Managing cardiac arrest is a key component of anesthesiology practice, and resuscitation of the hospitalized patient is a critical part of the anesthesiologist’s skill set. It’s something we do often as part of a code blue team, when a patient’s life is at stake and our role is critical. More than half a million cardiac arrests occur in the United States each year: approximately 400,000 out of hospital1 and 200,000 hospitalized patients.2 Although common, the event, however, possesses drama and never seems quotidian. The Institute of Medicine recently published “Strategies to Improve Cardiac Arrest Survival: A Time to Act,” a 459-page document providing a high-level overview of the current state of the art for cardiopulmonary resuscitation (CPR). The urgency of this report arises from both the magnitude of the problem and the disheartening fact that after >50 years of modern resuscitation, outcomes are generally very poor: 6% overall survival for out-of-hospital events in the United States and 24% for in-hospital arrest.3 The report makes several recommendations for improving these numbers including robust national data collection, community involvement, research, education, clinical translation, and quality improvement.
As could be expected, “A Time to Act” focuses primarily on cardiac arrest in the community with less attention to in-hospital cardiac arrest and almost none to perioperative cardiac arrest. Data show that survival from out-of-hospital cardiac arrest varies greatly according to the region and depends largely on the interval from arrest to initiating CPR.4 Thus, emphasizing systems improvement is logical, and such programmatic measures can dramatically improve outcomes. For instance, King County, Washington (Seattle metro), has a comprehensive strategy (Medic One/EMS Strategic Plan) for addressing cardiovascular emergencies and reports a 62% survival for witnessed out-of-hospital cardiac arrest. Similar systematic interventions have improved postarrest survival elsewhere.5 The Institute of Medicine committee has also called for more resources for both education and research. It is with this background that the review by Lurie et al.6 in this issue of Anesthesia & Analgesia provides us with a valuable overview of the physiology of CPR.
Clinical study of cardiac arrest is more difficult than that of many other clinical problems, because informed consent is impossible to obtain and ethical considerations often constrain comparator or control therapies. Supporting evidence for the elements of basic life support (BLS) and advanced life cardiac life support (ACLS) is thus limited because most recommendations are based on expert opinion and not prospective, randomized studies. However, scientific understanding of current resuscitation methods has grown steadily over the past 30 years, as insights from both laboratory and clinical studies have transformed recommendations and improved practice. We now recognize for instance that hyperventilation7 and hyperoxygenation8 each decrease survivorship. Hyperoxygenation worsens ischemia–reperfusion injury, a major cause of mortality after initial return of spontaneous circulation (ROSC), and hyperventilation impedes venous return and cardiac output, reducing the rate of ROSC and survival. Long intervals without chest compressions to allow physicians to identify native pulse and rhythm are also recognized as inhibiting successful resuscitation.9 Moreover, recent studies cast doubt on the efficacy of prehospital ACLS over bag-mask airway, chest compressions, and automated defibrillation.10 Epinephrine in particular is found to improve ROSC but not long-term outcome.11,12 Because certain elements of ACLS, including drugs, demonstrate little or no survival benefit,13 focus increases on the importance of BLS, especially high-quality chest compression.14 In this light, the analysis of the physiology of CPR provided by Lurie et al.6 is especially important.
In their review, Lurie et al.6 emphasize the benefit of lowering venous pressures in the heart, chest, and brain to improve cerebral perfusion pressure and venous return to the heart (read, cardiac output) and thus facilitate ROSC. Lurie et al.6 discuss 3 new approaches to facilitate this goal. The impedance threshold device (ITD), invented by Dr. Lurie, generates negative thoracic pressure during passive chest recoil after each compression. Placing an extrathoracic restriction on flow of gas into the lungs means that normal chest wall recoil lowers the pressure in the chest between compressions, and this device thereby improves venous drainage from the brain and venous return to the heart. The active compression decompression device, also developed by Dr. Lurie, exerts a “pulling” force during passive chest recoil, enhancing chest expansion between compressions such that during the “off” portion of the cycle, chest pressure drops even further than normal. Lurie et al.6 offer a compelling interpretation of the largest negative study of active ITD,15 showing that its effectiveness depended strongly on the quality of CPR delivered and suggesting a reconsideration of its role in BLS and ACLS.
In a large 2011 trial, the combination of active compression decompression device and ITD improved 1-year survival with good neurological function by 30% to 50% compared with controls.16 The newer intrathoracic pressure regulator device takes a step further by adding negative pressure directly to the airway between breaths to generate even more negative thoracic pressure, again with the aim of improving cardiac output and perfusion pressure of key organs. Finally, Lurie et al. also discuss head-up CPR, a method that takes advantage of gravity to further reduce intracranial pressure and improve venous return to the heart during resuscitation. The requirement for a mechanical system is the main limiter in the practical application of this approach, although use of a feedback device that informs the provider of compression depth can improve performance in simulations of head-up CPR; this could theoretically improve head-up CPR with manual compressions.
After delay of treatment, the quality of chest compressions continues to be the strongest predictor of good outcomes.14 The importance of properly performed chest compressions makes sense because CPR is substituting for left ventricular work. Without a contracting heart or lacking adequate compressions, improved venous return will not translate to improved cardiac output. Depth and rate of compression and compression “fraction” (read, chest compression with minimal interruptions) can each affect outcomes. Optimal depth for an adult patient is approximately 40 to 55 mm.17 Staying within the optimal rate range of 100 to 120/minutes is also key to providing quality CPR.18 Rates higher than 120/minutes impede venous return and reduce the depth of compressions, both effects that contribute to reduced cardiac output and lower ROSC rates. Interruption of compressions before and after shock, or to identify a pulse or native rhythm, should be kept to a minimal time, preferably <10 seconds before and <20 seconds after a shock.19
Lurie et al. are optimistic about improving the currently low rate of survival after CPR. They suggest that such poor outcomes may reflect a moving target and cite data that the incidence of ventricular fibrillation as the cause of cardiac arrest has declined over the past several decades. Recovery is probably much less likely from cardiac arrest because of other, nonshockable rhythms or physical–mechanical impediments to cardiac output (e.g., pulmonary embolism, hemorrhage, or cardiac tamponade) that render high-quality chest compressions ineffective. Viewed in this context, outcome studies that do not consider initial rhythm may underestimate the value of improvements in care over the past several decades. Moreover, research into aftercare as part of a “resuscitation bundle” should improve long-term outcomes from cardiac arrest. This will include targeted therapy to attenuate ischemia–reperfusion injury to the brain and heart. The need for such advances is made clear by the numbers of patients making the ROSC hurdle who do not survive to hospital discharge. Diminishing the acute and chronic effects of ischemia and reperfusion will improve the chance of survival.
Lurie et al. also note that mere survivorship is no longer considered an acceptable endpoint for resuscitation, and the preferred endpoint is discharge to home with good neurological status. They provide a succinct summary of the clinical science behind the decreasing enthusiasm for deliberate hypothermia, which is quickly falling from favor. Anesthesiologists are uniquely positioned to translate and administer other promising interventions to improve neurologic recovery. Inhaled argon, for instance, has generated very promising results in animal studies.20
The authors conclude with a statement of the value of a “back-to-basics” approach emphasizing “physiologic and biochemical first principles.” Their emphasis on high-quality CPR is especially logical when paired with improvements in larger scale systems factors that allow earlier effective intervention. Understanding the physiology of CPR and using devices that improve the calculus of arterial and venous pressure can help attain the goal of adequate perfusion of vital organs. It is important to continue research and advance education in the pathophysiology and molecular biology of cardiovascular collapse and our interventions to reverse it. Anesthesiologists possess a unique perspective and role in resuscitation; we should take advantage of that position to advance the science of resuscitation and influence how the drama of a life’s end game is resolved.
Name: Guy Weinberg, MD.
Contribution: This author helped write the manuscript.
Attestation: Guy Weinberg approved the final manuscript.
Conflicts of Interest: Guy Weinberg has equity interest in ResQ Pharma, Inc., and holds patents related to lipid resuscitation.
Name: Michael O’Connor, MD.
Contribution: This author helped write the manuscript.
Attestation: Michael O’Connor approved the final manuscript.
Conflicts of Interest: Michael O’Connor declares no conflicts of interest.
This manuscript was handled by: Avery Tung, MD.
2. Merchant RM, Yang L, Becker LB, Berg RA, Nadkarni V, Nichol G, Carr BG, Mitra N, Bradley SM, Abella BS, Groeneveld PWAmerican Heart Association Get With The Guidelines-Resuscitation Investigators. . Incidence of treated cardiac arrest in hospitalized patients in the United States. Crit Care Med. 2011;39:2401–6
3. Becker LB, Aufderheide TP, Graham R. Strategies to improve survival from cardiac arrest: a report from the institute of medicine. JAMA. 2015;314:223–4
4. Eisenberg MS, Horwood BT, Cummins RO, Reynolds-Haertle R, Hearne TR. Cardiac arrest and resuscitation: a tale of 29 cities. Ann Emerg Med. 1990;19:179–86
5. Fothergill RT, Watson LR, Chamberlain D, Virdi GK, Moore FP, Whitbread M. Increases in survival from out-of-hospital cardiac arrest: a five year study. Resuscitation. 2013;84:1089–92
6. Lurie KG, Nemergut EC, Yannoupoulos D, Sweeney M. The physiology of cardiopulmonary resuscitation. Anesth Analg. 2016;122:767–83
7. Aufderheide TP, Lurie KG. Death by hyperventilation: a common and life-threatening problem during cardiopulmonary resuscitation. Crit Care Med. 2004;32:S345–51
8. Kilgannon JH, Jones AE, Parrillo JE, Dellinger RP, Milcarek B, Hunter K, Shapiro NI, Trzeciak SEmergency Medicine Shock Research Network (EMShockNet) Investigators. . Relationship between supranormal oxygen tension and outcome after resuscitation from cardiac arrest. Circulation. 2011;123:2717–22
9. Brouwer TF, Walker RG, Chapman FW, Koster RW. Association between chest compression interruptions and clinical outcomes of ventricular fibrillation out-of-hospital cardiac arrest. Circulation. 2015;132:1030–7
10. Sanghavi P, Jena AB, Newhouse JP, Zaslavsky AM. Outcomes after out-of-hospital cardiac arrest treated by basic vs advanced life support. JAMA Intern Med. 2015;175:196–204
11. Hagihara A, Hasegawa M, Abe T, Nagata T, Wakata Y, Miyazaki S. Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest. JAMA. 2012;307:1161–8
12. Krishnamoorthy V, Vavilala MS, Fettiplace MR, Weinberg G. Epinephrine for cardiac arrest: are we doing more harm than good? Anesthesiology. 2014;120:792–4
13. Olasveengen TM, Sunde K, Brunborg C, Thowsen J, Steen PA, Wik L. Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial. JAMA. 2009;302:2222–9
14. Talikowska M, Tohira H, Finn J. Cardiopulmonary resuscitation quality and patient survival outcome in cardiac arrest: a systematic review and meta-analysis. Resuscitation. 2015;96:66–77
15. Aufderheide TP, Nichol G, Rea TD, Brown SP, Leroux BG, Pepe PE, Kudenchuk PJ, Christenson J, Daya MR, Dorian P, Callaway CW, Idris AH, Andrusiek D, Stephens SW, Hostler D, Davis DP, Dunford JV, Pirrallo RG, Stiell IG, Clement CM, Craig A, Van Ottingham L, Schmidt TA, Wang HE, Weisfeldt ML, Ornato JP, Sopko GResuscitation Outcomes Consortium (ROC) Investigators. . A trial of an impedance threshold device in out-of-hospital cardiac arrest. N Engl J Med. 2011;365:798–806
16. Aufderheide TP, Frascone RJ, Wayne MA, Mahoney BD, Swor RA, Domeier RM, Olinger ML, Holcomb RG, Tupper DE, Yannopoulos D, Lurie KG. Standard cardiopulmonary resuscitation versus active compression-decompression cardiopulmonary resuscitation with augmentation of negative intrathoracic pressure for out-of-hospital cardiac arrest: a randomised trial. Lancet. 2011;377:301–11
17. Stiell IG, Brown SP, Nichol G, Cheskes S, Vaillancourt C, Callaway CW, Morrison LJ, Christenson J, Aufderheide TP, Davis DP, Free C, Hostler D, Stouffer JA, Idris AHResuscitation Outcomes Consortium Investigators. . What is the optimal chest compression depth during out-of-hospital cardiac arrest resuscitation of adult patients? Circulation. 2014;130:1962–70
18. Idris AH, Guffey D, Pepe PE, Brown SP, Brooks SC, Callaway CW, Christenson J, Davis DP, Daya MR, Gray R, Kudenchuk PJ, Larsen J, Lin S, Menegazzi JJ, Sheehan K, Sopko G, Stiell I, Nichol G, Aufderheide TPResuscitation Outcomes Consortium Investigators. . Chest compression rates and survival following out-of-hospital cardiac arrest. Crit Care Med. 2015;43:840–8
19. Cheskes S, Schmicker RH, Verbeek PR, Salcido DD, Brown SP, Brooks S, Menegazzi JJ, Vaillancourt C, Powell J, May S, Berg RA, Sell R, Idris A, Kampp M, Schmidt T, Christenson JResuscitation Outcomes Consortium (ROC) Investigators. . The impact of peri-shock pause on survival from out-of-hospital shockable cardiac arrest during the Resuscitation Outcomes Consortium PRIMED trial. Resuscitation. 2014;85:336–42
20. Ristagno G, Fumagalli F, Russo I, Tantillo S, Zani DD, Locatelli V, De Maglie M, Novelli D, Staszewsky L, Vago T, Belloli A, Di Giancamillo M, Fries M, Masson S, Scanziani E, Latini R. Postresuscitation treatment with argon improves early neurological recovery in a porcine model of cardiac arrest. Shock. 2014;41:72–8