reversible causes are the mainstays of PEA management. However, because CPR is ineffective in cardiac arrest due to cardiac tamponade and tension pneumothorax, the rapid identification and treatment of these eminently reversible causes must be of primary importance. Reversible causes include the five H's and T's (hypoxia, hypovolemia, hydrogen ion (acidosis), hypo-/hyperkalemia, hypothermia, toxins [especially narcotics and benzodiazepines], tamponade [cardiac], tension pneumothorax, thrombosis [pulmonary], thrombosis [coronary]) as defined by the 2015 AHA guidelines ( table 1) [3]. While CPR with excellent chest compressions is performed, other rescuers should not be afraid to perform "heroic" procedures, even if no definitive confirmatory studies are available, for plausibly suspected causes of PEA. CPR should be provided throughout the resuscitative effort, except during brief pauses at two- minute intervals to analyze the rhythm and assess for return of spontaneous circulation (ROSC). In a cohort of 3960 patients with out-of-hospital cardiac arrest and a nonshockable cardiac rhythm, 1774 patients were treated with ACLS before and 2186 patients were treated with ACLS after the revised 2005 guidelines, which increased the emphasis on chest compressions during resuscitation [63]. Patients treated after 2005 with an increased emphasis on chest compressions had significantly greater ROSC (34 versus 27 percent), one month survival (6.2 versus 4.1 percent), and favorable neurologic outcomes (5.1 versus 3.4 percent). (See "Advanced cardiac life support (ACLS) in adults", section on 'Asystole and pulseless electrical activity'.) https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 11/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate PEA and vasopressors The efficacy of epinephrine (1 mg IV/IO push every three to five minutes) for PEA remains uncertain, but it remains a part of the 2015 AHA guidelines for the treatment of cardiac arrest with PEA [3,37]. In a secondary analysis of a cardiac arrest registry, among a cohort of 32,101 patients with out-of-hospital cardiac arrest and a nonshockable initial rhythm (published after the 2015 AHA guidelines), earlier administration of epinephrine was associated with improved survival, with a 4 percent decreased likelihood of survival for each additional minute of delay in epinephrine administration [64]. Improvements in one-year survival following in-hospital cardiac arrest have also been reported with early administration of epinephrine [25]. (See 'VF or VT arrest and vasopressors' above.) PEA and atropine Atropine is not recommended in the 2020 guidelines for PEA because of its lack of therapeutic benefit [3,29]. The administration of atropine (1 mg IV/IO every three to five minutes) may be considered for PEA when the rate is slow, ie, absolute bradycardia with a rate <50 beats/minute or a relative bradycardia (rate less than expected relative to the underlying condition) [26,27]. Atropine's effect is on vagally-mediated bradycardia, which is rarely a cause of cardiac arrest, and treatment successes are reportable. In a cohort study of 1029 patients with PEA published after the 2010 AHA guidelines, 30-day neurologic outcomes were no different in the groups treated with epinephrine and atropine versus epinephrine alone [65]. In addition, survival was significantly lower in the group treated with epinephrine and atropine (3.2 percent versus 7.1 percent in epinephrine only group; OR 0.43, 95% CI 0.19 to 0.91), suggesting that atropine may actually be harmful when used to treat PEA. Registry data on over 20,000 in-hospital cardiac arrests with a non-shockable rhythm, collected between 2006 and 2015, showed no difference in survival before and after atropine was removed from the treatment protocol in the 2010 AHA guidelines [66]. ASYSTOLE Sudden cardiac arrest in which asystole is the initial rhythm is associated with an extremely poor prognosis (0 to 2 percent survival to hospital discharge). Asystole is usually a secondary event, resulting from prolonged ventricular fibrillation or pulseless electrical activity (PEA) with subsequent loss of all electrical activity. It may also occur as a result of prolonged hypoxia, acidosis, and death of myocardial tissue ( waveform 1). (See "Prognosis and outcomes following sudden cardiac arrest in adults", section on 'Asystole'.) True asystole should be confirmed by checking the ECG and defibrillator cable connections, making certain that the gain is turned up and the monitor is working. Confirmation of asystole in another lead is recommended. The 2015 AHA guidelines recommend that asystole be treated https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 12/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate in the same manner as PEA, with excellent cardiopulmonary resuscitation (CPR), vasopressors, and the consideration of possible reversible causes ( table 1) [3]. Atropine is no longer recommended as therapy in asystole. CPR, with an emphasis on excellent chest compressions, should be provided throughout the resuscitative effort, stopping only at two-minute intervals during which brief rhythm analysis and defibrillation is provided if the patient has reverted to a shockable rhythm [63]. There is no benefit to defibrillation in patients with asystole. (See 'Pulseless electrical activity' above and "Advanced cardiac life support (ACLS) in adults", section on 'Asystole and pulseless electrical activity'.) Because randomized controlled trials and other data have not shown a survival benefit with the use of temporary pacing in asystole, its routine use is not recommended by the 2020 AHA guidelines [3,29,67-71]. Prolonged resuscitative efforts of patients in asystole are generally futile. Termination of resuscitation is discussed elsewhere. (See "Advanced cardiac life support (ACLS) in adults", section on 'Termination of resuscitative efforts'.) Asystole and vasopressors Epinephrine Epinephrine (1 mg IV/IO push every three to five minutes) is recommended in patients with asystole, although its benefit has not been clearly demonstrated in prospective trials [3,37]. In a secondary analysis of a cardiac arrest registry, among a cohort of 32,101 patients with out-of-hospital cardiac arrest and a nonshockable initial rhythm (published after the 2015 AHA guidelines), earlier administration of epinephrine was associated with improved survival, with a 4 percent decreased likelihood of survival for each additional minute of delay in epinephrine administration [64]. Improvements in one-year survival following in-hospital cardiac arrest have also been reported with early administration of epinephrine [25]. In a separate registry study that included more than 41,000 patients (not all of whom were in asystole), delay to epinephrine administration was also associated reduced survival [72]. (See 'VF or VT arrest and vasopressors' above.) Routine use of high-dose epinephrine is not supported by data and is not recommended [73,74]. In a randomized trial comparing repeated high doses and standard doses of epinephrine for out-of-hospital cardiac arrest, survival to hospital discharge was similar with high-dose and standard dose epinephrine [74]. Although high-dose epinephrine improved the rate of successful resuscitation in patients with asystole, it did not improve survival to hospital discharge. Vasopressin Vasopressin has been studied as a potential alternative to epinephrine. In one trial comparing vasopressin with epinephrine in 1186 patients with out-of-hospital arrest, the https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 13/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate 528 patients with asystole who received vasopressin were significantly more likely to survive until hospital admission (29 versus 20 percent with epinephrine, odds ratio [OR] 0.6, 95% CI 0.4- 0.9) and hospital discharge (4.7 versus 1.5 percent, OR 0.3, 95% CI 0.1-1.0) [43]. However, a subsequent meta-analysis, which included data from this and four smaller studies (1519 patients overall), found no significant benefit of vasopressin compared with epinephrine among patients with asystole, or any other initial cardiac rhythm [44]. Based upon these data, the 2020 AHA guidelines removed vasopressin as an option for the treatment of patients with asystole [3,29]. A more recent placebo-controlled randomized trial of 501 patients with in-hospital cardiac arrest showed that vasopressin given with methylprednisolone after epinephrine administration was associated with a higher rate of return of spontaneous circulation (42 versus 33 percent) but no difference in 30-day mortality or neurologic recovery [75]. These new data are unlikely to modify the 2020 guideline recommendation regarding vasopressin. Asystole and atropine Due to a paucity of data supporting the use of atropine for asystole, the 2020 AHA guidelines no longer recommend the routine use of atropine for the management of asystole [3,29]. In a cohort study of 6419 patients with asystole, return of spontaneous circulation was significantly greater in patients receiving epinephrine and atropine (33 versus 19 percent with epinephrine alone) [65]. However, overall survival and 30-day neurologic outcomes were no different in the two groups. Registry data on over 20,000 in-hospital cardiac arrests with a non-shockable rhythm, collected between 2006 and 2015, showed no difference in survival before and after atropine was removed from the treatment protocol in the 2010 AHA guidelines [66]. INEFFECTIVE THERAPIES A number of therapies have been shown to be generally ineffective in patients who present with sudden cardiac arrest, and therefore are not part of routine management: Sodium bicarbonate, except in patients with hyperkalemia (calcium is first-line therapy) or tricyclic antidepressant overdose Fibrinolytic therapy Cardiac pacing for asystole or pulseless electrical activity (PEA) Magnesium sulfate, except in patients who have drug-induced QT prolongation and develop torsades de pointes (see 'Magnesium sulfate' above) https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 14/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate Vasopressin for SCA of any cause Atropine for PEA The relevant data regarding these therapies are presented separately. (See "Therapies of uncertain benefit in basic and advanced cardiac life support".) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Basic and advanced cardiac life support in adults".) SUMMARY AND RECOMMENDATIONS In patients with sudden cardiac arrest (SCA), survival depends upon prompt resuscitative efforts, including excellent cardiopulmonary resuscitation (CPR) with chest compressions and, when indicated, defibrillation to reestablish organized electrical activity with a stable rhythm. Chest compressions should not be stopped until the defibrillator is fully charged and the patient is ready for defibrillation. (See 'Introduction' above.) Excellent CPR should be provided throughout the resuscitative effort until return of spontaneous circulation or termination of resuscitative efforts. Brief (10 second) pauses in CPR should only occur at two-minute intervals for rhythm analysis and defibrillation, if indicated. (See "Advanced cardiac life support (ACLS) in adults" and 'Introduction' above.) The only definitively effective treatment of ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) is defibrillation, as VF and VT rarely, if ever, terminate spontaneously or after delivery of an antiarrhythmic drug. The chances of successful defibrillation, and survival, are greatest when defibrillation is performed early after the onset of VF or VT. However, while awaiting the arrival and setup of a defibrillator, CPR should be performed. (See "Advanced cardiac life support (ACLS) in adults" and 'VF and pulseless VT' above and 'Defibrillation' above.) In shockable rhythms, the priority remains early defibrillation and excellent CPR. If return of spontaneous circulation is not achieved after the second defibrillation, epinephrine 1 mg IV/IO should be administered every three to five minutes while excellent CPR and defibrillation are continued. (See "Advanced cardiac life support (ACLS) in adults" and 'VF or VT arrest and vasopressors' above.) https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 15/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate VF and VT often persist despite defibrillation, or recur promptly after successful defibrillation. In such cases, intravenous antiarrhythmic drug therapy should be used, with amiodarone or lidocaine being the preferred antiarrhythmic drugs. Notably in the management of cardiac arrest, amiodarone did not provide any benefit when assessing the clinically relevant outcome of neurologically favorable survival as compared with lidocaine or placebo. (See "Advanced cardiac life support (ACLS) in adults" and 'Antiarrhythmic drugs' above.) In patients with recurrent VF or pVT thought to be due to torsades de pointes with a prolonged QT interval, the administration of intravenous magnesium sulfate should be considered. (See 'Magnesium sulfate' above.) In contrast to SCA caused by VF or pVT, there is no role for defibrillation in the management of pulseless electrical activity (PEA) or asystole. While CPR is ongoing, epinephrine should be administered as soon as possible (and repeated every three to five minutes). However, before vascular access and epinephrine administration are considered, excellent CPR must be in progress, and epinephrine should only administered after early identification and management of other etiologies of non-shockable rhythms ( table 1). (See "Advanced cardiac life support (ACLS) in adults" and 'Pulseless electrical activity' above and 'Asystole' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Charles Pozner, MD, who contributed to an earlier version of this topic review. 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Topic 1028 Version 43.0 https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 22/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate GRAPHICS Adult cardiac arrest algorithm https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 23/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 24/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate Reprinted with permission. Highlights of the 2020 American Heart Association Guidelines for CPR and ECC. Copyright 2020 American Association, Inc. Graphic 129983 Version 9.0 https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 25/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate Continuous electrocardigraphic (ECG) strip during an episode of ventricular fibrillation (VF) that progresses to fine VF and then asystole At the onset of ventricular fibrillation (VF), the QRS complexes are regular, widened, and of tall amplitude, suggesting a more organized ventricular tachyarrhythmia. Over a brief period of time, the rhythm becomes more disorganized with high amplitude fibrillatory waves; this is coarse VF. After a longer period of time, the fibrillatory waves become fine, culminating in asystole. Graphic 67777 Version 3.0 https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 26/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate Defibrillation waveforms in implantable cardioverter- defibrillators Figure A shows the monophasic, exponentially decaying pulse was the waveform used in the first generation of ICDs. Figure B shows the biphasic waveform, which is generated with a single capacitor by switching the output polarity during discharge. Each division is 2 milliseconds. ICD: implantable cardioverter-defibrillator. Graphic 51842 Version 3.0 https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 27/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate Treatable conditions associated with cardiac arrest Condition Common associated clinical settings Acidosis Diabetes, diarrhea, drug overdose, renal dysfunction, sepsis, shock Anemia Gastrointestinal bleeding, nutritional deficiencies, recent trauma Cardiac Post-cardiac surgery, malignancy, post-myocardial infarction, pericarditis, trauma tamponade Hyperkalemia Drug overdose, renal dysfunction, hemolysis, excessive potassium intake, rhabdomyolysis, major soft tissue injury, tumor lysis syndrome Hypokalemia* Alcohol abuse, diabetes mellitus, diuretics, drug overdose, profound gastrointestinal losses Hypothermia Alcohol intoxication, significant burns, drowning, drug overdose, elder patient, endocrine disease, environmental exposure, spinal cord disease, trauma Hypovolemia Significant burns, diabetes, gastrointestinal losses, hemorrhage, malignancy, sepsis, trauma Hypoxia Upper airway obstruction, hypoventilation (CNS dysfunction, neuromuscular disease), pulmonary disease Myocardial infarction Cardiac arrest Poisoning History of alcohol or drug abuse, altered mental status, classic toxidrome (eg, sympathomimetic), occupational exposure, psychiatric disease Pulmonary embolism Immobilized patient, recent surgical procedure (eg, orthopedic), peripartum, risk factors for thromboembolic disease, recent trauma, presentation consistent with acute pulmonary embolism Tension Central venous catheter, mechanical ventilation, pulmonary disease (eg, asthma, pneumothorax chronic obstructive pulmonary disease), thoracentesis, thoracic trauma CNS: central nervous system. Hypomagnesemia should be assumed in the setting of hypokalemia, and both should be treated. Adapted from: Eisenberg MS, Mengert TJ. Cardiac resuscitation. N Engl J Med 2001; 344:1304. Graphic 52416 Version 8.0 https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 28/29 7/6/23, 1:45 PM Supportive data for advanced cardiac life support in adults with sudden cardiac arrest - UpToDate Contributor Disclosures Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Richard L Page, MD No relevant financial relationship(s) with ineligible companies to disclose. Ron M Walls, MD, FRCPC, FAAEM Other Financial Interest: Airway Management Education Center [Health care provider education and resources]; First Airway [Health care provider education and resources]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/supportive-data-for-advanced-cardiac-life-support-in-adults-with-sudden-cardiac-arrest/print 29/29