e3 Abstract Cardiovascular assessment and monitoring in the pediat ric intensive care unit require careful integration of physical find ings, laboratory studies, and electronic data to make appropriat[.]
e3 Abstract: Cardiovascular assessment and monitoring in the pediatric intensive care unit require careful integration of physical findings, laboratory studies, and electronic data to make appropriate therapeutic decisions Multiple noninvasive and invasive monitoring techniques are available for clinicians For a given clinical scenario, an appreciation of the quantity of therapy required to achieve and sustain adequate systemic oxygen delivery and perfusion pressure is useful for the clinician to understand the patient’s overall condition, discern the patient’s trajectory, and anticipate associated consequences of current management choices Key words: cardiac output, oxygen delivery, cardiovascular assessment, invasive and noninvasive monitoring, quantity of therapy, streaming analytics 28 Cardiac Failure and Ventricular Assist Devices ANA LIA GRACIANO, JOSEPH PHILIP, AND KEITH C KOCIS • Pediatric Heart Failure Heart failure (HF) is the final pathway of many pathophysiologic states affecting cardiovascular performance leading to inadequate cardiac output (CO) and decreased end-organ perfusion with diminished oxygen delivery to the vital organs These include states of altered preload, afterload, contractility, and abnormal heart rate (HR) or rhythm The pathophysiologic syndrome of HF is the result of a complex interplay among circulatory, neurohormonal, and molecular abnormalities The etiology of HF in children differs from that of the adult and includes both primary cardiac and noncardiac causes, with the largest disease burden being due to congenital heart malformations and cardiomyopathies.1–3 HF in children leads to characteristic signs and symptoms—such as poor growth, feeding difficulties, respiratory distress, exercise intolerance, and fatigue The pathophysiology of HF includes volume overload (e.g., left-to-right shunting, semilunar valve regurgitation), pressure overload (e.g., congenital aortic stenosis), or a combination of both as seen in patients with complex congenital heart disease The primary goal in the management of HF is to ensure adequate tissue oxygen delivery, as an imbalance between delivery and consumption results in organ dysfunction, failure, and cardiogenic shock Acute decompensated HF (ADHF) is a common final pathway for children with congenital or acquired heart disease They can present with failed palliation of congenital heart disease, acquired cardiomyopathies, or acute exacerbations of chronic HF Initial therapies to treat ADHF target 248 • • Advances in medical management, surgical techniques, and mechanical circulatory support (MCS) for pediatric patients with congestive heart failure continue to improve patient outcomes Indications for the use of MCS continue to evolve Patient size, expected duration of support, and goals of support (i.e., bridge to recovery vs bridge to transplant) must be considered in the choice of an MCS device MCS is a lifesaving therapeutic option for patients with advanced heart failure Device options in children are expanding but remain limited due to size constraints • • • • PEARLS In children, most short-term MCS continues to be achieved with extracorporeal life support Small patients (,3 kg), renal failure, and the need for biventricular support greatly increase the risk of death during support A multidisciplinary team approach to the selection of the appropriate mechanical circulatory device is critical to a successful outcome providing respiratory support; decreasing metabolic demands (i.e., work of breathing); optimizing preload, afterload, and contractility; and optimizing HR and rhythm Despite advances in pharmacologic therapies beyond inotropes, diuretics, and antiarrhythmic agents, a group of patients will continue to deteriorate or require excessive cardiopulmonary support to maintain adequate CO This group should be evaluated early for mechanical circulatory support (MCS) before additional endorgan dysfunction or irreversible damage occurs Several innovative types of MCS are being created and brought into clinical care while extended indications and management strategies are currently being developed for older devices Simultaneously, extracorporeal life support (ECLS) continues to improve and remains the most commonly deployed form of MCS for infants and children.4–6 Low Cardiac Output Syndrome Low cardiac output syndrome (LCOS) describes a clinical state with a specific profile of biochemical markers in which there is inadequate systemic oxygen delivery (Do2) to meet the metabolic demands (oxygen consumption [Vo2]) of the patient The condition has been recognized since the 1960s; numerous studies have documented the predicted changes in physiologic parameters.7,8 LCOS has been an active area of research, and multiple reviews of current therapies are available to guide the intensivist.9 LCOS is frequently seen in myocarditis, cardiomyopathies, with prolonged bradyarrhythmias or tachyarrhythmias, and commonly after CHAPTER 28 Cardiac Failure and Ventricular Assist Devices complex pediatric cardiac surgery Postoperative physiologic changes secondary to cardiopulmonary bypass, myocardial ischemia during aortic cross-clamping, cardioplegia, residual uncorrected lesions (i.e., aortic arch obstruction), ventriculotomy, changes in the loading conditions to the myocardium, and dysrhythmias may all contribute to the development of LCOS A variety of proinflammatory triggers are activated during cardiopulmonary bypass as a result of blood contact with foreign surfaces, ischemia, reperfusion, oxygen free radicals, tissue trauma, and temperature fluctuations These complex inflammatory responses include complement activation, cytokine release, leukocyte and platelet activation, and the expression of adhesion molecules.10–12 LCOS has been reported to affect up to 25% of infants and children following cardiac surgery, typically occurs between and 18 hours after cardiac surgery, and results in a longer intensive care and hospital stay with increased morbidity and mortality It is associated with elevated systemic vascular resistance and pulmonary vascular resistance (PVR), impaired myocardial function, dysrhythmias, and capillary leak When unrecognized or inadequately treated, LCOS can result in irreversible end-organ failure, cardiac arrest, and death Prevention, early recognition, and optimal treatment are essential to ameliorate or reverse its course.13–15 Definitions The concepts of Do2 and Vo2 are of fundamental importance in managing critically ill children Systemic oxygen delivery (Do2) is defined as the amount of O2 delivered to peripheral tissues each minute and is determined by CO and the oxygen content of arterial blood (Cao2) CO is defined as the product of HR and stroke volume (SV), and the arterial oxygen content (Cao2) is determined by hemoglobin (Hb) concentration, the arterial oxygen saturation (Sao2), and the partial pressure of oxygen in the arterial blood (Pao2) Lastly, Vo2 can be measured by indirect calorimetry, or calculated using the Fick equation as the arterial venous difference in oxygen content (Cao2 Cvo2) multiplied by the CO: Do2 CO Cao2 CO HR SV Cao2 (Hb 1.36 Sao2) (Pao2 0.003) Vo2 CO (Cao2 – Cvo2) Achieving a positive balance between O2 supply and demand is essential and can be accomplished by decreasing Vo2 or increasing Do2 Vo2 is determined by tissue metabolism and is increased during periods of increased muscular activity (i.e., seizures, exercise), infection, fever, or with increased levels of circulating catecholamines Normally, the ratio between Do2 and Vo2 is 4:1; this ratio is high enough that cellular respiration is not supply dependent and Vo2 is mainly a function of tissue O2 demands When Vo2 increases based on increased metabolic demands, Do2 increases accordingly Therefore, consumption drives delivery Inability to maintain the normal Do2:Vo2 ratio is initially compensated by increased O2 extraction However, when the rate of Vo2 exceeds Do2, anaerobic metabolism begins Early studies in neonates with transposition of the great arteries (TGA) who underwent the arterial switch procedure documented the development of low CO to 12 hours after surgery.16 These findings led to a placebo-controlled intervention study whereby milrinone was randomly administered (bolus followed by continuous infusion) in a low (0.25 mg/kg per minute) versus 249 high (0.75 mg/kg per minute) dose to infants and children after cardiopulmonary bypass (CPB), in addition to the required inotropic agents needed to separate from CPB In those patients who received high-dose prophylactic milrinone, the development of LCOS in the first 36 hours after surgery was decreased to 12% compared with 26% in the placebo group Recent Cochrane reviews have failed to demonstrate a consistent improvement in the treatment of cardiogenic shock in infants and children after cardiac surgery with either milrinone or levosimendan, a calciumsensitizing agent.17,18 Assessment Although a complete assessment of Do2 and Vo2 in critically ill infants and children is extremely challenging, numerous hemodynamic and biochemical biomarkers can be readily obtained to help guide the bedside clinician Mixed venous oxygen saturation (SvO2) or central venous oxygen saturation (Scvo2), arterial lactate, and near-infrared spectroscopy (NIRS) are important clinical parameters that can be serially/continuously measured in patients at risk for LCOS Svo2 and Scvo2 are a reflection of the total body Do2/Vo2 ratio and can be important metrics to follow in critically ill patients.19,20 An elevated lactate level on admission (.4.5 mmol/L) and rising at 0.9 mmol/L per hour postoperatively is associated with major adverse events, including death, in infants after cardiac surgery.21–24 Furthermore, lower Svo2 may increase the predictive power of elevated arterial lactate levels for mortality after pediatric cardiac surgery.21,25 It is not uncommon to observe a disparity between direct measurements of Do2 and CO and estimates based on physical examination and interpretation of conventional laboratory and hemodynamic parameters.26–28 Compensatory increases in systemic vascular resistance maintain arterial blood pressure as CO decreases and central venous pressures may not correlate well with ventricular filling (preload).29,30 Femoral venous catheters are routinely placed in neonates and children, providing an additional factor (intraabdominal pressure) in the accurate interpretation of these continuous variables The effects of positive-pressure ventilation on these measurements are well described.31,32 Hemodynamic stability in the early postoperative period after Norwood palliation depends on an adequate total CO from the single ventricle and a balanced pulmonary-to-systemic blood flow ratio (Qp:Qs) Systemic oxygen saturation (Sao2) alone is a poor predictor of Qp:Qs because of variability in systemic venous oxygen saturation (Svo2) and pulmonary vein saturation (Spvo2) after the Norwood operation Monitoring and optimizing Svo2 have been shown to improve outcomes in pediatric patients at risk for developing shock, including hypoplastic left heart syndrome.33,34 Intermittent Svo2 monitoring can be obtained to assess oxygen transport balance, but the presence of intracardiac shunts (i.e., left-to-right shunting of pulmonary venous blood across the atrial septum) near the site of sampling and the need for repeated blood sampling limits its universal use It has been reported that when Svo2 monitoring is used in the postoperative care of critically ill neonates, significantly fewer adverse events are encountered Significant decreases in Svo2 can occur without appreciable changes in Sao2, blood pressure, or HR When low Svo2 is recognized, increased inodilator support and measures that decrease metabolic demands (i.e., sedation, neuromuscular blockade) often successfully return this metric toward the normal range In contrast, ventilator and inspired gas adjustments have less effect 250 S E C T I O N I V Pediatric Critical Care: Cardiovascular on correcting Svo2 The critical O2 extraction ratio is defined by the onset of shock and ranges from 50% to 60%.22,35 NIRS is a noninvasive technique used to monitor tissue oxygenation and perfusion NIRS was initially used in the operating room to monitor brain oxygenation during cardiopulmonary bypass but has expanded as a useful and frequent monitoring technique in the intensive care unit (ICU) Cerebral NIRS noninvasively assesses cerebral tissue oxygenation and relies on the relative lucency of biological tissue to near-infrared light where oxy- and deoxyhemoglobin have distinct absorption spectra.34,36–38 The oximeter monitors the nonpulsatile signal reflecting the microcirculation where 75% to 85% of the blood volume is venous Thus, the NIRS-derived oxygen saturation is an indicator of oxygen extraction for the region of brain beneath the optode There is a good correlation between cerebral oxygen saturations, jugular bulb, and superior vena cava saturations.39,40 Cerebral oxygen saturations are closely and inversely correlated with the oxygen extraction ratio in neonates following the Norwood procedure Strategies measuring NIRS in both cerebral and somatic regions provide better estimates of outcome.24,38,41 The pulse contour CO (Pulse index Continuous Cardiac Output [PiCCO]) measurement system allows continuous hemodynamic monitoring using a large (femoral or axillary) artery catheter and a central venous catheter This technology uses intermittent transpulmonary thermodilution and pulse contour analysis With the use of specific algorithms, various parameters such as CO, extravascular lung water (EVLW), global end-diastolic volume (GEDV), pulse pressure variation (PPV), and stroke volume variation (SVV) can be obtained PiCCO can assist in preload assessment in a volumetric manner The PiCCO system may give inaccurate measurements in patients with arrhythmias, rapid temperature changes, intra/extracardiac shunts, aortic aneurysm, aortic stenosis, pneumonectomy, pulmonary embolism, and extracorporeal circulation.35,42,43 The USCOM ultrasonic CO monitor (USCOM Pty Ltd.) is a noninvasive device that determines intermittent CO by continuous-wave Doppler ultrasound and estimates of the normal aortic valve annulus based on the weight or height of the patient Systemic vascular resistance can then be calculated when an invasive or noninvasive blood pressure is obtained simultaneously Although approved by the US Food and Drug Administration (FDA) for use in children, pediatric data are still limited.44–47 Specific Treatments to Improve Cardiac Function HF is a clinical and pathophysiologic syndrome that results from ventricular dysfunction and volume or pressure overload, either alone or in combination In contrast to adult patients, tremendous heterogeneity exists between the etiology and pathophysiology of HF in pediatric patients There are significant barriers in applying adult HF data to children owing to factors related to developmental cardiac physiology Despite these differences, treatment strategies for pediatric patients have often followed the recommendations from large, randomized multicenter trials in adult patients or “consensus” opinions based on single “best” institution clinical practices due to a lack of randomized, multicenter pediatric clinical trials With the expanded authority and mandates of the FDA Pediatric Advisory Committee and the origins of the National Institutes of Health Collaborative Pediatric Critical Care Research Network and the new Pediatric Cardiac Critical Care Consortium (PC4), the future is brighter for high-quality clinical trials in children.48,49 Management of chronic congestive HF with digitalis formed the basis of early therapy (1970s) despite its narrow therapeutic index for safety Volume overload is common, and loop and/or thiazide diuretics the addition of the potassium-sparing antimineralocorticoid, spironolactone are still also commonly used today, although drug compounding for children and potassium monitoring is problematic Patients with advanced pulmonary hypertension, right ventricular (RV) failure, or restrictive left ventricle (LV) physiology present a unique challenge, as CO may worsen in face of the rapid reduction in LVSV that can occur with aggressive diuresis.50 Although angiotensin-converting enzyme (ACE) inhibitors exert favorable effects on cardiac remodeling and survival in adults with congestive HF, their role in children is less clear as randomized placebo-controlled trials in children evaluating the effect of ACE inhibitors in single-ventricle patients have failed to demonstrate a beneficial effect.51–54 Selective b-blockers, such as metoprolol, are a mainstay in adult cardiac patients, with some utility in children.55,56 The nonselective b-blocker/a1-blocker, carvedilol, has been used commonly in pediatric HF treatment in recent years Most pediatric uses of these drugs have been extrapolated from the positive effects seen in adult trials that demonstrated a reduction in mortality and risk of hospitalization Single-center trials have demonstrated both improved ejection fraction with the use of carvedilol in children awaiting heart transplantation with dilated cardiomyopathy and a delayed time to transplantation or death.54,57 However, the most recent and largest multicenter, randomized, double-blind placebocontrolled trial of carvedilol in children and adolescents with symptomatic systolic HF did not demonstrate an improved survival benefit.58 A recent Cochrane systematic review of randomized controlled trials investigating the effect of b-blockers in pediatric HF concluded that there are not enough data to recommend or discourage the use of these drugs in pediatric HF.52,55 A current review from the PC4 database found that 6% of pediatric patients admitted to a cardiac intensive care unit (CICU) were diagnosed and treated for ADHF and that these patients had multiple comorbidities, high mortality rates, and frequent readmissions, particularly those with congenital heart disease (CHD) In this multicenter data collection, the median age at admission was 0.93 years and 57% of the cohort had CHD A total of 88% received vasoactive infusions while 59% required mechanical ventilation Common complications were arrhythmias (19%), cardiac arrest (10%), sepsis (7%), and acute renal failure requiring dialysis (3%) The median length of stay was 7.9 days and the readmission rate was 22% Overall, CICU mortality was 15% but 19% in those with CHD, compared with 11% in those without CHD Independent risk factors associated with CICU mortality included age less than 30 days, CHD, vasoactive infusions, ventricular tachycardia, mechanical ventilation, sepsis, pulmonary hypertension, extracorporeal membrane oxygenation (ECMO), and cardiac arrest.59 For hospitalized children with ADHF and/or LCOS, traditional first-line management is to use continuous infusions of catecholamines or their analogs (i.e., dopamine, epinephrine, norepinephrine, or dobutamine) to increase cardiac contractility (b1) However, when used in high doses these agents can be deleterious to global and myocardial Vo2, induce myocardial cell apoptosis, and lead to increased mortality In these patients, it is important to integrate diuretic, inotropic, and vasodilating therapy in conjunction with careful monitoring of hemodynamic parameters and end-organ perfusion Milrinone, a phospodiesterase-3 inhibitor, has emerged as an important inodilating agent, which is now widely used in children following open-heart surgery after a landmark study showed that the prophylactic use of milrinone was associated with a decreased likelihood of LCOS in children following open-heart surgery in a dose-dependent fashion.60 This benefit is thought to result from CHAPTER 28 Cardiac Failure and Ventricular Assist Devices both improved myocardial contractility and pulmonary and systemic vasodilatory effects Milrinone reduces RV and LV afterload through systemic and pulmonary vasodilation and improves diastolic relaxation (lusitropy) of the myocardium through its enhanced cyclic adenosine monophosphate–dependent diastolic reuptake of calcium.61–64 Sildenafil, an oral or intravenous drug that inhibits cyclic guanosine monophosphate–specific phosphodiesterase type causing smooth muscle relaxation, has proven to be beneficial in neonates with severe pulmonary hypertension and as an adjunct in weaning these patients from inhaled nitric oxide.65–67 Levosimendan, a newer drug, is a calcium sensitizer that enhances the contractility of the ventricle by binding to cardiac troponin C In addition, the drug acts as a vasodilator by opening ATPsensitive potassium channels in the vascular smooth muscle, resulting in decreases in systemic and pulmonary vascular resistance The improvement in myocardial performance is accomplished without an increase in intracellular calcium, thus providing a cardioprotective effect Finally, an active metabolite with a half-life of 3 days prolongs the duration of action for this continuously infused medication.68,69 A recent prospective observational study in 110 patients with a median age of 346.5 days (4 days–19.6 years) undergoing cardiac surgery reported the safety of levosimendan in all age groups and categories of congenital heart disease, demonstrating optimization of CO with a low incidence of arrhythmias Levosimendan was started at the initiation of the rewarming phase of bypass and continued for 48 hours.70 Despite these encouraging studies, a Cochrane review in 2017 concluded that the “current level of evidence is insufficient to judge whether prophylactic levosimendan prevents LCOS and mortality in pediatric patients undergoing surgery for congenital heart disease.” The authors concluded that “no 251 significant differences have been detected between levosimendan and standard inotrope treatments in this setting.”71 Fenoldopam, a selective dopamine-1 receptor partial agonist, causes systemic vasodilation and increased renal blood flow with improved renal function in adults Many studies have examined fenoldopam as a possible therapeutic agent capable of preventing the onset of postoperative acute kidney injury (AKI) Two most recent meta-analyses concluded that although fenoldopam decreases the incidence of postoperative AKI, it does not reduce the need for renal replacement therapy or mortality.72,73 Data on the use of fenoldopam in pediatric patients are sparse, with one retrospective study demonstrating a significant improvement in diuresis in neonates after CPB with the addition of fenoldopam to conventional diuretic therapy, whereas another prospective trial failed to demonstrate a beneficial effect Ricci et al demonstrated in a small randomized controlled trial that high-dose fenoldopam decreased urine neutrophil-gelatinase-associated lipocalin (NGAL) and cystatin C, suggesting a renoprotective effect.74 At this time, there is no strong evidence for the routine use of fenoldopam to prevent AKI after pediatric cardiac surgery.50 Broad Treatment Strategies Supportive care for ADHF begins with strategies aimed at improving the specific components of Do2 and Vo2 listed previously (Fig 28.1) This includes standard critical care therapies primarily focused on noncardiac support, such as intubation and mechanical support for respiratory insufficiency, temperature control, red cell transfusion for significant anemia, and control of pain and agitation with multimodal analgesia and anxiolysis Mechanical respiratory support decreases metabolic demands (Vo2) by Clinical symptoms Poor perfusion, hepatic congestion, nausea, vomiting, or respiratory distress Monitoring Decreased urine output, dysrhythmia, hypotension, elevated RAP, elevated PAP, low or elevated LAP, elevated lactate level, SVO2 acidosis, echocardiography/cardiac catheterization Treatment Decrease metabolic needs Optimize sedation and analgesia Control temperature Optimize ventilation Rate control Sinus rhythm Control temperature Optimize preload Consider transfusion of packed red blood cells Augment stroke volume Increase contractility epinephrine, dopamine, or dobutamine Decrease afterload systemic: milrinone or pulmonary: inhaled NO • Fig 28.1 Management of heart failure in children LAP, Left atrial pressure; NO; nitric oxide; PAP, pulmonary artery pressure; RAP, right atrial pressure; Svo2, mixed venous oxygen saturation ... causes, with the largest disease burden being due to congenital heart malformations and cardiomyopathies.1–3 HF in children leads to characteristic signs and symptoms—such as poor growth, feeding... disease They can present with failed palliation of congenital heart disease, acquired cardiomyopathies, or acute exacerbations of chronic HF Initial therapies to treat ADHF target 248 • • Advances... successful outcome providing respiratory support; decreasing metabolic demands (i.e., work of breathing); optimizing preload, afterload, and contractility; and optimizing HR and rhythm Despite advances