaining treatment should not be based on one variable alone but based on the integration of clinical scenario (e.g., comorbidities) and several clinical and diagnostic tests. Neuroprognostication should involve a multimodal approach and not be based on any single finding1 (AHA Class 1, LOE B-NR) and should be delayed until adequate time has passed to ensure avoidance of confounding by medication effect or a transiently poor examination in the early postinjury period.1 (AHA Class 1, LOE B-NR) The accuracy of clinical examinations may be confounded in post-cardiac arrest patients, due to slower metabolism of sedatives and neuromuscular blockers and residual sedation or paralysis.1 Neuroprognostication should be delayed until serum pentobarbital levels measure < 0.5 mcg/mL and for at least 72 hours after discontinuing sedatives and neuromuscular blockers. (UW Health Moderate quality evidence, C recommendation) It is reasonable to perform multimodal neuroprognostication at a minimum of 72 hours after the return to normothermia, though individual prognostic tests may be obtained earlier than this.1 (AHA Class 2a, LOE B-NR) A retrospective analysis of the Parisian Region OHCA Registry demonstrated that 29% of comatose survivors of cardiac arrest who recovered consciousness after TTM awoke more than 48 hours after discontinuation of sedation.50 Delayed awakening is more likely to occur in patients with renal insufficiency on admission, post-resuscitation shock, and older age (> 59 years).50 Teams caring for patients who remain comatose after ROSC should have regular and transparent multidisciplinary discussions with surrogates regarding neuroprognostication uncertainties and anticipated time course.1 (AHA Class 1, LEO C-EO) Neurological Assessments Clinical Examination The neurological examination is the most widely studied parameter to predict outcome in comatose post–cardiac arrest patients. Neurological examination for this purpose can be reliably undertaken only in the absence of confounding factors (hypotension, seizures, sedatives, or neuromuscular blockers).38 On the basis of existing studies, no clinical neurological signs reliably predict poor outcome < 24 hours after cardiac arrest.28,38,51 Among adult patients who remain comatose after ROSC, the absence of pupillary light reflex ≥ 72 hours after cardiac arrest is a reasonable exam finding with which to predict poor neurologic outcome.1 (AHA Class 2b, LOE B-NR) The bilateral absence of corneal reflexes ≥ 72 hours after cardiac arrest is also supportive of the prognosis of poor neurological outcome.1 (AHA Class 2b, LOE B-NR) The absence of vestibulo-ocular reflexes at ≥ 24 hours (FPR 0%, 95% CI 0% to 14%) or Glasgow Coma Scale (GCS) score < 5 at ≥ 72 hours (FPR 0%, 95% CI 0% to 6%) are less reliable for predicting poor outcome or were studied only in limited numbers of patients. Given their unacceptable FPR, the findings of either absent motor movements or extensor posturing should NOT be used alone for predicting a poor neurologic outcome.2,4,38 (AHA Class III, LOE B- NR) Other clinical signs, including the presence of myoclonus, are not recommended for predicting poor outcome.4 (AHA Class III, LOE B-NR) In combination with other diagnostic tests at ≥ 72 hours after cardiac arrest, the presence of status myoclonus during the first 72hours after cardiac arrest is a reasonable finding to help predict poor neurologic outcomes.1 (AHA Class 2b, LOE B-NR) If status myoclonus is present, an EEG is recommended to determine if there is underlying ictal activity.1 (AHA Class 2b, LOE B-NR) Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. EEG Findings In comatose patients it may be reasonable to consider persistent burst suppression on EEG after in the absence of sedatives at ≥ 72 hours after cardiac arrest to predict a poor outcome.1 (AHA Class 2b, LOE B-NR) Persistent status epilepticus ≥ 72 hours after cardiac arrest may be reasonable to predict poor outcome.1 (AHA Class 2b, LOE B-NR) In patients who remain comatose after cardiac arrest the usefulness of rhythmic period discharges and of seizures for neuroprognostication is uncertain.1(AHA Class 2b, LOE B-NR) Results obtained from patients who recently received, or who are receiving a barbiturate, propofol, or sedative at the time of the EEG, should be interpreted with caution. These agents may impact EEG results and therefore may not be an accurate indicator of prognosis. The effects of drug induced alteration of EEG findings are variable and can depend on both medication and patient characteristics, such as medication elimination half-life and organ dysfunction. Evoked Potentials SSEPs are less affected by sedatives or temperature manipulation than the EEG or clinical examination. In patients who are comatose after resuscitation from cardiac arrest regardless of treatment with TTM, it is reasonable to consider bilateral absence of the N20 SSEP wave > 24 hours after cardiac arrest a predictor of poor outcome.1 (AHA Class 2a, LOE B-NR) Imaging Tests In patients who are comatose after resuscitation, it may be reasonable to use the presence of a marked reduction of the gray-white ratio (GWR) on brain CT to predict poor outcome.1 (AHA Class 2b, LOE B-NR) It may be reasonable to consider extensive restriction of diffusion on brain MRI at 2-7 days after cardiac arrest in combination with other established predictors to predict a poor neurologic outcome.1 (AHA Class 2b, LOE B-NR) It may be reasonable to consider extensive areas of reduced apparent diffusion coefficient (ADC) on brain MRI at 2-7 days after cardiac arrest to predict poor outcome.1 (AHA Class 2b, LOE B-NR) Blood Markers When performed with other prognostic tests, it may be reasonable to consider high serum values of neuron-specific enolase (NSE) within 72 hours after cardiac arrest to support the prognosis of poor neurological outcome.1 (AHA Class 2b, LOE B-NR) The neuroprognostic usefulness of other serum biomarkers including S100 calcium-binding protein (S100B), Tau, neurofilament light chain, and glial fibrillary acidic protein is uncertain.1 (AHA Class 2b, LOE C-LD) 7. Organ Donation Despite maximal support and adequate observation, some patients will be brain-dead after cardiac arrest. Studies suggest that there is no difference in functional outcomes of organs transplanted from patients who are brain-dead as a consequence of cardiac arrest when compared with donors who are brain-dead due to other causes. Adult patients who progress to brain death after resuscitation from cardiac arrest should be evaluated for organ donation.2,4 (AHA Class IIb, LOE B-NR) For specific procedures (including contact information for the UW Organ and Tissue Donation team) refer to Policy 1.2.14. Patients who do not have ROSC after resuscitation efforts or who would otherwise have termination of efforts may be considered candidates for kidney or liver donation in settings where programs exist.4 (AHA Class IIb, LOE B-NR) Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. Table 1. Post-Cardiac Arrest Syndrome: Pathophysiology, Clinical Manifestations, and Potential Treatments Syndrome Pathophysiology Clinical Manifestation Potential Treatments Post–cardiac arrest brain injury • Impaired cerebrovascular autoregulation • Cerebral edema (limited) • Postischemic neurodegeneration • Coma •Seizures • Myoclonus • Cognitive dysfunction • Persistent vegetative state • Secondary parkinsonism • Cortical stroke • Brain death • Therapeutic hypothermia • Early hemodynamic optimization • Airway protection and mechanical ventilation • Seizure control • Controlled reoxygenation (SaO2 94%–96%) • Supportive care Post–cardiac arrest myocardial dysfunction • Global hypokinesis (myocardial stunning) • ACS • Reduced cardiac output • Hypotension • Dysrhythmias • Cardiovascular collapse • Early revascularization of AMI • Early hemodynamic optimization • Intravenous fluid • Inotropes • IABP • LVAD • ECMO Systemic ischemia/reperfusion response • Systemic inflammatory response syndrome • Impaired vasoregulation • Increased coagulation • Adrenal suppression • Impaired tissue oxygen delivery and utilization • Impaired resistance to infection • Ongoing tissue hypoxia/ischemia • Hypotension • Cardiovascular collapse • Pyrexia (fever) • Hyperglycemia • Multi-organ failure • Infection • Early hemodynamic optimization • IV fluid • Vasopressors • High-volume hemofiltration • Temperature control • Glucose control • Antibiotics for documented infection Persistent precipitating pathology • Cardiovascular disease (AMI/ACS, cardiomyopathy) • Pulmonary disease (COPD, asthma) • CNS disease (CVA) • Thromboembolic disease (PE) • Toxicological (overdose, poisoning) • Infection (sepsis, pneumonia) • Hypovolemia (hemorrhage, dehydration) • Specific to cause but complicated by concomitant PCAS • Disease-specific interventions guided by patient condition and concomitant PCAS ACS indicates acute coronary syndrome; AMI, acute myocardial infarction; CNS, central nervous system; COPD, chronic obstructive pulmonary disease; CVA, cerebrovascular accident; ECMO, extracorporeal membrane oxygenation; IABP, intra-aortic balloon pump; IV, intravenous; LVAD, left ventricular assist device; PCAS, post–cardiac arrest syndrome; and PE, pulmonary embolism. Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. Disclaimer Clinical practice guidelines assist clinicians by providing a framework for the evaluation and treatment of patients. This guideline outlines the preferred approach for most patients. It is not intended to replace a clinician’s judgment or to establish a protocol for all patients. It is understood that some patients will not fit the clinical condition contemplated by a guideline and that a guideline will rarely establish the only appropriate approach to a problem. Figure 1. GRADE Methodology adapted by UW Health Rating Scheme for the Strength of the Evidence/Recommendations: GRADE Ranking of Evidence High We are confident that the effect in the study reflects the actual effect. Moderate We are quite confident that the effect in the study is close to the true effect, but it is also possible it is substantially different. Low The true effect may differ significantly from the estimate. Very Low The true effect is likely to be substantially different from the estimated effect. GRADE Ratings for Recommendations for or Against Practice Strong (S) Generally should be performed (i.e., the net benefit of the treatment is clear, patient values and circumstances are unlikely to affect the decision.) Conditional (C) May be reasonable to perform (i.e., may be conditional upon patient values and preferences, the resources available, or the setting in which the intervention will be implemented.) Conflicts of Interest A conflict of interest declaration must be signed/submitted by guideline workgroup and/or committee members to ensure balance, independence, objectivity, and scientific rigor in activities pertaining to the guideline development process. Guideline members must complete a conflict of interest statement annually or as new interest(s) arises. Potential, current and Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. planned future, conflicts of interest will be identified and managed in accordance with institutional policies and procedures. This may include, but is not limited to, conflict disclosure, abstaining from voting, dismissal during comment and voting period, or recusal from requesting and/or participation in the decision-making process. Collateral Tools & Resources Companion Documents 1. Post –Cardiac Arrest Therapeutic Targeted Temperature Management (TTM) Care Algorithm 2. Post Cardiac Arrest Syndrome: Pathophysiology, Clinical Manifestations, and Potential Treatments 3. Continuous Infusion Neuromuscular Blocking Agents (NMBAs) – Adult – Inpatient Guideline 4. Assessment and Treatment of Pain, Agitation, and Delirium in the Mechanically Ventilated Intensive Care Unit Patient Guideline 5. Venous Thromboembolism Prophylaxis – Adult – Inpatient/Ambulatory Guideline 6. Vasoactive Continuous Infusions in Adult Patients – Adult – Inpatient Guideline Metrics 1. Evaluation of overall patient survival rate 2. Retrospective assessment of whether goal core temperature was achieved within 6 hours following initiation of TTM 3. Number of patients targeted core temperatures of 33°C vs. 36°C 4. Average length of inpatient hospitalization 5. Percent of patients receiving TTM and post arrest care with significant neurologic recovery 6. What % of patients remained at goal temperature for duration of therapy? 7. What % of patients achieved fever prophylaxis? What were temps 24-48 hours post TTM? 8. Method of cooling (IV vs. surface)? Order Sets & Smart Sets 1. IP – Targeted Temperature Management – Adult – Intensive Care – Admission [701] 2. IP – Comprehensive Donation After Cardiac Death (DCD) – Adult – Intensive Care – Supplemental [3627] Patient Resources 1. Health Facts For You #6583 What to Expect after Cardiac Arrest 2. Health Facts For You #5784- Organ Donation 3. Health Information- Cardiac Arrest Policies 1. Nursing Departmental Policy #1.42AP, Intravascular Cooling Catheter System – Thermogard XP (Adult & Pediatric) 1. UW Health Clinical Policy #2.1.2, Admission and Discharge of Patients to and from the Cardiac Intensive Care Unit UW Health Clinical Policy #1.2.14, Organ and Tissue Donation Protocols Wisconsin Insulin Infusion (HIGH DOSE) - Adult- Practice Protocol (ICU ONLY) Reporting Workbench Reports Targeted Temperature Management (TTM) Patients [190376] Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. Appendix A. Evidence Grading Schemes Figure 2. 2015 AHA Grading Scheme Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. Figure 3. 2020 AHA Grading Scheme Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. Appendix B. TTM Cooling Products UW Health Targeted Temperature Management (TTM) Cooling Products Note: No single cooling method has proven to be optimal38,49 and no formal comparative cost analyses have been completed. Method Equipment Type & Name Obtain From: Intravascular Cooling Thermogard machine by Zoll (formerly Coolgard) TLC, F4M5, F8/4 Sign equipment out from home unit Intravascular Catheter Quattro (4 balloon heat exchange catheter)- 9.3 Fr, 45 cm Central Services “Catheter femoral (Coolgard) trpl lumen” Item # 1004968 Note: Some units may stock this item on unit Tubing Central Services “Kit start-up Coolgard machine” Item# 1004957 Note: Some units may stock this item on unit Surface Temperature Regulation* Hyper/Hypothermia machines by Gaymar (bought by Stryker) Central Services “Hyper/hypothermia machine” Cooling Wraps Central Services “Vest hyper/hypothermia large 46”- 54” chest” Item# 1004749 “Vest hyper/hypothermia sm/med 32”- 46” chest” Item# 1005340 “Wrap leg hyper/hypothermia” Item# 1005342 Note: Some units may stock this item on unit Cooling Blanket Central Services “Blanket hyper/hypothermia 25” x 64”” Item# 1004749 Note: Some units may stock this item on unit Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. Appendix C. Post Cardiac Arrest Algorithm Post Cardiac Arrest Algorithm- Adult – Emergency Dept/Inpatient R EW A RM IN G M A IN TE N AN C E IN IT IA TI O N Presentation of Post Cardiac Arrest Does patient meet exclusion criteria? Proceed with standard of care (Outside scope of guidance document) 1. IV bolus normal saline (2 L) 2. Initiate Surface Cooling (Initial goal temp.: 36°C) 3. Obtain: • Non-contrasted head CT (if trauma/collapse) • 12-Lead ECG • Urgent echocardiogram • Troponin • Vital signs (including temperature at 2 sources) STEMI?*No ACS or other suspected cardiac etiology? Admit patient to Critical Care Unit Admit patient to Cardiac Cath Lab Admit patient to CCU Exclusion Criteria : 1. > 12 hours since ROSC 2. Motor component of Glasgow Coma Scale score ≥ 5 (i.e., purposeful movement) 3. Minimal pre-morbid cognitive status (i.e., advanced dementia, metastatic cancer) 4. Sepsis as cause of ar rest 5. DNR status 6. Core body temperature < 30°C Continue Targeted Temp Management (TTM)? Decision by Accepting Critical Care Team *Set goal core temperature: 33-37°C Goal temperature achieved within 2 hours? Continue Surface Cooling Initiate Intravascular Cooling Yes No • Arterial line placement • EEG (continuous) and neurological assessment • Wean FiO2 aggressively • Maintain oxyhemoglobin ≥ 94% • Monitor ScVO2 ≥ 70%. If < 70% consider PRBC, inotropic agents • Moderate glucose control (140-180 mg/dL) • Measure temperature continuously from 2 sources • Antishivering protocol • Draw electrolytes, BUN, creatinine, magnesium, phosphate, calcium, lactate labs (at least every 6 hours) MAP ≥ 65 mmHg achieved? MAP < 65 mmHg • IV fluids first • Consider vasoactive medications MAP > 100 mmHg • Consider IV nitroglycerin No Increase core temperature by 0.25-0.5°C/hr to 37°C Maintain goal core temperature for 24 hours Maintain core temperature of 37°C for 48 hours Continue care as appropriate by Critical Care team Prognosticate neurological assessment after patient warm for ≥ 72 hours Note: If difficulty maintaining core temperature at 37°C or rewarming faster than 0.5 °C/hr, consider: • Continuation of intravascular or surface cooling • Scheduled acetaminophen, if no significant liver disease Yes No No Yes YesYes No Yes Due to the severity of illness in post cardiac arrest patients, consider consulting Palliative Care. If patient is pregnant, consult Obstertrics. Goal Temperature Goal core temperature of 32-36°C (AHA Class 1, LOE B-R) for at least 24 hours (AHA Class 2a, LOE B-NR). Evidence suggests 37°C may be an appropriate goal temperature, particularly in patients not previously thought to be candidates for TTM (e.g., recent trauma, bleeding concerns, or hemodynamic instability) or those unable to tolerate 33°C goal temperature. Once the decision is made to proceed with TTM, the goal temperature is determined by the accepting critical care team. This decision is made after careful and timely review of the clinical data and patient factors that are available to the team at the time of the patient’s admission. *Contact Interventional Cardiology. VF/VT arrest and shockable rhythm should be strongly considered for emergent coronary angiography. Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. References 1. Panchal AR, Bartos JA, Cabañas JG, et al. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. Oct 20 2020;142(16_suppl_2):S366-s468. doi:10.1161/cir.0000000000000916 2. Morrison LJ, Neumar RW, Zimmerman JL, et al. Strategies for improving survival after in-hospital cardiac arrest in the United States: 2013 consensus recommendations: a consensus statement from the American Heart Association. Circulation. Apr 2013;127(14):1538-63. doi:10.1161/CIR.0b013e31828b2770 3. 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 (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council. Circulation. Dec 2008;118(23):2452-83. doi:10.1161/CIRCULATIONAHA.108.190652 4. Callaway CW, Donnino MW, Fink EL, et al. Part 8: Post-Cardiac Arrest Care: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. Nov 2015;132(18 Suppl 2):S465-82. doi:10.1161/CIR.0000000000000262 5. Dankiewicz J, Cronberg T, Lilja G, et al. Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest. N Engl J Med. 06 17 2021;384(24):2283-2294. doi:10.1056/NEJMoa2100591 6. Nielsen N, Wetterslev J, Cronberg T, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. Dec 2013;369(23):2197-206. doi:10.1056/NEJMoa1310519 7. Jacobs I, Nadkarni V. Targeted temperature management following cardiac arrest: An update. http://www.ilcor.org/data/TTM-ILCOR-updated-Dec-2013.pdf 8. Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. Feb 2002;346(8):557-63. doi:10.1056/NEJMoa003289 9. Chauhan A, Musunuru H, Donnino M, McCurdy MT, Chauhan V, Walsh M. The use of therapeutic hypothermia after cardiac arrest in a pregnant patient. Ann Emerg Med. Dec 2012;60(6):786-9. doi:10.1016/j.annemergmed.2012.06.004 10. Rittenberger JC, Kelly E, Jang D, Greer K, Heffner A. Successful outcome utilizing hypothermia after cardiac arrest in pregnancy: a case report. Crit Care Med. Apr 2008;36(4):1354-6. doi:10.1097/CCM.0b013e318169ee99 11. Mooney MR, Unger BT, Boland LL, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest: evaluation of a regional system to increase access to cooling. Circulation. Jul 2011;124(2):206-14. doi:10.1161/CIRCULATIONAHA.110.986257 12. Badjatia N. Therapeutic hypothermia protocols. Handb Clin Neurol. 2017;141:619-632. doi:10.1016/B978-0-444- 63599-0.00033-8 13. Badjatia N, Strongilis E, Gordon E, et al. Metabolic impact of shivering during therapeutic temperature modulation: the Bedside Shivering Assessment Scale. Stroke. Dec 2008;39(12):3242-7. doi:10.1161/STROKEAHA.108.523654 14. Badjatia N, Strongilis E, Prescutti M, et al. Metabolic benefits of surface counter warming during therapeutic temperature modulation. Crit Care Med. Jun 2009;37(6):1893-7. doi:10.1097/CCM.0b013e31819fffd3 15. Brophy GM, Human T, Shutter L. Emergency Neurological Life Support: Pharmacotherapy. Neurocrit Care. Dec 2015;23 Suppl 2:S48-68. doi:10.1007/s12028-015-0158-1 16. Choi HA, Ko SB, Presciutti M, et al. Prevention of shivering during therapeutic temperature modulation: the Columbia anti-shivering protocol. Neurocrit Care. Jun 2011;14(3):389-94. doi:10.1007/s12028-010-9474-7 17. Kuroda Y. Neurocritical care update. J Intensive Care. 2016;4:36. doi:10.1186/s40560-016-0141-8 18. Jain A, Gray M, Slisz S, Haymore J, Badjatia N, Kulstad E. Shivering Treatments for Targeted Temperature Management: A Review. J Neurosci Nurs. Apr 2018;50(2):63-67. doi:10.1097/JNN.0000000000000340 19. Badjatia N, Strongilis E, Buitrago M, et al. Assessment of the metabolic impact of shivering: the bedside shivering assessment scale (BSAS). Neurocritical Care. 2007;6(3):228. 20. Dippel DW, van Breda EJ, van Gemert HM, et al. Effect of paracetamol (acetaminophen) on body temperature in acute ischemic stroke: a double-blind, randomized phase II clinical trial. Stroke. Jul 2001;32(7):1607-12. doi:10.1161/01.str.32.7.1607 21. Kasner SE, Wein T, Piriyawat P, et al. Acetaminophen for altering body temperature in acute stroke: a randomized clinical trial. Stroke. Jan 2002;33(1):130-4. doi:10.1161/hs0102.101477 22. Mokhtarani M, Mahgoub AN, Morioka N, et al. Buspirone and meperidine synergistically reduce the shivering threshold. Anesth Analg. Nov 2001;93(5):1233-9. doi:10.1097/00000539-200111000-00038 23. Kimberger O, Ali SZ, Markstaller M, et al. Meperidine and skin surface warming additively reduce the shivering threshold: a volunteer study. Crit Care. 2007;11(1):R29. doi:10.1186/cc5709 Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. 24. Kurz A, Ikeda T, Sessler DI, et al. Meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold. Anesthesiology. May 1997;86(5):1046-54. doi:10.1097/00000542-199705000-00007 25. Zweifler RM, Voorhees ME, Mahmood MA, Parnell M. Magnesium sulfate increases the rate of hypothermia via surface cooling and improves comfort. Stroke. Oct 2004;35(10):2331-4. doi:10.1161/01.STR.0000141161.63181.f1 26. Doufas AG, Lin CM, Suleman MI, et al. Dexmedetomidine and meperidine additively reduce the shivering threshold in humans. Stroke. May 2003;34(5):1218-23. doi:10.1161/01.STR.0000068787.76670.A4 27. Lenhardt R, Orhan-Sungur M, Komatsu R, et al. Suppression of shivering during hypothermia using a novel drug combination in healthy volunteers. Anesthesiology. Jul 2009;111(1):110-5. doi:10.1097/ALN.0b013e3181a979a3 28. Polderman KH, Herold I. Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods. Crit Care Med. Mar 2009;37(3):1101-20. doi:10.1097/CCM.0b013e3181962ad5 29. Sessler DI. Thermoregulatory defense mechanisms. Crit Care Med. Jul 2009;37(7 Suppl):S203-10. doi:10.1097/CCM.0b013e3181aa5568 30. Dumas F, Bougouin W, Geri G, et al. Emergency Percutaneous Coronary Intervention in Post-Cardiac Arrest Patients Without ST-Segment Elevation Pattern: Insights From the PROCAT II Registry. JACC Cardiovasc Interv. 05 2016;9(10):1011-8. doi:10.1016/j.jcin.2016.02.001 31. Sunde K, Pytte M, Jacobsen D, et al. Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation. Apr 2007;73(1):29-39. doi:10.1016/j.resuscitation.2006.08.016 32. Breitkreutz R, Price S, Steiger HV, et al. Focused echocardiographic evaluation in life support and peri-resuscitation of emergency patients: a prospective trial. Resuscitation. Nov 2010;81(11):1527-33. doi:10.1016/j.resuscitation.2010.07.013 33. Berg KM, Soar J, Andersen LW, et al. Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. Oct 2020;142(16_suppl_1):S92-S139. doi:10.1161/CIR.0000000000000893 34. Siegel M, R H. Ventilator management strategies for adults with acute respiratory distress syndome. Accessed 6/3/2021, 2021. https://www.uptodate.com/contents/ventilator-management-strategies-for-adults-with-acute- respiratory-distress- syndrome?search=mechanical%20ventilation%20in%20acute%20respiratory%20distress%20syndrome&source=se arch_result&selectedTitle=1~150&usage_type=default&display_rank=1 35. Laurent I, Monchi M, Chiche JD, et al. Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest. J Am Coll Cardiol. Dec 2002;40(12):2110-6. doi:10.1016/s0735-1097(02)02594-9 36. Gaieski DF, Band RA, Abella BS, et al. Early goal-directed hemodynamic optimization combined with therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest. Resuscitation. Apr 2009;80(4):418-24. doi:10.1016/j.resuscitation.2008.12.015 37. Adrie C, Laurent I, Monchi M, Cariou A, Dhainaou JF, Spaulding C. Postresuscitation disease after cardiac arrest: a sepsis-like syndrome? Curr Opin Crit Care. Jun 2004;10(3):208-12. doi:10.1097/01.ccx.0000126090.06275.fe 38. Peberdy MA, Callaway CW, Neumar RW, et al. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. Nov 2010;122(18 Suppl 3):S768-86. doi:10.1161/CIRCULATIONAHA.110.971002 39. Sundgreen C, Larsen FS, Herzog TM, Knudsen GM, Boesgaard S, Aldershvile J. Autoregulation of cerebral blood flow in patients resuscitated from cardiac arrest. Stroke. Jan 2001;32(1):128-32. doi:10.1161/01.str.32.1.128 40. Young MN, Hollenbeck RD, Pollock JS, et al. Higher achieved mean arterial pressure during therapeutic hypothermia is not associated with neurologically intact survival following cardiac arrest. Resuscitation. Mar 2015;88:158-64. doi:10.1016/j.resuscitation.2014.12.008 41. Ameloot K, De Deyne C, Eertmans W, et al. Early goal-directed haemodynamic optimization of cerebral oxygenation in comatose survivors after cardiac arrest: the Neuroprotect post-cardiac arrest trial. Eur Heart J. 06 2019;40(22):1804-1814. doi:10.1093/eurheartj/ehz120 42. Jakkula P, Pettilä V, Skrifvars MB, et al. Targeting low-normal or high-normal mean arterial pressure after cardiac arrest and resuscitation: a randomised pilot trial. Intensive Care Med. Dec 2018;44(12):2091-2101. doi:10.1007/s00134-018-5446-8 43. Roberts BW, Kilgannon JH, Hunter BR, et al. Association Between Elevated Mean Arterial Blood Pressure and Neurologic Outcome After Resuscitation From Cardiac Arrest: Results From a Multicenter Prospective Cohort Study. Crit Care Med. 01 2019;47(1):93-100. doi:10.1097/CCM.0000000000003474 44. Lopez-de-Sa E, Rey JR, Armada E, et al. Hypothermia in comatose survivors from out-of-hospital cardiac arrest: pilot trial comparing 2 levels of target temperature. Circulation. Dec 2012;126(24):2826-33. doi:10.1161/CIRCULATIONAHA.112.136408 45. Moghissi ES, Korytkowski MT, DiNardo M, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care. Jun 2009;32(6):1119-31. doi:10.2337/dc09-9029 Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. 46. Scirica BM. Therapeutic hypothermia after cardiac arrest. Circulation. Jan 2013;127(2):244-50. doi:10.1161/CIRCULATIONAHA.111.076851 47. Polderman KH. Mechanisms of action, physiological effects, and complications of hypothermia. Crit Care Med. Jul 2009;37(7 Suppl):S186-202. doi:10.1097/CCM.0b013e3181aa5241 48. Laver S, Farrow C, Turner D, Nolan J. Mode of death after admission to an intensive care unit following cardiac arrest. Intensive Care Med. Nov 2004;30(11):2126-8. doi:10.1007/s00134-004-2425-z 49. Delhaye C, Mahmoudi M, Waksman R. Hypothermia therapy: neurological and cardiac benefits. J Am Coll Cardiol. Jan 2012;59(3):197-210. doi:10.1016/j.jacc.2011.06.077 50. Paul M, Bougouin W, Geri G, et al. Delayed awakening after cardiac arrest: prevalence and risk factors in the Parisian registry. Intensive Care Med. Jul 2016;42(7):1128-36. doi:10.1007/s00134-016-4349-9 51. Honarmand A, Safavi MR. Comparison of prophylactic use of midazolam, ketamine, and ketamine plus midazolam for prevention of shivering during regional anaesthesia: a randomized double-blind placebo controlled trial. Br J Anaesth. Oct 2008;101(4):557-62. doi:10.1093/bja/aen205 Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission Contact: CCKM@uwhealth.org Last Revised: 09/2021 Effective 10/6/2021. Contact CCKM@uwhealth.org for previous versions. Introduction Scope Recommendations 1. Targeted Temperature Management (TTM) Patient Eligibility Recommended Exclusion Criteria Systemic Cooling Prevention of Shivering 2. Identify and Treat the Etiology of the Arrest 3. Optimize Mechanical Ventilation to Minimize Lung Injury 4. Reduce the Risk of Multi-Organ Injury & Support Organ Function Hemodynamic Support Hypotension Treatment Blood Glucose Control Metabolic Considerations Central Nervous System Support 5. Rewarm Slowly 6. Prognostication of Neurological Outcome 7. Organ Donation Table 1. Post-Cardiac Arrest Syndrome: Pathophysiology, Clinical Manifestations, and Potential Treatments Appendix A. Evidence Grading Schemes Appendix B. TTM Cooling Products Appendix C. Post Cardiac Arrest Algorithm References