377CHAPTER 35 Pediatric Cardiopulmonary Bypass that the poor visibility in an open beating heart needed to be ad dressed It was difficult to operate on a beating heart, and lethal air embolism (i e ,[.]
Probability of “safe” circulatory arrest CHAPTER 35 Pediatric Cardiopulmonary Bypass 1.0 0.9 0.8 0.7 0.6 0.5 37°C 0.4 28°C 18°C 0.3 0.2 0.1 0.0 10 20 30 40 50 60 70 80 Duration of total circulatory arrest (minutes) 90 • Fig 35.10 Probability of a “safe” (absence of structural or functional damage) circulatory arrest according to duration Estimate at nasopharyngeal temperatures of 37°C, 28°C, and 18°C (From Kirklin JW, BarrattBoyes BG Hypothermia, circulatory arrest, and cardiopulmonary bypass In: Kirklin JW, Barratt-Boyes BG, eds Cardiac Surgery 2nd ed New York: Churchill-Livingstone; 1993:74.) that the poor visibility in an open beating heart needed to be addressed It was difficult to operate on a beating heart, and lethal air embolism (i.e., air ejected out the aortic valve) claimed the lives of many patients In 1955, Dr Melrose and his colleagues91 described a technique of stopping the heart to address these dangerous operative conditions The report outlines how potassium citrate is used to achieve elective cardiac arrest This sparked the interest of other investigators In 1958, Dr Sealy and his colleagues at Duke reported an additive modification to the Melrose method and coined the term cardioplegia.92 It is interesting to note that improving operative visibility, not protecting the heart, was the goal of arresting the heart Further investigation began to show that these techniques caused damage to the myocardium and cardioplegia was abandoned In the 1960s and early 1970s, a number of investigators tried to find an alternative protection technique Reports of using direct coronary perfusion with intermittent aortic occlusion, topical hypothermia, and normothermic ischemia with aortic occlusion failed to achieve consistent results, presented major time limitations for surgeons, and myocardial damage remained an issue The observation of “stone heart” by Dr Cooley and his colleagues92 highlighted the need to prioritize the protection of the myocardium They then proposed that depleting myocardium adenosine triphosphate (ATP) stores would leave the heart frozen in systole Fortunately, several European researchers continued to explore cardioplegia solutions throughout the 1960s They discovered that the chelating action of the citrate ion of the potassium-citrate solution was responsible for myocardial damage because it interferes with cellular calcium and magnesium traffic This finding resparked interest into pharmacologic cardiac arrest around the world, with a new focus on protecting the myocardium by membrane stabilization and managing calcium and other ion shifts During the 1970s, a sequence of landmark reports hailed the worldwide return of cardioplegia and its use in protecting the myocardium These publications identified potassium chloride as a safe arresting agent and, moreover, showed that cold cardioplegia significantly extends the safe is chemic period The use of cardioplegia additives—such as magnesium, procaine, lidocaine, mannitol, buffering agents, glucose, glutamate, and aspartate—has led to much debate and a plethora 377 of cardioplegia recipes By the late 1970s, these crystalloid cardioplegia solutions became the dominant form of myocardial protection A major shift occurred in 1978 when Dr Buckberg and his group at the University of California, Los Angeles, suggested that blood was an optimal cardioplegia vehicle.93 Blood cardioplegia was shown to be superior to a crystalloid cardioplegia solution because blood provides better O2 delivery, effective buf fering, free radical scavenging, and ideal oncotic pressure.94 Effective myocardial protection has allowed surgeons to approach increasingly complex surgical corrections The motivation to optimize cardioplegia techniques has led to an incredible variation of myocardial protection techniques Despite numerous advances and an extensive body of research, myocardial protection techniques continue to be largely program based because hard evidence, from prospective randomized trials, for instance, is lacking.95 The wide variation in protection techniques, however, makes randomized comparisons impractical A multi-institutional North American survey by Kotani et al.96 suggests that an observational study correlating markers of postoperative myocardial performance with myocardial preservation strategies is warranted A depolarizing cardioplegia solution uses a high dose of potassium, delivered to the coronary circulation in isolation, to decrease the cardiac membrane resting potential and arrest the heart in diastole Delivering a cold dose of depolarizing cardioplegia does add a degree of protection, but simply arresting and cooling the heart does not offer optimal protection An effective cardioplegia solution should (1) achieve quick arrest and minimize ATP depletion, (2) delay the onset of irreversible damage and limit reperfusion injury, (3) be reversible with prompt resumption of cardiac function upon washout, and (4) be nontoxic.97 Efforts to optimize an effective cardioplegia solution have focused on myocyte calcium management and pH buffering Modified depolarizing cardioplegia, a solution that combines a depolarizing agent with additional membrane-stabilizing additives (e.g., magnesium or lidocaine), has gained interest in attempting to optimize cardioplegia A modified depolarizing solution that is gaining popularity in congenital surgery is del Nido cardioplegia (Baxter Healthcare Inc.) (Table 35.6).96 Unlike most cardioplegia solutions that require frequent maintenance dosing to achieve effective protection, del Nido cardioplegia is known to provide excellent myocardial protection without the need to frequently redose.98 This reported advantage allows the surgeon to operate uninterrupted while reducing the aortic cross-clamp time Custodiol HTK (Essential Pharmaceuticals, LLC) is an intracellular cardioplegia that achieves electrical and mechanical arrest by equilibrating the intracellular and extracellular ion concentrations This solution is also gaining popularity in the congenital patient population because it does not require frequent maintenance doses TABLE Crystalloid Formula of del Nido Solution 35.6 Plasma-Lyte A 1000 mL Potassium chloride 26 mEq Sodium bicarbonate 8.4% 13 mEq Mannitol 25% 3.25 g Lidocaine 2% 130 mg Magnesium sulfate 50% 2g 378 S E C T I O N I V Pediatric Critical Care: Cardiovascular At Children’s Health Dallas, the surgical team uses del Nido cardioplegia with a customized pediatric cardioplegia circuit.99 The cardioplegia is mixed at a 1:4 blood-to-crystalloid ratio; upon aortic cross-clamp placement, a single cold (4–6°C), 20 mL/kg antegrade dose is administered via the aortic root Although there is no cardioplegia specifically designed for neonatal or congenital patients, several considerations are made to optimize protection As previously discussed, tolerance of intracellular calcium shifts into the immature myocardium is impaired The additives lidocaine and magnesium in del Nido cardioplegia both help to control intracellular calcium accumulation Lidocaine prevents sodium shifts by blocking fast voltage sodium channels, which, in turn, limits calcium shifting into the myocyte Magnesium, a calcium antagonist, inhibits calcium channel pumps and competes with calcium binding to troponin These additives help the impaired immature myocardium to maintain effective electrical and mechanical arrest Hypertrophic ventricles, as seen in tetralogy of Fallot, may not be adequately protected with standard cardioplegia doses They may require a higher cardioplegia dose and longer delivery time to properly cool and perfuse the hypertrophied myocardium Cyanotic patients with inadequate pulmonary blood flow often have increased bronchial collateral flow High collateral flow to the lungs ultimately returns to the heart via the pulmonary veins and is counterproductive while the aorta is cross-clamped Collateral flow can fill the heart, warm the myocardium, and wash out the cardioplegia from the myocardium Lowering the systemic temperature not only helps to offset myocardial warming but also allows the perfusionist to lower the perfusion flow and pressure, which, in turn, reduces this collateral flow Also, adequate left ventricle venting helps to minimize the effect of volume returning to the heart High sensitivity to the inflammatory response in the immature myocardium can cause edema and reduce ventricular compliance Mannitol is an additive in del Nido cardioplegia that helps reduce intracellular water accumulation Care must be taken to not perfuse the myocardium at too high a pressure This could injure fragile coronary vessels and create myocardial edema A pressure of 30 to 50 mm Hg has been shown to be adequate.100 Inflammatory Response to Cardiopulmonary Bypass The systemic inflammatory response syndrome (SIRS) instigated by CPB is well documented; limiting this response is associated with improved outcomes.101–103 Multiple factors—including blood exposure to nonendothelialized surfaces (e.g., CPB circuit, air), surgical trauma (e.g., intubation, sternotomy), ischemia-reperfusion, hypothermia, and allogenic transfusion—have been linked to this inflammatory activation This complex response includes cascade activations of complement, cytokine, coagulation-fibrinolytic, and various cellular activations Perioperative and postoperative consequences include multiple-organ failure (e.g., myocardium, renal, pulmonary, neurologic, hepatic), coagulopathy, edema, elaboration of injurious oxygen-free radicals, and hypotension.103 SIRS is more pronounced in neonates The degree of hemodilution, need for longer CPB and ischemic times, and more prevalent use of profound hypothermia are all known to exacerbate SIRS and are contributors to the increased postoperative morbidity seen in neonates compared with older infants and children.104–106 A number of contemporary pharmacologic strategies and CPB techniques are designed to attenuate the inflammatory reactions and remove mediators during CPB Corticosteroids have been used during CPB for many years and have been shown to mitigate many inflammatory processes, such as increased capillary permeability, edema, and leukocyte migration Various timing and dosing protocols have been suggested, with conflicting results.107,108 At Children’s Health Dallas, a 30 mg/kg (1 g maximum dose) perioperative dose of methylprednisolone is administered to the CPB circuit prime Additionally, 10 mg/kg of methylprednisolone is administered to 12 hours before the initiation of CPB in neonates A 2018 literature review by Fudulu et al.109 found that while the use of corticosteroids may attenuate markers of inflammation, this reduction does not correlate with improved clinical outcomes Additionally, Dreher et al.110 demonstrated that eliminating the routine administration of methylprednisolone to the CPB prime did not alter clinical outcomes and was associated with a significant reduction in the incidence of wound infection The conflicting data and lack of large multicenter, randomized controlled studies that follow a consistent dosing regimen warrants further research and an individualized approach to steroid therapy Common CPB-based techniques to attenuate SIRS include ultrafiltration, circuit miniaturization, and the use of biocompatible circuit coatings Ultrafiltration during CPB has been shown to reduce inflammatory mediators, pulmonary injury and edema, postoperative mechanical ventilation support time, and the perioperative need for blood transfusion.111–114 CPB circuit miniaturization and the use of biocompatible surface coatings provide two main benefits in attenuating the inflammatory response First, the smaller surface area of a miniaturized circuit and biocompatible coating reduces the bioreactivity of blood coming into contact with foreign surfaces.32,33 Second, smaller circuits reduce overall hemodilution and the need to transfuse donor blood, both of which have been shown to exacerbate the inflammatory response.69,70 Although the inflammatory response to CPB cannot be avoided, a multimodal approach can significantly reduce CPBrelated SIRS Termination of Cardiopulmonary Bypass Once the surgeon has completed the cardiac repair, the entry sites into the heart are sutured closed The venous return drainage is retarded, which fills the right heart The anesthesiologist inflates the lungs, which facilitates the movement of this blood across the pulmonary vasculature and back to the left heart Any active left heart venting is paused at this point, and the surgeon massages the filling heart to expel blood with any entrained air out of a vent hole in the aortic root Once there is no longer any air emanating from this site, the patient is placed into the Trendelenburg position, and the cross-clamp is removed from the aorta The perfusionist then returns to full venous drainage, and the left heart vent can be placed to gentle suction again The coronary circulation is now reperfused, washing out the cardioplegia The heart is observed for any return of electrical activity Temporary epicardial pacing wires are routinely placed, and pacing is initiated if the native rhythm does not promptly return The left heart vent is removed before initiating ventilation to avoid entrainment air Transesophageal echocardiography is then used to evaluate for the presence of air in the left heart as ventilation is restarted If air is present, the vent site in the ascending aorta is kept open to evacuate it Once the heart is confidently de-aired and the patient has returned to normothermia, the team agrees to wean from CPB The perfusionist steadily reduces pump flow and venous return until the pump is fully off and the venous line is fully clamped CHAPTER 35 Pediatric Cardiopulmonary Bypass The patient’s heart and lungs return to their native support roles at this point Transesophageal—or, in some cases, epicardial— echocardiography is used to assess the adequacy of the repair If the repair is deemed successful, a protamine dose, calculated by a heparin-protamine titration (discussed earlier in the Anticoagulation section), is administered The cannulas are removed and the purse strings are tied down Adequate reversal of heparin is verified by measuring the ACT and heparin-protamine titration Key References Algra SO, Jansen NJ, van der Tweel I, et al Neurological injury after neonatal cardiac surgery: a randomized, controlled trial of perfusion techniques Circulation 2014;129:224-233 Allan CK, Newburger JW, McGrath E, et al The relationship between inflammatory activation and clinical outcome after infant cardiopulmonary bypass Anesth Analg 2010;111:1244-1251 Blinder JJ, Goldstein SL, Lee VV, et al Congenital heart surgery in infants: effects of acute kidney injury on outcomes J Thorac Cardiovasc Surg 2012;143(2):368-374 Fudulu DP, Gibbison B, Upton T, et al Corticosteroids in pediatric heart surgery: myth or reality Front Pediatr 2018;6:112 Ginther Jr RM, Gorney R, Forbess JM Use of del Nido cardioplegia solution and a low-prime recirculating cardioplegia circuit in pediatrics J Extra Corpor Technol 2013;45:46-50 379 Kilic A, Whitman GJ Blood transfusions in cardiac surgery: indications, risks, and conservation strategies Ann Thorac Surg 2014;97:726-734 Mokhtari A, Lewis M Normoxic and hyperoxic cardiopulmonary bypass in congenital heart disease BioMed Res Int 2014;2014:678268 Newburger JW, Jonas RA, Soul J, et al Randomized trial of hematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery J Thorac Cardiovasc Surg 2008;135:347-354, 354.e1-e4 Sood ED, Benzaquen JS, Davies RR, Woodford E, Pizarro C Predictive value of perioperative near-infrared spectroscopy for neurodevelopmental outcomes after cardiac surgery in infancy J Thorac Cardiovasc Surg 2013;145(2):438-445.e431; discussion 444-435 Sturmer D, Beaty C, Clingan S, Jenkins E, Peters W, Si MS Recent innovations in perfusion and cardiopulmonary bypass for neonatal and infant cardiac surgery Transl Pediatr 2018;7(2):139-150 Taylor RL, Borger MA, Weisel RD, Fedorko L, Feindel CM Cerebral microemboli during cardiopulmonary bypass: increased emboli during perfusionist interventions Ann Thorac Surg 1999;68(1):89-93 Xiong Y, Sun Y, Ji B, Liu J, Wang G, Zheng Z Systematic review and meta-analysis of benefits and risks 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discussion 444-435 68 Richmond ME, Charette K, Chen JM, et al The effect of cardiopulmonary bypass prime volume on the need for blood transfusion after pediatric cardiac surgery J Thorac Cardiovasc Surg 2013;145:1058-1064 69 Kilic A, Whitman GJ Blood transfusions in cardiac surgery: indications, risks, and conservation strategies Ann Thorac Surg 2014;97: 726-734 70 Kipps AK, Wypij D, Thiagarajan RR, et al Blood transfusion is associated with prolonged duration of mechanical ventilation in infants undergoing reparative cardiac surgery Pediatr Crit Care Med 2011;12:52-56 71 Lavoie J Blood transfusion risks and alternative strategies in pediatric patients Paediatr Anaesth 2011;21:14-24 72 Whitney G, Daves S, Hughes A, et al Implementation of a transfusion algorithm to reduce blood product utilization in pediatric cardiac surgery Paediatr Anaesth 2013;23:639-646 73 Jonas RA, Wypij D, Roth SJ, et al The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: results of a randomized trial in infants J Thorac Cardiovasc Surg 2003;126:1765-1774 74 Newburger JW, Jonas RA, Soul J, et al Randomized trial of hematocrit 25% versus 35% during hypothermic cardiopulmonary bypass in infant heart surgery J Thorac Cardiovasc Surg 2008;135:347-354, 354.e1-e4 75 Naik SK, Knight A, Elliott MJ A successful modification of ultrafiltration for cardiopulmonary bypass in children Perfusion 1991;6:41-50 76 McRobb CM, Ing RJ, Lawson DS, Jaggers J, Twite M Retrospective analysis of eliminating modified ultrafiltration after pediatric cardiopulmonary bypass Perfusion 2017;32(2):97-109 77 Mejak BL, Lawson DS, Ing RJ Con: Modified Ultrafiltration in Pediatric Cardiac Surgery Is No Longer Necessary Journal of cardiothoracic and vascular anesthesia 2019;33(3):870-872 78 Bigelow WG, Callaghan JC, Hopps JA General hypothermia for experimental intracardiac surgery: the use of electrophrenic respirations, an artificial pacemaker for cardiac standstill, and radio-frequency rewarming in general hypothermia Ann Surg 1950;132:531-537 79 Sealy WC, Brown Jr IW, Young Jr WG A report on the use of both extracorporeal circulation and hypothermia for open heart surgery Ann Surg 1958;147:603-613 80 Algra SO, Jansen NJ, van der Tweel I, et al Neurological injury after neonatal cardiac surgery: a randomized, controlled trial of perfusion techniques Circulation 2014;129:224-233 81 Algra SO, Kornmann VN, van der Tweel I, et al Increasing duration of circulatory arrest, but not antegrade cerebral perfusion, prolongs postoperative recovery after neonatal cardiac surgery J Thorac Cardiovasc Surg 2012;143:375-382 82 Misfeld M, Leontyev S, Borger MA, et al What is the best strategy for brain protection in patients undergoing aortic arch surgery? A single center experience of 636 patients Ann Thorac Surg 2012;93:1502-1508 83 Algra SO, Schouten AN, van Oeveren W, et al Low-flow antegrade cerebral perfusion attenuates early renal and intestinal injury during neonatal aortic arch reconstruction J Thorac Cardiovasc Surg 2012;144:1323-1328, 1328.e1-e2 84 Wang J, Ginther RM, Riegel M, et al The impact of temperature and pump flow rate during selective cerebral perfusion on regional blood flow in piglets J Thorac Cardiovasc Surg 2013;145:188-194; discussion 194-195 85 Tsai JY, Pan W, Lemaire SA, et al Moderate hypothermia during aortic arch surgery is associated with reduced risk of early mortality J Thorac Cardiovasc Surg 2013;146:662-667 ... ischemia-reperfusion, hypothermia, and allogenic transfusion—have been linked to this inflammatory activation This complex response includes cascade activations of complement, cytokine, coagulation-fibrinolytic,... lungs, which facilitates the movement of this blood across the pulmonary vasculature and back to the left heart Any active left heart venting is paused at this point, and the surgeon massages the... The systemic inflammatory response syndrome (SIRS) instigated by CPB is well documented; limiting this response is associated with improved outcomes.101–103 Multiple factors—including blood exposure