e2 Abstract The physiology of the transplanted heart as well as pre operative and perioperative critical care all play important roles in the successful transplantation of critically ill children with[.]
e2 Abstract: The physiology of the transplanted heart as well as preoperative and perioperative critical care all play important roles in the successful transplantation of critically ill children with limited other options The overall transplant survival at year has improved to more than 90%, with an expected 5-year survival exceeding 80% The time at which 50% of recipients remain alive is 13.3 years for teenagers and 22.3 years for infants Individuals may have a good quality of life following heart transplantation but are likely destined for a repeat transplant This chapter reviews critical care management of the pediatric patient undergoing heart transplantation Key words: pediatric, heart transplant, critical care, immunosuppression, congenital, perioperative, posttransplant, mechanical support, milrinone, graft dysfunction 38 Physiologic Foundations of Cardiopulmonary Resuscitation ADNAN M BAKAR, KENNETH E REMY, SAREEN SHAH, AND CHARLES L SCHLEIEN With the development of basic cardiopulmonary resuscitation (CPR) in the early 1960s, skilled resuscitation teams both in and out of the hospital were formed The development of CPR saved lives; previously, every victim of cardiac arrest had died Soon thereafter, successful resuscitation of patients by basic life support measures, defibrillation, and medications became common even as long as hours after commencement of CPR Over the past decade, both survival and neurologic outcomes after in-hospital cardiac arrest have improved in adults and children.1–3 Data show that the success of CPR depends on many factors Rapid institution of basic life support measures (i.e., bystander CPR for sudden out-of-hospital cardiac arrest and immediate electrical countershock for ventricular fibrillation [VF]) improve the chances of survival for patients experiencing sudden out-of-hospital cardiac arrest.4 These measures led to the growing deployment of automatic external defibrillators (AEDs) in public places Immediate defibrillation is currently the standard of care in witnessed VF arrests However, evidence indicates that basic life support and other measures directed at restoring energy substrates to the myocardium before countershock in patients with unwitnessed, outof-hospital arrest may further improve outcome.5–8 Other preexisting factors that play a role in successful resuscitation include the patient’s age, prior medical condition, presenting cardiac rhythm, and the etiology of cardiac arrest In 2008, a multi-institutional prospective study was published that examined these preexisting factors and further described in two additional studies the clinical characteristics, hospital course, and outcomes of a cohort of children after in-hospital or out-of-hospital arrest In 420 • • Both the cardiac and thoracic pump mechanisms play a role in infants and children during cardiopulmonary resuscitation Thus, attention to excellent chest compression technique— with an emphasis on “push hard, push fast”—is critical to attaining sufficient cardiac output to maintain coronary and cerebral blood flow Use of any vasoconstrictor should be sufficient to raise aortic diastolic pressure during cardiopulmonary resuscitation above the critical level for resuscitation success (.15–20 mm Hg) • • • PEARLS Amiodarone or lidocaine may be the most effective pharmacologic treatments for shock-resistant ventricular tachycardia or fibrillation Use of the biphasic defibrillator is an important advance in the treatment of tachyarrhythmias and has advantages in its safety profile compared with monophasic defibrillators Resuscitative care following cardiac arrest is critical to survival and includes appropriate uses of inodilators and neuroprotective strategies, including avoidance of hyperthermia addition to demonstrating differences in clinical characteristics, these studies offered future considerations for the care of children who had experienced cardiac arrest and postresuscitative care, including hypothermia.9–12 The low resuscitation rate in children, even when the patient does not have preexisting disease, probably results from the high incidence of asystole as the presenting rhythm Asystole is the most common presenting rhythm in both in-hospital and out-of-hospital arrests, noted in 25% to 70% of victims.13–17 Bradycardia and pulseless electrical activity (PEA) are other common rhythms The high incidence of asystole in children who experience cardiac arrest can be explained by systemic disturbances—such as hypoxia, acidosis, sepsis, and hypovolemia— that commonly precede the arrest Although ventricular arrhythmias usually are reported to be infrequent (range, 1.3%–3.8%), out-of-hospital series report VF in 10% to 19% of victims younger than 20 years.18,19 These series, along with the observation that the frequency of witnessed arrest is much lower than in adults, suggests that ventricular rhythms may be more common than usually estimated and that delay in resuscitation results in progression of nonperfusing rhythms to asystole Increasing availability of AEDs may be contributing to the increased recognition of ventricular arrhythmias in out-of-hospital pediatric cardiac arrest.20 In specialized cardiac intensive care units (ICUs), ventricular arrhythmias account for as many as 30% of the arrests.3,21,22 In their original work on CPR, Kouwenhoven et al.23 proposed that blood flow during closed-chest compressions resulted from squeezing of the heart between the sternum and vertebral column, now termed the cardiac blood flow mechanism In fact, the precise CHAPTER 38 Physiologic Foundations of Cardiopulmonary Resuscitation mechanism by which forward circulatory flow is generated during closed-chest cardiac massage has major implications for current approaches to CPR Other methods—such as vest CPR, active compression-decompression CPR (ACD-CPR) both without and with an impedance threshold valve (ITV), and interposed abdominal compressions with CPR (IAC-CPR)—take into account advances in our understanding of the mechanism of blood flow during resuscitation The pharmacology of resuscitation remains controversial; these controversies have led to major changes in the guidelines for CPR Use of sodium bicarbonate, calcium chloride, and glucose remains unresolved at this time The role of high-dose epinephrine has been minimized because of concerns over postresuscitation deleterious effects on myocardial performance and poor outcomes Evidence for a role for vasopressin, with a relatively pure vasoconstrictor effect, is accumulating Data have been accumulating for the use of amiodarone or lidocaine as the antiarrhythmics of choice for ventricular ectopy in persons in cardiac arrest.3 Research is ongoing into alternative vasoconstrictors and the use of pharmacologic cocktails that may include b-blockers, antiarrhythmic agents, antioxidants, nitroglycerin, and a vasoconstrictor in attempts to improve the resuscitation outcome and postresuscitation cardiac function.24–26 Developments in the use of direct current countershock have occurred Biphasic defibrillators are now widely in use and appear to improve the success of defibrillation at lower delivered energies It is hoped that they decrease myocardial injury As noted, the role of “shock first” is being reassessed because the success of electrical countershock in restoring spontaneous circulation declines rapidly after to minutes have elapsed Although postresuscitation cerebral preservation has become an important area of focus, therapeutic hypothermia has not been found to improve neurologic outcome after pediatric cardiac arrest.11,12 This chapter discusses the physiologic foundations of CPR In the first section, the possible mechanisms of blood flow by the thoracic and cardiac pump mechanisms are discussed, including how the specific chest geometry of children and infants helps decide which of these mechanisms applies Newer CPR techniques, which consider the physiologic mechanisms discussed in the first section, are then discussed Controversies and advances in pharmacologic management during CPR and current guidelines for use of drugs for resuscitation are addressed New developments in the use of countershock—including the timing of shocks, energy used, and type of current delivery system used (biphasic or monophasic)—are discussed Finally, the role of therapeutic hypothermia is reviewed 421 Numerous clinical observations have conflicted with the cardiac pump hypothesis of blood flow In 1964, Mackenzie et al.27 found that closed-chest CPR produced similar elevations in arterial and venous intravascular pressures, the result of a generalized increase in intrathoracic pressure In 1976, Criley et al.28 made the dramatic observation that several patients in whom VF developed during cardiac catheterization produced enough blood flow to maintain consciousness by repetitive coughing The production of blood flow by increasing thoracic pressure without direct cardiac compression describes the thoracic pump mechanism of blood flow during CPR During normal cardiac function, the lowest pressure in the vascular circuit occurs on the atrial side of the atrioventricular valves This low-pressure compartment is the downstream pressure for the systemic circulation, which allows venous return to the heart Angiographic studies show that blood passes from the vena cava through the right heart into the pulmonary artery and from the pulmonary veins through the left heart into the aorta during a single chest compression Echocardiographic studies show that, unlike normal cardiac activity or during open-chest CPR, during closed-chest CPR in both dogs and humans, the atrioventricular valves are open during blood ejection and aortic diameter decreases rather than increases during blood ejection.29,30 These findings during closedchest CPR support the thoracic pump theory and argue that the heart is a passive conduit for blood flow (Fig 38.1).31 Initial measurements of hemodynamic data during chest compression for CPR found the generation of almost equal pressures in the left ventricle, aorta, right atrium, pulmonary artery, and esophagus.32 The finding that all intrathoracic vascular pressures are equal implies that suprathoracic arterial pressures must be higher than suprathoracic venous pressures The unequal transmission of intrathoracic pressure to the suprathoracic vasculature establishes the gradient necessary for blood flow The transmission of intrathoracic pressure to the suprathoracic veins may be modulated by venous valves The presence of these jugular venous valves has been demonstrated in animals and humans undergoing Direct Cardiac Compression Sternum Mitral valve closed Thoracic Pump Mitral valve opened Vertebra Mechanisms of Blood Flow Cardiac Versus Thoracic Pump Mechanism The cardiac pump hypothesis holds that blood flow is generated during closed-chest compressions when the heart is squeezed between the sternum and vertebral column This mechanism of flow implies that ventricular compression causes closure of the atrioventricular valves and that ejection of blood reduces ventricular volume During chest relaxation, ventricular pressure falls below atrial pressure, allowing the atrioventricular valves to open and the ventricles to fill This sequence of events resembles the normal cardiac cycle and occurs during cardiac compression when openchest CPR is used Chest compression force ↑ Rate of chest compression and and duty cycle cause ↑ Force of chest compression cause ↑ Pleural cavity pressure ↑ Blood flow from heart ↑ Pressure of heart chambers • Fig 38.1 Possible mechanisms for blood flow during cardiopulmonary resuscitation include direct cardiac compression (left) and the thoracic pump (right) With direct cardiac compression, an increase in chest compression rate causes an increase in blood flow by squeezing the heart between the vertebral column and sternum With the thoracic pump mechanism, factors that increase pleural pressure cause an increase in pressure within the heart chambers and, ultimately, an increase in blood flow (Modified from Schleien CL et al Controversial issues in cardiopulmonary resuscitation, Anesthesiology 1989;71:135.) 422 S E C T I O N I V Pediatric Critical Care: Cardiovascular CPR.33–35 An ultrasonography study of healthy children confirmed the presence of these valves in 84% of 239 jugular veins studied The valves were bilateral in 74% of children.36 Transmission of intrathoracic pressure to the intracranial vault during CPR indicates that any such valve function is partial Pathologic studies have also identified valves in the subclavian vein in the large majority of cadavers studied (87%) The absence of these valves in some patients is postulated to lead to failure of closed-chest CPR.37 Subsequent hemodynamic and echocardiographic studies found different results Deshmukh et al demonstrated in a porcine model that mitral valve function persisted throughout resuscitation in 17 of 22 animals and that in successfully resuscitated animals, maximal aortic pressure exceeded that in the right atrium throughout the resuscitation.33 In another porcine model of resuscitation, Hackl et al manipulated the compressive force and depth of resuscitation by using a mechanical resuscitator.38 The frequency of mitral valve closure during compressive systole was directly proportional to the force and depth of chest compression When the depth of compression reached 25% of the anteroposterior diameter, valve closure occurred in 95% of cycles They concluded that the mechanism of blood flow was dependent on the force and depth of compression In a study of CPR using transesophageal Doppler echocardiography in adults, Porter et al demonstrated mitral valve closure in compressive systole in the majority of patients (12 of 17) but not all patients.39 Peak mitral flow occurred in diastole and was significantly higher in the group with mitral valve closure Peak mitral flow occurred during compressive systole in those without valve closure Left ventricular (LV) fractional shortening correlated with change in anteroposterior chest wall diameter and not mitral valve flow These authors concluded that nonuniform increased intrathoracic pressure plays a role in determining whether valve closure occurs during chest compressions As noted, a decrease in aortic dimension during CPR has been demo nstrated by echocardiography and taken as evidence for the thoracic pump mechanism of blood flow Hwang et al readdressed this issue using transesophageal echocardiography.40 They studied the aortic dimension of the proximal and distal thoracic aorta and noted a decrease in the aortic dimension in the distal aorta directly inferior to the zone of direct compression and an increase in the dimension of the proximal aorta They also noted mitral valve closure in all subjects and a decrease in LV volume of almost 50% at end compression These findings were believed to be most consistent with the cardiac pump mechanism of blood flow.41 Kim et al also used transesophageal echocardiography to explore the role of the left ventricle during nontraumatic arrests.42 They noted that during the compression phase of CPR, there was anterograde flow from the ventricle to the aorta and retrograde flow toward the mitral valve The mitral valve remained closed during compression and open during relaxation, while the aortic valve remained open during compression and closed during relaxation, which they concluded to be consistent with the cardiac pump mechanism The cardiac pump mechanism appears to predominate during closed-chest CPR in specific clinical situations As noted, increasing the applied force during chest compressions increases the likelihood of direct cardiac compression A smaller chest size may allow for more direct cardiac compression.38,42 Adult dogs with small chests have better hemodynamics during closed-chest CPR than dogs with large chests Because the infant chest is smaller and more compliant than the adult chest, direct compression of the heart during CPR is more likely to occur Blood flow during closed-chest CPR in a piglet model of cardiac arrest is higher than that achieved in adult models.43 A study of 20 randomized swine to either a patient-centric blood pressure targeted approach with titration of compression depth to a systolic blood pressure of 100 mm Hg and vasopressors to a coronary perfusion pressure greater than 20 mm Hg or current usual practice, the blood pressure targeted group demonstrated improved 24-hour survival (8 of 10 vs of 10 survival; P 001).44 This study suggests that physiologic targets rather than absolute depths by age may in fact confer better outcomes Rate and Duty Cycle In 2015, the American Heart Association (AHA) recommended a rate of chest compressions of at least 100 per minute.45–49 At faster rates, blood flow is enhanced whether the thoracic pump mechanism or cardiac pump mechanism is invoked Duty cycle is defined as the ratio of the duration of the compression phase to the entire compression-relaxation cycle, expressed as a percent For example, at a rate of 30 compressions/min, a 1.2-second compression time produces a 60% duty cycle If blood flow is generated by direct cardiac compression, then the stroke volume is determined primarily by the force of compression Prolonging the compression (increasing the duty cycle) beyond the time necessary for full ventricular ejection should have no additional effect on stroke volume Increasing the rate of compressions should increase cardiac output because a fixed, relatively small volume of blood is ejected with each cardiac compression In contrast, if blood flow is produced by the thoracic pump mechanism, the volume of blood to be ejected comes from a large reservoir of blood contained within the capacitance vessels in the chest With the thoracic pump mechanism, flow is enhanced by increasing either the force of compression or the duty cycle but is not affected by changes in compression rate over a wide range of rates.34 Additionally, the “push hard, push fast” recommendation is based on the maintenance of a higher compression rate with a higher force of compression Allowing total recoil of the chest allows for full blood return during the relaxation phase of the cycle.50 It appears from experimental animal data that both the thoracic pump and cardiac pump mechanisms can effectively generate blood flow during closed-chest CPR Differences between various studies may be attributed to differences in animal models or compression techniques Important differences in animal models include chest wall geometry, compliance and elastic recoil, compliance of the diaphragm, and intraabdominal pressure Differences in technique include the magnitude of sternal displacement; compression force; and momentum of chest compression, compression rate, and duty cycle Experimental and clinical data support both mechanisms of blood flow during CPR in human infants Results of several studies in dogs demonstrated a benefit of a compression rate of 120 per minute compared with slower rates during conventional CPR.51,52 In studies of piglets, puppies, and humans, no differences were found comparing different rates of compression during conventional CPR.34,53–55 In a study of piglet CPR, duty cycle was the major determinant of cerebral perfusion pressure (CPP) The duty cycle at which venous return became limited varied with age A longer duty cycle was more effective in younger piglets.55 In a more recent study of 22 pigs randomized to head-up tilt versus supine CPR using an automated CPR device plus an impedance threshold device after VF arrest, CPP and ICP improved substantially with head-up tilt position.56 This suggests that gravity has an effect on the venous circulation with 423 CHAPTER 38 Physiologic Foundations of Cardiopulmonary Resuscitation Chest Geometry Chest geometry plays an important role in the ability of extrathoracic compressions to generate intrathoracic pressure Shape, compliance, and deformability, which change greatly with age, are the chest characteristics that have the greatest impact during CPR The change in cross-sectional area of the chest during anterior to posterior delivered compressions is related to its shape (Fig 38.2).58 The ratio of the chest anteroposterior diameter to the lateral diameter is referred to as the thoracic index A keel-shaped chest, as seen in an adult dog, has a greater anteroposterior diameter and, thus, a thoracic index greater than A flat chest, as in a thin human, has a greater lateral diameter and, thus, a thoracic index less than A circular chest has a thoracic index equal to A circle has a larger cross-sectional area than either of these elliptical chests As an anteroposterior compression flattens a circle, the cross-sectional area decreases and compresses its contents In contrast, as an anteroposterior compression is applied to the keelshaped chest, the cross-sectional area increases as a circular shape is approached The cross-sectional area of the keel-shaped chest does not decrease until the chest compression continues past the circular shape to flatten the chest This implies a threshold past which the compression must proceed before intrathoracic contents are decreased and squeezed.58 Thus, the rounder, flatter chests of small dogs and pigs may require less chest displacement than the keel-shaped chests of adult dogs to generate thoracic ejection of blood This dynamic has been demonstrated in small dogs having round chests compared with adult dogs having keelshaped chests.59 As humans age, the cartilage of the rib cage calcifies and chest wall compliance decreases Older patients may require greater compression force to generate the same sternal displacement A 3-month-old piglet requires a much greater compression force for anteroposterior displacement than its 1-month-old counterpart.58 Direct cardiac compression is more likely to occur in the more compliant chest of younger animals Cerebral and myocardial blood flow during closed-chest CPR was much higher in infant piglets than in adults (Figs 38.3 and 38.4).60 This finding supports the cardiac pump mechanism of blood flow in infants because the level of organ blood flow achieved during closed-chest CPR in piglets approaches the level achieved during open-chest cardiac massage in adults Marked deformation of the chest can occur during prolonged CPR and may alter the effectiveness of CPR (Fig 38.5).60 Over time, the chest assumes a flatter shape, producing a larger percent decrease in cross-sectional area at the same absolute chest displacement Progressive deformation may be beneficial if it leads to more direct cardiac compression Unfortunately, too much deformation may decrease the recoil of the chest wall during the 50 rlat Area = 13% A rap ‡ 10 1.0 rap rlat * 20 20% rap ‡ 0.8 0.6 Area = 13% ‡ ‡ ‡ ‡ ‡ * ‡ ‡ ‡ B • Fig 38.2 Changes in area of ellipses with constant circumference Each ellipse is labeled with the anteroposterior (ap) and lateral (lat) radii, and a 20% anteroposterior compression is applied Indicated change in area equals relaxed area – compressed area (A) Initial anteroposterior/lateral ratio 0.7, and compression leads to positive ejection because relaxed area – compressed area is negative (B) Initial anteroposterior/lateral ratio 1.4, and compression toward a circular shape results in an increase in area (Modified from Dean JM, Koehler RC, Schleien CL, et al Age-related changes in chest geometry during cardiopulmonary resuscitation J Appl Physiol 1987;62[6]:2212–2219.) ‡ Without epinephrine With epinephrine P < 05 from prearrest P < 05 between groups ‡ * Cerebral O2 uptake rlat ‡ ‡ 0.4 rlat * Cerebral fractional O2 extraction rap * 30 RELAXATION PHASE COMPRESSION PHASE 20% ‡ 40 Cerebral blood flow high-quality CPR and head tilted up positioning on cerebral perfusion The discrepant importance of rate and duty cycle in various models (by different investigators) is confusing; however, increasing the rate of compressions during conventional CPR to 100 per minute satisfies both those who prefer the faster rates and those who support a longer duty cycle Appropriate chest compression rate, depth, and fraction are still being investigated Niles et al characterized these in-hospital CPR metrics and compliance to the 2015 AHA guidelines by evaluating the pediRES-Q database.57 They found that meeting all three of these AHA-derived CPR targets was extremely difficult to accomplish Their study was not powered to address short- or long-term survival but was an important step in evaluating the optimal cutoffs for survival * ‡ * ‡ Pre- arrest • Fig 38.3 Total 10 20 30 * ‡ ‡ 40 50 Time (min) cerebral blood flow, cerebral fractional oxygen (O2) extraction, and cerebral O2 uptake before cardiac arrest and during 50 minutes of cardiopulmonary resuscitation in the groups with and without epinephrine ... guidelines for CPR Use of sodium bicarbonate, calcium chloride, and glucose remains unresolved at this time The role of high-dose epinephrine has been minimized because of concerns over postresuscitation... hypothermia has not been found to improve neurologic outcome after pediatric cardiac arrest.11,12 This chapter discusses the physiologic foundations of CPR In the first section, the possible mechanisms... lowest pressure in the vascular circuit occurs on the atrial side of the atrioventricular valves This low-pressure compartment is the downstream pressure for the systemic circulation, which allows