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Eur J Emerg Med 2001;8(4):263-269 224 Berg RA, Reeder RW, Meert KL, et al End-tidal carbon dioxide during pediatric in-hospital cardiopulmonary resuscitation Resuscitation 2018;133:173-179 225 Sheak KR, Wiebe DJ, Leary M, et al Quantitative relationship between end-tidal carbon dioxide and CPR quality during both in-hospital and out-of-hospital cardiac arrest Resuscitation 2015;89:149-154 226 Bersin RM, Arieff AI Improved hemodynamic function during hypoxia with Carbicarb, a new agent for the management of acidosis Circulation 1988;77(1):227-233 227 Sun JH, Filley GF, Hord K, Kindig NB, Bartle EJ Carbicarb - an effective substitute for Nahco3 for the treatment of acidosis Surgery 1987;102(5):835-839 228 Beech JS, Nolan KM, Iles RA, Cohen RD, Williams SCR, Evans SJW The effects of sodium bicarbonate and a mixture of sodium bicarbonate and carbonate (“Carbicarb”) on skeletal muscle pH and hemodynamic status in rats with hypovolemic shock Metabolism 1994;43(4):518-522 229 Stacpoole PW The pharmacology of dichloroacetate Metabolism 1989;38(11):1124-1144 230 Stacpoole PW Dichloroacetate in the treatment of lactic acidosis Ann Intern Med 1988;108(1):58 231 Stacpoole PW, Gonzalez MG, Vlasak J, Oshiro Y, Bodor N Dichloroacetate derivatives metabolic effects and pharmacodynamics in normal rats Life Sci 1987;41(18):2167-2176 232 Wargovich TJ, MacDonald RG, Hill JA, Feldman RL, Stacpoole PW, Pepine CJ Myocardial metabolic and hemodynamic effects of dichloroacetate in coronary artery disease Am J Cardiol 1988;61(1):65-70 233 Stacpoole PW, Wright EC, Baumgartner TG, et al A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults N Engl J Med 1992;327(22):1564-1569 234 Morley P, Hogan MJ, Hakim AM Calcium-mediated mechanisms of ischemic injury and protection Brain Pathol 1994;4(1):37-47 235 White BC, Winegar CD, Wilson RF, Hoehner PJ, Trombley JH Possible role of calcium blockers in cerebral resuscitation Crit Care Med 1983;11(3):202-207 236 Clark RE, Christlieb IY, Henry PD, et al Nifedipine: a myocardial protective agent Am J Cardiol 1979;44(5):825-831 237 Burke TJ, Arnold PE, Gordon JA, Bulger RE, Dobyan DC, Schrier RW Protective effect of intrarenal calcium membrane blockers before or after renal ischemia Functional, morphological, and mitochondrial studies J Clin Invest 1984;74(5):1830-1841 238 Howard M, Carrubba C, Foss F, Janiak B, Hogan B, Guinness M Interposed abdominal compression-CPR: Its effects on parameters of coronary perfusion in human subjects Ann Emerg Med 1987;16(3):253-259 239 Resnekov L Calcium antagonist drugs—myocardial preservation and reduced vulnerability to ventricular fibrillation during CPR Crit Care Med 1981;9(5):360-361 240 Urban P, Scheidegger D, Buchmann B, Skarvan K The hemodynamic effects of heparin and their relation to ionized calcium levels J Thorac Cardiovasc Surg 1986;91(2):303-306 241 Urban P Cardiac arrest and blood ionized calcium levels Ann Intern Med 1988;109(2):110 242 Burchard KW Hypocalcemia during sepsis Arch Surg 1992; 127(3):265 243 Cairns CB, Niemann JT, Pelikan PCD, Sharma J Ionized hypocalcemia during prolonged cardiac arrest and closed-chest CPR in a canine model Ann Emerg Med 1991;20(11):1178-1182 244 Srinivasan V, Morris MC, Helfaer MA, Berg RA, Nadkarni VM Calcium use during in-hospital pediatric cardiopulmonary resuscitation: a report from the National Registry of Cardiopulmonary Resuscitation Pediatrics 2008;121(5):e1144-e1151 245 Myers R Lactic Acid Accumulation as A Cause of Brain Edema and Cerebral Necrosis Resulting from Oxygen Deprivation New York: Spectrum; 1979 246 Siemkowicz E, Hansen AJ Clinical restitution following cerebral ischemia in hypo-, normo- and hyperglycemic rats Acta Neurol Scand 1978;58(1):1-8 e7 247 Chopp M, Welch KM, Tidwell CD, Helpern JA Global cerebral ischemia and intracellular pH during hyperglycemia and hypoglycemia in cats Stroke 1988;19(11):1383-1387 248 Prado R, Ginsberg MD, Dietrich WD, Watson BD, Busto R Hyperglycemia increases infarct size in collaterally perfused but not end-arterial vascular territories J Cereb Blood Flow Metab 1988; 8(2):186-192 249 Ashwal S, Schneider S, Tomasi L, Thompson J Prognostic implications of hyperglycemia and reduced cerebral blood flow in childhood near-drowning Neurology 1990;40(5):820-820 250 LeBlanc MH, Huang M, Patel D, Smith EE, Devidas M Glucose given after hypoxic ischemia does not affect brain injury in piglets Stroke 1994;25(7):1443-1447 251 Voll CL, Auer RN The effect of postischemic blood glucose levels on ischemic brain damage in the rat Ann Neurol 1988;24(5):638-646 252 Voll CL, Auer RN Insulin attenuates ischemic brain damage independent of its hypoglycemic effect J Cereb Blood Flow Metab 1991; 11(6):1006-1014 253 Van den Berghe G, Wouters P, Weekers F, et al Intensive insulin therapy in critically ill patients N Engl J Med 2001;345(19):13591367 254 Van den Berghe G, Schoonheydt K, Becx P, Bruyninckx F, Wouters PJ Insulin therapy protects the central and peripheral nervous system of intensive care patients Neurology 2005;64(8):1348-1353 255 Van den Berghe G, Wilmer A, Hermans G, et al Intensive insulin therapy in the medical ICU N Engl J Med 2006;354(5):449-461 256 Watkinson P Strict glucose control in the critically ill BMJ 2006;332(7546):865-866 257 Agus MS, Wypij D, Hirshberg EL, et al Tight glycemic control in critically ill children N Engl J Med 2017;376(8):729-741 258 Auer RN Progress review: hypoglycemic brain damage Stroke 1986;17(4):699-708 259 Hickey RW, Cohen DM, Strausbaugh S, Dietrich AM Pediatric patients requiring CPR in the prehospital setting Ann Emerg Med 1995;25(4):495-501 260 Lehnart SE Sudden death in familial polymorphic ventricular tachycardia associated with calcium release channel (ryanodine receptor) leak Circulation 2004;109(25):3208-3214 261 Nof E, Lahat H, Constantini N, et al A novel form of familial bidirectional ventricular tachycardia Am J Cardiol 2004;93(2): 231-234 262 Spar DS, Bianco NR, Knilans TK, Czosek RJ, Anderson JB The US experience of the wearable cardioverter-defibrillator in pediatric patients Circ Arrhythm Electrophysiol 2018;11(7):e006163 263 Caffrey SL, Willoughby PJ, Pepe PE, Becker LB Public use of automated external defibrillators N Engl J Med 2002;347(16): 1242-1247 264 Valenzuela TD, Roe DJ, Nichol G, Clark LL, Spaite DW, Hardman RG Outcomes of rapid defibrillation by security officers after cardiac arrest in casinos N Engl J Med 2000;343(17):1206-1209 265 Samson RA, Berg RA, Bingham R Use of automated external defibrillators for children: an update—an advisory statement from the Pediatric Advanced Life Support Task Force, International Liaison Committee on Resuscitation Pediatrics 2003;112(1):163-168 266 de Caen AR, Berg MD, Chameides L, et al Part 12: pediatric advanced life support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care (Reprint) Pediatrics 2015;136(suppl 2): S176-S195 267 Topol EJ, Califf RM Textbook of Cardiovascular Medicine 3rd ed Philadelphia: Lippincott Williams & Wilkins; 2007 268 Kern KB, Garewal HS, Sanders AB, et al Depletion of myocardial adenosine triphosphate during prolonged untreated ventricular fibrillation: effect on defibrillation success Resuscitation 1990;20(3): 221-229 269 Noc M, Weil MH, Gazmuri RJ, Sun S, Biscera J, Tang W Ventricular fibrillation voltage as a monitor of the effectiveness of cardiopulmonary resuscitation J Lab Clin Med 1994;124(3):421-426 270 Atkinson E, Mikysa B, Conway JA, et al Specificity and sensitivity of automated external defibrillator rhythm analysis in infants and children Ann Emerg Med 2003;42(2):185-196 271 Gutgesell HP, Tacker WA, Geddes LA, Davis JS, Lie JT, Mcnamara DG Energy dose for ventricular defibrillation of children Pediatrics 1976;58(6):898-901 272 Berg RA, Hilwig RW, Kern KB, Sanders AB, Xavier LC, Ewy GA Automated external defibrillation versus manual defibrillation for prolonged ventricular fibrillation Ann Emerg Med 2003;42(4): 458-467 273 Yu T Adverse outcomes of interrupted precordial compression during automated defibrillation Circulation 2002;106(3):368-372 274 Atkins DL, Kerber RE Pediatric defibrillation: current flow is improved by using “adult” electrode paddles Pediatrics 1994;94(1):90-93 275 Deakin CD, McLaren RM, Petley GW, Clewlow F, DalrympleHay MJR A comparison of transthoracic impedance using standard defibrillation paddles and self-adhesive defibrillation pads Resuscitation 1998;39(1-2):43-46 276 Kerber RE, Martins JB, Kelly KJ, et al Self-adhesive preapplied electrode pads for defibrillation and cardioversion J Am Coll Cardiol 1984;3(3):815-820 277 Kerber RE, Martins JB, Ferguson DW, et al Experimental evaluation and initial clinical application of new self-adhesive defibrillation electrodes Int J Cardiol 1985;8(1):57-66 278 Bennetts SH, Deakin CD, Petley GW, Clewlow F Is optimal paddle force applied during paediatric external defibrillation? Resuscitation 2004;60(1):29-32 279 Cruz B, Niemann JT Experimental studies on precordial compression or defibrillation as initial interventions for ventricular fibrillation Crit Care Med 2000;28(suppl):N225-N227 280 Kolarova J, Ayoub IM, Yi Z, Gazmuri RJ Optimal timing for electrical defibrillation after prolonged untreated ventricular fibrillation Crit Care Med 2003;31(7):2022-2028 281 Mitani Y, Ohta K, Ichida F, et al Circumstances and outcomes of out-of-hospital cardiac arrest in elementary and middle school students in the era of public-access defibrillation Circ J 2014; 78(3):701-707 282 Hunt EA, Duval-Arnould JM, Bembea MM, et al Association between time to defibrillation and survival in pediatric in-hospital cardiac arrest with a first documented shockable rhythm JAMA Netw Open 2018;1(5):e182643 283 Faddy SC, Powell J, Craig JC Biphasic and monophasic shocks for transthoracic defibrillation: a meta analysis of randomised controlled trials Resuscitation 2003;58(1):9-16 284 Tang W, Weil MH, Sun S, et al The effects of biphasic waveform design on post-resuscitation myocardial function J Am Coll Cardiol 2004;43(7):1228-1235 285 Schneider T, Martens PR, Paschen H, et al Multicenter, randomized, controlled trial of 150-J biphasic shocks compared with 200to 360-J monophasic shocks in the resuscitation of out-of-hospital cardiac arrest victims Circulation 2000;102(15):1780-1787 286 Gurnett CA, Atkins DL Successful use of a biphasic waveform automated external defibrillator in a high-risk child Am J Cardiol 2000;86(9):1051-1053 287 Clark CB, Zhang Y, Davies LR, Karlsson G, Kerber RE Pediatric transthoracic defibrillation: biphasic versus monophasic waveforms in an experimental model Resuscitation 2001;51(2):159-163 288 Tang W, Weil MH, Jorgenson D, et al Fixed-energy biphasic waveform defibrillation in a pediatric model of cardiac arrest and resuscitation Crit Care Med 2002;30(12):2736-2741 289 Jacobs IG, Tibballs J, Morley PT, et al Energy levels for biphasic defibrillation Med J Aust 2003;179(8):451 290 Cecchin F, Jorgenson DB, Berul CI, et al Is Arrhythmia detection by automatic external defibrillator accurate for children?: sensitivity and specificity of an automatic external defibrillator algorithm in 696 pediatric arrhythmias Circulation 2001;103(20):2483-2488 291 Rossano JW, Jones WE, Lerakis S, et al The use of automated external defibrillators in infants: a report from the American Red e8 Cross Scientific Advisory Council Pediatr Emerg Care 2015; 31(7):526-530 292 Dorian P, Cass D, Schwartz B, Cooper R, Gelaznikas R, Barr A Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation N Engl J Med 2002;346(12):884-890 293 Path GJ, Dai XZ, Schwartz JS, Benditt DG, Bache RJ Effects of amiodarone with and without polysorbate 80 on myocardial oxygen consumption and coronary blood flow during treadmill exercise in the dog J Cardiovasc Pharmacol 1991;18(1):11-16 294 Etheridge SP, Craig JE, Compton SJ Amiodarone is safe and highly effective therapy for supraventricular tachycardia in infants Am Heart J 2001;141(1):105-110 295 Burri S, Hug MI, Bauersfeld U Efficacy and safety of intravenous amiodarone for incessant tachycardias in infants Eur J Pediatr 2003;162(12):880-884 296 Silvetti MS, Drago F, Bevilacqua M, Ragonese P Amiodarone-induced torsade de pointes in a child with dilated cardiomyopathy Ital Heart J 2001;2(3):231-236 297 Maghrabi K, Uzun O, Kirsh JA, Balaji S, Von Bergen NH, Sanatani S Cardiovascular collapse with intravenous amiodarone in children: a multi-center retrospective cohort study Pediatr Cardiol 2019;40(5):925-933 298 Kudenchuk PJ, Brown SP, Daya M, et al Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest N Engl J Med 2016;374(18):1711-1722 299 McLeod SL, Brignardello-Petersen R, Worster A, et al Comparative effectiveness of antiarrhythmics for out-of-hospital cardiac arrest: a systematic review and network meta-analysis Resuscitation 2017;121:90-97 300 Laurent I, Monchi M, Chiche J-D, et al Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest J Am Coll Cardiol 2002;40(12):2110-2116 301 Müllner M, Domanovits H, Sterz F, et al Measurement of myocardial contractility following successful resuscitation: quantitated left ventricular systolic function utilising non-invasive wall stress analysis Resuscitation 1998;39(1-2):51-59 302 Topjian AA, French B, Sutton RM, et al Early postresuscitation hypotension is associated with increased mortality following pediatric cardiac arrest Crit Care Med 2014;42(6):1518-1523 303 Topjian AA, Telford R, Holubkov R, et al Association of early postresuscitation hypotension with survival to discharge after targeted temperature management for pediatric out-of-hospital cardiac arrest: secondary analysis of a randomized clinical trial JAMA Pediatr 2018;172(2):143-153 304 Bailey JM, Miller BE, Lu W, Tosone SR, Kanter KR, Tam VKH The pharmacokinetics of milrinone in pediatric patients after cardiac surgery Anesthesiology 1999;90(4):1012-1018 305 Barton P Hemodynamic Effects of IV milrinone lactate in pediatric patients with septic shock Chest 1996;109(5):1302 306 Lewis TC, Aberle C, Altshuler D, Piper GL, Papadopoulos J Comparative effectiveness and safety between milrinone or dobutamine as initial inotrope therapy in cardiogenic shock J Cardiovasc Pharmacol Ther 2019;24(2):130-138 307 Eisenburger P, Sterz F, Holzer M, et al Therapeutic hypothermia after cardiac arrest Curr Opin Crit Care 2001;7(3):184-188 308 Zeiner A, Holzer M, Sterz F, et al Hyperthermia after cardiac arrest is associated with an unfavorable neurologic outcome Arch Intern Med 2001;161(16):2007-2012 309 Nielsen N, Wetterslev J, Cronberg T, et al Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest N Engl J Med 2013;369(23):2197-2206 310 Bro-Jeppesen J, Kjaergaard J, Wanscher M, et al The inflammatory response after out-of-hospital cardiac arrest is not modified by targeted temperature management at 33 degrees C or 36 degrees C Resuscitation 2014;85(11):1480-1487 311 Cronberg T, Lilja G, Horn J, et al Neurologic function and healthrelated quality of life in patients following targeted temperature management at 33 degrees C vs 36 degrees C after out-of-hospital cardiac arrest: a randomized clinical trial JAMA Neurol 2015;72(6):634-641 312 Dragancea I, Horn J, Kuiper M, et al Neurological prognostication after cardiac arrest and targeted temperature management 33 degrees C versus 36 degrees C: results from a randomised controlled clinical trial Resuscitation 2015;93:164-170 313 Donnino MW, Andersen LW, Berg KM, et al Temperature management after cardiac arrest: an advisory statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation Circulation 2015;132(25):2448-2456 314 Slomine BS, Silverstein FS, Christensen JR, et al Neurobehavioral outcomes in children after out-of-hospital cardiac arrest Pediatrics 2016;137(4):e20153412 315 Slomine BS, Silverstein FS, Christensen JR, et al Neurobehavioural outcomes in children after In-Hospital cardiac arrest Resuscitation 2018;124:80-89 316 Ichord R, Silverstein FS, Slomine BS, et al Neurologic outcomes in pediatric cardiac arrest survivors enrolled in the THAPCA trials Neurology 2018;91(2):e123-e131 317 Moler FW Resuscitation research and the final rule: Is there an impasse? Pediatrics 2004;114(3):859-861 318 Morris MC Exception from informed consent for pediatric resuscitation research: community consultation for a trial of brain cooling after in-hospital cardiac arrest Pediatrics 2004;114(3):776-781 e9 Abstract: The development and advancement of cardiopulmonary resuscitation (CPR) techniques, life support measures, and postresuscitation care have dramatically improved survival and neurologic outcomes in adults and children suffering from cardiac arrest Many factors play a role in successful resuscitation, from the characteristics of chest compressions (rate, depth, duty cycle) to medication choice This chapter discusses the physiologic mechanisms underlying CPR, taking into account both new and established CPR techniques, discussion of pharmacologic management, shock delivery, and postresuscitation care, including the role of therapeutic hypothermia Key words: Cardiopulmonary resuscitation, CPR, ventricular fibrillation, epinephrine, vasopressors, antiarrhythmics, postresuscitation management, therapeutic hypothermia 39 Performance of Cardiopulmonary Resuscitation in Infants and Children RYAN W MORGAN, ROBERT A BERG, ALEXIS A TOPJIAN, VINAY M NADKARNI, AND ROBERT M SUTTON Pediatric cardiac arrest is not a rare event More than 20,000 children are treated with cardiopulmonary resuscitation (CPR) for a cardiac arrest in the United States annually.1–4 In the past, survival outcomes were dismal, and many surviving children had severe neurologic sequelae With advances in resuscitation science, survival from pediatric cardiac arrest has improved substantially since the 1990s.5 This chapter focuses on pediatric cardiac arrest, CPR, and therapeutic interventions that impact clinical outcomes Controversies related to pediatric cardiac arrest management are also discussed Four Phases of Cardiac Arrest The four distinct phases of cardiac arrest and CPR interventions are (1) prearrest, (2) “no-flow” (untreated cardiac arrest), (3) “lowflow” (CPR), and (4) postarrest Interventions to improve the outcome of pediatric cardiac arrest should optimize therapies targeted to the time and phase of CPR, as suggested in Box 39.1 and Table 39.1 Prearrest The prearrest phase refers to relevant preexisting conditions of the child (e.g., respiratory insufficiency/failure, sepsis, pulmonary hypertension, neurologic disability) and the events that precipitated cardiac arrest (e.g., respiratory decompensation, progressive hypotension and shock, pulmonary hypertensive 444 • • There are four distinct phases of cardiac arrest and cardiopulmonary resuscitation (CPR): prearrest, no-flow (untreated cardiac arrest), low-flow (CPR), and postarrest The most common precipitating event for cardiac arrests in children is respiratory insufficiency; restoration of adequate ventilation and oxygenation remain a high priority High-quality CPR (i.e., push hard, push fast, allow full chest recoil, minimize interruptions in chest compressions) improves cardiac arrest outcomes • • • • PEARLS Real-time monitoring and feedback combined with reflective debriefings of team performance improves CPR quality and survival outcomes Attention to meticulous postresuscitation care—specifically, avoidance of hypotension and fever—improves survival outcomes Physiology-directed CPR, in which CPR is titrated to a patient’s physiologic response, is a promising technique to save more children’s lives from cardiac arrest crisis, drug overdose) Because pediatric patients usually exhibit changes in their physiologic status in the hours leading up to their arrest event,6–9 interventions during the prearrest phase should focus on identifying children at risk for arrest, with special attention to early recognition and treatment of respiratory failure and shock Rapid response teams or medical emergency teams (METs) are in-hospital emergency teams designed specifically for this purpose While the composition and operating characteristics of these teams vary widely,10 their existence has become almost universal across pediatric institutions Implementation of pediatric METs has been successful in that they have been temporally associated with decreased cardiac arrest frequency and mortality.8,11–15 Although METs cannot identify all children at risk for cardiac arrest, it seems reasonable to assume that transferring critically ill children to an intensive care unit (ICU) early in their disease progression for better monitoring and more aggressive interventions would improve clinical outcome Supporting this contention, late transfers to the ICU (e.g., unrecognized situational awareness failure events [UNSAFE]) are associated with a higher risk of in-hospital mortality.8,11 No-Flow/Low-Flow To improve outcomes from pediatric cardiac arrest, it is imperative to shorten the no-flow phase of untreated cardiac arrest To that end, it is important to monitor high-risk patients to facilitate ... resuscitation, from the characteristics of chest compressions (rate, depth, duty cycle) to medication choice This chapter discusses the physiologic mechanisms underlying CPR, taking into account both new and... resuscitation science, survival from pediatric cardiac arrest has improved substantially since the 1990s.5 This chapter focuses on pediatric cardiac arrest, CPR, and therapeutic interventions that impact... teams or medical emergency teams (METs) are in-hospital emergency teams designed specifically for this purpose While the composition and operating characteristics of these teams vary widely,10 their