Pediatric Critical Care: Text and Study Guide

Preface
Acknowledgments
Contents
Contributors
I: Essential Physiologic Principles
	1: Genomics and Genetic Predisposition to Critical Illness in the Pediatric Intensive Care Unit
		1.1 Introduction
		1.2 Human Genetics
			1.2.1 Structure and Function of Genes
			1.2.2	 Genetic Recombination and Mapping of Genes and Genetic Variants
			1.2.3	 Genetic Mutations and Other Genetic Variants
			1.2.4	 Gene Expression
			1.2.5	 Phenotype
		1.3 Genetics of Common Complex Disorders
		1.4 Genetic and Genomic Studies in Critical Care
			1.4.1	 Genomics Studies in the ICU
			1.4.2	 Genetic Predisposition in the ICU
			1.4.3	 Influence of Genetic Variation in Patients with Sepsis
			1.4.4	 Influence of Genetic Variation on Lung Injury and Acute Respiratory Distress Syndrome
			1.4.5	 Other Potential Areas of Interest in Genetic Variation in the ICU
		1.5 Conclusion
		Suggested Reading
	2: Oxygen Delivery and Oxygen Consumption in Pediatric Critical Care
		2.1 Introduction
		2.2 Biochemical Basis
		2.3 Oxygen Delivery
			2.3.1	 Arterial Oxygen Content
				2.3.1.1	 Arteriovenous Oxygen Content Difference
			2.3.2	 Cardiac Output
				2.3.2.1	 Heart Rate
				2.3.2.2	 Stroke Volume
		2.4 Interdependence of the Heart, Lungs, and Blood on Peripheral Oxygen Delivery
		Box 2.1 Compensatory Responses to Poor Cardiac Output That Act to Preserve DO2
		2.5 Oxygen Consumption
			2.5.1	 Measurement Techniques
				2.5.1.1	 Mixed Venous and Central Venous Oxygen Saturation
		2.6 Oxygen Consumption Variability
			2.6.1	 Factors That Affect Oxygen Consumption
		2.7 Oxygen Extraction
		2.8 Assessment of Oxygen Delivery/Oxygen Consumption
		2.9 Summary
		Suggested Reading
	3: Endothelial Interactions and Coagulation
		3.1	 Introduction
		3.2	 Endothelial Interactions and Coagulation
		3.3	 Conclusion
		Suggested Readings
	4: The Inflammatory Response
		4.1 Introduction
		4.2 SIRS and CARS
		4.3 Leukocytes and Inflammation
		4.4 Innate Immunity
			4.4.1	 Pathogen Recognition
			4.4.2	 Migration
			4.4.3	 Antigen Presentation
			4.4.4	 NK Cells
		4.5 Adaptive Immunity
		4.6 Circulating Mediators of Inflammation
			4.6.1	 Cytokines
			4.6.2	 Chemokines
			4.6.3	 The Complement System
			4.6.4	 The Acute Phase Response
			4.6.5	 Other Pro-inflammatory Mediators
			4.6.6	 Glucocorticoids
			4.6.7	 Heat-Shock Proteins
		4.7 Intracellular Signaling
			4.7.1	 Toll-Like Receptors and the NFκB Pathway
			4.7.2	 JAK/STAT Signaling
			4.7.3	 MAP Kinase Signaling
			4.7.4	 G-Protein-Mediated Signaling
			4.7.5	 The Inflammasome
			4.7.6	 Interrelationships
		4.8 Clinical Immunomodulation: Targeting Hyperinflammation
		4.9 Immunoparalysis
		4.10 Immunoparalysis as a Target of Therapy
		4.11 Secondary Hemophagocytic Lymphohistiocytosis and Macrophage Activation Syndrome
		4.12 Critical Illness and the Inflammatory Response
			4.12.1	 The Impact of Critical Illness
			4.12.2	 Effects of the ICU Pharmacopeia
		4.13 Summary and Future Directions
		Suggested Reading
	5: Nutrition in Critical Illness
		5.1	 Nutrition in Healing
		5.2	 Determining Nutritional Needs
			5.2.1	 Energy
			5.2.2	 Calorimetry
			5.2.3	 Respiratory Quotient
			5.2.4	 Fick Equation
			5.2.5	 Formulas and Tables
		5.3	 Protein and Nitrogen Balance
		5.4	 Micronutrients
		5.5	 Immunonutrition
		5.6	 Monitoring
		5.7	 Glycemic Control
		5.8	 Nutrition Delivery
		5.9	 Enteral Nutrition
		5.10	 Enteral Formulas: Standard
			5.10.1	 Enteral Formulas: Modified
			5.10.2	 Enteral Formulas: Specialized
			5.10.3	 Probiotics
			5.10.4	 Parenteral Nutrition
		5.11	 Summary
		Suggested Readings
	6: Pharmacology
		6.1 Introduction
		6.2 Pharmacokinetics
		6.3 Absorption
		6.4 Distribution
		6.5 Metabolism
		6.6 Elimination
			6.6.1	 Elimination Kinetics: First-Order vs. Zero-Order
			6.6.2	 Half-Life and Steady-State
		6.7 Pharmacodynamics
		6.8 Pharmacokinetic and Pharmacodynamic Issues in the Pediatric ICU Setting
		6.9 Pharmaceutics
		6.10 Summary
		Suggested Reading
II: Respiratory
	7: Pulmonary Structure and Function
		7.1	 Developmental Biology/Anatomy
		7.2	 Anatomy of the Lung
			7.2.1	 Airways
			7.2.2	 The Pulmonary Lobule and Acinus
			7.2.3	 Pulmonary Vasculature
			7.2.4	 Pleura/Chest Wall/Diaphragm
		7.3	 Lung Physiology
			7.3.1	 Lung Compliance/Elastance
			7.3.2	 What Is Surfactant?
			7.3.3	 Transmural Pressure and Volume
			7.3.4	 Hysteresis
			7.3.5	 Factors Affecting Compliance
			7.3.6	 Compliance of the Respiratory System
			7.3.7	 Determinants of FRC
			7.3.8	 Airways resistance
			7.3.9	 Ventilation/Perfusion Matching and Gas Exchange
		7.4	 Summary
		Suggested Readings
	8: Fundamentals of Gas Exchange and the Assessment of Oxygenation and Ventilation
		8.1	 Introduction
		8.2	 The Process of Gas Exchange
			8.2.1	 Alveolar Ventilation and the Oxygen Cascade
			8.2.2	 Distribution of Alveolar Ventilation
			8.2.3	 Carbon Dioxide Elimination
			8.2.4	 Assessing Adequacy of Gas Exchange
				8.2.4.1	 In the Bloodstream
				8.2.4.2	 To the Tissues
		8.3	 Mechanisms of Hypoxemia
			8.3.1	 Hypoventilation
			8.3.2	 Ventilation-Perfusion Mismatch
			8.3.3	 Shunting of Pulmonary Blood
			8.3.4	 Diffusion Limitation
		8.4	 Monitoring of Gas Exchange
			8.4.1	 Arterial Blood Gas Determination
			8.4.2	 Pulse Oximetry
			8.4.3	 Capnometry
			8.4.4	 Transcutaneous Oxygen and CO2 Monitoring
		8.5	 Summary
		Suggested Readings
	9: Upper Airway Obstruction
		9.1	 Introduction
		9.2	 Anatomic and Physiologic Considerations
		9.3	 Differential Diagnosis of Upper Airway Obstruction
			9.3.1	 Early Infancy
			9.3.2	 Acquired Infectious Causes of Airway Obstruction
			9.3.3	 Other Acquired Causes of Airway Obstruction
		9.4	 Assessment
			9.4.1	 Examination
			9.4.2	 Diagnostic Evaluation
		9.5	 Management
			9.5.1	 Triage and Initial Stabilization
			9.5.2	 Definitive Therapy
			9.5.3	 Mechanical Support of the Upper Airway
		9.6	 The Difficult Airway
			9.6.1	 Pharmacologic Considerations
			9.6.2	 Ventilation Without Intubation
			9.6.3	 Nonconventional Intubation Techniques
		9.7	 Further Care
		9.8	 Summary
		Suggested Readings
	10: Severe Asthma
		10.1 Introduction
		10.2 Genetic Factors
		10.3 Environmental Factors
		10.4 Triggers of Asthma
		10.5 Pathophysiology
			10.5.1 Inflammation
			10.5.2 Bronchospasm and Airway Resistance
			10.5.3 Mucous Production
			10.5.4 Cardiopulmonary Interactions
		10.6 Evaluation of Status Asthmaticus
		10.7 Treatment Algorithm for Severe Asthma in Children
		10.8 Therapies for Status Asthmaticus (. Table 10.2)
			10.8.1 First-Tier Therapies
				10.8.1.1 Oxygen
				10.8.1.2 Intravenous Fluids
				10.8.1.3 Inhaled Beta-Agonists
				10.8.1.4 Inhaled Anticholinergic Agents
				10.8.1.5 Corticosteroids
			10.8.2 Second-Tier Therapies
				10.8.2.1 Magnesium
				10.8.2.2 Helium/Oxygen Mixture
				10.8.2.3 Intravenous Beta-Agonists
				10.8.2.4 Methylxanthines
				10.8.2.5 High-Flow Nasal Cannula
				10.8.2.6 Noninvasive Ventilation
			10.8.3 Third-Tier Therapies
				10.8.3.1 Ketamine
				10.8.3.2 Inhaled Anesthetics
				10.8.3.3 Extracorporeal Membrane Oxygenation (ECMO)
		10.9 Mechanical Ventilation for Severe Asthma in Children
		10.10 Monitoring During Mechanical Ventilation
		10.11 Complications During Mechanical Ventilation of Asthma
		Suggested Readings
	11: Pediatric Acute Respiratory Distress Syndrome
		11.1 Introduction
			11.1.1	 PALICC Definition of PARDS
			11.1.2	 Epidemiology
			11.1.3	 Etiology, Initiation, and Subtypes of PARDS
		11.2 Anatomic and Physiologic Considerations in PARDS
			11.2.1	 Starling’s Hypothesis and Lung Fluid in PARDS
			11.2.2	 Alveolar Surface Tension
			11.2.3	 Compliance
			11.2.4	 Functional Residual Capacity (FRC)
			11.2.5	 Intrapulmonary Shunting in PARDS
		11.3 Inflammatory Mediators in PARDS
		11.4 Pathologic Phases of PARDS
			11.4.1	 Acute Exudative Phase
			11.4.2	 Subacute Proliferative Phase
			11.4.3	 Fibrosis With or Without Recovery
		11.5 Management
			11.5.1	 Ventilatory Management: Maximize PEEP, Minimize VILI
				11.5.1.1	 Optimizing PEEP
				11.5.1.2	 Minimizing VILI
				11.5.1.3	 High-Frequency Oscillatory Ventilation (HFOV)
				11.5.1.4	 Airway Pressure Release Ventilation (APRV)
			11.5.2	 Improving Oxygen Delivery
			11.5.3	 Fluid Balance
			11.5.4	 Prone Positioning
			11.5.5	 Corticosteroids
			11.5.6	 Inhaled Nitric Oxide
			11.5.7	 Exogenous Surfactant
				11.5.7.1	 Neuromuscular Blockade
			11.5.8	 Extracorporeal Membrane Oxygenation (ECMO)
		11.6 Summary
		Suggested Readings
	12: Conventional Mechanical Ventilation
		12.1 Introduction
		12.2 Pulmonary Physiology and Conventional Mechanical Ventilation
			12.2.1	 Indications for Mechanical Ventilation and Mechanisms of Respiratory Failure
			12.2.2 Pathophysiology of Hypoxemia and Application to Mechanical Ventilation
			12.2.3 Pathophysiology of Ventilation Failure (Hypercarbia) and Application to Mechanical Ventilation
			12.2.4 Impact of MV on the Respiratory and the Cardiovascular Systems
		12.3 Basics of the Ventilator Functioning
			12.3.1	 Negative Pressure Ventilation
			12.3.2 Positive Pressure Ventilation
			12.3.3 The Different Ventilation Modes
			12.3.4 The Control Variable: Volume-Controlled Ventilation, Pressure-Controlled Ventilation, and Pressure-Regulated Volume Control
			12.3.5 Supported Ventilation
			12.3.6 How to Set the Control Variable (Tidal Volume or Delta Pressure)
			12.3.7 How to Set the Positive End-Expiratory Pressure (PEEP)?
			12.3.8 How to Set the Respiratory Rate and Inspiratory and Expiratory Times?
			12.3.9 Balancing the Contribution of the Patient to the Ventilation: Benefit/Risk of Spontaneous Breathing
			12.3.10 Weaning the Mechanical Ventilation and Extubation Readiness Test
				12.3.10.1 Techniques of Weaning
				12.3.10.2 Criteria for Readiness for Extubation
				12.3.10.3 Impact of Endotracheal Tubes on Weaning and Spontaneous Breathing Trials
				12.3.10.4 Assessment of Post-extubation UAO
			12.3.11 Role of Automation and Clinical Decision Support System
			12.3.12 Monitoring of the Mechanical Ventilation
				12.3.12.1	 Blood Gas
				12.3.12.2 Capnography
			12.3.13 Pleural Pressure Monitoring
			12.3.14 Chest Radiography
			12.3.15 Diaphragm Ultrasound
			12.3.16 Diaphragm Electrical Activity Monitoring
		12.4 Summary
		Suggested Readings
	13: Nonconventional Mechanical Ventilation
		13.1 Introduction
		13.2 Noninvasive Ventilation
		13.3 Negative Pressure Ventilation
		13.4 Noninvasive Positive Pressure Ventilation
		13.5 High-Frequency Oscillatory Ventilation
		13.6 High-Frequency Percussive Ventilation
		13.7 Airway Pressure-Release Ventilation
		13.8 Long-Term Mechanical Ventilation
		13.9 Conclusion
		Suggested Readings
III: Cardiovascular
	14: Hemodynamics
		14.1 Introduction
		14.2 Cardiac Physiology and Function
			14.2.1	 Cardiac Structure and Cycle
			14.2.2	 Myocardial Contraction: Cellular Components
			14.2.3	 Cardiac Pump Function
			14.2.4	 Stroke Volume: Preload
			14.2.5	 Stroke Volume: Afterload
			14.2.6	 Stroke Volume: Contractility
			14.2.7	 Stroke Volume: Lusitropy
		14.3 Cardiopulmonary Interactions
			14.3.1	 Neural Regulation of Cardiopulmonary Interactions
			14.3.2	 Intrathoracic Pressure Changes During Respiration
			14.3.3	 The Effect of Respiration on Cardiac Function
			14.3.4	 Right Ventricular Preload/Systemic Venous Return
			14.3.5	 Right Ventricular Afterload
			14.3.6	 Left Ventricular Preload/Pulmonary Venous Return
			14.3.7	 Left Ventricular Afterload
			14.3.8	 Negative Pressure Ventilation
			14.3.9	 Positive Pressure Ventilation
			14.3.10	 Effect of PPV on Contractility
			14.3.11	 Cardiac Effects on Respiratory Function
			14.3.12	 Cardiopulmonary Interactions in Patients with Fontan Physiology
		14.4 Summary of Cardiopulmonary Interactions
		Suggested Readings
	15: Regional Circulations
		15.1 Regulation of Blood Flow and Oxygen Consumption at the Major Tissue Beds
			15.1.1	 Local Hormonal/Nervous System Factors Affecting Vascular Tone
		15.2 Potassium Channels
		15.3 Temperature Regulation of Blood Flow
		15.4 Blood Flow and Oxygen Consumption
		15.5 Mechanisms of Regional Blood Flow Regulation during Stress and Pathological Conditions
			15.5.1	 Hemodynamic Coherence and the Microcirculation
		15.6 Coronary Circulation
			15.6.1	 Anatomy, Histology, and Physiology
			15.6.2	 Local Regulation of Coronary Blood Flow
			15.6.3	 Specific Determinants of Coronary Blood Flow
				15.6.3.1	 Transmural Distribution of Coronary Blood Flow
				15.6.3.2	 Metabolic Regulation of Coronary Blood Flow
			15.6.4	 Adrenergic Control of Coronary Blood Flow
				15.6.4.1	 α-Adrenergic Effects on Coronary Blood Flow
				15.6.4.2	 β-Adrenergic Effects on Coronary Blood Flow
			15.6.5	 Coronary Blood Flow during CPR
			15.6.6	 Effects of Acidosis, Hypocapnia, and Hypercapnia on Coronary Blood Flow
		15.7 Cerebral Circulation
			15.7.1	 Anatomy and Histology
			15.7.2	 Cerebral Circulation Autoregulation
			15.7.3	 Hypoxia and Carbon Dioxide–Related Cerebral Autoregulation
			15.7.4	 Flow-Mediated Regulation
			15.7.5	 Cerebral Blood Flow with Brain Injury
		15.8 Pulmonary Circulation
			15.8.1	 Anatomy, Histology, and Physiology
			15.8.2	 Normal Pulmonary Pressures
			15.8.3	 Pulmonary Vascular Resistance
			15.8.4	 Hypoxic Pulmonary Vasoconstriction
			15.8.5	 Pulmonary Vascular Tone and Clinical Implications
			15.8.6	 Pulmonary Vasoconstrictors
			15.8.7	 Pulmonary Vasodilators
			15.8.8	 Vasomediators in the Pathogenesis of Pulmonary Artery Hypertension (PAH)
			15.8.9	 Autonomic Neural Regulation of Pulmonary Vascular Tone
		15.9 Renal Circulation
			15.9.1	 Major Arteries
			15.9.2	 Renal Blood Flow and Autoregulation
			15.9.3	 Medullary Blood Flow and Oxygen Demand
			15.9.4	 Medullary Blood Flow
			15.9.5	 Cortical Blood Flow
			15.9.6	 Sympathetic Nervous System (SNS) and Renin-Angiotensin-Aldosterone System (RAAS) Effects on Renal Blood Flow
			15.9.7	 Vasoactive Mediators
			15.9.8	 Adenosine and Renal Circulation
		15.10 Splanchnic Circulation
			15.10.1	 Vascular Anatomy and Distribution
			15.10.2	 Baseline Vascular Tone Regulation
			15.10.3	 Postprandial Blood Flow Regulation
			15.10.4	 Pathological States
		15.11 Cutaneous Circulation
			15.11.1	 Cutaneous Vasodilation
			15.11.2	 Cutaneous Vasoconstriction
			15.11.3	 Local Temperature Control of Cutaneous Blood Flow
		Suggested Readings
	16: Assessment of Cardiovascular Function
		16.1 Noninvasive and Minimally Invasive Assessment of Cardiovascular Status
			16.1.1 Physical Examination
				16.1.1.1 Respiratory Signs
				16.1.1.2 Urine Output
			16.1.2 Noninvasive Blood Pressure
				16.1.2.1 Systolic Arterial Pressure
				16.1.2.2 Diastolic Arterial Pressure
				16.1.2.3 Pulse Pressure
				16.1.2.4 Mean Arterial Pressure (MAP)
			16.1.3 Echocardiography
				16.1.3.1 Pericardial Disease
				16.1.3.2 Systolic Function
				16.1.3.3 Volume Status and Fluid Responsiveness
				16.1.3.4 Pulmonary Artery Systolic Pressure
			16.1.4 Near-Infrared Spectroscopy
		16.2 Invasive Measures of Cardiovascular Function
			16.2.1	 Arterial Waveform Analysis
				16.2.1.1 Arterial Waveform Technical Considerations
					Wave Frequency and Resonance
					Damping
					Fast Flush Test
					Leveling and Zeroing
				16.2.1.2 Variations in Arterial Waveforms
					Pulsus Paradoxus
					Systolic Pressure Variation
				16.2.1.3 Complications of Invasive Arterial Pressure Monitoring
					Box 16.1 Complications of Arterial Cannulation
					Ischemic Injury
					Infection
					Vasospasm and Catheter Malfunction
			16.2.2 Central Venous Pressure Monitoring
				16.2.2.1 Variations in CVP Waveform
				16.2.2.2 Complications of Central Venous Catheters
			Box 16.2 Complications of Central Venous Catheters
			Box 16.3 Factors Increasing Risk of Catheter-Related Thrombosis
			16.2.3 Invasive Measurement of Cardiac Output
				16.2.3.1 Conservation of Mass
				16.2.3.2 Dye Dilution
				16.2.3.3 Fick Method
				16.2.3.4 Thermodilution
				16.2.3.5 Pulmonary Artery Catheterization
					Cardiac Output Determination Using Pulmonary Artery Catheterization
					Intracardiac Pressure Determination Using Pulmonary Artery Catheterization
					Obtaining and Interpreting Pulmonary Artery Occlusion Pressures
					Box 16.4 Conditions Resulting in Discrepant PAOP and LVEDP Measurements
					Pulmonary Artery Diastolic Pressure (PADP)
					Derived Hemodynamic Variables
			Box 16.5 Complications Related to Pulmonary Artery Catheter Insertion and Use
			16.2.4 Novel Techniques for Cardiac Output Assessment
				16.2.4.1	 Pulse Contour Analysis
				16.2.4.2 Transesophageal Doppler Echocardiography
				16.2.4.3 Inadequate Oxygen Delivery Index (IDO2)
			16.2.5 Cardiac Biomarkers
				16.2.5.1	 Mixed Venous and Central Venous Oxygen Saturation
				16.2.5.2 Lactate
				16.2.5.3 B-Type Natriuretic Peptide
				16.2.5.4 Cardiac Troponin
		Suggested Reading
	17: Circulatory Failure/Shock
		17.1 Introduction
		17.2 Shock Classifications
		17.3 Determinants of Oxygen Delivery
		17.4 Cardiogenic Shock
		17.5 Hypovolemic Shock
		17.6 Distributive Shock
		17.7 Septic Shock
		17.8 Shock at the Cellular Level
		17.9 Clinical Monitoring of Shock
			Box 17.1 Selected variables measured by pulmonary artery catheters
		17.10 Therapy for Shock
		Suggested Readings
	18: Disorders of Cardiac Rhythm
		18.1 Fundamental Electrophysiology
		18.2 General Arrhythmia Mechanisms
			18.2.1	 Reentry Disorders
			18.2.2	 Disorders of Automaticity
			18.2.3	 Triggered Tachycardias
			18.2.4	 Rapid Evaluation of Acute Arrhythmia
		18.3 Specific Arrhythmias and Their Treatment
			18.3.1	 Bradycardia
				Box 18.1 Selected Causes of Bradycardia in Children
				Box 18.2 Pacer Terminologya
		18.4 Common Atrial Tachyarrhythmias
			18.4.1	 Sinus Tachycardia
			18.4.2	 Supraventricular Tachycardias
			18.4.3	 Paroxysmal SVT
			18.4.4	 Wolff-Parkinson-White Syndrome (WPW)
			18.4.5	 Wide Complex SVTs
			18.4.6	 SVT Treatment
			18.4.7	 Atrial Flutter
			18.4.8	 Junctional Ectopic Tachycardia (JET)
			18.4.9	 Ventricular Ectopy and Tachycardia
			18.4.10	 Lidocaine
			18.4.11	 Amiodarone
		18.5 Miscellaneous Antiarrhythmic Agents and Arrhythmias
			18.5.1	 Sotalol
			18.5.2	 Magnesium for Torsades De Pointes/Long QT Syndrome
			18.5.3	 Other Treatment/General Principles
		18.6 Summary
		Suggested Reading
			Texts/Monographs
	19: Postoperative Cardiac Care
		19.1 Introduction
		19.2 Epidemiology of Congenital Heart Disease
		19.3 Cardiopulmonary Bypass
			19.3.1	 Cardiopulmonary Bypass-Induced Inflammation and Organ Dysfunction
		19.4 Perioperative Monitoring
			19.4.1	 Near-Infrared Spectroscopy (NIRS) Monitoring
		19.5 Mechanical Ventilation
		19.6 Low Cardiac Output Syndrome
		19.7 Pulmonary Arterial Hypertension
			Box 19.1 Congenital Heart Disease Categories Associated with Increased Risk of Pulmonary Vascular Disease
			19.7.1	 Pathophysiology of PAH
			19.7.2	 Diagnosis
			19.7.3	 Management of PAH
		19.8 Postoperative Arrhythmias
			19.8.1	 Sinus Tachycardia
			19.8.2	 Junctional Ectopic Tachycardia (JET)
			19.8.3	 Atrial Ectopic Tachycardia (AET)
			19.8.4	 Reentrant Supraventricular Tachycardia (SVT)
			19.8.5	 Bradyarrhythmias
		19.9 Acute Kidney Injury Following Congenital Heart Surgery
		19.10 Immediate Postoperative Encounter
		19.11 Postoperative Management of Selected Congenital Heart Defects
			19.11.1	 Left-to-Right Shunting Defects
				19.11.1.1	 Patent Ductus Arteriosus (PDA)
				19.11.1.2	 Atrial Septal Defect (ASD)
				19.11.1.3	 Ventricular Septal Defect (VSD)
				19.11.1.4	 Atrioventricular Septal Defect (AVSD)
			19.11.2	 Left-Sided Obstructive Lesions
				19.11.2.1	 Critical Aortic Stenosis (AS)
				19.11.2.2	 Coarctation of Aorta (CoA)
				19.11.2.3	 Interrupted Aortic Arch (IAA)
			19.11.3	 Ductal-Independent Mixing Lesions
				19.11.3.1	 Transposition of the Great Arteries and the Arterial Switch Operation (D-TGA, ASO)
				19.11.3.2	 Total Anomalous Pulmonary Venous Return (TAPVR)
				19.11.3.3	 Truncus Arteriosus
			19.11.4	 Lesions with Ductal-Dependent Pulmonary Blood Flow
				19.11.4.1	 Tetralogy of Fallot (TOF)
			19.11.5	 Single Ventricle Lesions
				19.11.5.1	 Stage 1: Norwood Procedure
				19.11.5.2	 Stage II Palliation: Bidirectional Glenn Shunt (BDG)
				19.11.5.3	 Stage 3: Fontan Operation
		19.12 Postoperative Heart Transplantation Patient
		19.13 Other Postoperative Issues
			19.13.1	 Nutrition
			19.13.2	 Chylothorax
			19.13.3	 Diaphragmatic Paresis
			19.13.4	 Vocal Cord Paresis or Paralysis
		19.14 Summary
		Suggested Reading
	20: Cardiovascular Agents
		20.1 Introduction
		20.2 Physiologic Considerations of Vasoactive Agents
			20.2.1	 Overview of Adrenergic Receptor-Cell Interactions
				20.2.1.1	 Adrenergic Receptor Density
				20.2.1.2	 Alpha- and Beta-Adrenoceptors
					Alpha1 (α1)-Adrenoceptors
					Alpha2 (α2)-Adrenoceptors
					Beta1 (β1)-Adrenoceptors
					Beta2 (β2)-Adrenoceptors
				20.2.1.3	 Dopamine Receptors
					Dopamine1 (DA1)
					Dopamine2 (DA2)
				20.2.1.4	 Genetics of Adrenoceptors
				20.2.1.5	 Complexity of Adrenoceptor Activation
				20.2.1.6	 Phosphodiesterase Inhibition
			20.2.2	 Pharmacokinetics of Vasoactive Infusions
			20.2.3	 Pharmacodynamics of Vasoactive Infusions
		20.3 Specific Agents and Clinical Indications
			20.3.1	 Norepinephrine
				20.3.1.1	 Pharmacology
				20.3.1.2	 Clinical Effects
				20.3.1.3	 Clinical Indications
				20.3.1.4	 Adverse Effects
			20.3.2	 Epinephrine
				20.3.2.1	 Pharmacology
				20.3.2.2	 Clinical Effects
				20.3.2.3	 Clinical Indications
				20.3.2.4	 Adverse Effects
			20.3.3	 Phenylephrine
				20.3.3.1	 Pharmacology
				20.3.3.2	 Clinical Effects
				20.3.3.3	 Clinical Indications
				20.3.3.4	 Adverse Effects
			20.3.4	 Dobutamine
				20.3.4.1	 Pharmacology
				20.3.4.2	 Clinical Effects
				20.3.4.3	 Clinical Indications
				20.3.4.4	 Adverse Effects
			20.3.5	 Dopamine
				20.3.5.1	 Pharmacology
				20.3.5.2	 Clinical Effects
				20.3.5.3	 Clinical Indications
				20.3.5.4	 Adverse Effects
			20.3.6	 Isoproterenol
				20.3.6.1	 Pharmacology
				20.3.6.2	 Clinical Effects
				20.3.6.3	 Clinical Indications
				20.3.6.4	 Adverse Effects
			20.3.7	 Vasopressin
				20.3.7.1	 Pharmacology
				20.3.7.2	 Clinical Effects
				20.3.7.3	 Clinical Indications
				20.3.7.4	 Adverse Effects
		20.4 Vasodilators for Circulatory Support
			20.4.1	 Physiologic Effects
		20.5 Specific Vasodilators
			20.5.1	 Milrinone
				20.5.1.1	 Pharmacology
				20.5.1.2	 Clinical Effects
				20.5.1.3	 Clinical Indications
				20.5.1.4	 Adverse Effects
			20.5.2	 Sodium Nitroprusside
				20.5.2.1	 Pharmacology
				20.5.2.2	 Clinical Effects
				20.5.2.3	 Clinical Indications
				20.5.2.4	 Adverse Effects
			Box 20.1 Overview of Cyanide Toxicity
			Box 20.2 Overview of Thiocyanate Toxicity
			20.5.3	 Nitroglycerine (NTG)
				20.5.3.1	 Pharmacology
				20.5.3.2	 Clinical Effects
				20.5.3.3	 Clinical Indications
				20.5.3.4	 Adverse Effects
			20.5.4	 Phentolamine and Phenoxybenzamine
				20.5.4.1	 Pharmacology
				20.5.4.2	 Clinical Effects
				20.5.4.3	 Clinical Indications
				20.5.4.4	 Adverse Effects
		20.6 Novel Agents
			20.6.1	 Levosimendan
				20.6.1.1	 Pharmacology
				20.6.1.2	 Clinical Effects
				20.6.1.3	 Clinical Indications
				20.6.1.4	 Adverse Effects
			20.6.2	 Tolvaptan
			20.6.3	 Istaroxime
		20.7 Use of Cardiovascular Agents in Septic Shock
		20.8 Control of Severe Hypertension
			20.8.1	 Nicardipine
				20.8.1.1	 Pharmacology
				20.8.1.2	 Clinical Effects
				20.8.1.3	 Clinical Indications
				20.8.1.4	 Adverse Effects
			20.8.2	 Esmolol
				20.8.2.1	 Pharmacology
				20.8.2.2	 Clinical Effects
				20.8.2.3	 Clinical Indications
				20.8.2.4	 Adverse Effects
			20.8.3	 Labetalol
			20.8.4	 Enalaprilat
			20.8.5	 Fenoldopam
		Suggested Readings
	21: Mechanical and Electrical Myocardial Support
		21.1 Cardiopulmonary Resuscitation
			21.1.1 Physiologic Basis of CPR and Patterns of Blood Flow
			21.1.2 Rationale of Pharmacotherapy for Patients with Cardiac Arrest
			21.1.3 Outcomes After Cardiac Arrest
			21.1.4 2015 AHA Pediatric Guidelines for Basic and Advanced Life Support for Healthcare Providers
		21.2 Extracorporeal Life Support
			21.2.1 Mechanics of ECMO
				21.2.1.1 Veno-Venous (VV) ECMO
				21.2.1.2 Veno-Arterial (VA) ECMO
			21.2.2 Indications for ECMO
			21.2.3 Outcomes
				21.2.3.1 Outcomes for ECMO Used for Respiratory Indications
				21.2.3.2 Outcomes for ECMO Used for Cardiac Indications
			21.2.4 Extracorporeal Cardiopulmonary Resuscitation (ECPR)
		21.3 Mechanical Assist Devices
			21.3.1 Intraaortic Balloon Pumps (IABP)
			21.3.2 Ventricular Assist Devices (VADs)
				21.3.2.1 Impella (Abiomed Inc.)
				21.3.2.2 TandemHeart (CardiacAssist, Pittsburgh, Pennsylvania, United States of America)
			21.3.3 Indications for Use of a VAD
			21.3.4 Complications Associated with the Use of a VAD
			21.3.5 Outcomes of Patients Who Require VAD
		21.4 Temporary Pacemakers in the PICU
			21.4.1 Normal Cardiac Conduction
			21.4.2 Special Considerations for Pediatric Patients
			21.4.3 Which Temporary Pacemaker Should Be Used?
			21.4.4 Types of Temporary Pacemakers
			21.4.5 Use of Controls
				21.4.5.1 Single-Chamber Pacemaker
				21.4.5.2 Dual-Chamber Pacemaker
			21.4.6 Nomenclature and Parameters to Aid Pacemaker Setting
			21.4.7 Thresholds
				21.4.7.1	 Pacing or Capture Threshold
					How to Check the Pacing Threshold?
					Why Should the Pacing Threshold Be Checked?
				21.4.7.2 Sensing Threshold
					Why Is It Important to Know the Sensitivity Threshold?
					How to Check Sensitivity Threshold?
					How to Set Sensitivity Level?
			21.4.8 Intrinsic Rhythm
				21.4.8.1 Battery
				21.4.8.2 Documentation
			21.4.9 Contraindications and Precautions
			21.4.10 Sites and Techniques of Placement
				21.4.10.1	 Temporary Epicardial (Post-Cardiac Surgery)
				21.4.10.2 Temporary Transvenous
				21.4.10.3 Temporary Transesophageal Pacing
				21.4.10.4 Temporary External Transcutaneous Pacing
			21.4.11 Troubleshooting Pacemaker Malfunction
		Suggested Readings
			Cardiopulmonary Resuscitation
			Extracorporeal Membrane Oxygenation
			Ventricular Assist Devices
			Pacemakers
IV: Central and Peripheral Nervous System
	22: Central and Peripheral Nervous Systems: Development, Structure, and Function
		22.1	 Introduction
		22.2	 Development of the Nervous System
			22.2.1	 CNS Development
			22.2.2	 Glial Cells
			22.2.3	 Development of CNS Vasculature and Blood Brain Barrier
		22.3	 Structure and Functions of the Nervous System
			22.3.1	 Central Nervous System: Spinal Cord
			22.3.2	 Central Nervous System: Brain
				22.3.2.1	 Brainstem
				22.3.2.2	 Medulla
				22.3.2.3	 Pons
				22.3.2.4	 Cerebellum
				22.3.2.5	 Midbrain
				22.3.2.6	 Reticular Formation
				22.3.2.7	 Cerebrum
					Diencephalon
					Cerebral Hemispheres
					Basal Ganglia
				22.3.2.8	 Vascular Supply to the Brain and Spinal Cord
					Arterial Blood Supply to the Brain
					Arterial Blood Supply to the Spine
					Cerebral Autoregulation
						Pressure Autoregulation
						Oxygen-Related Autoregulation
						pH-Based Autoregulation
						Metabolic Coupling
				22.3.2.9	 Ventricular System and CSF
				22.3.2.10	 Meninges
			22.3.3	 Peripheral Nervous System
		22.4	 Summary
		Suggested Readings
	23: Physiology of Skeletal Muscle and the Neuromuscular Junction
		23.1	 Skeletal Muscle
		23.2	 Neuromuscular Junction
			23.2.1	 Presynaptic Nerve Terminal
			23.2.2	 Acetylcholine Receptor
			23.2.3	 Muscle Action Potential and Electromechanical Coupling
		23.3	 Contractile Apparatus and Development of Muscle Tension
			23.3.1	 Energy Requirements and Limitations
		23.4	 Neuromuscular Function in the Newborn
		23.5	 Inhibition at the Neuromuscular Junction
			23.5.1	 Non-depolarizing Neuromuscular Blockers
			23.5.2	 Depolarizing Neuromuscular Blockers
			23.5.3	 Other Non-competitive Inhibition of the Neuromuscular Junction
		23.6	 Sensitivity to Neuromuscular Blockade
		23.7	 Abnormalities of Skeletal Muscle and the Neuromuscular Junction
		Suggested Readings
	24: Assessment of Neurologic Function
		24.1	 Introduction
		24.2	 Examination
			24.2.1	 Consciousness
			24.2.2	 Brainstem
				24.2.2.1	 Cranial Nerve Exam
					Pupillary Light Response
					Corneal Reflex
					Eye Movements
					Gag Reflex
				24.2.2.2	 Integrated Assessment of Brainstem Activity
					Motor Responses
					Respiratory Patterns
					Brainstem-Mediated Hemodynamic Changes
				24.2.2.3	 Herniation Syndromes
			24.2.3	 Spinal Cord
				24.2.3.1	 Dermatomal Distribution
				24.2.3.2	 Spinal Syndromes
			24.2.4	 Peripheral Nerve Function
			24.2.5	 Brain Death Determination
		24.3	 Assessment of Cerebral Blood Flow
		24.4	 Intracranial Pressure Monitoring
		24.5	 Evaluation of Cerebrospinal Fluid
		24.6	 Neurophysiologic Monitoring
			24.6.1	 Electroencephalogram
			24.6.2	 Evoked Potentials
			24.6.3	 Train of Four
			24.6.4	 Multimodality Monitoring
		24.7	 Neuroimaging
			24.7.1	 Computed Tomography
			24.7.2	 Magnetic Resonance Imaging
		24.8	 Biomarkers
		24.9	 Conclusion
		Suggested Readings
	25: Cerebral Resuscitation and Traumatic and Hypoxic-Ischemic Brain Injury
		25.1	 Introduction
		25.2	 Mechanisms of Brain Injury
			25.2.1	 Ischemia
			25.2.2	 Excitotoxicity
			25.2.3	 Oxidative Stress
			25.2.4	 Cerebral Edema
			25.2.5	 Inflammation
			25.2.6	 Conclusion
		25.3	 Neurointensive Care Monitoring
			25.3.1	 Non-invasive Monitoring
			25.3.2	 Intracranial Pressure
			25.3.3	 Cerebral Perfusion Pressure
			25.3.4	 Cerebral Blood Flow
			25.3.5	 Transcranial Doppler Ultrasonography
			25.3.6	 Cerebral Metabolic Monitoring
			25.3.7	 Brain Tissue Oximetry
			25.3.8	 Cerebral Microdialysis
			25.3.9	 EEG
			25.3.10	 Computed Tomography
			25.3.11	 Magnetic Resonance Imaging/Spectroscopy
		25.4	 Clinical Management Guidelines
			25.4.1	 Traumatic Brain Injury
				25.4.1.1	 Acute Management
				25.4.1.2	 Intensive Care Unit Management
				25.4.1.3	 ICP-Directed Therapies
			25.4.2	 Cardiac Arrest
				25.4.2.1	 Acute Management
				25.4.2.2	 Intensive Care Unit
		25.5	 Epidemiology and Clinical Outcomes
			25.5.1	 Traumatic Brain Injury
			25.5.2	 Cardiac Arrest
		25.6	 Summary
		Suggested Readings
	26: Neurological Diseases in Pediatric Critical Care
		26.1	 Introduction
		26.2	 Altered Mental Status
			26.2.1	 Infectious Causes of Altered Mental Status
			26.2.2	 Inflammatory Causes of Altered Mental Status
				26.2.2.1	 Acute Disseminated Encephalomyelitis (ADEM)
				26.2.2.2	 Autoimmune Encephalitis (AE)
			26.2.3	 Vascular Causes of Altered Mental Status
				26.2.3.1	 Reversible Posterior Leukoencephalopathy Syndrome
			26.2.4	 Metabolic/Toxic Causes of Altered Mental Status
			26.2.5	 Structural Causes of Altered Mental Status
			26.2.6	 Evaluation of the Child with Altered Mental Status
		26.3	 Status Epilepticus
		26.4	 Disorders of Muscular Tone and Strength: Infants
		26.5	 Disorders of Muscular Tone and Strength: Older Children and Adolescents
		Suggested Readings
	27: Sedation and Analgesia
		27.1 Introduction
		27.2 Sedation: Analgesia Definitions and Scales
		27.3 Pre-sedation Assessment for the Non-intubated Patient
			27.3.1	 History
			Box 27.1 Pre-sedation Assessment
			27.3.2	 Physical Examination
			27.3.3	 Monitoring
		27.4 Sedative Medications
			27.4.1	 Benzodiazepines
				27.4.1.1	 Pharmacology
				27.4.1.2	 Clinical Effects
				27.4.1.3	 Clinical Indications
				27.4.1.4	 Adverse Effects
			27.4.2	 Midazolam
			27.4.3	 Diazepam
			27.4.4	 Lorazepam
			27.4.5	 Benzodiazepine Antagonist
			27.4.6	 Non-benzodiazepine Sedatives
				27.4.6.1	 Propofol
					Pharmacology
					Clinical Effects
					Clinical Indications
					Adverse Effects
			27.4.7	 Ketamine
				27.4.7.1	 Pharmacology
				27.4.7.2	 Clinical Effects
				27.4.7.3	 Clinical Indications
				27.4.7.4	 Adverse Effects
			27.4.8	 Barbiturates
				27.4.8.1	 Pharmacology
				27.4.8.2	 Clinical Effects
				27.4.8.3	 Clinical Indications
				27.4.8.4	 Adverse Effects
			27.4.9	 Alpha 2 Adrenergic Agonists
			27.4.10	 Clonidine
			27.4.11	 Dexmedetomidine
				27.4.11.1	 Pharmacology
				27.4.11.2	 Clinical Effects
				27.4.11.3	 Clinical Indications
				27.4.11.4	 Adverse Effects
			27.4.12	 Chloral Hydrate
		27.5 Analgesic Medications
			27.5.1	 Opioid Analgesics
				27.5.1.1	 Pharmacology
				27.5.1.2	 Clinical Effects and Indications
				27.5.1.3	 Adverse Effects
			27.5.2	 Morphine
			27.5.3	 Fentanyl
			27.5.4	 Remifentanil
			27.5.5	 Hydromorphone
			27.5.6	 Methadone
			27.5.7	 Non-opioid Analgesics
			27.5.8	 Opioid Antagonist
		27.6 Tolerance and Dependence
		27.7 Benzodiazepine and Opioid Withdrawal: Prevention and Treatment
		Box 27.2 Key Elements in the Prevention of Opioid Tolerance and Treatment of Opioid Withdrawal
		27.8 Conclusions
		Suggested Readings
	28: Neuromuscular Blockade
		28.1 Introduction
		28.2 Indications and General Issues
		Box 28.1 Indications for Neuromuscular Blockade in the PICU
		28.3 Pharmacology of Muscle Relaxants in Children
			28.3.1	 Dosage and Administration
		28.4 Physiology of the Neuromuscular Junction
		28.5 Specific Agents
			28.5.1	 Depolarizing Agents
			28.5.2	 Mechanism of Action and Kinetics
			28.5.3	 Cholinesterase Deficiency and Dysfunction
			28.5.4	 Adverse Effects of Succinylcholine
		28.6 Recommendations for Use
		28.7 Non-depolarizing Neuromuscular Blockers
			28.7.1	 Benzylisoquinolines
			28.7.2	 Aminosteroids
			28.7.3	 Interactions and Adverse Effects of Neuromuscular Blockade
			28.7.4	 Tolerance
			28.7.5	 Myopathy
		28.8 Monitoring of Neuromuscular Blockade
		28.9 Reversal of Neuromuscular Blockade
		28.10 Conclusions
		Suggested Readings
V: Renal and Electrolyte
	29: Overview, Structure, and Function of the Nephron
		29.1 Structure of the Nephron
			Box 29.1 Factors Necessary to Generate a Concentrated or Dilute Urine
		29.2 Regulation of Renal Blood Flow
			29.2.1 Regulation of Renal Blood Flow, Determinants of Glomerular Filtration Rate
		29.3 Determination of Glomerular Filtration Rate (GFR)
			29.3.1 Changes in GFR with Age
			29.3.2 Exogenous GFR Markers
			29.3.3 Creatinine Clearance
			29.3.4 Serum Creatinine
			29.3.5 Urea
			29.3.6 Cystatin C
		29.4 Water and Salt Balance: Overview
			29.4.1 Maintenance of Effective Circulating Volume
			29.4.2 Effects of Renin/Angiotensin II
			29.4.3 Aldosterone
			29.4.4 Renal Sodium Handling
				29.4.4.1	 Atrial Natriuretic Peptide (ANP)
			29.4.5 Water Balance
			29.4.6 Role of Renal Prostaglandins
		29.5 Potassium Regulation
		29.6 Diuretics
		29.7 Energy Requirement of the Normal Kidney
		29.8 Acid Base
			Box 29.2 Sources of Acid Load
			29.8.1 Regulation of Renal Hydrogen Excretion
			29.8.2 Defects in Acidification
			29.8.3 Treatment of RTA
			29.8.4 Lactic Acidosis
		Suggested Reading
	30: Fluid/Electrolyte/Acid-Base Abnormalities
		30.1 Volume Depletion (Dehydration)
			30.1.1	 Treatment
				30.1.1.1	 Isotonic Solution Versus Balanced Solution for Fluid Resuscitation
		30.2 Hypernatremia
			30.2.1	 Pathogenesis
			30.2.2	 Diagnosis
			30.2.3	 Clinical Manifestations of Hypernatremia
			30.2.4	 Treatment
			30.2.5	 Central Diabetes Insipidus
			30.2.6	 Hypernatremia in the Edematous Patient
		30.3 Hyponatremia
			30.3.1	 Pathogenesis
			30.3.2	 Diagnosis
			30.3.3	 Hospital-Acquired Hyponatremia and its Prevention
			30.3.4	 Hyponatremic Encephalopathy
				30.3.4.1	 Clinical Symptoms
				30.3.4.2	 Risk Factors for Developing Hyponatremic Encephalopathy
					Age
					Hypoxia
					Syndrome of Inappropriate Antidiuretic Hormone Production (SIADH)
					Cerebral Salt Wasting (Also See 7 Chap. 43)
				30.3.4.3	 Treatment of Hyponatremic Encephalopathy
					Cerebral Demyelination Complicating the Correction of Hyponatremia
			30.3.5	 Hyponatremia in Edematous States
				30.3.5.1	 Pathophysiology
				30.3.5.2	 Increased Capillary Hydraulic Pressure
				30.3.5.3	 Decreased Plasma Oncotic Pressure
				30.3.5.4	 Increased Capillary Permeability
				30.3.5.5	 Treatment of Hyponatremia in Edema-Forming States
		30.4 Hypocalcemia
			30.4.1	 Calcium Homeostasis
			30.4.2	 Etiology of Hypocalcemia (. Table 30.4)
			30.4.3	 Hypocalcemia in the Critical Care Setting
			30.4.4	 Acute Management of Hypocalcemia
		30.5 Hypokalemia
			30.5.1	 Potassium Homeostasis
			30.5.2	 Clinical Effects of Hypokalemia
			30.5.3	 Causes of Hypokalemia in the Critical Care Settings (7 Box 30.2)
			30.5.4	 Treatment of Hypokalemia
		30.6 Hyperkalemia
			30.6.1	 Patients at Risk for Hyperkalemia (7 Box 30.3)
			30.6.2	 Clinical Effects of Hyperkalemia
			30.6.3	 Treatment of Hyperkalemia
		30.7 Magnesium
			30.7.1	 Hypomagnesemia
			30.7.2	 Hypermagnesemia
		30.8 Phosphorus
			30.8.1	 Hypophosphatemia
			30.8.2	 Hyperphosphatemia
		30.9 Metabolic Acidosis
			30.9.1	 Hyperchloremic Metabolic Acidosis (7 Box 30.5)
				30.9.1.1	 Gastrointestinal Losses of Bicarbonate
				30.9.1.2	 Dilutional Acidosis
				30.9.1.3	 Renal Tubular Acidosis
			30.9.2	 Elevated Anion Gap Acidosis (7 Box 30.6)
				30.9.2.1	 Lactic Acidosis
				30.9.2.2	 Toxic Ingestions
			30.9.3	 Clinical Effects of Acidemia (7 Box 30.7)
			30.9.4	 Treatment of Metabolic Acidosis with Bicarbonate: The Pros and Cons
				30.9.4.1	 Diabetic Ketoacidosis
				30.9.4.2	 Lactic Acidosis
				30.9.4.3	 Cardiac Arrest
		30.10 Metabolic Alkalosis
			30.10.1	 Chloride-Sensitive Alkalosis
			30.10.2	 Chloride-Resistant Alkalosis
			30.10.3	 Post-hypercapnic Metabolic Alkalosis
			30.10.4	 Adverse Clinical Effects of Alkalemia (7 Box 30.9)
			30.10.5	 Treatment of Metabolic Alkalosis
		Suggested Reading
			Dehydration
			Hyponatremia/Hypernatremia
			Hypocalcemia
			Hypokalemia/Hyperkalemia
			Magnesium and Phosphorous
			Acid-Base
	31: Acute Kidney Injury
		31.1 Assessing Renal Function in Children
		31.2 Definition of Acute Kidney Injury
		31.3 Early Biomarkers of Acute Kidney Injury
		31.4 Epidemiology
		31.5 Causes of Acute Kidney Injury
			31.5.1	 Classification
			31.5.2	 Pre-renal Acute Kidney Injury
			31.5.3	 Intrinsic Acute Kidney Injury
			31.5.4	 Acute Tubular Necrosis
			31.5.5	 Ischemic Renal Injury
			31.5.6	 Sepsis-Associated Intrinsic Kidney Injury
			31.5.7	 Solid Organ and Hematopoietic Cell Transplantation
			31.5.8	 Nephrotoxins
			31.5.9	 Tumor Lysis Syndrome
		31.6 Primary Renal Disorders
			31.6.1	 Hemolytic Uremic Syndrome
			31.6.2	 Glomerulonephritis
			31.6.3	 Interstitial Nephritis
			31.6.4	 Post-renal Acute Kidney Injury
		31.7 Manifestations and Evaluation
		31.8 Management
			31.8.1	 Fluid Management
			31.8.2	 Diuretics
			31.8.3	 Vasopressors
			31.8.4	 Correction of Electrolyte Imbalances
			31.8.5	 Indications for Renal Replacement Therapy
			31.8.6	 Peritoneal Dialysis
			31.8.7	 Hemodialysis
			31.8.8	 Continuous Renal Replacement Therapies
			31.8.9	 Pharmacologic Considerations in Acute Kidney Injury
		31.9 Prevention of Acute Kidney Injury
		31.10 Effect of Renal Failure on Other Diseases
		31.11 Prognosis
		31.12 Summary
		Suggested Reading
	32: Renal Replacement Therapies
		32.1 Introduction
		32.2 Peritoneal Dialysis (PD)
			32.2.1	 PD Access
			32.2.2	 Solutions for PD
			32.2.3	 PD Tubing
			32.2.4	 Heating Units in PD
			32.2.5	 Initiation of PD
			32.2.6	 Antibiotics in PD
			32.2.7	 Complications of PD
			32.2.8	 Solute Clearance in PD
			32.2.9	 Ultrafiltration of PD
		32.3 Continuous-Flow Peritoneal Dialysis
		32.4 Hemodialysis
			32.4.1	 Vascular Access
			32.4.2	 Blood Flow Rate for Hemodialysis
			32.4.3	 Dialysate Flow Rate
			32.4.4	 Extracorporeal Blood Volume in Hemodialysis
			32.4.5	 The Standard Prescription for Hemodialysis
			32.4.6	 Anticoagulation in Hemodialysis
		32.5 Sustained Low-Efficiency Dialysis
		32.6 Continuous Renal Replacement Therapy (CRRT)
			32.6.1	 Selection of CRRT Modality
			32.6.2	 Anticoagulation in CRRT
			32.6.3	 CRRT Use with Extracorporeal Membrane Oxygenation (ECMO)
		32.7 Nutrition Losses in Renal Replacement Therapy
		32.8 Medication Clearance
		32.9 Indications
			32.9.1	 Inborn Errors of Metabolism
			32.9.2	 Intoxications
		32.10 Summary
		Suggested Reading
VI: Infectious Disease
	33: Acute Pulmonary Infections
		33.1 Introduction
		33.2 Bronchiolitis
			33.2.1	 Epidemiology
			33.2.2	 Etiology of Viral Bronchiolitis
			33.2.3	 General Presentation and Pathophysiology
			33.2.4	 Respiratory Syncytial Virus (RSV)
			33.2.5	 Pathophysiology
				33.2.5.1	 Antibody-Mediated Immunity
				33.2.5.2	 Cell-Mediated Immunity
			33.2.6	 Clinical Presentation and Course
			33.2.7	 High-Risk Populations
			33.2.8	 Non-RSV Bronchiolitis
				33.2.8.1	 Rhinovirus/Enterovirus
				33.2.8.2	 Parainfluenza
				33.2.8.3	 Metapneumoviruses
				33.2.8.4	 Human Bocavirus
				33.2.8.5	 Coronavirus
				33.2.8.6	 Influenza A and B
				33.2.8.7	 Diagnosis
				33.2.8.8	 Treatment
				33.2.8.9	 Prevention
		33.3 Pneumonia
			33.3.1	 Clinical Presentation
			33.3.2	 Epidemiology
			33.3.3	 Normal Host Defense Mechanisms
			33.3.4	 Pathophysiology
		33.4 Specific Etiologies
			33.4.1	 Bacterial Pneumonia
				33.4.1.1	 Streptococcus pneumoniae
				33.4.1.2	 Chlamydia trachomatis
				33.4.1.3	 Chlamydia pneumoniae and Mycoplasma pneumoniae
				33.4.1.4	 Staphylococcus aureus
				33.4.1.5	 Group A Beta-hemolytic Streptococcus
				33.4.1.6	 Group B Streptococcus
				33.4.1.7	 Bordetella pertussis
			33.4.2	 Viral Pneumonia
				33.4.2.1	 Influenza
				33.4.2.2	 Avian Influenza
				33.4.2.3	 Novel H1N1 Influenza A
				Box 33.1 High-Risk Conditions Associated with Life-Threatening H1N1 Infection
				33.4.2.4	 Adenovirus
				33.4.2.5	 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV)
				33.4.2.6	 Hantavirus Cardiopulmonary Syndrome (HCPS)
			33.4.3	 Pneumonia in the Immunocompromised Host
				33.4.3.1	 Pneumocystis jirovecii Pneumonia (PJP)
		33.5 Diagnosis of Pneumonia
		33.6 Treatment
		Box 33.2 Light Criteria with Individual Sensitivity and Specificity of Tests to Distinguish Exudative From Transudative Effusions
		33.7 Conclusion
		Suggested Readings
	34: Sepsis
		34.1 Introduction
		34.2 Definitions
		Box 34.1 Criteria for SIRS, Severe Sepsis, and Septic Shock
		34.3 Epidemiology
		34.4 Clinical Presentation
		34.5 Pathogenesis of Sepsis
			34.5.1	 Inflammatory Cascade of Sepsis
			34.5.2	 Signal Transduction Pathways
			34.5.3	 Principal Gene Products/Mediators of the Septic Response
			34.5.4	 Tumor Necrosis Factor-α
			34.5.5	 Interleukin-1β
			34.5.6	 Adhesion Molecules
			34.5.7	 Nitric Oxide
			34.5.8	 Putative Role of “Late” Mediators in the Pathogenesis of Sepsis
			34.5.9	 Role of Host Mediators in the Resolution of Sepsis
			34.5.10	 Role of the Coagulation Cascade in Sepsis
			34.5.11	 Genetic Regulation of the Septic Response
		34.6 Treatment Strategies
			34.6.1	 Overview
			34.6.2	 Initial Resuscitation
			34.6.3	 Invasive Monitoring
			34.6.4	 Elimination of Pathogen
			34.6.5	 Maintenance of Oxygen Delivery
			34.6.6	 Additional Therapeutic Modalities
			34.6.7	 Institutional Level Care Bundles
		34.7 Summary
		Suggested Readings
	35: Overwhelming Infections in Pediatric Critical Care
		35.1 Introduction
		35.2 Bloodstream Infections
			Box 35.1 Risk Factors for Fungal Bloodstream Infections
			35.2.1	 Toxic Shock Syndrome
			35.2.2	 Endocarditis
			Box 35.2 Risk Factors for Infectious Endocarditis
			Box 35.3 Modified Duke Criteria
			35.2.3	 Endovascular Infections
		35.3 Necrotizing Skin and Soft Tissue Infections (SSTI)
		35.4 Central Nervous System (CNS) Infections
			35.4.1	 Acute Bacterial Meningitis
			35.4.2	 Focal Suppurative CNS Infections
			35.4.3	 Ventricular Shunt Infections
			35.4.4	 Encephalitis
		35.5 Pneumonia/Pulmonary Infections
		35.6 Special Populations
			35.6.1	 Sepsis in Oncological Patients with Neutropenia
			35.6.2	 Hematopoietic Cell Transplant (HCT) Patients
			35.6.3	 Solid Organ Transplant Patients
		35.7 Less Common and/or Travel-Related Infections
			35.7.1	 Rickettsia
			35.7.2	 Viral Hemorrhagic Fevers
			35.7.3	 Malaria
			35.7.4	 Tuberculosis (TB)
		35.8 Summary
		Suggested Readings
			Bloodstream Infections
			Toxic Shock
			Endocarditis
			Necrotizing Fasciitis
			CNS Infections
			Pneumonia
			Special Populations
			Travel
	36: Multiple Organ Dysfunction Syndrome
		36.1 Introduction
		36.2 Epidemiology
		36.3 Clinical Presentation
			36.3.1	 Cardiovascular
			36.3.2	 Respiratory
			36.3.3	 Neurologic
			36.3.4	 Gastrointestinal
			36.3.5	 Hematologic
			36.3.6	 Renal
			36.3.7	 Other Systems
		36.4 Outcomes and Predictors of Outcome
		36.5 Cellular Mechanisms and Pathology
		36.6 Therapy
			36.6.1	 Supportive Care in Multiple Organ Dysfunction Syndrome (MODS)
		36.7 Specific Therapeutic Consideration in MODS
		36.8 Summary
		Suggested Readings
	37: Healthcare-Associated Infections
		37.1 Introduction
		37.2 Epidemiology
		37.3 Risk Factors
		37.4 Bloodstream Infection
			37.4.1 Prevention
			37.4.2 Treatment
		37.5 Respiratory Infection
			37.5.1 Prevention
			37.5.2 Treatment
		37.6 Urinary Tract Infection
			37.6.1 Prevention
			37.6.2 Treatment
		37.7 Special Populations
			37.7.1 Surgical Patients
				37.7.1.1 Cardiothoracic Surgery
				37.7.1.2 Neurosurgery and Craniofacial Surgery
				37.7.1.3 Burns
			37.7.2 Immunocompromised Patients
			37.7.3 Clostridium difficile Infections (CDI)
		37.8 General Principles for the Prevention and Diagnosis of Healthcare-Associated Infections
			37.8.1 Maintain Good Hand Hygiene
			37.8.2 Follow Standard Isolation Practices
			37.8.3 Manage Devices Meticulously and Remove as Soon as Possible
			37.8.4 Use Standard Criteria for Diagnosing Infections
			37.8.5 Use Antibiotics When Clearly Indicated
			37.8.6 Minimize Exposure of Patients to Visitors/Staff with Transmittable Infections
		37.9 Conclusion
		Suggested Readings
VII: Hematology
	38: Disseminated Intravascular Coagulation
		38.1 Introduction
			Box 38.1 Clinical Conditions That May Be Associated With Disseminated Intravascular Coagulation
		38.2 Pathophysiology
			Box 38.2 Primary Pathophysiologic Mechanisms Contributing to Inflammation-Induced Disseminated Intravascular Coagulation
		38.3 Clinical Aspects
		38.4 Diagnosis
		38.5 DIC Treatment
		38.6 Conclusion
		Suggested Reading
	39: Oncological Critical Care Considerations in Children
		39.1 Introduction
		39.2 Oncological Emergencies
			39.2.1 Tumor Lysis Syndrome
				39.2.1.1 Hyperuricemia
				39.2.1.2 Hyperphosphatemia
				39.2.1.3 Hyperkalemia
				39.2.1.4 Hypocalcemia
				39.2.1.5 Monitoring
			39.2.2 Hyperleukocytosis Syndrome
			39.2.3 Mediastinal Mass
				39.2.3.1 Pathophysiology
				39.2.3.2 Identification of High-Risk Patients
				39.2.3.3 Management and Approach to the Diagnostic Work-Up
				39.2.3.4 Use of Anesthesia or Deep Sedation
			39.2.4 Cardiac Emergencies
				39.2.4.1 Monitoring and Diagnosis
				39.2.4.2 Management
			39.2.5 Neurological Emergencies
				39.2.5.1 Posterior Reversible Encephalopathy Syndrome (PRES)
				39.2.5.2 Spinal Cord Compression
			39.2.6 Infections
				39.2.6.1 Hematological Infections
				39.2.6.2 Invasive Fungal Infections
				39.2.6.3 Hematogenous Fungal Infections
				39.2.6.4 Pulmonary Infections
				39.2.6.5 Invasive Sinopulmonary Fungal Disease
				39.2.6.6 Pneumocystis Jiroveci Pneumonia
				39.2.6.7 CNS Infections
			39.2.7 Febrile Neutropenia
			39.2.8 Special Considerations in Sepsis
		39.3 Hemophagocytic Lymphohistocytosis Syndrome
			39.3.1 Primary HLH
			39.3.2 Secondary HLH
			39.3.3 Management of HLH
		39.4 Anticancer Therapies
			39.4.1 Agents Disrupting the DNA Helix
				39.4.1.1 Alkylating Agents
			39.4.2 Agents Interfering with DNA-Related Proteins
				39.4.2.1 Antimetabolites
				39.4.2.2 Topoisomerase I and II Inhibitors
			39.4.3 Antitumor Antibiotics
			39.4.4 Vinca Alkaloids and Taxanes
			39.4.5 Kinase Inhibitors
			39.4.6 Cancer Immunotherapies
			39.4.7 Checkpoint Inhibitors
			39.4.8 Antibody Therapy
				39.4.8.1 Monoclonal Antibodies
				39.4.8.2 Bispecific Monoclonal Antibodies
			39.4.9 Adoptive Therapy
				39.4.9.1 Autologous Chimeric Antigen Receptor (CAR) T-Cell Therapy
				39.4.9.2 Cytokine Release Syndrome (CRS)
				39.4.9.3 CAR T-Cell Related Encephalopathy Syndrome (CRES) or Immune Effector Cell Asscociated Neurotoxicity Syndrome (ICANS)
				39.4.9.4 Radiation Therapy
		39.5 Summary
		Suggested Readings
	40: Care of the Critically Ill Pediatric Hematopoietic Cell Transplant Patient
		40.1 Introduction
		40.2 Hematopoietic Cell Transplantation Process
			40.2.1	 Indications and Types of Transplants
			40.2.2	 Conditioning (or Preparative) Regimens
			40.2.3	 Timeline
		40.3 Respiratory Complications Post-HCT
			40.3.1	 Infectious Complications
			40.3.2	 Noninfectious Complications
		40.4 Cardiovascular Complications Post-HCT
		40.5 Endotheliopathies Post-HCT
			40.5.1	 Sinusoidal Obstruction Syndrome (SOS)
			40.5.2	 Transplant Associated Thrombotic Microangiopathy (TA-TMA)
		40.6 Infectious Complications Post-HCT
			40.6.1	 Bacterial Infections
			40.6.2	 Fungal Infections
			40.6.3	 Viral Infections
			40.6.4	 Protozoal Infections
		40.7 Engraftment Syndrome
		40.8 Graft Versus Host Disease
		40.9 Neurologic Complications Post-HCT
		40.10 Post-transplant Lymphoproliferative Disease
		40.11 Chimeric Antigen Receptor (CAR)-Immune Effector Cell Therapy
			40.11.1	 Cytokine Release Syndrome (CRS)
			40.11.2	 CAR T-Cell Related Encephalopathy Syndrome (CRES) or Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS)
		40.12 Summary
		Suggested Readings
	41: Transfusion Medicine
		41.1 Introduction
		41.2 Red Blood Cell Transfusions
			41.2.1 Physiology
			41.2.2 Indications
			41.2.3 Alloimmunization
			41.2.4 Storage
			41.2.5 Administration
		41.3 Platelet Transfusions
			41.3.1	 Indications
		41.4 Types of Platelet Units and Storage Procedures
		41.5 Administration
		41.6 Fresh-Frozen Plasma
		41.7 Prothrombin Complex Concentrate
		41.8 Cryoprecipitate
		41.9 Granulocyte Transfusions
		41.10 Blood-Derived Albumin
		41.11 Intravenous Immune Globulin
		41.12 Activated Protein C
		41.13 Recombinant Factor VIIa
		41.14 Blood Processing
			41.14.1	 Leukoreduction
		41.15 Irradiation
		41.16 Washing
		41.17 Transfusion-Related Immunomodulation
		41.18 Transfusion Reactions
		41.19 Hemolytic Reactions
		41.20 Febrile Nonhemolytic Reactions
		41.21 Allergic/Anaphylactic Reactions
		41.22 Other Transfusion Complications
		41.23 Platelet-Specific Transfusion Reactions
		41.24 Infectious Risks
			41.24.1	 Identifying Risk
		41.25 Human Immunodeficiency Virus (HIV)
		41.26 Hepatitis B and C
		41.27 Cytomegalovirus
		41.28 West Nile Virus
		41.29 Adult T-Cell Lymphoma/Leukemia
		41.30 Zika Virus
		41.31 Other Viruses
		41.32 Transfusions in Special Patient Populations
			41.32.1	 Neonates
		41.33 Congenital Heart Disease
		41.34 Extracorporeal Membrane Oxygenation (ECMO)
		41.35 Uremic Patients
		41.36 Patients with Inherited Bleeding Disorders
		41.37 Oncology/Transplant Patients
		41.38 Sickle Cell Disease
		41.39 Alternative Therapy
			41.39.1	 Erythropoietin
		41.40 Hemostatic and Other Agents and Blood Substitutes
		41.41 Summary
		Suggested Readings
VIII: Gastrointestinal
	42: Acute Liver Injury and Failure in Children
		42.1 Introduction
		42.2 Anatomy and Physiology
		42.3 Definitions and Etiologies
			42.3.1	 Metabolic Liver Disease
			42.3.2	 Infection Induced Liver Disease
			42.3.3	 APAP Induced Liver Injury
			42.3.4	 NonAPAP Induced Liver Injury
			42.3.5	 Amatoxin Induced Liver injury
			42.3.6	 Autoimmune Liver injury
			42.3.7	 Miscellaneous Causes of Liver injury
		42.4 Clinical Presentation
		42.5 Diagnostic Evaluation
		42.6 Monitoring and Management of Complications
			42.6.1	 Hepatic Encephalopathy and Cerebral Edema
			42.6.2	 Management of Hyperammonemia and Elevated ICP
			42.6.3	 Coagulopathy
			42.6.4	 Nutritional and Metabolic Support
			42.6.5	 Cardiopulmonary Support
			42.6.6	 Renal Failure
			42.6.7	 Immune Dysfunction and Infections
			42.6.8	 Liver Support Devices
			42.6.9	 Transplant
			42.6.10	 Prognosis
		42.7 Summary
		Suggested Readings
IX: Endocrine and Metabolic
	43: Critical Care Endocrinology
		43.1 Introduction
		43.2 Hypoglycemia
			43.2.1	 Laboratory Evaluation
			43.2.2	 Treatment
		43.3 Diabetic Ketoacidosis (DKA)
			43.3.1	 Pathophysiology
			43.3.2	 Clinical Manifestations
			43.3.3	 Treatment
			43.3.4	 Morbidities
		43.4 Hyperglycemic Hyperosmolar State (HHS)
			43.4.1	 Pathophysiology
			43.4.2	 Clinical Manifestations
			43.4.3	 Morbidities
			43.4.4	 Treatment
		43.5 Pheochromocytoma
			43.5.1	 Clinical Presentation
			43.5.2	 Diagnosis
			43.5.3	 Treatment
		43.6 Adrenal Insufficiency
			43.6.1	 Clinical Presentation
			43.6.2	 Diagnosis
			43.6.3	 Treatment
		43.7 Congenital Adrenal Hyperplasia
			43.7.1	 Presentation
			43.7.2	 Laboratory Findings
			43.7.3	 Treatment
		43.8 Thyroid Abnormalities
			43.8.1	 Normal Actions of Thyroid Hormone
			43.8.2	 Acute Hyperthyroidism
			43.8.3	 Treatment
			43.8.4	 Hypothyroidism
			43.8.5	 Nonthyroidal Illness
		43.9 Calcium Homeostasis and Regulation of Extracellular Calcium
			43.9.1	 Hypocalcemia
			43.9.2	 Hypercalcemia
		43.10 Diabetes Insipidus and SIADH
			43.10.1	 Diabetes Insipidus
			43.10.2	 Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)
			43.10.3	 Cerebral Salt Wasting
		43.11 Endocrine Complications of Pediatric Brain Tumors
		43.12 Tight Glucose Control
		43.13 Summary
		Suggested Readings
	44: Metabolic Crises
		44.1 Introduction
		44.2 Pathophysiology
			44.2.1	 Biological Stress Response
			44.2.2	 Glucose Homeostasis and Metabolic Adaptation to Fasting
			44.2.3	 Protein Turnover and Endogenous Intoxication
			44.2.4	 Acid-Base Physiology
				44.2.4.1	 Organic Acids
				44.2.4.2	 Ammonia
		44.3 Clinical Presentation
		44.4 Laboratory Studies
		44.5 Neuroimaging
		44.6 Treatment
			44.6.1	 Evidence and Practice
			44.6.2	 Treatment Paradigms
			44.6.3	 General Strategies
			44.6.4	 Energy Requirements
			44.6.5	 Glucose and Insulin Infusions
			44.6.6	 L-Carnitine Therapy
			44.6.7	 Ammonia Removal
				44.6.7.1	 General Considerations
				44.6.7.2	 Pharmacology
		44.7 Hemodialysis
		44.8 Summary
		44.9 Online Point-of-Care Resources
		Suggested Readings
X: Special Topics and Populations
	45: Trauma/Burn
		45.1	 Overview of Pediatric Trauma Systems
			Box 45.1 Contributors to the Multidisciplinary Care of the Injured Child
		45.2	 Demographics of Childhood Injury
		45.3	 Initial Evaluation of the Traumatically Injured Child-Role of PCCM
		45.4	 Radiologic Imaging in Pediatric Trauma Patients
		45.5	 Evaluation of the Airway in a Multiply Injured Child
		45.6	 Establishing Vascular Access in the Injured Child
		45.7	 Hemodynamic Monitoring as a Guide to Therapy in the Multiply Injured Child
		45.8	 Stabilization and Evaluation of the Axial Skeleton
		45.9	 Supportive Care and Treatment for Cervical Spine Injury
		45.10	 Supportive Care and Treatment for Chest Injuries
			45.10.1	 Chest Imaging
			45.10.2	 Pulmonary Contusion
			45.10.3	 Pneumothorax/Hemothorax
			45.10.4	 Rib Fractures
			45.10.5	 Injury to the Great Vessels
		45.11	 Supportive Care and Treatment of Abdominal Injuries
			45.11.1	 Spleen Injury
			45.11.2	 Liver Injury
			45.11.3	 Kidney Injury
			45.11.4	 Pancreas Injury
			45.11.5	 Intestine Injury
		45.12	 Special Problems Associated with Orthopedic Injuries
			45.12.1	 Fat Embolism Syndrome
			45.12.2	 Compartment Syndrome
			45.12.3	 Hemorrhage
		45.13	 Deep Venous Thrombosis and Pulmonary Embolism
		45.14	 Approach to the Injured Child Who May Be the Victim of Non-accidental Injury
		45.15	 Head Injury
		45.16	 Initial Evaluation, Fluid Resuscitation, and Care of the Severely Burned Child
			45.16.1	 First Priorities
			45.16.2	 Carbon Monoxide Poisoning
			45.16.3	 Types of Burns and Extent of Burn Injury
			45.16.4	 Fluid Resuscitation
			45.16.5	 Criteria for Transfer
		45.17	 Summary
		Suggested Reading
	46: Toxicology for the Pediatric Intensivist
		46.1	 Epidemiology
		46.2	 Pediatric Considerations
		46.3	 Approach to the Child with the Unknown Ingestion
			46.3.1	 History
			46.3.2	 Physical Examination
			46.3.3	 Laboratory Evaluation
		46.4	 Stabilization
		46.5	 Decontamination and Prevention of Absorption
			46.5.1	 Ipecac
			46.5.2	 Activated Charcoal
			46.5.3	 Multiple-Dose Activated Charcoal
			46.5.4	 Cathartics
			46.5.5	 Gastric Lavage
			46.5.6	 Whole Bowel Irrigation (WBI)
			46.5.7	 Enhanced Excretion and Forced Diuresis
			46.5.8	 Urine Alkalinization
			46.5.9	 Extracorporeal Techniques
			46.5.10	 Intravenous Lipid Emulsion Therapy
		46.6	 Antidotes
		46.7	 Selected Overdoses of Importance to the Pediatric Intensivist
			46.7.1	 Acetaminophen
			46.7.2	 Salicylates
			46.7.3	 Tricyclic Antidepressants (TCAs)
			46.7.4	 Serotonergic and Non-serotonergic Antidepressants
				Box 46.1 Distinguishing Features of Serotonin Syndrome and Neuroleptic Malignant Syndrome
			46.7.5	 Anticholinergics
			46.7.6	 Muscle Relaxants
			46.7.7	 Organophosphates and Carbamates
			46.7.8	 Alcohols
			46.7.9	 β-Blockers and Calcium Channel Blockers
			46.7.10	 Clonidine
			46.7.11	 Digoxin
			46.7.12	 Sympathomimetics
			46.7.13	 Opioids and Synthetic Opioids
			46.7.14	 Cannabinoids and Synthetic Cannabinoids
			46.7.15	 GHB (γ-Hydroxybutyrate)
			46.7.16	 Dextromethorphan
			46.7.17	 Caustics
			46.7.18	 Hydrocarbons
			46.7.19	 Carbon Monoxide
			46.7.20	 Cyanide Toxicity
			46.7.21	 Methemoglobinemia
		Suggested Reading
	47: The Approach to the Critically Ill Infant
		47.1	 Introduction
		47.2	 Infant Anatomic and Physiologic Considerations
			47.2.1	 Airway
			47.2.2	 Breathing
				47.2.2.1	 Lung Volumes
				47.2.2.2	 Oxygen Metabolism
				47.2.2.3	 Airway Resistance
				47.2.2.4	 Respiratory Muscles
			47.2.3	 Cardiovascular
				47.2.3.1	 Intrauterine to Extrauterine Transition
				47.2.3.2	 Developmental Considerations
			47.2.4	 Central Nervous System
		47.3	 Initial Management of the Infant Presenting with Life-Threatening Critical Illness
			47.3.1	 Airway
			47.3.2	 Breathing
			47.3.3	 Circulation
			47.3.4	 Establishing Vascular Access
				47.3.4.1	 Peripheral Access
				47.3.4.2	 Interosseous Access
				47.3.4.3	 Central Venous Access
			47.3.5	 3 Ds
				47.3.5.1	 Disability
				47.3.5.2	 Dextrose
				47.3.5.3	 Drugs
				47.3.5.4	 Euthermia/Equipment
				47.3.5.5	 Foley
				47.3.5.6	 Gastric Tube
				47.3.5.7	 Hemoglobin/Hydrocortisone
			47.3.6	 Initial Investigations
		47.4	 Differential Diagnosis and Specific Diagnostic Considerations
		47.5	 Specific Diagnostic Considerations
			47.5.1	 Infectious
				47.5.1.1	 Neonatal Sepsis (Sepsis Neonatorum)
				47.5.1.2	 Group B Streptococcal Disease (GBSD)
					Clinical Manifestations
					Treatment
				47.5.1.3	 Herpes Simplex Virus
			47.5.2	 Cardiac
				47.5.2.1	 Congenital Heart Disease
					The Cyanotic Infant
					The Infant in Cardiogenic Shock
					The Infant with Congestive Heart Failure (CHF)
			47.5.3	 Neurologic
				47.5.3.1	 Infantile Botulism
				47.5.3.2	 Abusive Head Trauma in Infancy
					Box 47.1 Overview of Cerebral Protective Strategies Used in the Management of Traumatic Brain Injury (TBI) Secondary to Abusive Heads Trauma
			47.5.4	 Hematologic
				47.5.4.1	 Methemoglobinemia
				47.5.4.2	 Hemorrhagic Shock and Encephalopathy Syndrome
				47.5.4.3	 Metabolic
					Clinical Presentations
					Diagnosis
						Box 47.2 Initial Laboratory Studies in the Evaluation of an IEM
				47.5.4.4	 Management
		Suggested Reading
	48: Child Abuse
		48.1 Epidemiology
		48.2 Barriers and Biases
			48.2.1 Presentation of the Critically Ill Abused Child
		48.3 Cutaneous Injuries
		48.4 Abusive Head Trauma
			48.4.1 Definitions
			48.4.2 Mechanisms and Forces
			48.4.3 Radiologic Imaging
			48.4.4 Subdural and Subarachnoid Hemorrhages
			48.4.5 Spine Injuries
			48.4.6 Retinal Hemorrhages
			48.4.7 Constellation of Findings in AHT
		48.5 Abdominal Injuries
			48.5.1	 Solid Organ Injury
			48.5.2 Hollow Viscus Organ Injury
		48.6 Protocolized Evaluation of Child Physical Abuse
		48.7 Overdose and Self-Harm
		48.8 Caregiver-Fabricated Illness in a Child
		48.9 Mandated Reporting
		Suggested Readings
			Cutaneous Injury
			Abusive Head Injury
			Retinal Hemorrhages
			Abdominal Injury
			Fractures
			Medical Child Abuse
	49: Palliative Care in Pediatric Critical Care
		49.1 Introduction: Epidemiology of Pediatric Death
		49.2 Definitions of Death
			49.2.1	 The Determination of Cardiopulmonary Death
			49.2.2	 Brain Death Determination
		49.3 End-of-Life Care in the PICU
			49.3.1	 Physical Needs
			49.3.2	 Psychosocial Needs
			49.3.3	 Environmental Needs
			49.3.4	 Communication
		49.4 Ethical Issues
		49.5 Parental Bereavement Care After the Death of a Child in the PICU
			49.5.1	 Definitions
			49.5.2	 Health Outcomes of Bereavement
			49.5.3	 Risk and Resilience Factors Contributing to Parents’ Health Outcomes
			49.5.4	 The Role of the Critical Care Provider in Family Bereavement
				49.5.4.1	 What Can Critical Care Health Professionals Do to Help Parents Through the Bereavement Process?
			49.5.5	 Bereavement Interventions
			49.5.6	 Bereavement Support Considerations for Siblings
		49.6 Summary
		Suggested Readings
	50: Outcome-Based Clinical Decision-Making in Pediatric Critical Illness
		50.1 Introduction
		50.2 Defining Quality and Outcomes
		50.3 Understanding Value
		50.4 Error and Adverse Event Prevention in the Intensive Care Unit
		50.5 Safety-Related Outcome Measures: Improving Quality by Prevention of Adverse Events
			50.5.1 Accidental Extubation
			50.5.2 Central Venous Catheter-Related Blood Stream Infection
			50.5.3 Catheter-Associated Urinary Tract Infection (CAUTI)
			50.5.4 Ventilator-Associated Events
		50.6 Measurement of Outcomes in Pediatric Critical Care Medicine
			50.6.1 Risk Adjustment
			50.6.2 The Virtual PICU and the Use of PICU Mortality Prediction Tools
			50.6.3 The Society of Thoracic Surgeons Database
			50.6.4 Functional Outcomes and Morbidities Following Pediatric Critical Illness
			50.6.5 Assessment of Cost and Length of Stay
		50.7 Future Directions
			50.7.1 Quality Measures
			50.7.2 Practice Development
			50.7.3 Standards of Care
			50.7.4 Sharing Best Practices
			50.7.5 What Does Good Critical Care Look Like
		Suggested Reading
	51: Biostatistics and Evaluating Published Studies
		51.1 Introduction
		51.2 Study Design
		51.3 Interpreting Results
			51.3.1 General Principles
				51.3.1.1 Confidence Intervals
				51.3.1.2	 Hypothesis Testing
					Common Tests
				51.3.1.3	 The Concept of Statistical Power
				51.3.1.4	 Clinical Versus Statistical Significance
				51.3.1.5	 Number Needed to Treat
			51.3.2	 Interpretation of Statistical Models
				51.3.2.1	 Logistic Regression
					A Careful Look at Odds Ratios
					Receiver Operating Characteristic (ROC) Curves
				51.3.2.2	 Ordinary Linear Regression
				51.3.2.3	 Cox Proportional Hazards Regression
				51.3.2.4	 Additional Concepts in Statistical Modeling
					Categorical Predictors with More than Two Levels
					Continuous Predictor Variables
					Controlling for Other Variables
					Explanatory Variable Selection
		51.4 Understanding Limitations
			51.4.1	 Treatment Assignment
			51.4.2	 Uncontrolled Confounders
			51.4.3	 Generalizability
			51.4.4	 Pre-specified Hypotheses
			51.4.5	 Outcome
		51.5 Summary
		References
Index