252 SECTION IV Pediatric Critical Care Cardiovascular plication in children is limited In postoperative pediatric cardiac patients, terlipressin demonstrated an improvement in respira tory, hemodynami[.]
252 S E C T I O N I V Pediatric Critical Care: Cardiovascular decreasing the work of breathing, reduces LV afterload (wall stress), and can improve Sao2 by the administration of O2 and positive end-expiratory pressure (PEEP), thus increasing Cao2 However, endotracheal intubation can be risky in decompensated patients with HF, as the induction agents, laryngoscopy, and conversion to positive-pressure ventilation can induce cardiac arrest The benefits of noninvasive positive-pressure ventilation (i.e., bilevel positive airway pressure) have not been proven, and the risks remain significant, particularly with regard to delay in timing of intubation and the need for additional sedation in children Cao2 can also be increased by transfusing packed red blood cells to increase hemoglobin concentrations in significant anemia Research in the PICU has not demonstrated a negative impact on patient outcomes when a restrictive transfusion practice was embraced, though the study did not examine complex or high-risk congenital cardiac patients or those with unrepaired or palliated cyanotic cardiac defects where a relative polycythemia is normally maintained to compensate for the decrease in Sao2.75 Clearly, numerous significant deleterious effects on the recipient occur after allogenic blood transfusion, and the risk of donor-directed blood can be greater In patients who are euvolemic, hypervolemia with worsening pulmonary edema must be avoided when the decision to transfuse red cells is made.76,77 CPB results in numerous significant neurohormonal perturbations in neonates, infants, and children after cardiac surgery A pattern of sick euthyroid syndrome has been identified in pediatric patients after CPB Several studies have demonstrated acute salutary effects of preoperative thyroid prophylaxis78 or postoperative therapy with triiodothyronine resulting in increases in specific hemodynamic parameters, improved diuresis, and a decreased need for additional cardiopulmonary support without significant adverse effects79,80 although better outcomes have yet to be shown.81 Critical illness–related corticosteroid insufficiency (CIRCI) has been demonstrated imprecisely in clinical trials in neonates, infants, and children after cardiac surgery Stress-dose hydrocortisone replacement similarly has resulted in positive acute hemodynamic improvements and, yet again, this has not translated into improved survival or decrease in morbidities in these patients All of these studies are confounded by the use of differing adrenal corticosteroids in varying doses used in the preoperative/intraoperative anesthetic/perfusion protocols.82–84 The STRESS trial is an ongoing randomized double-blind placebo-controlled trial evaluating the safety and efficacy of single-dose intraoperative methylprednisolone 30 mg/kg versus placebo in infants (,1 year of age) undergoing cardiac surgery with CPB.85 A multicenter randomized controlled study evaluating two levels of glycemic control was stopped prematurely by the data safety monitoring committee owing to futility in reaching significance and apparent harm (hypoglycemia and hospital-acquired infections) in the low-glucose (80–110 mg/dL) compared with the high-glucose target (150–180 mg/dL) groups.86 Interestingly, pediatric cardiac surgery patients were excluded from enrollment Despite the results of this large multicenter pediatric trial, the physiology and pathophysiology of hyperglycemia in the stress response to critical illness remains significant, and other well-controlled studies point to differing conclusions based on the details of the management strategy.87,88 Finally, a Pediatric Cardiac Intensive Care Society’s consensus statement could not recommend any hormonal replacement/monitor strategies (thyroid, corticosteroid, or insulin) owing to the lack of robust double-blinded randomized clinical trials.89 Terlipressin, a synthetic long-acting analog of vasopressin with a higher affinity for vascular V1-receptors than vasopressin, has been used in adult patients to treat extremely low CO, but its ap- plication in children is limited In postoperative pediatric cardiac patients, terlipressin demonstrated an improvement in respiratory, hemodynamic, and renal indices in refractory LCOS.90 Although these results are encouraging, further investigation with prospective randomized trials is needed to provide data regarding the efficacy and safety of terlipressin in infants and children.91 Inhaled nitric oxide (iNO) is a potent short-acting vasodilator resulting in numerous beneficial cardiopulmonary effects on the pulmonary, systemic, and coronary circulations Its use is standard for severe, reversible pulmonary arterial hypertension (PAH) in the neonate and in children with congenital heart disease It is also useful in the treatment of RV failure A variety of other drugs (e.g., nitroprusside) and amino acids (arginine, citrulline) are precursors to NO and thus increase its circulating levels Pediatric patients with severe PAH can also be treated with intravenous prostacyclin analogues, such as epoprostenol or treprostinil,92,93 or continuously inhaled epoprostenol In studies in neonates with persistent pulmonary hypertension88,94 and critically ill noncardiac pediatric patients,95,96 this therapy has proven to be equally efficacious as iNO and, in extreme cases, they can be used synergistically in a child.97 Mechanical Circulatory Support in Pediatric Patients Medical therapy for HF has improved survival and quality of life, although a large number of patients still require advance treatment with intravenous inotropic support, mechanical ventilation, and/or heart transplantation MCS should be considered for children with decompensated HF who cannot be stabilized with medical therapy alone Rapid advances in the field of MCS have dramatically changed the management of children with end-stage HF with emphasis on timely evaluation of ventricular assist devices (VADs) to preserve or recover end-organ function When medical treatment is maximized or ineffective, patients should be considered for MCS for temporary support until heart function recovers, as a bridge to heart transplantation, or as a destination therapy (life with permanent VAD) MCS through a variety of devices can be used to treat right, left, or biventricular failure This is accomplished with devices that are either extracorporeal (outside the human body), paracorporeal (partial within and outside the human body), or intracorporeal or implantable (residing completely within the human body) MCS devices can provide either pulsatile flow or continuous flow depending on the specific design MCS can also be provided to the left ventricle alone with an intraaortic balloon pump or it can replace the entire function of the heart with a total artificial heart Finally, cardiac and pulmonary support can be provided with the addition of a membrane oxygenator in specific types of ECLS devices Venoarterial (VA) ECLS provides cardiopulmonary support, whereas venovenous (VV) ECLS provides only pulmonary support for severe respiratory failure Despite improvements in operative techniques, management of CPB, and myocardial protection, myocardial dysfunction and failure can occur after surgery for CHD with involvement of the left and/or right ventricles Approximately 5% of children undergoing cardiac surgery require MCS The patient’s underlying pathophysiology, size, and expected length of support dictate which technique is most suitable In children, most MCS continues to be achieved with ECLS Since ECLS and VADs have advantages and disadvantages, determining the most appropriate modality for the individual patient requires significant experience and expertise CHAPTER 28 Cardiac Failure and Ventricular Assist Devices Extracorporeal Life Support ECLS is the most utilized form of short-term MCS for pediatric patients with decompensated HF unresponsive to medical therapy Adaptations and simplification of the traditional CPB circuit have resulted in the standard VA ECLS circuit (Fig 28.2) through either extrathoracic (i.e., carotid artery/jugular vein or femoral vessels) or transthoracic (right atrium/ascending aorta) placement after median sternotomy The venous cannula allows for drainage of blood from the patient by a negative pressure created by the servo-regulated centrifugal pump or, previously, a roller-head that propels blood through the remainder of the system at high pressure Gas exchange (O2 addition and CO2 removal) occurs next through an artificial lung (oxygenator comprised of hollow fibers) where countercurrent sweep gas composed of O2/air mixture titrated to a specific fraction of inspired oxygen (Fio2) passes external to the blood phase Blood temperature is controlled by a heat exchanger before blood is returned to the body through a major artery Additional components include ports for infusion of medications, arterial and venous pressure monitors, Svo2 and/or blood gas analyzers, and flow and bubble detectors There can be placement of a hemofilter for fluid control or a dialysis circuit (venovenous, arteriovenous, arterial-arterial) and, frequently, a bridge connecting the venous and arterial sides of the circuit is used during trials off ECLS or in case of a circuit emergency Individual centers customize their ECMO circuits to serve their patient population by creating a less complicated circuit that is easier to manage with fewer connectors to reduce the number of potential sites for blood stasis.98,99 VA ECLS provides biventricular and pulmonary support It is important to note that complete cardiac bypass cannot be provided by VA ECLS owing to incomplete capture and drainage of the cardiac systemic venous return by the venous cannula Routine cannulation for VA ECLS occurs via one of three vascular access points: (1) The transcervical approach places the venous cannula in the right atrium (RA) via the right internal jugular vein and the arterial cannula in the transverse aortic arch via the right carotid artery (2) The transthoracic approach results in direct cannulation of the RA and ascending aorta through a median sternotomy for patients who either cannot be weaned from cardiopulmonary bypass or require MCS in the immediate postoperative period (3) Femoral artery and vein cannulation for adolescents and adults uses longer cannulae to reach the RA and descending aorta A combination of these approaches with more than one venous cannulation site can be employed when very high flows are required The transcervical and transthoracic approaches are the preferred methods for small children Fig 28.3 is a chest radiograph • Fig 28.3 Chest radiograph showing venoarterial extracorporeal membrane oxygenation cannulas ECMO SYSTEM O2 blender Membrane oxygenator Premembrane pressure monitor Warmed H2O input Postmembrane pressure monitor Pump 253 Heat exchanger F l u i d s H e p a r i n RV LV Venous reservoir • Fig 28.2 Extracorporeal membrane oxygenation circuit ECMO, Extracorporeal membrane oxygenation; H2O, water; LV, left ventricle; O2, oxygen; RV, right ventricle 254 S E C T I O N I V Pediatric Critical Care: Cardiovascular A • Fig 28.4 (A) Venovenous extracorporeal membrane oxygenB obtained for evaluation of cannula placement in a patient supported by VA ECLS VV ECLS provides pulmonary support without cardiac support In VV ECLS, a single double-lumen cannula (Fig 28.4) is placed in the RA through a transcervical approach This cannula provides both inflow and outflow for the circuit VV ECLS can improve RV function as a result of oxygenated, pH-balanced blood flowing to the lungs, thus decreasing PVR and right heart afterload Although some patients experience improvement in overall cardiac function with VV ECLS, it might not be sufficient or sustained Therefore, when significant myocardial dysfunction exists, VA ECLS is the preferred modality ation double-lumen cannula (B) Chest radiograph showing position of double-lumen cannula Extracorporeal Membrane Oxygenation Indications and Contraindications It is widely accepted that all patients considered for MCS should have either a reversible physiologic process or should be a candidate for bridge to transplant or destination therapy The severity of organ dysfunction and estimated time frame for recovery of cardiac and other organ failure both are used in determining optimal device selection Several studies emphasize the importance of early institution of ECLS before a prolonged period of low CO results in multiorgan dysfunction Appropriate patient selection is vital to maximize survival.100–102 CHAPTER 28 Cardiac Failure and Ventricular Assist Devices Myocarditis and Extracorporeal Life Support The clinical course of myocarditis is variable, with some patients presenting with subclinical disease, others with an indolent course progressing to a dilated cardiomyopathy, and a distinct subset of patients with fulminant disease Without MCS, patients with rapidly progressive disease had expected survival rates of only 25% to 50% Patients with acute fulminant myocarditis have worse short- and long-term outcomes when there are decreased LV ejection, ventricular arrhythmias, and/or LCOS.103 With aggressive utilization of ECLS as a bridge to transplantation or recovery, survival rates for patients are now reported to be as high as 90%.104–107 It has been shown that the institution of MCS can normalize ventricular geometry, cellular composition, metabolism, and, ultimately, function—a phenomenon referred to as reverse remodeling This process is thought to improve ventricular dysfunction because of favorable influences on the neurohormonal cardiovascular milieu and ventricular unloading.108–110 For patients with end-stage dilated cardiomyopathy secondary to myocarditis, the use of MCS without transplantation has resulted in survival rates as high as 67% to 80%.64 Postcardiopulmonary Bypass Failure to wean from CPB occurs in approximately 1% to 3.2% of pediatric congenital cardiac surgery cases.111–113 Individual institutions have reported survival rates to hospital discharge between 32% and 54% for pediatric patients who require MCS after cardiac surgery The use of MCS is currently widely accepted to support vital organs while allowing for myocardial recovery It is imperative that these patients be evaluated for the presence of residual cardiac defects that may be causing or worsening cardiovascular collapse Intraoperative transesophageal echocardiography (TEE), transthoracic echocardiography (TTE), and diagnostic cardiac catheterization may identify the need for reoperation or interventional cardiac catheterization to improve the patient’s hemodynamic status.114 In one large center, 2% of cardiac surgeries resulted in an early postoperative catheterization, 50% diagnostic and 50% interventional, and there was no procedural mortality Importantly, 30% of those undergoing catheterization required reoperation.115 Balloon valvuloplasty, angioplasty of aortic arch obstructions, device closure of residual septal defects, coil occlusion of aortopulmonary collateral vessels, or atrial septostomy all may be crucial interventions to improve the patient’s hemodynamic state and allow for separation from MCS Untreated and significant residual cardiac defects have been shown to be almost universally fatal for patients requiring MCS.116 The use of MCS for postcardiotomy support in neonates and infants with single-ventricle physiology is technically more complex with worse outcomes.117,118 Thus, previously this could have been considered a relative contraindication to MCS.119,120 The 2020 Extracorporeal Life Support Organization (ELSO) Registry (2015–20) reports a 44% survival rate for ECLS use in neonates with hypoplastic left heart (eTables 28.1 and 28.2) Extracorporeal Cardiopulmonary Resuscitation Survival from pediatric cardiac arrest has improved tremendously over the last 20 years However, half of the children who suffered in-hospital cardiac arrest not survive to hospital discharge and those who survive have significant morbidity.121 Although neurocognitive outcome has improved for survivors of cardiac 255 arrest, the duration of cardiopulmonary resuscitation (CPR) remains inversely proportional to survival The American Heart Association guidelines for in-hospital pediatric cardiac arrest now recommend consideration of extracorporeal CPR (ECPR) during CPR if the conditions leading to the arrest are likely to be reversible or amenable to heart transplantation.122 One of the most important aspects of the decision to institute ECPR is adequate patient selection There is sufficient data to support the use of ECPR in children with cardiac disease who suffer an in-hospital cardiac arrest.123–126 However, wide variability in patient selection and the ability to institute ECLS in a timely fashion (ideally, ,60 minutes) has led to variable success, with survival rates ranging from 0% to 100%.118,127–129 Thus, some large centers have created systems for rapid-deployment ECLS using a team that is immediately available to cannulate with a preprimed circuit.6,130,131 Children with CHD have increased risk for an in-hospital cardiac arrest Their survival to discharge after ECPR has been reported to be up to 50%, yet single-ventricle patients suffer more cardiac arrests and have the worst outcome.117,130,132,133 Reduced survival of ECPR has been associated with lower postcannulation pH, higher lactic acid, and end-organ injury Post–cardiac arrest management (temperature control, target flow rates, target perfusion pressure) is beyond the scope of this chapter but constitutes an extremely important factor that can impact outcome The January 2020 ELSO Registry for neonatal and pediatric patients supported with ECLS following cardiac arrest (ECPR) reported a survival to hospital discharge of 46% for neonates and 37% for children Bridge to Transplantation Although heart transplantation is the treatment of choice for endstage myocardial failure, many children die every year waiting for a suitable organ to become available As a result, MCS is now increasingly used as a bridge to heart transplantation.127,134 The most common indications for MCS as a bridge to transplant include cardiac failure due to CHD, cardiomyopathy, and graft rejection after heart transplantation Children with myocardial failure secondary to fulminant myocarditis also demonstrate increased shortterm survival when treated with MCS and transplantation.104,135–138 Complications associated with ECLS generally limit the duration of support to approximately weeks, but as long as complications precluding transplant have not developed, no arbitrary cutoff for duration of ECLS has been determined An analysis of the United States Scientific Registry of Transplant Recipients demonstrated that waitlist mortality varied as much as 10-fold based on recipient factors Over the last decade, the proportion of pediatric heart transplant candidates with CHD increased from 48% in 2008 to 62.2% in 2018 From the pediatric heart transplantations performed in 2018, 7.8% were in children younger than 10 years The overall percentage of candidates with VADs at the time of listing increased from 11.8% in 2008 to 32.6% in 2018 Recipient characteristics associated with waitlist mortality included ECMO, mechanical ventilation, listing status 1A, CHD, dialysis support, and non-white race Waitlist mortality for infants was significantly higher than for older patients (Fig 28.5) Although waitlist mortality remains high, VAD support has been an important factor in reducing waitlist mortality in small children.139 An analysis of the United Network of Organ Sharing (UNOS) database comparing the pre-VAD (1999–2004) and post-VAD (2005–15) eras reported more than 50% reduction in waitlist mortality in the post-VAD era,140 supporting the importance of centers of excellence that can provide these state-of-the-art therapies 255.e1 eTABLE Neonatal Cardiac Runs by Diagnosis (ELSO Registry, January 2020) 28.1 Total Runs Congenital heart defect Average Run Time (h) Longest Run Time (h) Survived % Survived 963 144 1463 464 48 Cardiac arrest 14 133 309 35 Cardiogenic shock 70 172 1746 39 55 Cardiomyopathy 15 363 2109 53 Myocarditis 13 210 478 61 539 175 3566 298 55 Other eTABLE Neonatal Cardiac Runs by Congenital 28.2 Heart Defect (ELSO Registry, January 2020) Left-to-right shunt Total Runs Average Run Time (h) Survived (n) Survived (%) 74 161 37 50 Left-sided obstructive 89 135 41 46 Hypoplastic left heart 427 136 192 44 Right-sided obstructive 50 133 24 44 Cyanotic increased pulmonary blood flow 64 177 25 39 Cyanotic decreased pulmonary blood flow 299 1271 39 58 ... ECLS, a single double-lumen cannula (Fig 28.4) is placed in the RA through a transcervical approach This cannula provides both inflow and outflow for the circuit VV ECLS can improve RV function as... composition, metabolism, and, ultimately, function—a phenomenon referred to as reverse remodeling This process is thought to improve ventricular dysfunction because of favorable influences on the... single-ventricle physiology is technically more complex with worse outcomes.117,118 Thus, previously this could have been considered a relative contraindication to MCS.119,120 The 2020 Extracorporeal