(BQ) Part 2 book Pediatric critical care medicine (Volume 2: Respiratory, cardiovascular and central nervous systems) includes: The cardiovascular system in critical illness and injury, the central nervous system in critical illness and injury.
Part II The Cardiovascular System in Critical Illness and Injury Applied Cardiovascular Physiology in the PICU 17 Katja M Gist, Neil Spenceley, Bennett J Sheridan, Graeme MacLaren, and Derek S Wheeler Abstract Normal cellular function is critically dependent upon oxygen, as evidenced by the relative complexity of the organ systems that have evolved to transport oxygen from the surrounding environment to the cells – namely, the cardiac, respiratory, peripheral vascular, and hematopoietic systems Cells not have the means to store oxygen, and are therefore dependent upon a continuous supply that closely matches the changing metabolic needs that are necessary for normal metabolism and cellular function If oxygen supply is not aligned with these metabolic requirements, hypoxia will ensue, eventually resulting in c ellular injury and/or death In addition to the body’s compensatory mechanisms to a ugment oxygen delivery to the tissues, most of the management of critical illness is directed at restoring the normal balance between oxygen delivery and oxygen consumption A thorough understanding of cardiovascular physiology, particularly as it applies to the management of the critically ill child in the Pediatric Intensive Care Unit (PICU) is therefore of utmost importance Keywords Hemodynamics • Oxygen delivery • Venous return • Cardiac output • Neuroendocrine stress response • Shock • Mean circulatory filling pressure • Excitation-contraction coupling • Fetal circulation K.M Gist, DO, MA, MSCS Department of Pediatrics, Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, MLC 2005, Cincinnati, OH 45229, USA N Spenceley, MB ChB, MRCPCH Department of Pediatric Critical Care, Yorkhill Children’s Hospital, Dalnair Street, Glasgow G3 8SJ, Scotland, UK e-mail: nspenceley@gmail.com B.J Sheridan, MBBS, FRACP, FCICM (*) Division of Paediatric Intensive Care, Department of Paediatrics, The Royal Children’s Hospital, Melbourne, VIC 3052, Australia e-mail: bennett.sheridan@rch.org.au G MacLaren, MBBS, DipEcho, FCICM, FCCM Division of Paediatric Cardiology and Paediatric Intensive Care, Department of Paediatrics, National University Health System, Singapore, Singapore Paediatric ICU, Royal Children’s Hospital, Melbourne, Flemington Rd, Parkville, 3052, VIC Australia e-mail: gmaclaren@iinet.net.au D.S Wheeler et al (eds.), Pediatric Critical Care Medicine, DOI 10.1007/978-1-4471-6356-5_17, © Springer-Verlag London 2014 Introduction Normal cellular function is critically dependent upon oxygen, as evidenced by the relative complexity of the organ systems that have evolved to transport oxygen from the surrounding environment to the cells – namely, the cardiac, respiratory, peripheral vascular, and hematopoietic systems Cells not have the means to store oxygen and are therefore dependent upon a continuous supply that closely matches the changing metabolic needs that are necessary for normal metabolism and D.S Wheeler, MD, MMM Division of Critical Care Medicine, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA e-mail: derek.wheeler@cchmc.org 303 304 K.M Gist et al cellular function If oxygen supply is not aligned with these metabolic requirements, hypoxia will ensue, eventually resulting in cellular injury and/or death As early as 1872, Pflueger suggested that variables such as arterial oxygen content (CaO2), arterial blood pressure, cardiac output, and respiratory rate are all incidental and subordinate to the needs of the cell Several years later, Guyton followed that The main goal of the circulation is to serve the needs of body tissues, ensuring optimal function and survival Physiology has changed little, if any, since the recognition of its important role centuries ago However, over the years, by investigating the theoretical, animal, and human aspects of physiology, our understanding of this discipline has improved considerably Advances in hemodynamic monitoring have further allowed physicians to apply this knowledge to the management of critical illness, to detect and manipulate the disturbed physiology in critically ill patients, and, most importantly, improve outcome By substituting circulation with physician, Guyton’s statement now describes the specific role of the bedside provider in the Pediatric Intensive Care Unit (PICU) Avoiding hypoxia (through either inadequate oxygen delivery (DO2) or excessive VO2) is one of the most fundamental tenets of critical care medicine Assessing whether DO2 is sufficient at the bedside relies on more than just clinical acumen Advanced hemodynamic monitoring is mandatory, but with our understanding of oxygen delivery becoming more complex there is a tendency to match this complexity from a technological standpoint Detecting an obvious or evolving picture of abnormal physiology, and subsequently assessing the efficacy of intervention is fundamentally linked to our interpretation of DO2 and VO2 Neither of these variables can be routinely measured at the bedside, therefore resulting in the bedside providers reliance on indirect indicators of DO2, VO2, and oxygen extraction When the basic physiological processes of DO2 are interrupted or overwhelmed by disease, an imbalance between supply and demand occurs In the critically ill child, this is the principle derangement, but inadequate utilization or a combination of these derangements is also recognized Either way the end point is the same – hypoxia, organ dysfunction, morbidity, and eventually death Cellular hypoxia will eventually have obvious consequences, and clinical evidence of a disturbance in this fragile physiological balance will reveal itself with time Evolving hypoxia is subtler, yet early detection is desirable Therefore, the successful understanding and application of physiology aims to detect faltering oxygen delivery early, provide oxygen to the cells commensurate with their demand, and facilitate its use prior to established hypoxia DO2 is defined as the amount of oxygen transported to the tissues per minute: (1.36 × Hb × SaO ) DO = CO × CaO = CO × + ( 0.003 × PaO ) (17.1) where CO is the cardiac output (L/min), CaO2 is the arterial oxygen content (mL O2/dL blood), Hb is the hemoglobin concentration (g/dL), 1.36 is the amount of oxygen (mL) that g of hemoglobin can carry (this constant varies from 1.34 to 1.39, depending upon how it is measured), and PaO2 is the partial pressure of O2 in the blood (mmHg) Importantly, oxygen delivery is not homogeneous throughout the body and its distribution is determined by central upstream (macro circulation) and peripheral downstream (microcirculation) factors Although the process of oxygen utilization and cellular function occurs at the microcirculatory level, the most important component is providing an adequate gradient across the capillary beds to ensure a constant supply Adequate DO2 is facilitated by combining the arterial oxygen content (CaO2) (a reflection of pulmonary function, hemoglobin concentration and its percentage saturation) with cardiac output (CO) Cardiac output is the most important element in DO2, by quickly being able to compensate for a reduction in CaO2 for whatever cause The reverse is not necessarily true The fundamental principles of cardiopulmonary resuscitation (CPR) support this contention, as chest compressions alone can deliver sufficient oxygen, even though effective ventilation with no chest compressions cannot, at least in adults [1, 2] In this chapter, we will review the basic principles of cardiovascular physiology, specifically how these principles apply to the manipulation of both cardiac output and arterial oxygen content in the clinical setting Developmental Cardiac Anatomy While a detailed discussion of cardiac development is beyond the scope of this chapter, we have provided a brief summary of the salient points The critical period of cardiac development begins just prior to the third week in the growing embryo During the third week, there is formation of the primary heart tube, and by 22 days the heart begins to beat Cardiac looping begins by the fourth week, as does development of the vasculature (Fig. 17.1) The early right and left ventricles begin to form between the fourth and fifth weeks, along with the atrioventricular cushions and the pulmonary veins During the fifth week, the right and left ventricles are formed, and growth of the pulmonary veins into the left atrium occurs Formation of the aortic arches also begins at this time Truncal septation and formation of the semilunar valves begins just prior to the 6th week of cardiac development, and by the 7th week, ventricular septation is complete The patent foramen ovale (PFO) and patent ductus arteriosus (PDA) remain until birth (discussed below) By weeks, there is complete development of the heart [3–5] Neural crest and other cells contribute to cardiac formation, and abnormalities within these cells and signal transduction may lead to alterations in cardiac morphogenesis leading to the large variety of congenital cardiac defects [6] Several excellent and detailed reviews on cardiac development, and the current knowledge of abnormal cardiac development have been published, and we refer the reader to these articles for additional details [3–9] 305 17 Applied Cardiovascular Physiology in the PICU a b c Aortic roots Pericardium Bulbis cordis Pericardial cavity Ventricle Left atrium Bulboventricular sulcus Atrium Sinus venous Sinus venous Fig 17.1 Primitive heart tube is shown with the five embryologic structures that will form all future cardiac anatomy From caudal to cranial, these structures are the (1) sinus venosus; (2) atrium; (3) ventricle; (4) bulbus cordis divided into a proximal (a) conus cordis and distal (b) truncus arteriosus; and (5) aortic sac The progression from panels (a–c) illustrate the normal looping in which the heart tube rotates to the right to form the normal heart structures Chambers of the Heart contraction The oblique orientation of the fibers in the LV free wall and septum allow for the ringing or twisting that is required to eject blood [10] The ventricular septum is an important component of the RV, and plays an important role in ventriculoventricular interactions (discussed below) Fiber orientation of the RV free wall and the septum play a significant role in determining ejection The RV free wall contains predominantly transverse fibers, while the septum contains oblique fibers While the LV fiber orientation allows for the twisting motion, the transverse fibers in the RV free wall generate a compressive force, allowing the ventricle to eject blood into the low resistance pulmonary vascular bed under normal conditions [10] When the PVR is raised, the oblique fibers play a significant role in determining ventricular function [10–12] The end result of normal cardiac development results in the formation of a heart that is composed of four chambers, two atria and two ventricles The heart acts as a large pump connected to a network of blood vessels that carry blood with all of its metabolic substrates either toward or away from the peripheral tissues The two ventricles function in series, with the right ventricle (RV) pumping blood to the pulmonary circulation, and the left ventricle (LV) pumping blood to the systemic circulation The atrioventricular (AV) valves separate the atria from the ventricles, with the tricuspid valve separating the right atrium (RA) and RV The left atrium (LA) and LV are separated by the mitral valve The pulmonary and aortic valve are also known as semilunar valves and separate the RV and LV from the pulmonary artery and aorta, respectively The atrial septum separates the atria, and in utero, there is a flap permitting right-to-left shunting across the PFO The ventricular septum separates the right and left ventricles Persistent defects in both the atrial and ventricular septum can occur, leading to persistent shunting beyond fetal life, which may bear consequences to the underlying hemodynamics and cardiac physiology The LV cavity is conical shaped during diastole (ventricular relaxation), and assumes a more spherical shape as the intraventricular pressure increases at the end of isovolumetric Pericardium The heart is surrounded by the pericardium that is composed of two layers, the visceral pericardium and the parietal pericardium The visceral pericardium is in direct contact with the myocardium The parietal pericardium is composed of several layers of elastic and collagen fibers and is separated from the visceral pericardium by a small amount of fluid creating a potential space (which normally contains a small amount of pericardial fluid) The pericardium encloses the 306 K.M Gist et al great arteries superiorly at the junction between the ascending aorta and the transverse aortic arch, the pulmonary artery just beyond its bifurcation, and the superior vena cava below the azygous vein The inferior pericardial attachment includes a segment of the inferior vena cava and the posterior attachment includes the proximal pulmonary veins The function of the pericardium is to prevent excessive motion of the heart within the chest The pericardium also limits to some extent how much the heart itself can distend as it fills with blood (called “pericardial constraint”) [13–19] These concepts are discussed further in the chapters on cardiorespiratory interactions and diseases of the pericardium arteries become smaller, the quantity of elastic tissue decreases, with the arterioles having the least Contraction of the smooth muscle decreases compliance, making it stiffer with an overall smaller luminal diameter Capillaries are small, thin-walled vessels that lack all the components of the normal vasculature, except the endothelial cell layer Their structure makes them ideal for transporting and receiving substances from the tissues that they supply Veins differ from arteries in that they have thinner walls and larger luminal diameters Veins also contain unidirectional valves that prevent blood from moving backward away from the heart Coronary Circulation rom Fetus to Newborn: The Transitional F Circulation The heart receives its blood supply from coronary arteries that originate from the left and right aortic sinuses The left common coronary artery divides into the left anterior descending and the circumflex coronary artery The right coronary supplies blood to a large portion of the right ventricle, and approximately 25–35 % to the left ventricle From the origin of the right coronary artery at the aortic sinus, it travels in the atrioventricular groove toward the crux of the heart About 75–85 % of the population have a right dominant coronary system [20], where the posterior descending coronary artery branches from the right coronary artery – in this case, the inferior portion of the interventricular septum receives its blood supply from the right coronary artery via the right posterior descending coronary artery, or PDA branch (not to be confused with a PDA, patent ductus arteriosus) [20, 21] The coronary artery supplying the sinoatrial (SA) node branches off the right coronary artery in 60 % of the population and from the circumflex artery in 40 % of the population (this has no relation to whether the coronary artery is right dominant or not) Peripheral Vasculature The systemic vasculature is composed of concentric layers, which includes the intima, media and adventitia (from inside to outside) There are some portions of the vasculature that may be missing a layer The intima contains the vascular endothelium that is responsible for the critical vascular metabolic processes It also acts as a barrier to the movement of substances of varying permeability into the interstitial space The larger arteries contain an internal elastic lamina that separates the intima from the media, and is composed of smooth muscle The vasa vasorum are the intervening interface that contain nerves and perforating vessels that nourish the arteries themselves The external elastic lamina separates the media from the adventitia, and contains vasa vasorum, nerves and connective tissue As The fetal circulation differs significantly from the adult circulation The placenta has an extremely large surface area resulting in a low vascular resistance It receives deoxygenated blood from the fetal systemic organs, and returns oxygen rich blood to the fetal systemic arterial circulation In addition, certain adaptations have occurred such that the most oxygenated blood is delivered to the myocardium and brain through preferential streaming and the presence of intracardiac and extracardiac shunts Oxygenated and nutrient rich blood is transported from the placenta via an umbilical vein to the fetus The deoxygenated blood is returned to the placenta via two umbilical arteries The saturation of fetal blood is 80–90 % Approximately 50 % of this blood enters the ductus venosus and enters the inferior vena cava (IVC) The remainder enters the liver through the hepatic veins In the IVC, the more oxygenated blood is thought to stream separately from the extremely desaturated systemic venous blood that is returning from the lower portions of the body The saturation of this desaturated blood ranges from 25 to 40 % (Fig 17.2) A small tissue flap at the junction of the right atrium and IVC, known as the Eustachian valve, directs oxygenated blood across the PFO and into the LA The blood then enters the LV and is ejected into the ascending aorta The majority of the LV blood is delivered to the brain and coronary circulation Desaturated blood (25–40 % saturated) returning to the heart via the superior vena cava (SVC) and the coronary sinus (20–30 % saturated), as well as that from the hepatic vessels is directed across the tricuspid valve and into the RV (Fig 17.2) It is then ejected into the pulmonary artery Because the lungs are collapsed and fluid filled, only about 8–12 % of the RV output enters the pulmonary circulation, with the remaining portion crossing the ductus arteriosus (DA) into the descending aorta The lower half of the body is therefore supplied with relatively desaturated blood As a result of intracardiac and extracardiac shunting in the fetus, the stroke volume of the LV is not equal to that of the RV The RV receives about 65 % of the 307 17 Applied Cardiovascular Physiology in the PICU 60 Pulmonary arterial mean pressure mmHg CCA 50 40 30 20 10 DA AO 160 AO PA 65 60 Pulmonary blood flow ml/kg/min 120 80 40 55 SVC 1.8 45 1.6 LA 1.4 FO PV FO 45 RA RHV LV DV MHV LHV P 85 35 Fig 17.2 Fetal circulation, including oxygen saturation values (in numbers) Red blood is directed through the ductus venosus (DV) across the inferior vena cave (IVC) through the patent foramen ovale (FO), left atrium (LA) and left ventricle (LV) and up the ascending aorta to join the deoxygenated blood (blue) in the descending aorta Additional deoxygenated blood (blue) form the superior vena cava (SVC) and IVC flows through the right atrium, and is directed into the right ventricle (RV) via streaming and the Eustachian valve, then to the pulmonary artery (PA) and ductus arteriosus (DA) The aortic isthmus is represented by the arrow RHV right hepatic vein, LHV left hepatic vein, CCA Common carotid artery, AO Aorta, UV umbilical vein, MHV middle hepatic vein, PV pulmonary vein (Reprinted from Kiserud and Acharya [103] With permission from John Wiley & Sons, Inc.) Oxygen disassociation curves 100 A B 75 C 50 HbA: P50 = 27 torr 25 10 20 30 40 Birth –5 –3 –1 Weeks Fig 17.4 Changes in pulmonary artery pressure, pulmonary blood flow and pulmonary vascular resistance during the terminal portion of pregnancy, birth and the first several weeks after birth IVC –7 UV HbF: P50 = 21 torr 1.2 Pulmonary 1.0 vascular resistance mmHg/ml/min/kg 50 60 Fig 17.3 Oxygen dissociation curve of fetal hemoglobin (HbF) (curve A) compared with adult haemoglobin (HbA) (curve B) as well as the rightward shift of the HbA curve (curve C) associated with several physiology processes, including 2,3-diphosphoglycerate venous return and the LV about 35 % Therefore, cardiac output in the fetus is described as combined ventricular output, where about 45 % is directed to the placental circulation and % entering the pulmonary circulation Oxygen content is determined by the quantity of hemoglobin and its oxygen saturation The fetal hemoglobin at term is high (approximately 16 g/dL), of which the largest proportion, is comprised of fetal hemoglobin (HbF) HbF has a lower concentration of 2,3-diphosphoglycerate, and thus shifts the oxy-hemoglobin saturation curve leftward resulting in a higher affinity for oxygen (Fig 17.3) The partial pressure of oxygen at which fetal hemoglobin is approximately 50 % saturated (i.e., the P50) is 19 mmHg, compared to 27 mmHg in the adult Despite the low partial pressure of oxygen (PO2), the combined ventricular output, high hemoglobin concentration, and the presence of HbF help to maintain oxygen delivery in the fetus The changes in the central circulation after birth are primarily a result of external events, rather than changes in the circulation itself There is a rapid and large decrease in pulmonary vascular resistance (PVR) with disruption of the umbilical-placental circulation With this decrease in PVR, there is an increase in pulmonary blood flow and a concomitant decrease in pulmonary artery pressure (Fig. 17.4) Gas exchange is transferred from the placenta to the lungs, the fetal circulatory shunts close, and the LV output increases Several factors are involved in the cessation of placental circulation at birth The umbilical vessels are reactive and con- 308 strict in response to longitudinal stretch and an increased PO2 in the blood External clamping of the cord augments this process [22] With the removal of the placenta, there is a dramatic fall in the flow through the ductus venosus and a significant fall in the venous return through the IVC The ductus venosus closes passively between and 10 days after birth During late gestation, there is a gradual decline in pulmonary PVR At birth, expansion of the lungs results in an abrupt and dramatic fall in PVR accompanied by an eight to tenfold increase in pulmonary blood flow Studies in fetal lambs have demonstrated that mechanical expansion of the lungs with deoxygenated gas results in a massive fall in PVR [22] The process is thought to be mediated by pulmonary stretch receptors resulting in reflex vasodilation and increased flow through the pulmonary vessels [22] The increase in PO2 also decreases the hypoxic pulmonary vasoconstriction, thereby further decreasing PVR Because the pulmonary blood flow increases, and there is a decrease in IVC flow, there is an increase in pulmonary venous return to the left atrium, with a subsequent increase in left atrial pressure above the right atrial pressure As a result, the flap of the foramen ovale is pushed against the atrial septum and the atrial shunt is effectively closed Flap closure of the atrial septum can occur within minutes to hours after birth Anatomical closure typically occurs weeks to years later with proliferation of tissue over the flap Patency of the foramen ovale can persist for many years, but it is not usually hemodynamically significant Atrial level shunts of any significance occur only in the setting of a deficiency of the primum septum, resulting in a secundum atrial septal defect, or when there is failure of fusion of the endocardial cushions leading to a primum atrial septal defect At the same time that PVR falls, the shunt at the ductus arteriosus (DA) becomes bidirectional and then all left to right Closure of the DA occurs in phases, the first being functional closure of the lumen by smooth muscle constriction, and the second being anatomic closure which occurs several days later by neo-intimal thickening and loss of the smooth muscle cells from the inner muscle media [23] Smooth muscle constriction resulting in functional closure of the DA is secondary to an increase in arterial PO2, a decrease in blood pressure within the DA lumen (due to the decrease in PVR) and a decrease in circulating prostaglandin E2 (PGE2) After delivery, there is loss of PGE2 production and an increase in removal from the lung with a concomitant decrease in PGE2 receptors in the ductal tissue [24] ardiac Contraction and Relaxation: C From Cell to Function Cardiac Myocyte The cardiac myocytes are elongated specialized striated cells, with the sarcomere being the basic contractile unit of K.M Gist et al the muscle The sarcomere contains all the myofibril contractile elements Cardiac myocytes differ from regular striated muscle in that they have the ability to spontaneously depolarize – therefore, neural innervation is not required for the heart to contract The heart also contains specialized cardiac conduction (pacemaker) cells with relatively few contractile elements These specialized cells are localized to the sinoatrial (SA) node, the atrioventricular (AV) node, and the purkinje cells [25] Cardiac myocytes increase in number and size with maturation of the heart This maturation occurs mainly in fetal life and shortly after birth [26] In the mature myocyte, contractile elements are organized into myofibrils that are arranged in rows parallel to the long axis of the cell, alternating with mitochondria This is in contrast to the immature myocyte, where the arrangements of the contractile elements are more haphazard, and where there are overall less myofibrils [27–29] Myocardial Bioenergetics The mitochondria are the powerhouses of the cell, and their size and relative volume increase during development [30] The process of energy conversion and utilization in the cell is complex Energy, in the form of adenosine triphosphate (ATP) is derived from several sources These energy sources differ in the fetus, neonate, and adult [31–33] The fetus utilizes carbohydrates in the form of lactate (60 %), glucose (35 %), and pyruvate (5 %), whereas the adult heart consumes free fatty acids (90 %), with little energy derived from carbohydrate and amino acids At birth, a glucagon surge occurs that switches the utilization of energy substrates from carbohydrates to fatty acids [34] Nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2) are produced in the Krebs cycle and pass through the electron transport chain system, transferring electrons to oxygen Oxidative phosphorylation takes place in the cristae of the mitochondria after a hydrogen ion gradient is established, thus producing ATP, which is then transported out of the mitochondria (Fig. 17.5) Defects within the mitochondria and its membrane are known to contribute to heart failure [35] The adult heart consumes 8–15 mL O2/min/100 g tissue at rest, which can increase to 70 ml O2/min/100 g tissue with exercise [33] These needs can only be met by aerobic metabolism Myocardial oxygen consumption is directly proportional to wall tension generated by the ventricle, defined by the pressure volume area [36] and heart rate Because myocardial wall stress is one of the determinants of oxygen consumption, it is important to have an understanding of Laplace’s law [37, 38] Laplace’s law states that wall tension is directly proportional to the pressure generated within the ventricle and the radius of the ventricle, and inversely proportional to the thickness of the ventricular wall 309 17 Applied Cardiovascular Physiology in the PICU Fig 17.5 Energy substrates for the generation of adenosine triphosphate in the cardiomyocyte come predominantly from Promotes glycolysis (fetus) and B oxidation of free fatty acids (adult) These energy sources create acetyl CoA, which then generates nicotinamide Glucagon adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2) necessary for oxidative phosphorylation in the mitochondria The glucagon surge shifts the cardiomyocytes into utilizing free fatty acids rather Blocks than glucose CoA coenzyme-A, NAD nicotinamide adenine dinucleotide, FAD flavin adenine dinucleotide, FFA free fatty acids Metabolism in cytosol FFA Metabolism within mitochondria R-COOH = Acetyl CoA Carmitine Glucose 2-NAD 2-NADH2 Glycolysis 2-ADP 2-ATP Pyruvate 2-NAD 2-NADH2 β-Oxidation R-CH2-C-S-CoA FAD FADH2 Pyruvate + CoA-SH + NAD• NADH2 + Co2 + acety-CoA NAD NADH2 Acetyl-CoA Ketones Lactate NAD NADH2 Kreps cycle FAD FADH2 NAD NADH2 NAD NADH2 oxidative phosphorylation Wall stress Wall thickness Pressure Radius Fig 17.6 Ventricle demonstrating the Law of Laplace Wall stress increases the tension in the myocardium and reduces myocardial blood flow, counteracting myocardial shortening Wall stress is directly proportional to the pressure generated within the ventricle and the radius of the ventricle, and indirectly proportional to wall thickness (Fig. 17.6) [39, 40] The ventricular pressure and wall stress change as blood is ejected from the ventricle from shortening to force generation Certain conditions may lead to increased wall stress, and as a result, there is increased oxygen consumption These conditions include certain disease states that result in a dilated ventricle (ventricular septal defect, dilated cardiomyopathy) or increased pressure within the ventricle (aortic stenosis) [40–44] Cardiac hypertrophy is adaptive in some conditions to decrease wall tension, and those with hypertrophic cardiomyopathy have less wall stress [45, 46] Excitation Contraction Coupling (ECC) The sarcolemma (plasma membrane) contains the ion channels, ion pumps and exchangers that contribute to maintenance of the chemical gradient between the intracellular and extracellular spaces The flux of ions across this membrane controls membrane depolarization and repolarization Defects in specific ion channels cause arrhythmias that may result in sudden death – the discussion of these specific ion channel defects is beyond the scope of this chapter (see the accompanying Chap 27 for additional information) Of the ions involved in contraction and relaxation of the heart, calcium is crucial for the process of excitation contraction coupling (ECC) [47] ECC is the process from electrical excitation of the myocyte to contraction of the heart Calcium is the activator of myofilaments that causes contraction of the heart, and is discussed below There are two major parts of ECC – namely, excitation and contraction The immature myocardium is more dependent on the L-type calcium channels for normal ECC, whereas more mature myocardium depends upon calcium-induced calcium release (CICR) Excitation begins with generation of the normal action potential (Fig. 17.7) [47] Cardiac myocytes have a resting membrane potential (phase 4) that is near the equilibrium potential of potassium (−90 mV) During the equilibrium phase, potassium channels are open, and fast sodium and slow (L-type) calcium channels are closed This results in the net movement of potassium ions out of the cell (down the concentration gradient) Spontaneous depolarization occurs when the L-type calcium channels open to allow entry of calcium ions into the cell Once a critical threshold voltage is reached (−70 mV), voltage gated fast sodium channels open, resulting in a rapid influx of sodium ions and subsequent rapid 310 K.M Gist et al Transmembrane potential (mV) Phase Phase Phase Phase –50 Phase ARP –100 RRP Absolute refractory period (ARP) Relative refractory period (RRP) Fig 17.7 Phases of the cardiomyocyte action potential Diastolic depolarization occurs during phase until threshold is met, initiating phase depolarization (systole) Phase follows as an overshoot of the voltage within, followed by phase or the plateau phase when voltage remains slightly less than Phase begins the return to resting maximal negative potential (−90 mV) During specific time periods within phase are the absolute refractory period (ARP) and the relative refractory period (RRP) Finally, onset of phase begins, when there is maximally negative potential within the cardiomyocyte (Reprinted from Gjesdal et al [39] With permission from Nature Publishing Group) depolarization (phase 0) At the same time, potassium channels close, and the outward net movement of potassium ions decreases The net effect is that the membrane potential of the cardiac myocyte approaches the equilibrium potential for sodium, which is approximately 10 mV Phase of the action potential begins with inactivation of the fast sodium channels, and opening of a different type of potassium (KTO) channel, resulting in transient hyperpolarization and an outward potassium current The plateau phase of the cardiac action potential (phase 2) is sustained by a balance between the influx of calcium through L-type calcium channels (also known as dihydropyridine receptors, due to their sensitivity to the dihydropyridine class of calcium channel blockers), and outward movement of potassium through slow delayed rectifier potassium channels This inward movement of calcium ions begins when the membrane potential is approximately −40 mV, and prolongs the action potential This phase is absent in pacemaker cells, and distinguishes the action potential in the cardiac cell from that in skeletal and neuronal cells It is during this phase that actin-myosin cross bridge formation occurs (discussed below) Phase 3, also known as rapid repolarization occurs as the L-type calcium and the slow delayed rectifier potassium channels close Myocytes have a refractory period There is an absolute refractory period, in which no amount of stimulation will evoke an action potential This lasts from phase to near completion of phase The relative refractory period, lasting from phase to phase can result in depolarization and an action potential, if there is a stronger than usual stimulus The sodium-calcium exchanger functions to extrude calcium from the myocyte after each contraction in order maintain appropriate intracellular calcium content The driving force for the maintenance of calcium is the sodium gradient between the intracellular and extracellular spaces and is maintained by ATP dependent sodium pumps Calcium also enters the cell by way of the sodium-calcium exchanger The inotropic effects of some cardiac glycosides are mediated by the sodium-calcium exchanger (e.g., digoxin) Inhibition of the sodium pump by cardiac glycosides will increase cytosolic sodium concentration This sodium is extruded from the cell by the exchanger and therefore increases intracellular calcium concentrations, which is an important determinant of contractility The ATP dependent calcium pump in the sarcolemma also removes calcium from the myocytes Both calmodulin (calcium binding protein) and the binding of calcium stimulate the pump by increasing calcium sensitivity and thus velocity of contraction The sarcoplasmic reticulum (SR) is a tubular membrane that surrounds the myofibrils and regulates cytosolic calcium concentration through uptake, storage, and release Neonatal cardiomyocytes are much more dependent on extracellular calcium influx for contraction because of the immaturity of the SR [48–53] In the mature heart, the SR regulates the intracellular calcium concentration and is the most important source of activator calcium for binding to troponin C The content of the SR is decreased and less organized in the immature heart, and thus age related changes in the SR structure and function is likely to affect myocardial function These developmental differences further explain the extreme sensitivity of neonates to calcium channel antagonists [49] Indeed, some authors have suggested that calcium chloride is an effective inotrope in neonates after cardiopulmonary bypass [54] The uptake of calcium occurs in the longitudinal portion of the SR, which is connected to the junctional portion (responsible for storage and release) by anastomosing strands This connection area within the SR is rich in ATP calcium pumps, which are encoded by the SR calcium ATPase (SERCA) 2a gene [55–57] The calcium release channels (also known as the ryanodine receptor due to its ability to bind the plant alkaloid ryanodine) and sarcolemmal L-type calcium channels are grouped in functional clusters, also known as calcium release units with several binding proteins including calsequestrin, tricodin, and junction [58] Calsequestrin is a low affinity calcium binding protein that stores large amounts of releasable calcium within the SR Mutations in calsequestrin are linked to catecholaminergic polymorphic ventricular tachycardia [59] Active transport of calcium into the SR by calcium pumps results in muscle relaxation An intrinsic SR protein known as phospholamban 311 17 Applied Cardiovascular Physiology in the PICU Sarcomere-basic unit of contraction Myosin a A M I Thin filaments Myosin Z heavy chains (rod & head) c light chains ( head) Rod b Troponin tropomyosin d MHC f Actin Head MLC e Thin filaments actin double stranded a Tropomyosin troponin (T,I,C) I band Z disc A band H zone I band Z disc M line Sarcolemma Triad Mitochondria Myofibrils Tubules of sarcoplasmic reticulum Terminal cisterna of the sarcoplasmic reticulum T tubule Fig 17.8 Anatomy of the sarcomere, the basic unit of contraction (see text for full explanation) MHC myosin heavy chain, MLC myosin light chain mediates regulation of the SR calcium pump activity [60] Phospholamban is an important regulator of baseline calcium cycling and of contractility It is a critical determinant of the cardiac response to sympathetic stimulation [60] The sarcomere, the basic unit of the muscle, is composed of the myofibril contractile elements (Fig 17.8) It is bound on both ends by z-discs, and composed of proteins that are organized into strands (filaments) The I band is composed of thin filaments (actin), as well as the troponin complex and tropomyosin The Z disk bisects the I band Thick filaments are polymers composed of myosin (and titin) The A band contains overlapping thick and thin filaments The M band in the center of the A band consists of thick filaments crosslinked to titin by myosin binding protein C (Fig 17.9) [50] It is the mutations in the contractile proteins that can lead to clinical phenotypes of hypertrophic cardiomyopathy [61] Myosin is the most abundant contractile protein Its head contains ATPase activity that contributes to fiber shortening during contraction Tropomyosin is composed of two helical chains that binds to troponin T at multiple sites along the major groove of the actin filament and modulates the interaction between actin and myosin The troponin complex is composed of three separate proteins Troponin T binds the complex to tropomyosin Troponin I inhibits interactions between actin and myosin, and troponin C binds calcium Together with tropomyosin, troponin complexes allow for changes in calcium sensitivity for the process of cross-bridge formation Calcium induced changes in the actin binding affinity of Troponin I provide a molecular switch that identifies an increase in intracellular calcium and acts as a signal to induce contraction The final process of ECC resulting in cross bridge formation and subsequent muscle contraction is a complex interplay of proteins, beginning with initiation of the action potential in the sarcolemma for depolarization, followed by calciuminduced-calcium release from the SR (during phase of the AP) Contraction is then initiated by binding to the amino acid terminal end of troponin C Troponin C then undergoes a conformation change that increases its affinity for troponin I Troponin I then moves from being tightly bound to actin in diastole to being tightly bound to troponin C The inhibitory portion of troponin I moves away from actin Tropomyosin shifts within the groove between the actin strands, which alters the actin-myosin interaction, and eventually allows for formation of tightly bound cross-bridges Binding of ATP causes a conformational change in the actin-myosin interaction, resulting in displacement of actin toward the center of the sarcomere and subsequent contractile element shortening The amount of force developed by the contracting myocyte is dependent upon the number of cross-bridges formed This Index Astrocytomas, 556, 558–559 Atelectasis, 149 Atelectrauma, 241 Athetosis, 713 Atrial septal defects (ASD) CHD lesions, 418 chest radiograph, 345 clinical features, 345–346 clinical symptoms and natural history, 346 coronary sinus, 348 echocardiogram, 346 electrocardiogram, 345 embryology, 344 pathophysiology, 344–345 postoperative management, 346 secundum, 344 sinus venosus defects, 347 surgical management, 346 transcatheter device closure, 346–347 types, 343–344 Atrial switch, 423 Atrioventricular canal defects (AVCD), 418–419 Ausculatory method, 523–524 Autoimmune myasthenia gravis (AIMG), 700–701 Automatic tube compensation (ATC), 141 B Bacterial pericarditis, 511 Bacterial tracheitis, 28–29 Bag mask ventilation anesthesia bag, 167, 170 E-C clamp technique, 167–168 self-inflating bags, 167, 170 triple airway maneuver, 167, 169 Ballismus, 713 Barbiturate intracranial hypertension and, 583 refractory status epilepticus, 683 Barotrauma, 149, 238 Berlin Heart EXCOR® ADHF, 506 blood pumps, 443 North American recipients, 443–444 silicon cannulae, 443 Beta-adrenergic agonists albuterol, 57 epinephrine, 56–57 helium-oxygen, 60 ipratropium bromide, 58 isoproterenol, 58 ketamine, 60–61 magnesium, 58–59 terbutaline, 57–58 theophylline, 59–60 Bidirectional cavopulmonary anastomosis (BCPA) completion, 406, 407 Fontan procedure, 408 hypoxemia, 407 Biomarkers ADHF, 503 dilated cardiomyopathy, 484 stroke, 547 troponin, 477 Botulism, 291, 699–700 BPD See Bronchopulmonary dysplasia (BPD) Bradyarrhythmia, 460–462 723 Bradycardia, 455–457 Brain abscess epidemiology, 662–663 imaging in, 664 incidence, 662–663 medical management, 664–665 outcome and complications, 665 pathophysiology, 663–664 predisposing factors, 662–663 signs and symptoms, 663 stereotactic aspiration, 665 surgical management, 665 Brain biopsy, 611 Brain death, 629 Brain injury acetylcholine receptors, 536 cell death apoptotic pathway, 541 caspase-dependent apoptosis, 540–541 extrinsic pathway, 541–542 mitochondrial permeability transition pore, 542 necrosis, 539–540 PARP suicide hypothesis, 542 cholinergic anti-inflammatory pathway, 536 GABA/glycine, 537 glutamate, 537–538 NMDA receptors, 537–538 serotonin, 537 excitotoxicity, 538 extracellular matrix proteases, 546–548 intracranial hypertension, 574, 576 neurologic dysfunction after, 544–545 neurotransmitters, 535–536 oxidative stress, 542 and apoptosis, 545–546 and neuroinflammation, 544–545 reactive nitrogen species, 543–544 reactive oxygen species, 543 Brain tumors craniopharyngiomas, 562–563 ependymomas, 561–562 gliomas, 557–560 incidence, 556 medulloblastomas, 560–561 peri-operative care, 563–564 signs and symptoms, 557 Bronchiolitis, 184 epidemiology, 78 extrapulmonary manifestations/effects, 80 immune response, RSV infection, 77–78 mortality clinical diagnosis, 78–79 clinical phenotype, 79 laboratory confirmation, 79 preventive therapies and treatments new anti-RSV agents, 83–84 RSV immunotherapy, 83 vaccination, 83 respiratory syncytial virus, 75–76 severity of disease and risk factors, 79–80 therapeutic options, PICU antibiotics, 81–82 bronchodilators, 80–81 chest physiotherapy, nebulised hypertonic saline, 81 corticosteroids, 81 epinephrine, 81 exogenous surfactant, 82 724 Bronchiolitis (cont.) heliox, 82 inhaled nitric oxide, 82 methylxanthines, 81 oxygen, 80 recombinant human DNAse, 82 respiratory support, 82–83 ribavirin, 81 Bronchodilators, 80–81 Bronchopulmonary dysplasia (BPD) neonatal lung diseases clinical findings, 258 low birth weight, 259 ventilator-induced lung injury alveolar arrest, 242 atelectasis, 241, 242 classical BPD vs new BPD, 241–242 CPAP, 241 definition, 241 targeted therapy, 245–246 VEGF, 242–243 C Calcium-channel antagonists, 530 Calsequestrin, 310 Carbon dioxide regulation, 576 Carbon monoxide, 167 Cardiac arrhythmias bradycardia, 455–457 with normal heart rate, 459–460 tachycardia (see Tachycardia) Cardiac myocyte, 308 Cardiac tamponade clinical presentation, 514–515 diagnosis cMRI, pericardium, 516, 517, 520 diastole, 515, 517 ECG (see Electrocardiogram (ECG)) Echocardiogram (see Echocardiogram) electrical alternans, 516, 517 mitral valve inflow doppler, 517, 520 pulsus paradoxus, 514, 515 management, 517–519 pathophysiology, 513–514 Cardiomyopathies dilated (see Dilated cardiomyopathy (DCM)) hypertrophic (see Hypertrophic cardiomyopathy) restrictive, 490–491 Cardiopulmonary interactions cardiac disease, respiration effects cardiopulmonary resuscitation, 330 cavopulmonary anastomosis, 329–330 diastolic heart failure, 329 left ventricular systolic heart failure, 328–329 cardiovascular function, respiration effects left ventricular afterload, 327–328 left ventricular preload, 327 right ventricular afterload, 326–327 right ventricular preload, 324–326 heart failure effects, 330 respiratory disease effects, 330–331 volume-pressure vs pressure-flow, 323–324 Cardiopulmonary resuscitation (CPR), 330 Cardiovascular physiology cardiac output, stroke volume afterload, 315 contractility, 315 Index mean circulatory filling pressure, 316–317 preload, 313–315 right atrial pressure, 317 venous resistance, 317 venous return, 315–316 contraction and relaxation cardiac myocytes, 308 ECC (see Excitation contraction coupling (ECC)) myocardial bioenergetics, 308–309 developmental cardiac anatomy chambers of the heart, 304–305 coronary circulation, 306 pericardium, 305–306 peripheral vasculature, 306 primitive heart tube, 304–305 hemodynamic monitoring, 304 neuroendocrine stress response afferent limb, 318 efferent limb, 318–319 oxygen delivery, 304 transitional circulation, from fetus to newborn, 306–308 Caspase-dependent apoptosis, 540–541 Cavopulmonary anastomosis, 329–330, 409–411 CBF See Cerebral blood flow (CBF) CDH See Congenital diaphragmatic hernia (CDH) Cell death, acute brain injury apoptotic pathway, 541 caspase-dependent apoptosis, 540–541 extrinsic pathway, 541–542 mitochondrial permeability transition pore, 542 necrosis, 539–540 PARP suicide hypothesis, 542 Cellular edema, 576 Central nervous system (CNS) craniopharyngiomas, 562–563 ECMO, 227 ependymomas, 561–562 gliomas, 557–560 incidence, 556 infection brain abscess, 662–665 cerebral malaria, 660–662 definitions, 644 encephalitis, 656–660 meningitis (see Meningitis) shunt infection, 666–668 subdural empyema, 665–666 injury matrix metalloproteinases in, 546–547 metabotropic glutamate receptors, 538–539 malignant spinal cord compression, 564–565 medulloblastomas, 560–561 peri-operative care, 563–564 physiology, 628 signs and symptoms, 557 vasculitis, 591 angiography-negative, small vessel cPACNS, 604–606 angiography-positive nonprogressive cPACNS, 602–603 angiography-positive progressive cPACNS, 604 human immunodeficiency virus, 606 infection-associated, 606 primary angiitis of the central nervous system, 602 rheumatic and systemic inflammatory diseases, 606–607 systemic diseases/exposures, 607 varicella zoster virus, 606 Centrifugal pumps, ECMO, 223 Cerebral angiography, 596–597 Index Cerebral blood flow (CBF) cerebral malaria, 661 hypertension, 525–526 Cerebral edema (CE), 576–577 Cerebral malaria clinical features, 660–661 diagnosis, 660–661 management, 662 pathophysiology, 661–662 Cerebral perfusion pressure (CPP), 582–583 Cerebral sinovenous thrombosis (CSVT), 595, 596 Cerebrospinal fluid (CSF) drainage, 581 dynamics, 571–572 in meningitis, 647 CHD See Congenital heart disease (CHD) Chest radiograph (CXR) Amplatzer Septal Occluder device, 347 ARDS, 104 atrial septal defect, 345 cyanotic neonates, 359 Ebstein’s anomaly, 371 hyperinflation, 34 patent ductus arteriosus, 352 pericardium, 517, 518 venovenous ECMO, 219 Chest retractions, 251 Chest wall compliance of lung and, 5–6 EMG study, 702 neuromuscular diseases changes, 288 dysfunction, 287 respiratory muscles vs lungs, 286 and respiratory muscles, 251 Cholinergic anti-inflammatory pathway, 536 GABA/glycine, 537 glutamate, 537–538 NMDA receptors, 537–538 serotonin, 537 Chorea, 713–714 Chronic intrauterine hypoxia, 257 Clevidipine, 530 Clonidine, 530 Clostridium botulinum, 291, 699–700 CNS See Central nervous system (CNS) Coarctation of the aorta (CoA) CHD lesions, 422–423 clinical presentation, 390 management, 390–391 postoperative care, 391 Collectins, 198–199 Coma, 629 depth, duration and cause of, 662 hypoglycemic, 632 Community-acquired pneumonia (CAP), 89 Compensatory anti-inflammatory response syndrome (CARS), 110 Complete tracheal rings, 47 Computed tomography (CT) ARDS, 104–105 brain abscess, 664 inflammatory brain diseases, 601 stroke, 596 Confusion, 629 Congenital airway anomalies complete tracheal rings, 47 laryngomalacia, 43–44 PICU setting 725 difficult intubation, 42 prevention of complications, 41–42 single-stage airway reconstruction, 42–43 tracheotomy, 42 posterior laryngeal clefts, 45–46 retrognathia/glossoptosis, 43 subglottic stenosis, 44–45 vascular compression, 46–47 vocal cord paralysis, 44 Congenital diaphragmatic hernia (CDH), 183, 260–261 Congenital heart disease (CHD) ADHF, 498 Anderson’s sequential segmental approach, 336 chromosomal anomalies/syndromes, 430, 433–434 classification and nomenclature, 338–340 coarctation of the aorta clinical presentation, 390 management, 390–391 postoperative care, 391 functional classification, 337 interrupted aortic arch, 391–392 left sided obstructive aortic stenosis, 421–422 coarctation of the aorta, 422–423 subaortic stenosis, 422 left-to-right shunts atrial septal defects, 418 atrioventricular canal defects, 418–419 ventricular septal defects, 418 miscellaneous ALCAPA, 425 double aortic arch, 426 pulmonary artery sling, 425–426 subclavian artery, 426 vascular rings and sling, 425 mixing arterial switch, 423–424 double aortic arch, 426 D-Transposition, great arteries, 423 L-TGA, 424 total anomalous pulmonary venous return, 425 truncus arteriosus, 424–425 neurodevelopmental outcomes AAP statement, 429–432 biologic risk factors, 428 prevalence, 428, 429 nomenclature and database, 336–337 right sided obstructive, 419–421 single ventricle physiology arrhythmias, 428 hypoxemia, 427 liver dysfunction, 428 PLE, 427 surgical palliation, 426 thromboembolism, 427–428 ventricular dysfunction, 427 subvalvar aortic stenosis clinical presentation, 393–394 management, 394 postoperative care, 394 supravalvar aortic stenosis (see Supravalvar aortic stenosis (SAS)) valvar aortic stenosis aortic annular hypoplasia, 387 clinical presentation, 388 endocardial fibroelastosis, 388 management, 388–389 postoperative care, 389–390 Van Praagh’s segmental approach, 336 726 Congenital myasthenic syndromes (CMS), 696, 703 Consciousness, altered levels definitions, 628–629 etiologic diagnosis, 629, 631 further studies, 631 Glasgow Coma Scale, 629, 630 management, 631 severity diagnosis, 629 syndromic diagnosis, 629, 631 topographic diagnosis, 629 Contractility, 314–315 Control mode mechanical ventilation (CMV), 137–138 Coronary circulation, 306 Coronary sinus ASD, 343, 348 Corticosteroids adjunctive, 650–651 ARDS, 115 bronchiolitis, 81 inflammatory brain diseases, 611 inhaled, 56 systemic, 55 CPR See Cardiopulmonary resuscitation (CPR) Cranial vault, 574 Craniopharyngiomas, 562–563 Critical illness polyneuropathy and myopathy (CIPNM), 294, 704 Croup See Viral laryngotracheobronchitis Cyanotic lesions decreased pulmonary blood flow, CHD pulmonary vasculature, 385 single ventricle physiology, 385 TAPVC (see Total anomalous pulmonary venous connections (TAPVC)) TGA (see Transposition of the great arteries (TGA)) truncus arteriosus (see Truncus arteriosus) increased pulmonary blood flow chest radiograph, 359 Ebstein’s anomaly (see Ebstein’s anomaly) hyperoxia test, 359, 360 newborns, 360 PGE1, 360, 361 pulmonary atresia, 368–370 pulmonary valve stenosis, 366–368 TOF (see Tetralogy of Fallot (TOF)) Cytokines ARDS anti-inflammatory, 109–110 blocking, 119 endothelial cell-leukocyte adhesion cascade, 108–109 molecular regulation, gene expression, 110 neutralization, 117 pathophysiologic mechanism, 106–107 production, 117 TNF-a and IL-1ß, 107–108 cerebral malaria, 661 inflammatory effects of, 645 Cytotoxic edema See Cellular edema D DCM See Dilated cardiomyopathy (DCM) DeBakey VAD, 505 Decompressive craniectomy (DC), 583–584 Delirium, 629 Demyelinating diseases, 607–608 Diabetic ketoacidosis (DKA), 632–633 Index Diastolic heart failure, 329 Diffuse alveolar disease and airleak, HFOV hypercarbia, 181 indications, 177–179 leak pressure, 181–182 low frequency HFOV, 180 open lung ventilation strategy, 180–181 Dilated cardiomyopathy (DCM) ADHF, 498–499 anesthesia, 487–488 biomarkers, 484 cardiac resynchronization, 487 causes, 486 clinical signs and symptoms, 483–484 definition and incidence, 483 etiology, 485 familial and genetic causes of, 485–486 heart failure classification, 484 heart transplantation, 487 histology, 484–485 implantable cardiac defibrillator, 487 infectious causes of, 486 management, 486 mechanical circulatory support, 487 outcomes, 488 peripartum, 486 pharmacologic therapy, 486–487 surgical intervention, 487 toxicity, 486 Direct trauma, 34–35 Double aortic arch (DAA), 426 Duchenne muscular dystrophy (DMD), 292 Dynamic hyperinflation, 51 Dystonia acute dystonic reactions secondary to drugs, 712 adductor laryngeal breathing dystonia, 712 classification, 713 Intrathecal Baclofen therapy, 713 primary vs secondary, 711 spasmodic dysphonia, 712 status dystonicus, 713 Dystrophia myotonica (DM) See Myotonic dystrophy E Ebstein’s anomaly anatomy, 370 clinical presentation, 370–371 outcome, 372–373 pathophysiology, 370–371 postoperative care, 372–373 preoperative evaluation, 371 surgical/transcatheter intervention, 371–372 of tricuspid valve, 421 Echocardiogram aortopulmonary window, 354 atrial septal defect, 346 patent ductus arteriosus, 352 pericardium apical 4-chamber, 517, 519 arasternal short axis, 517, 519 pulse-oximetry waveforms, 515, 516 ventricular septal defects, 349 ECMO See Extracorporeal membrane oxygenation (ECMO) ECPR See Extracorporeal cardiopulmonary resuscitation (ECPR) Elective cesarean section, 256 Index Electrocardiogram (ECG) arrhythmias atrial tachycardia, 454, 455 QRS complex, 454, 455 recording, 452, 453 ventricular tachycardia, 454 ventriculo-atrial block, 454 atrial septal defect, 345 hypertrophic cardiomyopathy, 488–489 pericardium electrical alternans, 516, 517 pulse-oximetry waveforms, 515, 516 ST segment elevation, 518 tachycardia, 458, 459 Electromyography (EMG), 696–697, 705–707 Empyema and effusion, 95–98 Encephalitis anti-NMDAR, 608 arthropod-borne viruses, 659–660 clinical presentation, 656–657 diagnosis, 656–657 enteroviral, 659 HSV, 658–659 Mycoplasma pneumonia, 657 pathophysiology, 656 rabies, 659 Rasmussen encephalitis, 609–610 therapy, 657 viral, 640, 664 Encephalopathy immune-mediated, 640–641 post-transplant, 640 toxic-metabolic (see Toxic-metabolic encephalopathy) Endocardial fibroelastosis (EFE), 388 Endomyocardial biopsy, 477 Endothelial injury, 661 Endothelin, 271–272, 525 Enteroviral encephalitis, 659 Ependymomas, 561–562 Epiglottitis See Supraglottis Epinephrine, 56–57, 81 Esmolol, 530 Euvolemic hyponatremia, 634 Excitation contraction coupling (ECC) cardiomyocyte action potential phases, 309–310 cross bridge formation, 311–312 sarcomere anatomy, 311 sarcoplasmic reticulum, 310 sodium-calcium exchanger functions, 310 Excitotoxicity, 538, 661 Exogenous surfactant, 82, 196, 203–204 Expiratory grunting, 251 Extracellular matrix proteases, 546–548 Extracorporeal cardiopulmonary resuscitation (ECPR), 230 Extracorporeal membrane oxygenation (ECMO) cardiomyopathies, 487 circuit components and equipment centrifugal pumps, 223 roller-head pumps, 221–223 venous reservoir, 221 venous saturation monitor, 221, 222 complications bleeding, 227–228 central nervous system, 227 infection, 228 mechanical complications, 227 727 future directions, 231–232 hemodynamics, venoarterial, 224–225 history of, 215–216 inter-hospital transport, 231 oxygenators, 223–224 patient management anticoagulation, 225–226 nutrition and fluid, 226 sedation and analgesia, 226–227 ventilator management, 226 patient selection, 216–217 patients outcomes adults, 230–231 ECPR, 230 long-term outcome, 231 non-traditional, respiratory failure, 229–230 rates of, 229 respiratory failure and ECPR, 229 septic shock, 229 pediatric ICU, 167 univentricular/single ventricle heart, 406 venoarterial support arterial cannulation, 217–218 femoral artery cannulation, 218 venoarterial vs venovenous, 220 venovenous support advantage, 220–221 blood recirculation, 219–220 cannulation, 218 chest radiograph, 219 weaning, 227 F Fabry disease, 592–593 Febrile infection-related epilepsy syndrome (FIRES), 610, 689 Fenoldopam, 530 Fetal circulation oxygen dissociation curve, 307 oxygen saturation values, 306, 307 pulmonary artery pressure changes, 307 PVR, 307–308 Fever-induced refractory epileptic encephalopathy, 689 Focal cerebral arteriopathy, 590 Foreign body aspiration, 33–34 Fosphenytoin, 678 Fungal meningitis, 656 G Glasgow Coma Scale (GCS) score abusive head trauma, 621, 622 altered levels of consciousness, 629, 630 Gliomas, 557–560 Glucose metabolism diabetic ketoacidosis, 632–633 hyperglycemic hyperosmolar state, 631 hypoglycemic coma, 632 Glutamate cholinergic anti-inflammatory pathway, 537–538 metabotropic receptor, 538–539 Glycine, 537 Gosling index, 580 Granulomatous inflammatory brain diseases, 610 Group B streptococcus (GBS), 256, 645 Guillain-Barré Syndrome (GBS), 290–291, 698–699 728 H Hashimoto encephalopathy, 609 HCM See Hypertrophic cardiomyopathy (HCM) Heart failure acute decompensated heart failure Berlin Heart EXCOR® VAD, 506 clinical presentation, 500 DeBakey VAD, 505 heart diseases, 498–499 hemodynamic monitoring, 500–503 inotropes, 503–505 milrinone, 503 pathophysiology, 499–500 American Heart Association staging, 484 classification, 484 systolic, 328–329 HeartWare ventricular assist system, 444 Helium-oxygen, 60, 82 Hemodynamics cardiovascular physiology, PICU, 304 differential diagnosis, 408 kidney, 524 morphology, 266 pulmonary hypertension, 266–267 venoarterial ECMO, 224–225 Hemorrhagic stroke (HS), 590, 594–595 Herpes simplex encephalitis, 658–659 HFOV See High frequency oscillatory ventilation (HFOV) HFPV See High frequency percussive ventilation (HFPV) High-frequency chest wall oscillation (HFCWO), 294 High frequency oscillatory ventilation (HFOV) adolescent and adult, 185–186 ARDSNet, 176 child diffuse alveolar disease, 184–185 lower airways disease, 185 diffuse alveolar disease and airleak hypercarbia, 181 indications, 177–179 leak pressure, 181–182 low frequency HFOV, 180 open lung ventilation strategy, 180–181 gas transport and gas exchange control alveolar recruitment, 177 aplitude attenuation, 177, 179 lung’s opening pressure, 177, 178 Pendelluft, 176 pressure-volume relationships, 177–178 Taylor dispersion, 176 lung volume non-invasive assessment, 186–188 modalities of, 176 neonate and infant air leak syndromes, 184 bronchiolitis, 184 congenital diaphragmatic hernia, 183 neonatal respiratory distress syndrome, 182–183 persistent pulmonary hypertension, 184 open lung ventilation techniques, 176 revisiting high frequency percussive ventilation, 188–190 tidal volume reduction, 176 weaning, 188 High frequency percussive ventilation (HFPV), 188–190 High frequency ventilation (HFV), 112, 176 High-mobility group box (HMGB1) protein, 245 Homocystinuria, 593 Human leukocyte antigen (HLA) sensitization, 448 Huntington disease (HD), 717 Index Hydrocephalus, 577–578 Hyperammonemia allograft-specific neurologic complications, 670 causes, 635 acute liver failure, 636–638 immune-mediated encephalopathies, 640–641 inborn errors of metabolism, 639–640 inherited metabolic disorders, 639–640 post-transplant encephalopathy, 640 Reye’s syndrome, 638–639 signs and symptoms, 635–636 Hypercyanotic spells, 419 Hyperkinetic movement disorders in ICU athetosis, 713 ballismus, 713 chorea, 713–714 dystonia (see Dystonia) myoclonus, 714–716 tremor, 716 Hypernatremia, 635 Hypertension blood pressure measurement, 523–524 clinical presentation cardiac and vascular injury, 528 neurologic manifestations, 526–528 ophthalmologic manifestations, 528 definitions, 523 etiologies, 526, 527 evaluation, 528 management, 528–529 pathophysiology arginine vasopressin, 525 CBF, 525–526 endothelin, 525 kidney, 524 nitric oxide, 525 renin, 524–525 therapeutic agents ACE, 530–531 adrenoreceptor antagonists, 530 calcium-channel antagonists, 530 vasodilators, 529–530 Hypertrophic cardiomyopathy (HCM) causes, 490 clinical signs and symptoms, 488 echocardiography/MRI, 488–489 electrocardiography/Holter, 489 exercise testing, 489 familial and genetic causes, 489–490 histology, 489 management, 490 Hyperventilation, 582 Hypervolemic hyponatremia, 634–635 Hypoglycemic coma, 632 Hypokalemia, 54 Hyponatremia, 633–635 Hypoplastic left heart syndrome, 401 Hypothermia intracranial hypertension management, 584 meningitis, 651 therapeutic, 87 Hypovolemic hyponatremia, 634 I Immunocompromised pneumonia, 89–90 Inborn errors of metabolism, 639–640 Index Infectious endocarditis (IE) antimicrobial therapy, 470 clinical findings, 468 complications, 470 diagnosis, 468 echocardiography, 470 epidemiology, 468 laboratory findings, 469–470 pathogenesis, 468 prophylaxis, 470–471 risk factors, 468–469 surgical management, 470 Infectious mononucleosis, 30 Inflammatory brain diseases, 601 brain biopsy, 611 demyelinating diseases, 607–608 diagnosis, 602 febrile infection-related epilepsy syndrome, 610 granulomatous, 610 immunosuppression, 604, 606 intravenous immunoglobulin, 612 laboratory testing, 611 management, 611 disease modifying drugs, 612 novel biologic therapies, 612 MRI, 601 neuroimaging, 611 neuronal antibodies, 608–609 non-vasculitic, 607–610 posterior reversible encephalopathy syndrome, 610–611 primary CNS vasculitis angiography-negative, small vessel cPACNS, 604–606 angiography-positive nonprogressive cPACNS, 602–603 angiography-positive progressive cPACNS, 604 primary angiitis of the central nervous system, 602 rituximab, 612 secondary CNS vasculitis infection-associated, 606 rheumatic and systemic inflammatory diseases, 606–607 systemic diseases/exposures, 607 T-cell mediated, 609–610 Inhalational injury, 34 Inhaled anesthetic gases, 172 Inhaled nitric oxide (iNO) ARDS, 115–116 bronchiolitis, 82 mechanical ventilation, 147 pulmonary blood flow, 257 Inherited metabolic disorders (IMD), 639–640 Inlet septum, 348 Inlet ventricular septal defects, 348 Intensive care unit (ICU) movement disorders akinetic-rigid, 716–718 bradykinetic disorders, 716 drug induced, 712 hyperkinetic (see Hyperkinetic movement disorders in ICU) malignant hyperthermia, 718 neurodegeneration with brain iron accumulation, 717 parkinsonism-hyperpyrexia syndrome, 718 rabies, 718 serotonin syndrome, 718 strychnine toxicity, 718 tetanus, 718 peripheral nervous system admission, 697 729 critical illness neuropathy and myopathy, 704 electromyography in, 696–697, 705–707 mononeuropathies, 704–705 Interrupted aortic arch (IAA), 391–392 Intracranial hypertension, 569 under abnormal circumstances, 574–576 abusive head trauma, 622 acute bacterial meningitis, 646–648 and blood pressure, 575–576 carbon dioxide regulation, 576 causes, 576–577 cerebral malaria, 661 clinical manifestations, 578 external ventricular drain placement, 581 factors associated with, 571 hepatic encephalopathy and, 637 hydrocephalus, 577–578 invasive measurement, 579 management barbiturate therapy, 583 basic measurement, 581 cerebral perfusion pressure, 582–583 CSF drainage, 581 CT features, 580 decompressive craniectomy, 583–584 hyperventilation, 582 hypothermia, 584 osmotherapy, 582 removal of mass lesions, 581–582 sedation and analgesia, 581 setting targets, 580 measurement, 578–580 metabolic regulation, 576 monitoring indications for, 578–579 in traumatic brain injury, 570 Monro–Kellie doctrine, 570 neurocritical care, 578, 581 non-invasive measurement, 580 normal, 575 outcome of multiple factors, 570 cerebrospinal fluid dynamics, 571–572 circulatory system, 572–573 cranial vault, 574 waveforms, 574–575 Intraparenchymal hematoma, 577 Intrathecal Baclofen therapy, 713 Invasive mechanical ventilation adaptive pressure control ventilation, 136–137 airway pressure release, 140–141 assist/control ventilation, 137–138 automatic tube compensation, 141 control mode, 137–138 inverse ratio, 141 neurally adjusted ventilatory assist, 141–142 pressure control, 135–136 pressure support, 138–140 proportional assist, 141 synchronized intermittent mandatory, 137–139 ventilator modes, 137 volume control, 136 volume support, 140 Inverse ratio ventilation (IRV), 112, 141 Ipratropium bromide, 58 Ischemic stroke, 590, 591 Isoflurane, 62–63, 684–685 Isoproterenol, 58 730 J Japanese encephalitis, 660 Jarvik 2000® device, 445 Junctional ectopic tachycardia (JET), 364 Juvenile Parkinsonism, 717 K Kawasaki disease, 607 diagnosis clinical, 473–474 laboratory manifestations, 474 echocardiography, 474 epidemiology, 471 etiology, 473 incomplete, 474 long-term management, 475–476 management, 474–475 pathogenesis, 473 thrombosis, 475 Ketamine, 60–61, 686–687 Ketogenic diet, 687–688 Kommerell diverticulum, 426 L Labetolol, 530 Laryngeal neoplasms and mediastinal masses, 31–32 Laryngomalacia, 43–44 Left ventricular noncompaction (LVNC) clinical features, 491–492 diagnosis, 491–492 epidemiology, 491–492 etiology, 492–493 management, 493 Left ventricular outflow tract (LVOT) obstruction See Congenital heart disease (CHD) Leigh’s syndrome, 640 Lethargy, 629, 638 Leukotriene modifying agents (LMAs), 61 Levetiracetam, 679–680 Life-threatening diseases, upper respiratory tract acute airway obstruction, 20 causes, 21 clinical manifestations, 22–25 extrathoracic airway, 21, 23 intrathoracic airway, 21, 24 normal inspiration, 21–22 Venturi effect and Bernoulli’s principle, 21, 25 airway trauma direct trauma, 34–35 foreign body aspiration, 33–34 inhalational injury, 34 post-extubation stridor, 32–33 developmental anatomy, 19–20 infectious disorders bacterial tracheitis, 28–29 infectious mononucleosis, 30 peritonsillar abscess, 30 recurrent respiratory papillomatosis, 30 retropharyngeal abscess, 29–30 supraglottis, 27–28 viral laryngotracheobronchitis, 25–27 non-infectious disorders acquired subglottic stenosis, 31 Index adenotonsillar hypertrophy, 31 angioedema, 30–31 laryngeal neoplasms and mediastinal masses, 31–32 obesity, 30 Lipidomics, 545–546 Liver dysfunction, 428 L-TGA, 424 Lung abscess, 97–98 Lung recruitment, 239, 242 Lung surfactant See Pulmonary surfactant Lung volume alveolar recruitment, 186, 187 cardiovascular effects of change, 153 EIT, 186–187 in-line techniques, 186 plethysmography, 186 three dimensional depiction, 187–188 LVNC See Left ventricular noncompaction (LVNC) M Magnesium, 58–59 Magnetic resonance imaging (MRI) brain abscess, 664 inflammatory brain diseases, 601 stroke, 595, 596 Malignant hyperthermia, 718 Malignant spinal cord compression, 564–565 Matrix metalloproteinases (MMPs) in acute CNS injury, 546–547 stroke biomarkers, 547 tissue plasminogen activator, 547–548 Mean circulatory filling pressure, 316–317 Mechanical ventilation ARDS, 110–112 complications air leak, 148 atelectasis, 149 auto-PEEP, 149–151 cardiovascular effects, 150–151, 153 central nervous system effects, 150 hepatic effects, 154 left ventricular afterload, 153 renal effects, 153–154 respiratory, 147 upper airway injury, 147–148 venous return, 153 ventilation associated respiratory infections, 148–149 ventilator-induced lung injury, 149 ventricular interdependence, 153 weaning, 154 indications, 132 invasive adaptive pressure control, 136–137 airway pressure release, 140–141 assist/control, 137–138 automatic tube compensation, 141 control mode, 137–138 inverse ratio, 141 neurally adjusted ventilatory assist, 141–142 pressure control, 135–136 pressure support, 138–140 proportional assist, 141 synchronized intermittent mandatory, 137–139 ventilator modes, 137 Index volume control, 136 volume support, 140 nitric oxide, 147 non-invasive negative pressure ventilation, 134–135 non-invasive positive pressure ventilation, 133–134 patient-ventilator dyssynchrony, 146 physiology alveolar ventilation, 10 children vs adults, 129–132 mechanics of, 10–13 oxygenation, 9–10 respiratory system equation of motion, 127–129 work of breathing, 4–9, 11–14 prone positioning, 147 recruitment maneuvers, 147 status asthmaticus, 61–62 surfactant administration, 147 ventilator settings FiO2, 144–145 frequency, 145 inspiratory pressures, 143–144 positive end-expiratory pressure, 144–145 tidal volume, 142–143 ventilator triggering, 145–146 Mechanics of breathing airway resistance, lung and chest wall, 5–6 lung volumes, 7–9 Mechanotransduction, 113, 243–244 Meconium aspiration syndrome (MAS), 254–255 Medulloblastomas, 560–561 Membranous/perimembranous defects, 348 Membranous septum, 348 Meningitis, 643 acute bacterial antibiotic therapy, 648–650 anti-inflammatory agents, 650–652 causes, 644 clinical manifestations, 645 definitions, 644 diagnosis, 645–646 etiology, 644–645 intracranial pressure, 646–648 pathophysiology, 645 prevention, 652–654 therapy duration, 652 cerebrospinal fluid in, 647 fungal, 656 tuberculous meningitis, 655–656 viral, 654–655 Meningococcal disease, 511 Metabolic acidosis, 54 Metabotropic receptors glutamate, 538–539 ionotropic receptors vs., 536 Methylxanthines, 81 Midazolam, refractory status epilepticus, 680–682 Milrinone, 503 Minimum alveolar concentration (MAC), 684 Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), 592 Mitochondrial permeability transition (MPT) pore, 542 Mitral valve inflow doppler, 517, 520 Modified Blalock–Taussig shunt (mBTS), 402, 403 MODS See Multiple-organ dysfunction syndrome (MODS) 731 Monoclonal antibody therapies, 612 Motor neuronopathy, 705 Moya moya disease, 591 Multiple-organ dysfunction syndrome (MODS), 244–245, 636 Multiple sclerosis (MS), 607–608 Muscarinic acetylcholine (Ach) receptors, 536 Muscular ventricular septal defects, 348 Myasthenia gravis (MG), 291 Mycobacterium tuberculosis, 511 Mycoplasma pneumonia, encephalitis, 657 Myocardial bioenergetics, 308–309 Myocarditis diagnosis biomarkers, 477 clinical, 476–477 endomyocardial biopsy, 477 imaging and testing, 477 epidemiology, 476 etiology, 476 pathogenesis, 476 treatment, 478 Myoclonus, 714–716 Myopathies, neuromuscular disease DMD, 292 myotonic dystrophy, 292–293 polyneuropathy and, 294 Pompe disease, 293 Myotonic dystrophy, 292–293, 704 N Nasal flaring, 251 Near infrared spectroscopy (NIRS), ADHF, 503 Nebulised hypertonic saline, 81 Neonatal lung diseases apnea of prematurity, 259 bronchopulmonary dysplasia, 258–259 clinical presentation, 251 congenital diaphragmatic hernia, 260–261 elective Cesarean section, 256 fetal lung development, 250 meconium aspiration syndrome, 254–255 persistent pulmonary hypertension, 256–258 pneumonia, 256 pulmonary air leaks, 259–260 respiratory distress syndrome, 252–254 respiratory monitoring, 252 respiratory physiology chest wall and respiratory muscles, 251 collateral airways, 251 lung liquid, 250 pulmonary vessels and pulmonary blood flow, 250–251 transient tachypnea of the newborn, 254 Neonatal stroke, 595 Neonate and infant, HFOV air leak syndromes, 184 bronchiolitis, 184 congenital diaphragmatic hernia, 183 neonatal respiratory distress syndrome, 182–183 persistent pulmonary hypertension, 184 Neurally adjusted ventilatory assist (NAVA), 141–142 Neurodegeneration with brain iron accumulation (NBIA), 717 Neuroendocrine stress response, 318–319 Neuroinflammation, 544–545 Neuroleptic malignant syndrome (NMS), 717–718 732 Neuromuscular diseases botulism, 291 chest wall function, 285–286 chest wall vs lungs, 286 in children, 285 management approach feeding and nutrition, 295 invasive mechanical ventilation, extubation, 296–297 non-invasive ventilation, 295–296 palliative care, 297 secretion clearance, 294–295 tracheostomy, 297 myasthenia gravis, 291 myopathies DMD, 292 myotonic dystrophy, 292–293 polyneuropathy and, 294 Pompe disease, 293 neuropathies Guillain–Barré syndrome, 290–291 spinal cord injury, 290 spinal muscular atrophy, 289–290 respiratory muscle function characterization, 286 diaphragmatic paralysis, 284 downstream effects, 289 MIP and MEP, 287 muscle fatigue, 287 muscle force, 284 Neuromyelitis optica (NMO), 607, 608 Neurotransmitters, 536 New-onset RSE (NORSE), 678 Nicardipine, 530 Nicotinic acetylcholine (nACh) receptors, 536–537 Nitric oxide (NO) administration, 169 clinical applications acute respiratory distress syndrome, 169–170 persistent pulmonary hypertension, 169 pulmonary hypertension, 170–171 hypertension, 525 inhaled nitric oxide, 169–170 key signaling pathways, 168, 171 S-nitrosylation, 169 synthase, 543–544 toxicity and complications, 171–172 N-methyl-D-aspartate (NMDA) receptor, 537–538 NO-cGMP cascade, 270–271 Non-bacteriolytic antibiotics, 651 Non-invasive negative pressure ventilation, 134–135 Non-invasive positive pressure ventilation (NIPPV), 133–134 O Obesity, 30, 526 Obtundation, 629 Open lung approach, 111, 149 Orthotopic liver transplant (OLT), 637 Oscillation for ARDS Treated Early (OSCILLATE), 185–186 Oscillometric method, 524 Osmotherapy, 582 Outlet septal defects, 348 Oxidative lipidomics and apoptosis, 545–546 Oxidative stress in acute brain injury, 542–545 and apoptosis, 545–546 Index Oxygen administration bag mask ventilation, 167 contact devices and techniques, 166–167 non-contact devices and techniques, 165–166 cardiovascular physiology, PICU, 304 historical perspective, 164 physiology of alveolar oxygen and carbon dioxide tensions, 164–165 delivery, 165, 166 Oxygenators, 223–224 P Palliative care, 297 Papilledema, 578, 664 Parasympathetic nervous system, 536–537 Parkinsonism-hyperpyrexia syndrome, 718 PARP suicide hypothesis, 542 Patent ductus arteriosus (PDA) anatomy and physiology, 351 clinical features, 352 embryology, 351 epidemiology, 351 management, 353 natural history, 352 pathophysiology, 351 surgical ligation, 353 Peak expiratory flow rate (PEFR), 52–53 PediaFlow® pediatric VAD, 445 Pediatric and adult, ARDS, 206–207 Pediatric intensive care unit (PICU) cardiovascular physiology (see Cardiovascular physiology) difficult intubation, 42 pneumonia, 88 prevention of complications, 41–42 single-stage airway reconstruction, 42–43 therapeutic gases carbon dioxide, 167 carbon monoxide, 167 helium, 172 inhaled anesthetic gases, 172 nitric oxide (see Nitric oxide (NO)) oxygen, 164–167 therapeutic options, bronchiolitis antibiotics, 81–82 bronchodilators, 80–81 chest physiotherapy, nebulised hypertonic saline, 81 corticosteroids, 81 epinephrine, 81 exogenous surfactant, 82 heliox, 82 inhaled nitric oxide, 82 methylxanthines, 81 oxygen, 80 recombinant human DNAse, 82 respiratory support, 82–83 ribavirin, 81 toxic-metabolic encephalopathy glucose metabolism disorders, 631–633 hyperammonemia (see Hyperammonemia) hypernatremia, 635 hyponatremia, 633–635 sodium homeostasis disorders, 633 tracheotomy, 42 Index Penn State PVAD, 445, 446 Pentobarbital anesthesia, 683–684 cerebral metabolic rate for oxygen, 682 inhaled anesthetic isoflurane, 684 pediatric critical care studies, 683 Pericardiocentesis, 512, 517–519 Pericardium, 305–306 cardiac tamponade (see Cardiac tamponade) illnesses, 509, 510 innervation, 509 pericarditis clinical presentation, 511–512 etiology, 510–511 management, 512–513 Peripheral nervous system (PNS), 695 acquired disorders acute inflammatory demyelinating polyneuropathy, 698–699 anterior horn cell disease, 698 hereditary conditions anterior horn cell disease, 701 spinal muscle atrophy with respiratory distress, 702–703 intensive care unit admission, 697 critical illness neuropathy and myopathy, 704 electromyography in, 696–697, 705–707 mononeuropathies, 704–705 muscle disease myotonic muscular dystrophy, 704 other myopathies, 704 neuromuscular junction abnormalities acute muscle disease, 701 autoimmune myasthenia gravis, 700–701 botulism, 699–700 tick paralysis, 700 Peripheral vasculature, 306 Peritonsillar abscess (PTA), 29, 30 Permissive hypercapnia, 61–62, 113 Persistent pulmonary hypertension (PPHN) neonatal lung diseases, 256–258 newborn, 184 pediatric ICU, therapeutic gases, 169 Persistent vegetative state, 629 Phasitron®, 189 Phenobarbital, 679 Phenoxybenzamine, 530 Phentolamine, 530 PiCCO, 502–503 PICU See Pediatric intensive care unit (PICU) Pilocytic astrocytomas, 558–559 Plethysmography, 186 Pneumonia anti-inflammatory therapy, 92, 95 antimicrobial therapy, 92, 95 complications empyema and effusion, 95–98 lung abscess, 97–98 diagnostic approach imaging, 90–92 invasive pathogen identification, 91–92 non-invasive pathogen identification, 91, 93–94 etiologies aspiration pneumonia, 90 community-acquired pneumonia, 89 immunocompromised pneumonia, 89–90 733 neonatal lung diseases, 256 pathogenesis, 88–89 PICU, 88 prevention, 97 PNS See Peripheral nervous system (PNS) Pompe disease, 293, 489 Positive end-expiratory pressure (PEEP), 62, 144–145, 238–239, 401 Positive pressure ventilation (PPV) application, 505 central nervous system effects, 150 hepatic effects, 154 Posterior laryngeal clefts, 45–46 Posterior reversible encephalopathy syndrome (PRES), 610–611 Post-extubation stridor, 32–33 Post-pericardiotomy syndrome, 511 Post-transplant encephalopathy, 640 Post-ventricular atrial refractory period (PVARP), 461 PPV See Positive pressure ventilation (PPV) Prazocin, 530 Preload cardiovascular physiology, PICU diastolic compliance curve, 313 EDP vs SV, 313, 314 pressure-volume loop, 314–315 left ventricule, 327 right ventricule intrathoracic pressure, 325 mean systemic pressure, 324 positive pressure ventilation, 325 right atrial pressure vs venous return, 324–325 venous return, 324 ventricular filling pressure, 325–326 Pressure control ventilation (PCV), 135–136 Pressure support ventilation, 138–140 Preterm infants apneas, 259 BPD, 258 bronchopulmonary dysplasia, 241–242 palivizumab, 84 SpO2 range, 252 surfactant deficiency, 201 Primary angiitis of the central nervous system (PACNS), 602 Primitive neuroectodermal tumor (PNET), 556 Primum ASD, 343 Programmed cell death, 541 Proportional assist ventilation (PAV), 141 Prostacyclin (PGI2), 257, 410 Prostaglandin E1 (PGE1), 360, 361 Prostanoids, 271 Protein-losing enteropathy (PLE), 427 Pseudoglandular stage, fetal lung development, 250 Pulmonary air leaks, 259–260 Pulmonary artery catheter (PAC), 501–502 Pulmonary artery (PA) sling, 425–426 Pulmonary atresia with intact ventricular septum anatomy, 368 clinical presentation, 368 outcome, 370 pathophysiology, 368 postoperative care, 370 preoperative evaluation, 368–369 surgical/transcatheter intervention, 368–369 tetralogy of fallot with, 420 734 Pulmonary blood flow ADHF, 498 cyanotic lesions (see Cyanotic lesions) distribution of, 17 excessive, 498 pulmonary vessels and, 250–251 Pulmonary edema development of, 105–106 fluid management, 114–115 and lung inflammation, 131 Pulmonary hypertension (PH) clinical classification and etiology, 263–265 definition, 263 diagnosis, 265 management strategies and therapeutic options active pulmonary vasoconstriction, 270 endothelin-1, 271–272 NO-cGMP cascade, 270–271 prostanoids, 271 pulmonary hypertensive crises, 269–270 right ventricular support, 272–273 underlying disease treatment, 273 vasodilator therapy, 270 pathophysiology hemodynamics and morphology, 266–267 pulmonary vascular endothelium, 267–269 pulmonary vascular smooth muscle, 269 pediatric ICU, therapeutic gases, 170–171 Pulmonary surfactant ALI/ARDS animal studies, 205 clinical trial data, 207–208 drugs relative activity, 203–204 dysfunction, 201–202 human studies, 205–207 new synthetic lung surfactant development, 204–205 pathophysiology, 201 pharmaceutical surfactants, 202–203 biophysically-functional composition average mass composition, 198 molecular characteristics and activities, 198, 199 and exogenous surfactant therapy, 196 innate immune function collectins, 198–199 SP-A and SP-D, 199–200 metabolism and recycling, 200–201 physiological actions, 197–198 pressure-volume, 197 surface tension, 196–197 Pulmonary valve stenosis anatomy, 366–367 clinical presentation, 367 outcome, 368 pathophysiology, 367 postoperative care, 368 preoperative evaluation, 367–368 surgical/transcatheter intervention, 368 Pulmonary vascular resistance (PVR) arterial or venous pressure, 16 effects on, 16 respiration effects, 326 Pulsus paradoxus, 514, 515 Purple glove syndrome, 678 Purulent pericarditis, 511–512 R Rabies, 659, 719 Rasmussen encephalitis, 609–610 Index Reactive nitrogen species (RNS), 543–544 Reactive oxygen species (ROS), 543 Recombinant human DNAse (rhDNAse), 82 Recruitment maneuver (RM), 147, 240 Recurrent respiratory papillomatosis (RRP), 30 Refractory status epilepticus (RSE) approaches to, 690 barbiturate anesthesia, 683 diagnostic considerations, 685 and electroencephalographic features, 677–678 high-dose midazolam, 680 pediatric critical care studies, 680–681 strategy, 681–682 inhaled anesthetics, 684–685 intensive care treatment, 686 isoflurane anesthesia, 684–685 ketogenic diet/modified Atkins diet for, 687 midazolam, 680–682 pentobarbital anesthesia, 682–684 second-tier intravenous anticonvulsants for, 678 Renin, 524–525 Respiratory disease cardiovascular function, 330–331 heart failure effects, 330 Respiratory distress syndrome (RDS), 196 See also Acute respiratory distress syndrome (ARDS) classification, 252–253 therapy, 254 Respiratory muscle, neuromuscular diseases characterization, 286 diaphragmatic paralysis, 284 downstream effects, 289 MIP and MEP, 287 muscle fatigue, 287 muscle force, 284 Respiratory physiology developmental anatomy, 4–5 mechanical ventilation alveolar ventilation, 10 mechanics of, 10–13 oxygenation, 9–10 work of breathing, 4–9, 11–14 mechanics of breathing airway resistance, lung and chest wall, 5–6 lung volumes, 7–9 pulmonary circulation, 13 blood flow distribution, 14–15 pulmonary vascular pressure, 14–15 pulmonary vascular resistance, 15–16 ventilation-perfusion relationship, 16–17 Restrictive cardiomyopathy (RCM), 490–491 Retinal hemorrhages, 620 Retrognathia/glossoptosis, 43 Retropharyngeal abscess, 29–30 Reversible posterior leukoencephalopathy syndrome (RPLS), 610–611 Reye’s syndrome (RS) diagnostic criteria, 638 encephalopathy stages, 639 hyperammonemia, 638–639 pathogenesis, 638 Rheumatic diseases, 606–607 Ribavirin, 81 Right atrial pressure (PRA), 317 Right ventricular dependent coronary circulation (RVDCC), 368 Right ventricular function, PH atrial septostomy, 273 principles of, 272 vasopressors role, 273 Index Rituximab, 612 Roller-head pump, ECMO, 221–222 RSE See Refractory status epilepticus (RSE) S Saccular stage, fetal lung development, 250 SE See Status epilepticus (SE) Secundum ASD, 343, 344 Sedation ECMO, 226–227 intracranial hypertension management, 581 Septic shock, ECMO, 229 Serotonin syndrome, 537, 718 Shunt aortopulmonary window, 353–354 atrial septal defect, 343–348 infection clinical manifestations, 668 diagnosis, 668 epidemiology, 667 pathophysiology, 667–668 treatment, 668 patent ductus arteriosus, 351–353 ventricular septal defects, 348–351 Sildenafil, 257, 271, 410 Sinus venosus ASD, 343, 347 Sodium nitroprusside, 529 Spasmodic dysphonia, 712 Spinal cord injury, 290 Spinal cord tumors, 556, 564–565 Spinal muscle atrophy with respiratory distress (SMARD), 702–703 Spinal muscular atrophy (SMA), 289–290, 701 Status asthmaticus clinical manifestations assessment, 53 Becker score, 53 hypokalemia, 54 hypoxemia, 52 metabolic acidosis, 54 pulse oximetry, 52 tachycardia, 52 epidemiology, 50–51 management albuterol, 57 epinephrine, 56–57 helium-oxygen, 60 inhaled corticosteroids, 56 ipratropium bromide, 58 isoproterenol, 58 ketamine, 60–61 leukotriene modifying agents, 61 magnesium, 58–59 mechanical ventilation, 61–62 oxygen, 54–55 systemic corticosteroids, 55 terbutaline, 57–58 theophylline, 59–60 volatile anesthetics, 62–63 pathophysiology, 51–52 Status dystonicus, 713 Status epilepticus (SE) definitions, 675, 676 electrographic SE, 688 febrile infection-related epilepsy syndrome, 689 fever-induced refractory epileptic encephalopathy, 689 fosphenytoin, 678 impending, 676–677 levetiracetam, 679–680 735 non-convulsive seizures, 688 phenobarbital, 679 refractory status epilepticus, 675 approaches to, 690 barbiturate anesthesia, 683 diagnostic considerations, 685 high-dose midazolam, 680–682 inhaled anesthetics, 684–685 intensive care treatment, 686 isoflurane anesthesia, 684–685 ketogenic diet/modified Atkins die for, 687 midazolam, 680–682 pentobarbital anesthesia, 682–684 second-tier intravenous anticonvulsants for, 678 seizures forms in, 677 super-refractory, 678 general anesthesia, 685–688 intensive care treatment, 686 ketamine, 686–687 ketogenic diet, 687–688 therapeutic hypothermia, 687 valproic acid, 679 Stimulation single fiber electromyography (StimSFEMG), 697, 701 Streptococcus pneumonia, 648–649, 653–654 Stroke approach to suspected stroke, 597–598 arterial ischemic stroke metabolic causes, 592–593 outcome from, 593–594 patent foramen ovale and, 592 thrombotic causes, 591–592 treatment, 593 vascular causes, 590–591 biomarkers, 547 cardiac imaging, 597 cerebral angiography, 596–597 cerebral sinovenous thrombosis, 595, 596 computed tomography in, 596 diffusion-weighted imaging and apparent diffusion coefficient, 596 epidemiology, 590 etiology, 590 Fabry disease, 592–593 hemorrhagic, 590, 594–595 homocystinuria, 593 hypercoagulable state testing, 591–592 ischemic, 590, 591 magnetic resonance imaging in, 595, 596 neonatal, 590, 595 transcranial Doppler, 597 transthoracic echocardiogram, 597 types, 590 Stroke volume afterload, 315 contractility, 315 mean circulatory filling pressure, 316–317 preload diastolic compliance curve, 313 EDP vs SV, 313, 314 pressure-volume loop, 314–315 right atrial pressure, 317 venous resistance, 317 venous return, 315–316 Strychnine toxicity, 718 Subaortic stenosis, 422 Subarachnoid hemorrhage (SAH), 594–595 Subclavian artery (SCA), 426 Subdural empyema See Brain abscess Subdural hematoma, 577 Subglottic stenosis (SGS), 44–45 736 Subvalvar aortic stenosis (SVAS) clinical presentation, 393–394 management, 394 postoperative care, 394 Superoxide production, 543 Super-refractory status epilepticus (SE), 678 general anesthesia, 685–688 intensive care treatment, 686 ketamine, 686–687 ketogenic diet, 687–688 therapeutic hypothermia, 687 Supraglottis, 27–28 Supravalvar aortic stenosis (SAS) clinical presentation, 392 management, 393 postoperative care, 393 Supraventricular tachycardia (SVT), 421, 498 Surfactant proteins, 198–200 Surfactant proteins and innate immune function, 198–200 Synchronized intermittent mandatory ventilation (SIMV), 137–139 Syndrome of inappropriate antidiuretic hormone secretion (SIADH), 634, 647 Systolic heart failure, 328–329 T Tachyarrhythmias antiarrhythmic medications, 462–463 defibrillation and pacing, 462 total cavo-pulmonary anastomosis, 411 treatment and cardioversion, 462 Tachycardia, 52 atrial, 458, 459 AV reentrant, 458 ECG appearance and responses, 458, 459 Tachypnea clinical manifestations, 146 definition, 251 newborn, 254 TAPVC See Total anomalous pulmonary venous connections (TAPVC) TAPVR See Total anomalous pulmonary venous return (TAPVR) Terbutaline, 57–58 Tetanus, 718 Tetralogy of Fallot (TOF) with absent pulmonary valve, 420–421 anatomy, 361–362 clinical presentation, 362 complex variants, 365–366 elective surgical repair, 419–420 outcomes, 366 pathophysiology, 362 postoperative care, 363–364 preoperative evaluation, 362 with pulmonary atresia, 420 surgical/transcatheter intervention, 362–363 TGA See Transposition of the great arteries (TGA) Theophylline, 59–60 Therapeutic hypothermia (TH), 687 Thromboembolism, 427–428 Thrombosis, 475 Tick-borne encephalitis, 660 Tick paralysis, 700 Tissue plasminogen activator (tPA), 547–548 Total anomalous pulmonary venous connections (TAPVC) anatomy and pathophysiology, 383 clinical presentation and pre-operative care, 383 Index post-operative care, 384–385 prognosis, 385 surgical intervention, 383–384 Total anomalous pulmonary venous return (TAPVR), 425 Total cavo-pulmonary anastomosis Fontan procedure, 409 myocardial dysfunction, 409, 410 pulmonary resistance, 410 tachyarrythmias, 411 Toxicity and complications, PICU, 171–172 Toxic-metabolic encephalopathy and altered levels of consciousness (see Altered levels of consciousness) central nervous system, 628 pediatric intensive care unit glucose metabolism disorders, 631–633 hyperammonemia (see Hyperammonemia) hypernatremia, 635 hyponatremia, 633–635 sodium homeostasis disorders, 633 Trabecular septum, 348 Tracheostomy, 297 Transient tachypnea of the newborn (TTN), 254 Transmural pressure, 323 Transposition of the great arteries (TGA) anatomy, 378 clinical presentation and diagnosis, 378–379 complications, 380–381 pathophysiology, 378 post-operative care, 380 pre-operative care, 379–380 surgical intervention, 380 Transpulmonary thermodilution technique, 502 Transverse myelitis (TM), 608 Traumatic brain injury (TBI) abusive head trauma (see Abusive head trauma (AHT)) complexity, 580 inducible NOS in, 544 intracranial hypertension monitoring, 570 in pediatric, 583 Tremor, 716 Truncus arteriosus anatomy, 381–382 associated lesions, 382 CHD lesions, 424–425 clinical presentation and pre-operative care, 382 prognosis, 383 surgical intervention and post-operative care, 382 Tuberculous meningitis (TBM), 655–656 Tumor necrosis factor receptor (TNFR), 541–542 Tumors craniopharyngiomas, 562–563 ependymomas, 561–562 gliomas, 557–560 incidence, 556 malignant spinal cord compression, 564–565 medulloblastomas, 560–561 peri-operative care, 563–564 primitive neuroectodermal tumor, 556 signs and symptoms, 557 spinal cord, 556, 564–565 U Univentricular/single ventricle heart anatomic diagnoses, 398 BCPA (see Bidirectional cavopulmonary anastomosis (BCPA)) Index factors affecting resistance, 398 interstage management, 406 perinatal management, 399–400 physiology in newborn before and after surgery, 398–399 in older infant and child, 409–411 post-operative management ACEi, 405–406 low total cardiac output, 404–405 preoperative management hypoxic gas therapy, 400 lesion-specific, 401 parenteral nutrition, 402 PEEP, 401 pulmonary and systemic vascular resistance, 401 pulmonary outflow obstruction, 402 systemic outflow obstruction, 401 unobstructed pulmonary/systemic venous return, 402 surgical management, 402–404 total cavo-pulmonary anastomosis (see Total cavo-pulmonary anastomosis) Upper airway injury, 147–148 V Vagus nerve, electrical stimulation, 535–536 Valproic acid, 679 Valvar aortic stenosis aortic annular hypoplasia, 387 clinical presentation, 388 endocardial fibroelastosis, 388 management, 388–389 postoperative care, 389–390 Van Praagh’s segmental approach, 336 Vascular compression, 46–47 Vascular endothelial growth factor (VEGF), 242–243 Vascular endothelium, PH arachidonic acid metabolism, 268 endothelial derived factors, 268–269 signaling pathways, 268, 269 Vascular occlusion test (VOT), 503, 504 Vascular smooth muscle, PH, 269 Vasculitis, CNS angiography-negative, small vessel cPACNS, 604–606 angiography-positive nonprogressive cPACNS, 602–603 angiography-positive progressive cPACNS, 604 human immunodeficiency virus, 606 infection-associated, 606 primary angiitis of the central nervous system, 602 rheumatic and systemic inflammatory diseases, 606–607 systemic diseases/exposures, 607 varicella zoster virus, 606 Vasoconstriction, PH, 270 Vasodilator therapy, 270, 529–530 Vasogenic edema, 576 VEGF See Vascular endothelial growth factor (VEGF) Venoarterial ECMO arterial cannulation, 217–218 femoral artery cannulation, 218 Venous reservoir, ECMO, 221 Venous resistance (RV), 317 Venous return, 315–316 vs right atrial pressure, 324–325 right ventricular preload, 324 Venovenous ECMO advantage, 220–221 blood recirculation, 219–220 737 cannulation, 218 chest radiograph, 219 Ventilation associated respiratory infections (VARI), 148–149 Ventilator-induced lung injury (VILI) adults vs infants, 240–241 bronchopulmonary dysplasia, 241–243 low tidal volume lessens, 238 mechanical ventilation, 149 mechanotransduction, 243–244 multiple-organ dysfunction syndrome, 244–245 positive end-expiratory pressure, 238–239 recruitment maneuver, 240 targeted therapy, 245–246 Ventilator management, 226 Ventricular assist devices adult, 442 anticoagulation, 446 Berlin heart EXCOR®, 443–444 management during support, 447 outcomes, 447–448 patients, 447 pre-implantation variables, 447 sensitization, 448–449 BiVADs vs LVAD, 442 complications, 446 heartware system, 444 micromed heart assist system, 444 NHLBI, 444–445 sensitization, 446–447 surgical procedure, 445–446 timing, 442 Ventricular dysfunction, 427 Ventricular septal defects (VSD) anatomy, 348–349 CHD lesions, 418 clinical features, 349–350 embryology, 348 hybrid techniques, 351 management, 350 natural history, 350 pathophysiology, 349 postoperative management, 350 surgery, 350 transcatheter device closure, 350–351 types, 348 Viral encephalitis, 640, 664 Viral laryngotracheobronchitis, 25–27 Viral meningitis, 654–655 Viral pericarditis, 510–511 Vocal cord paralysis, 44 Volatile anesthetics, 62–63 Volume control ventilation (VCV), 136 Volume support ventilation, 140 Volutrauma, 238 W Weaning ECMO support, 227 HFOV, 188 mechanical ventilation, 154 West Nile virus, 660, 698 Wilson disease, 717 Wilson–Mikity syndrome, 241 Windkessel effect, 573 ... R-COOH = Acetyl CoA Carmitine Glucose 2- NAD 2- NADH2 Glycolysis 2- ADP 2- ATP Pyruvate 2- NAD 2- NADH2 β-Oxidation R-CH2-C-S-CoA FAD FADH2 Pyruvate + CoA-SH + NAD• NADH2 + Co2 + acety-CoA NAD NADH2... Parkville, 30 52, VIC Australia e-mail: gmaclaren@iinet.net.au D.S Wheeler et al (eds.), Pediatric Critical Care Medicine, DOI 10.1007/97 8-1 -4 47 1-6 35 6-5 _17, © Springer-Verlag London 20 14 Introduction... Hospital, 6 621 Fannin St, Suite WT 6-0 06, Houston, TX 77037, USA e-mail: bronicki@bcm.edu D.S Wheeler et al (eds.), Pediatric Critical Care Medicine, DOI 10.1007/97 8-1 -4 47 1-6 35 6-5 _18, © Springer-Verlag