Pediatric Critical Care Medicine: Volume 3: Gastroenterological, Endocrine, Renal, Hematologic, Oncologic and Immune Systems

Foreword to the First Edition
Preface to the Second Edition
Preface to the First Edition
Acknowledgements
Contents
Contributors
Part I: The Respiratory System in Critical Illness and Injury
	1: Applied Respiratory Physiology
		Introduction
		Developmental Anatomy
		Developmental Mechanics of Breathing
			Elastic Properties of the Lung and Chest Wall
			Compliance of the Lung and Chest Wall
			Airway Resistance
			Lung Volumes
		Physiologic Effects of Mechanical Ventilation
			Maintenance of Oxygenation
			Maintenance of Alveolar Ventilation
			Mechanics of Ventilation
			Work of Breathing
		Developmental Anatomy and Physiology of the Pulmonary Circulation
			Pulmonary Vascular Pressures
			Distribution of Blood Flow
			Pulmonary Vascular Resistance
			Ventilation-Perfusion Relationships
		References
	2: Life-Threatening Diseases of the Upper Respiratory Tract
		Introduction
		Developmental Anatomy
		Acute Airway Obstruction
			Physiology of Airway Obstruction
			Clinical Manifestations of Airway Obstruction
		Infectious Disorders of the Pediatric Airway
			Viral Laryngotracheobronchitis (“Croup”)
			Supraglottis (“Epiglottitis”)
			Bacterial Tracheitis
			Retropharyngeal Abscess
			Peritonsillar Abscess (“Quinsy” Tonsillitis)
			Recurrent Respiratory Papillomatosis
			Infectious Mononucleosis
		Non-infectious Disorders of the Pediatric Airway
			Obesity
			Angioedema
			Adenotonsillar Hypertrophy
			Acquired Subglottic Stenosis
			Laryngeal Neoplasms and Mediastinal Masses
		Airway Trauma
			Post-extubation Stridor
			Foreign Body Aspiration
			Inhalational Injury
			Direct Trauma
		References
	3: Congenital Airway Anomalies
		The Pediatric Airway in the PICU Setting: General Considerations
			Prevention of Complications
			Difficult Intubation
			The Child with a Tracheotomy
			Single-Stage Airway Reconstruction
		Congenital Anomalies of the Airway
			Retrognathia/Glossoptosis
			Laryngomalacia
			Vocal Cord Paralysis
			Subglottic Stenosis
			Posterior Laryngeal Clefts
			Vascular Compression
			Complete Tracheal Rings
		References
	4: Status Asthmaticus
		Introduction
		Epidemiology
		Pathophysiology
		Clinical Manifestations
		Management
			Oxygen
			Systemic Corticosteroids
			Inhaled Corticosteroids
			Beta-Adrenergic Agonists (Table  4.4)
				Epinephrine
				Albuterol (Salbutamol)
				Terbutaline
				Isoproterenol
			Ipratropium Bromide
			Magnesium
			Theophylline (Table  4.5)
			Helium-Oxygen
			Ketamine
			Leukotriene Modifying Agents
			Mechanical Ventilation
			Volatile Anesthetics
		Conclusion
		References
	5: Bronchiolitis
		Introduction
		Pathogens, Pathogenesis and Pathophysiology
		Immune Response to RSV Infection
		Epidemiology
		Mortality
			Clinical Diagnosis
			Laboratory Confirmation of Bronchiolitis
			Clinical Phenotype
		Severity of Disease and Risk Factors
		Extrapulmonary Manifestations/Effects
		Therapeutic Options in PICU
			Oxygen
			Bronchodilators
			Adrenergics: Epinephrine (Adrenaline)
			Corticosteroids
			Methylxanthines
			Chest Physiotherapy, Nebulised Hypertonic Saline
			Ribavirin
			Antibiotics
			Exogenous Surfactant
			Helium – Oxygen (Heliox) Mixture
			Inhaled Nitric Oxide (iNO)
			Recombinant Human DNAse (rhDNAse)
			Respiratory Support
		Preventive Therapies and Treatments
			RSV Immunotherapy
			Vaccination
			New Anti-RSV Agents
		Conclusion
		References
	6: Pneumonia
		Introduction
		Definition of Pneumonia and Guidelines for Admission to the Pediatric Intensive Care Unit
		Pathogenesis
		Etiologies
			Community-Acquired Pneumonia
			Immunocompromised Pneumonia
			Aspiration Pneumonia
		Diagnostic Approach
			Imaging
			Non-invasive Pathogen Identification
			Invasive Pathogen Identification
		General Treatment Principles
			Antimicrobial Therapy
			Anti-inflammatory Therapy
		Complications
			Empyema and Effusion
			Lung Abscess
		Prevention
		References
	7: Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS)
		Introduction
		Epidemiology
		Etiology
		Risk Factors and Outcomes
		Clinical Course and Histopathology
		Pathophysiologic Mechanisms in ARDS
			Development of Pulmonary Edema
			Cytokines
			Leukocyte Chemotaxis Related to Acute and Transitional Inflammation
			Role of Anti-inflammatory Cytokines in Regulating ARDS
			Molecular Regulation of Cytokine Gene Expression
		Conventional Therapeutics in ARDS
			Conventional Mechanical Ventilation
			Inverse Ratio Ventilation and High Frequency Ventilation
			Lung Protective Strategies
			Permissive Hypercapnia
			Prone Positioning
			Fluid Management
			Corticosteroids
			Inhaled Nitric Oxide (iNO)
			Extracorporeal Life Support (ECLS)
		Experimental Therapies
			Targeting Cytokine Production
			Cytokine Neutralization
			Modulating the Regulation of Lung Edema Clearance
			Blocking Adhesion Molecules
			Blocking of Chemokines or Chemokine Receptors
			Application of Genomics to ALI/ARDS
		Conclusion
		References
	8: Mechanical Ventilation
		Introduction
		Physiology of Mechanical Ventilation
			Respiratory System Equation of Motion
			Children Are Not Small Adults!
		I ndications for Mechanical Ventilation
		Non-invasive Mechanical Ventilation
			Non-invasive Positive Pressure Ventilation (NIPPV)
			Non-invasive Negative Pressure Ventilation
		Invasive Mechanical Ventilation
			Pressure Control Versus Volume Control
				Pressure Control Ventilation
				Volume Control Ventilation
				Adaptive Pressure Control Ventilation
			Ventilator Modes
				Control Mode Mechanical Ventilation (CMV)
				Assist/Control Mechanical Ventilation
				Synchronized Intermittent Mandatory Ventilation (SIMV)
				Pressure Support Ventilation
				Volume Support Ventilation
				Airway Pressure Release Ventilation (APRV)
				Inverse Ratio Ventilation
				Automatic Tube Compensation (ATC)
				Proportional Assist Ventilation (PAV)
				Neurally Adjusted Ventilatory Assist (NAVA)
		Determining Initial Ventilator Settings
			Tidal Volume (V T)
			Inspiratory Pressures
			Positive End-Expiratory Pressure (PEEP)
			FIO 2
			Rate (Frequency)
		Triggering the Ventilator
		Patient-Ventilator Dyssynchrony
		Adjuncts to Mechanical Ventilation
			Recruitment Maneuvers
			Prone Positioning
			Nitric Oxide
			Surfactant Administration
		Complications of Mechanical Ventilation
			Respiratory Complications
				Upper Airway Injury
				Air Leak
				Ventilation Associated Respiratory Infections (VARI)
				Atelectasis
				Ventilator-Induced Lung Injury (VILI)
				Auto-PEEP
			Central Nervous System Effects
			Cardiovascular Effects
				Venous Return
				Left Ventricular Afterload
				Cardiovascular Effects of Change in Lung Volume
				Ventricular Interdependence
			Renal Effects
			Hepatic Effects
		Weaning from Mechanical Ventilation
		Conclusion
		References
	9: Therapeutic Gases in the Pediatric ICU
		Introduction
		Therapeutic Gases Used in the PICU
		Oxygen
			Historical Perspective
			The Physiology of Oxygen Delivery
				Alveolar Oxygen and Carbon Dioxide Tensions
				Oxygen Delivery
			Oxygen Administration
				Non-contact Devices and Techniques
				Contact Devices and Techniques
				Bag Mask Ventilation
		Carbon Dioxide
		Carbon Monoxide
		Nitric Oxide
			Background
			Administration
			Clinical Applications
				Persistent Pulmonary Hypertension
				Acute Respiratory Distress Syndrome
				Pulmonary Hypertension
			Toxicity and Complications
		Inhaled Anesthetic Gases
		Helium
		References
	10: High Frequency Oscillatory Ventilation
		Introduction
		Modalities of High Frequency Ventilation
		Gas Transport and Control of Gas Exchange in HFOV
		Strategies for Initiating HFOV: Diffuse Alveolar Disease and Airleak
		HFOV in the Neonate and Infant
			Neonatal Respiratory Distress Syndrome
			Congenital Diaphragmatic Hernia
			Persistent Pulmonary Hypertension of the Newborn
			Air Leak Syndromes
			Bronchiolitis
		HFOV in the Child
			Diffuse Alveolar Disease
			Other Conditions
		HFOV in the Adolescent and Adult
		Adjuncts to HFOV: Non-invasive Assessment of Lung Volume
		Weaning from HFOV
		Other Developments: Revisiting High Frequency Percussive Ventilation
		Conclusions
		References
	11: Surfactant Therapy
		Overview of Lung Surfactant and Exogenous Surfactant Therapy
		Pulmonary Surfactant and Its Functions
			Surface Tension and Surfactants
			Effects of Lung Surfactant on Respiratory Physiology
			Biophysically-Functional Composition of Lung Surfactant
			Surfactant Proteins and Innate Immune Function
			Surfactant Metabolism and Recycling
		Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS)
		Surfactant Dysfunction in ALI/ARDS
		Surfactant Therapy in ALI/ARDS
			Pharmaceutical Surfactants
			Relative Activity and Inhibition Resistance of Exogenous Surfactant Drugs
			New Synthetic Lung Surfactant Development
			Animal Studies of Surfactant Therapy in ALI/ARDS
			Human Studies of Surfactant Replacement Therapy in ALI/ARDS
				Infant Investigations
				Pediatric and Adult Investigations
			The Future of Surfactant Therapy and Related Combination Therapies in ALI/ARDS
		References
	12: Extracorporeal Life Support
		History of Extracorporeal Life Support (ECLS)
		Patient Selection for ECLS
		Modes of ECMO Support
			Venoarterial ECMO
			Venovenous ECMO
		ECMO Circuit Components and Equipment
			Venous Reservoir
			Venous Saturation Monitor
			ECMO Pumps
				Roller-Head Pumps
				Centrifugal Pumps
			Oxygenators
				Gas Exchange
		Hemodynamics of Venoarterial ECMO
		Management of the Patient Supported with ECMO
			Anticoagulation
			Ventilator Management
			Nutrition and Fluid Management
			Sedation and Analgesia
		Weaning of ECMO Support
		Complications of ECMO
			Mechanical Complications
			Central Nervous System Complications
			Bleeding
			Infection
		Outcomes of Patients Supported with ECMO
			Septic Shock
			“Non-traditional” Patients with Respiratory Failure
			ECPR
			ECMO Support for Adults with Respiratory Failure
			Long-Term Outcome After ECMO Support
		Inter-hospital Transport of Patients Supported with ECMO
		Future Directions in ECMO Support
		References
	13: Ventilator-Induced Lung Injury
		Introduction
		Low Tidal Volume Lessens Ventilator-
		High Positive End-Expiratory Pressure Protects Against Injury with Low Tidal Volumes
		Recruitment Is Essential to Lung Protection
		Susceptibility to Ventilator-Induced Lung Injury: Adults vs. Infants
		Bronchopulmonary Dysplasia and Ventilator-Induced Lung Injury
		Stretch Increases Production of Biochemical Mediators (Mechanotransduction)
		Does Ventilator-Induced Lung Injury Lead to Multiple-Organ Dysfunction Syndrome?
		Potential Targeted Therapy of Ventilator-
		Conclusion
		References
	14: Neonatal Lung Diseases
		Introduction
		Lung Development
		Neonatal Respiratory Physiology
			Lung Liquid
			Pulmonary Vessels and Pulmonary Blood Flow
			Collateral Airways
			Chest Wall and Respiratory Muscles
		Clinical Presentation of Respiratory Disorders in the Neonate
		Respiratory Monitoring of the Neonate
		Respiratory Diseases of the Neonate
			Respiratory Distress Syndrome
			Transient Tachypnea of the Newborn
			Meconium Aspiration Syndrome
			Respiratory Dysfunction in Infants Born by Elective Cesarean Section
			Neonatal Pneumonia
			Persistent Pulmonary Hypertension
			Bronchopulmonary Dysplasia
			Apnea of Prematurity
			Pulmonary Air Leaks
			Congenital Diaphragmatic Hernia
		Conclusion
		References
	15: Pulmonary Hypertension
		Introduction
		Clinical Classification and Etiology
		Diagnosis
		Pathophysiology
			Hemodynamics and Morphology
			Pulmonary Vascular Endothelium
			Pulmonary Vascular Smooth Muscle
		Management Strategies and Therapeutic Options
			Prevention and/or Treatment of Active Pulmonary Vasoconstriction
				Vasodilator Therapy
			NO-cGMP Cascade
			Prostanoids
			Endothelin-1
			The Support of Right Ventricular Function
			Treatment of Underlying Disease
		Future Directions
		Conclusions
		References
	16: Neuromuscular Respiratory Failure
		Introduction
		General Anatomic and Physiologic Considerations
			Respiratory Muscle Function
			Chest Wall Function
			Interactions Between Respiratory Muscles, Chest Wall, and Lungs in NMD
			Measurement of Respiratory Muscle Function
		Neuropathies
			Spinal Muscular Atrophy
			Spinal Cord Injury
			Guillain-Barré Syndrome
		Diseases of the Neuromuscular Junction
			Myasthenia Gravis
			Botulism
		Myopathies
			DMD
			Myotonic Dystrophy
			Pompe Disease
			Critical Illness Polyneuropathy and Myopathy
		Management Approach
			Secretion Clearance
			Feeding and Nutrition
			Non-invasive Ventilation
			Invasive Mechanical Ventilation and Strategy for Extubation
			Tracheostomy
			Palliative Care
		Conclusion
		References
Part II: The Cardiovascular System in Critical Illness and Injury
	17: Applied Cardiovascular Physiology in the PICU
		Introduction
		Developmental Cardiac Anatomy
			Chambers of the Heart
			Pericardium
			Coronary Circulation
			Peripheral Vasculature
		From Fetus to Newborn: The Transitional Circulation
		Cardiac Contraction and Relaxation: From Cell to Function
			Cardiac Myocyte
			Myocardial Bioenergetics
			Excitation Contraction Coupling (ECC)
		Determinants of Cardiac Output
			Stroke Volume
			Preload
				Contractility
				Afterload
			Venous Return
				Mean Circulatory Filling Pressure
				Venous Resistance (R V)
				Right Atrial Pressure (P RA)
		Control of Circulation
			The Afferent Limb of the Neuroendocrine Stress Response
			The Efferent Limb of the Neuroendocrine Stress Response
		Conclusion
		References
	18: Cardiopulmonary Interactions
		Introduction
		Volume-Pressure and Pressure-Flow Relationships
		The Effects of Respiration on Cardiovascular Function
			The Effects of Respiration on Right Ventricular Preload
			The Effects of Respiration on Right Ventricular Afterload
			The Effects of Respiration on Left Ventricular Preload
			The Effects of Respiration on Left Ventricular Afterload
		The Effects of Respiration on Cardiovascular Function in Patients with Cardiac Disease
			Left Ventricular Systolic Heart Failure
			Diastolic Heart Failure
			Cavopulmonary Anastomosis
			The Effects of Respiration on Cardiopulmonary Resuscitation
		The Effects of Heart Failure on Respiratory Function
		The Effects of Respiratory Disease on Cardiovascular Function
		Conclusion
		References
	19: The Classification and Nomenclature of Congenital Heart Disease
		Introduction
		Van Praagh’s Segmental Approach
		Anderson’s Sequential Segmental Approach
		International Congenital Heart Surgery Nomenclature and Database
		Functional Classification
		References
	20: Shunt Lesions
		Introduction
		Atrial Septal Defect (ASD)
			Embryology
			Secundum ASD’s
				Pathophysiology
				Clinical Features
				Natural History
				Surgical Management
				Postoperative Management
				Transcatheter Device Closure
			Sinus Venosus ASD’s
			Coronary Sinus ASD’s
		Ventricular Septal Defects (VSD’s)
			Embryology
			Anatomy
			Pathophysiology
			Clinical Features
			Natural History
			Management
				Surgery
				Postoperative Management
				Transcatheter Device Closure of VSD
				Hybrid Procedures
		Patent Ductus Arteriosus (PDA)
			Embryology
			Anatomy and Physiology
			Epidemiology
			Pathophysiology
			Clinical Features
			Natural History
			Management
		Aortopulmonary (AP) Window
			Embryology
			Anatomy
			Pathophysiology
			Clinical Features
			Natural History
			Management
		References
	21: Cyanotic CHD Lesions with Decreased Pulmonary Blood Flow
		Initial Evaluation and Stabilization of the Cyanotic Neonate
		Tetralogy of Fallot
			Anatomy
			Pathophysiology and Clinical Presentation
			Preoperative Evaluation
			Surgical or Transcatheter Intervention
			Postoperative Care
			Tetralogy of Fallot: Complex Variants
			Outcomes
		Pulmonary Valve Stenosis
			Anatomy
			Pathophysiology and Clinical Presentation
			Preoperative Evaluation
			Surgical or Transcatheter Intervention
			Postoperative Care and Outcome
		Pulmonary Atresia with Intact Ventricular Septum
			Anatomy
			Pathophysiology and Clinical Presentation
			Preoperative Evaluation
			Surgical or Transcatheter Intervention
			Postoperative Care and Outcome
		Ebstein’s Anomaly
			Anatomy
			Pathophysiology and Clinical Presentation
			Preoperative Evaluation
			Surgical or Transcatheter Intervention
			Postoperative Care and Outcome
		References
	22: Cyanotic Lesions with Increased Pulmonary Blood Flow
		Introduction
		Transposition of the Great Arteries
			Anatomy
			Pathophysiology
			Clinical Presentation and Diagnosis
			Pre-operative Care
			Surgical Intervention
			Post-operative Care
			Complications
		Truncus Arteriosus
			Anatomy
			Associated Lesions
			Pathophysiology
			Clinical Presentation
			Pre-operative Care
			Surgical Intervention
			Post-operative Care
			Prognosis
		Total Anomalous Pulmonary Venous Connections (TAPVC)
			Anatomy
			Pathophysiology
			Clinical Presentation
			Pre-operative Care
			Surgical Intervention
			Post-operative Care
			Prognosis
		Lesions with Physiology of Single Ventricle and Unobstructed Pulmonary Blood Flow
		References
	23: Congenital Heart Disease: Left Ventricular Outflow Tract Obstruction
		Valvar Aortic Stenosis
			Clinical Presentation
			Management
			Postoperative Management
		Coarctation of the Aorta
			Clinical Presentation
			Management
			Postoperative Care
		Interrupted Aortic Arch
			Clinical Presentation
			Management
			Postoperative Care
		Supravalvar Aortic Stenosis
			Clinical Presentation
			Management
			Postoperative Care
		Subvalvar Aortic Stenosis
			Clinical Presentation
			Management
			Postoperative Care
		References
	24: Single Ventricle Lesions
		Introduction
		Single Ventricle Physiology in the Newborn Before and After Surgery
		Perinatal Management
		Preoperative Management
			General Considerations
			Management of Pulmonary Over-Circulation
			Lesion-Specific Management
				Systemic Outflow Obstruction
				Pulmonary Outflow Obstruction
				Obstructed Venous Return
			Other Considerations
		Surgical Management
		Post-operative Management
			Management of Low Total Cardiac Output
			Other Management Considerations
		Interstage Management
		A Rationale Approach to Single Ventricle Physiology in the Older Infant and Child
			The Bidirectional Cavo-Pulmonary Anastomosis (BCPA)
			Total Cavo-Pulmonary Anastomosis
		Conclusion
		References
	25: Long-Term Outcomes in Congenital Heart Disease
		Introduction
		Categories of Lesions
			Left-to-Right Shunts
				Atrial Septal Defects (ASD)
				Ventricular Septal Defects (VSD)
				Atrioventricular Canal Defects (AVCD)
			Right Sided Obstructive Lesions
				Tetralogy of Fallot (TOF)
				Tetralogy of Fallot with Pulmonary Atresia (TOF/ PA)
				Tetralogy of Fallot with Absent Pulmonary Valve
				Ebstein Anomaly of the Tricuspid Valve
			Left Sided Obstructive Lesions
				Aortic Stenosis
				Subaortic Stenosis
				Coarctation of the Aorta
			Mixing Lesions
				D-Transposition of the Great Arteries
				Atrial Switch
				Arterial Switch
				Congenitally Corrected Transposition of the Great Arteries (L-TGA)
				Truncus Arteriosus
				Total Anomalous Pulmonary Venous Return (TAPVR)
			Miscellaneous Lesions
				Anomalous Left Coronary Artery from the Pulmonary Artery (ALCAPA)
				Vascular Rings and Sling
				Left Pulmonary Artery Sling
				Double Aortic Arch
				Right Aortic Arch with Aberrant Left Subclavian Artery
			Single Ventricle Physiology
				Ventricular Dysfunction
				Hypoxemia
				Protein-Losing Enteropathy
				Thromboembolism
				Arrhythmias
				Liver Dysfunction
		Neurodevelopmental Outcomes
		Genetic Anomalies and Associated Congenital Heart Disease
		References
	26: Ventricular Assist Device Support in Children
		Introduction
		Preoperative Considerations
			Timing
			Biventricular Assist Devices (BiVADs) Versus Left Ventricular Assist Device (LVAD)
		Device Options
			Adult Ventricular Assist Devices
			Berlin Heart EXCOR Ventricular Assist Device
			The Micromed Heart Assist 5
			HeartWare Ventricular Assist System
			The National Heart, Lung, and Blood Institute (NHLBI) Pediatric Circulatory Support Program
		Operative and Postoperative Considerations
			Surgical Procedure
			Anticoagulation
			Complications
			Sensitization
		Saint Louis Children’s Hospital Berlin Heart Experience
			Patients
			Preoperative Status
			Management During Support
			Outcomes
			Sensitization
		Conclusion
		References
	27: Arrhythmias
		Introduction
		Interpretation of Electrocardiograms
		Basic Mechanisms of Cardiac Arrhythmias
			Bradycardia Mechanisms
			Tachycardia Mechanisms
			Mechanisms of Arrhythmia with Normal Heart Rate
		Treatment of Bradyarrhythmia
		Treatment of Tachyarrhythmia
			Immediate Treatment, Cardioversion, Defibrillation and Pacing
			Antiarrhythmic Medications
		Special Circumstances Involving Arrhythmia in the PICU
			Electrolyte Imbalance
			Thermal Imbalance
			Endocrine Imbalance
			CNS Injury
			Infection
			Toxins
		References
	28: Inflammatory Diseases of the Heart
		Infectious Endocarditis
			Epidemiology
			Pathogenesis
			Diagnosis
			Clinical Findings
			Risk Factors
			Laboratory Findings
			Echocardiography
			Antimicrobial Management
			Surgical Management
			Complications
			Prophylaxis
		Kawasaki Disease
			Epidemiology
			Etiology
			Pathogenesis
			Diagnosis
				Clinical
				Laboratory Manifestations
			Incomplete Kawasaki Disease
			Cardiac Findings
			Management
			Thrombosis
				Prevention of Coronary Thrombosis
				Treatment of Coronary Thrombosis
			Long-Term Management
		Myocarditis
			Epidemiology
			Etiology
			Pathogenesis
			Diagnosis
				Clinical
				Biomarkers
				Imaging and Testing
				Endomyocardial Biopsy
			Treatment
		References
	29: Cardiomyopathies in Children
		Dilated Cardiomyopathy
			Clinical Features, Epidemiology, and Diagnosis
				Definition and Incidence
				Clinical Signs and Symptoms
				Classification of Heart Failure
				Biomarkers
				Histology
			Etiology
				Familial and Genetic Causes of DCM
				Infectious Causes of DCM
				Peripartum DCM
				Toxicity-Related DCM
				Other Causes of DCM
			Management
				Pharmacologic Therapy
				Cardiac Resynchronization and Implantable Cardiac Defibrillators
				Mechanical Circulatory Support
				Surgical Intervention
				Heart Transplantation
			Special Considerations: Anesthesia
			Outcomes
		Hypertrophic Cardiomyopathy
			Clinical Features and Diagnosis
				Clinical Signs and Symptoms
				Echocardiography/MRI
				Electrocardiography/Holter
				Exercise Testing
				Histology
			Etiology
				Familial and Genetic Causes of HCM
				Other Causes of HCM
			Management
			Special Considerations: Sudden Cardiac Death
		Restrictive Cardiomyopathy
			Clinical Features, Epidemiology, and Diagnosis
			Etiology
			Management
		Left Ventricular Noncompaction
			Clinical Features, Epidemiology, and Diagnosis
			Etiology
			Management
			Outcomes
		References
	30: Acute Decompensated Heart Failure
		Introduction
		Heart Diseases Leading to ADHF
			Congenital Heart Disease
				Excessive Pulmonary Blood Flow
				Critical Aortic Stenosis
				Anomalous Left Coronary Artery Arising from the Pulmonary Artery (ALCAPA)
				Arrhythmias
			Dilated Cardiomyopathy
		Pathophysiology of ADHF
		Clinical Approach to ADHF
		Advanced Hemodynamic Monitoring of Patients with ADHF
			PAC
			PiCCO
			NIRS
			Biomarkers
		Care of the Pediatric ADHF Patient
		Conclusion
		References
	31: Diseases of the Pericardium
		Introduction
		Pericarditis
			Etiology
				Clinical Presentation and Diagnosis
				Management
			Cardiac Tamponade
				Pathophysiology
				Clinical Presentation and Diagnosis
				Management
		References
	32: Hypertensive Emergencies
		Definitions of Terms Related to Hypertension
		Measurement of Blood Pressure
		Pathophysiology
			Renal Regulation of Blood Pressure
				Hemodynamics of the Kidney
				Renin-Aldosterone-Angiotensin System
				Hormonal Mediators
			Endothelial Control over Systemic Vascular Resistance
				Nitric Oxide
				Endothelin
			Autoregulation of Cerebral Blood Flow
		Etiologies
			Obesity and Metabolic Syndrome
		Clinical Presentation
			Neurologic Manifestations
			Cardiovascular Manifestations
			Renal Manifestations
			Ophthalmologic Manifestations
		Evaluation
		Management
			Therapeutic Goals
			Therapeutic Agents by Class
				Vasodilators
				Adrenoreceptor Antagonists
					Alpha-Adrenergic Antagonists
					Beta-Adrenergic Antagonists
						Calcium-Channel Antagonists
						Angiotensin Converting Enzyme Inhibitors
		References
Part III: The Central Nervous System in Critical Illness and Injury
	33: Molecular Biology of Brain Injury: 2012
		Neurotransmitters and Their Receptors
			Introduction
			Neurotransmitters: Definition
			Neurotransmitter Receptors
			Acetylcholine
		The Cholinergic Anti-inflammatory Response
			Serotonin
			GABA and Glycine
			Glutamate
			Glutamate Receptors
		Excitotoxicity
		Metabotropic Glutamate Receptors in Acute CNS Injury
		Cell Death After Acute Brain Injury
			Necrosis
			Caspase-Dependent Apoptosis
			Intrinsic Pathway of Apoptotic Cell Death
			The Extrinsic Cell Death Pathway
			The PARP Suicide Hypothesis
			The Mitochondrial Permeability Transition Pore
		Oxidative Damage in Acute Brain Injury
			Reactive Oxygen Species (ROS)
			Reactive Nitrogen Species (RNS)
			Oxidative Stress and Neuroinflammation: Mediators of Neurologic Dysfunction After Brain Injury
		Oxidative Stress, Oxidative Lipidomics, and Apoptosis
		Extracellular Matrix Proteases
			Matrix Metalloproteinases in Acute CNS Injury
			Matrix Metalloproteinases in CNS Recovery
			Matrix Metalloproteinases as Stroke Biomarkers
			Tissue Plasminogen Activator
		References
	34: Tumors of the Central Nervous System
		Brain Tumors
			Incidence
			Presenting Signs and Symptoms
			Gliomas
			Medulloblastomas
			Ependymomas
			Craniopharyngiomas
			Peri-operative Care of Brain Tumors
		Malignant Spinal Cord Compression
		References
	35: Intracranial Hypertension
		Introduction
		Intracranial Pressure: The Outcome of Multiple Factors
			Cerebrospinal Fluid Dynamics
			Circulatory System
			The Cranial Vault (the Significance of the Fontanelle)
		Intracranial Pressure Under Abnormal Circumstances
			Intracranial Pressure Waveforms
			“Normal” Intracranial Pressure
			Pressure Regulation
			Metabolic Regulation
			Carbon Dioxide Regulation
		Causes of Intracranial Hypertension
			Cerebral Edema
			Mass Lesions
		Hydrocephalus
		Clinical Manifestations of Intracranial Hypertension
		ICP Measurement
			Indications for Monitoring
			Invasive Measurement
			Non-invasive Measurement
		Management of Intracranial Pressure
			Setting Targets
			How Do You Approach an ICP Number?
			Basic Measures
			Sedation and Analgesia
			Drainage of CSF
			Removal of Mass Lesions
			Hyperventilation
			Osmotherapy
			Treatment Directed as Cerebral Perfusion Pressures
			Barbiturate Therapy
			Decompressive Craniectomy
			Hypothermia
		Future Directions
		References
	36: Stroke
		Introduction
		Epidemiology
		Etiology
		Arterial Ischemic Stroke (AIS)
			Vascular Causes
			Thrombotic Causes
			Metabolic Causes
			Treatment of AIS
			Outcome from AIS
		Hemorrhagic Stroke
		Neonatal Stroke
		Cerebral Sinovenous Thrombosis (CSVT)
		Diagnostic Imaging in Stroke
			Magnetic Resonance Imaging (MRI)
			Computed Tomography (CT)
			Cerebral Angiography
			Cardiac Imaging
		Conclusion
			Approach to a Patient with a Suspected Stroke
		References
	37: Inflammatory Brain Diseases
		Introduction
		Vasculitic Inflammatory Brain Diseases
			Primary CNS Vasculitis
				Angiography-Positive Nonprogressive cPACNS (NP-cPACNS)
				Angiography-Positive Progressive cPACNS (P-cPACNS)
				Angiography-Negative, Small Vessel cPACNS (SV-cPACNS)
			Secondary CNS Vasculitis
				Infection-Associated Secondary CNS Vasculitis
				Secondary CNS Vasculitis in Rheumatic and Systemic Inflammatory Diseases
				Secondary CNS Vasculitis in Other Systemic Diseases/Exposures
		Non-vasculitic Inflammatory Brain Diseases
			Demyelinating Diseases
			Neuronal Antibody Mediated Inflammatory Brain Diseases
			T-cell Mediated Inflammatory Brain Diseases; Rasmussen Encephalitis
			Granulomatous Inflammatory Brain Diseases
			Febrile Infection-Related Epilepsy Syndrome (FIRES)
		Non-inflammatory Brain Disease Mimics
			Posterior Reversible Encephalopathy Syndrome
		Diagnostic Approach to Inflammatory Brain Diseases
			Laboratory Testing
			Neuroimaging
			Brain Biopsy
		Management of Inflammatory Brain Diseases
			Disease Modifying Drugs
			Novel Biologic Therapies
		Conclusion
		References
	38: Abusive Head Trauma
		Introduction
		Terminology
		Epidemiology
		Clinical Presentation
		Mechanism of Injury and Pathophysiology
		Evaluation of Suspected AHT
			Intracranial Injuries
			Extra-Cranial Injuries
				Fractures
				Retinal Hemorrhages
				Abdominal Injury
				Evaluation for Bleeding Disorders
				Evaluation for Disorders Which Can Mimic AHT
		Management and Treatment of AHT
		Outcomes After AHT
		Reporting and Legal Issues
		Conclusion
		References
	39: Toxic Metabolic Encephalopathy
		Introduction
		Central Nervous System Physiology
		Toxic-Metabolic Encephalopathy and Altered Levels of Consciousness
			Definitions of Altered Levels of Consciousness
			Clinical Assessment of Altered Levels of Consciousness
				Diagnosis of Severity
				Topographic Diagnosis
				Syndromic Diagnosis
				Etiologic Diagnosis
			General Management of Altered Levels of Consciousness
		Toxic-Metabolic Encephalopathies in the PICU
			Disorders of Glucose Metabolism
				Hypoglycemic Coma
				Diabetic Ketoacidosis
			Disorders of Sodium Homeostasis
				Hyponatremia
			Hypovolemic Hyponatremia
			Euvolemic Hyponatremia
			Hypervolemic Hyponatremia
				Hypernatremia
			Hyperammonemia
				Acute Liver Failure (ALF)
				Reye’s Syndrome
				Inborn Errors of Metabolism and Mitochondrial Disorders
				Post-transplant Encephalopathy
				Immune-Mediated Encephalopathies
		References
	40: CNS Infections
		Introduction
		Meningitis
			Acute Bacterial Meningitis
				Etiology
				Pathophysiology
				Clinical Manifestations
				Diagnosis
					Partially Treated Bacterial Meningitis
				Treatment
					Neuroprotective Strategies and the Management of Raised Intracranial Pressure
					Antibiotic Therapy
						Streptococcus pneumonia
						Neisseria meningitidis
						Haemophilus influenzae Type B
							Evaluation of Newer Antibiotics
					Anti-Inflammatory Agents
						Adjunctive Corticosteroids
						Inhibition of Leukocyte Recruitment
						Non-bacteriolytic Antibiotics
						Hypothermia
						Other Agents
					Duration of Therapy
				Prevention of Bacterial Meningitis
					Hib
					N. meningitidis
					S. pneumonia
			Viral Meningitis
			Tuberculous Meningitis
			Fungal Meningitis
		Encephalitis
			Pathophysiology
			Clinical Presentation and Diagnosis
			Therapy
			Mycoplasma pneumoniae Encephalitis
			Herpes Simplex Encephalitis
			Enteroviral Encephalitis
			Rabies
			Arthropod-Borne Encephalitis Viruses
				Japanese Encephalitis
				Tick-Borne Encephalitis
				West Nile Virus
		Cerebral Malaria
			Clinical Features and Diagnosis
			Pathophysiology
				Parasitic Sequestration in Cerebral Microvasculature
				Cytokines, Chemokines and Excitotoxicity
				Endothelial Injury, Apoptosis, BBB Dysfunction and Intracranial Hypertension
				Cerebral Blood Flow and Perfusion
				Seizures
				Depth, Duration and Cause of Coma
			Management
		Brain Abscess/Subdural Empyema
			Predisposing Factors, Incidence and Epidemiology
			Pathophysiology
			Imaging in Brain Abscesses
			Surgical and Medical Management of Brain Abscesses
				Medical Management
				Surgical Management
			Outcome and Complications
			Subdural Empyema
		Shunt Infection
			Epidemiology
			Pathophysiology
			Clinical Manifestations
			Diagnosis
			Treatment
		References
	41: Status Epilepticus
		Introduction
		Definitions
			Impending Status Epilepticus
			Refractory Status Epilepticus
			Super-Refractory Status Epilepticus
		Second-Tier Intravenous Anticonvulsants for Refractor SE
			Fosphenytoin
			Phenobarbital
			Valproic Acid
			Levetiracetam
			High-Dose Midazolam for Refractory Status Epilepticus
				Pediatric Critical Care Studies of High-Dose Midazolam
					Efficacy
					Dosing
					Electroencephalography to Guide Therapy
					Breakthrough Seizure and Recurrences
					Hemodynamic Instability
				Strategy When Using High-Dose Midazolam
		General Anesthesia for Refractory Status Epilepticus
			Pentobarbital
				Pediatric Critical Care Studies of Pentobarbital for Refractory Status Epilepticus
				Strategy When Using Pentobarbital Anesthesia for Refractory Status Epilepticus
			Inhaled Anesthetics
				Isoflurane for Pediatric Refractory Status Epilepticus
				Strategy When Using Isoflurane Anesthesia for Refractory Status Epilepticus
		General Anesthesia for Super-Refractory SE
			Duration of Anesthesia
			Other Medications and Approaches During Anesthesia
				Ketamine
				Therapeutic Hypothermia
				Ketogenic Diet
		Electroencephalography and Non-
		Fever-Induced Refractory Epileptic Encephalopathy and FIRES
			General Anesthesia
			Other Therapies for FIRES
		Conclusion
		References
	42: Diseases of the Peripheral Nervous System
		Introduction
		Electromyography in the Intensive Care Unit
		Peripheral Nerve Diseases Resulting in ICU Admission
			Acquired Disorders
				Anterior Horn Cell Disease
				Disorders of Peripheral Nerve
			Neuromuscular Junction Abnormalities
				Botulism
				Tick Paralysis
				Autoimmune Myasthenia Gravis (AIMG)
				Acute Muscle Disease
			Hereditary Conditions
				Anterior Horn Cell Disease
				Spinal Muscle Atrophy with Respiratory Distress (SMARD)
					Disorders of the Nerve
					Neuromuscular Junction Disorders
			Muscle Disease
				Myotonic Muscular Dystrophy
				Other Myopathies
		Peripheral Nerve Diseases Acquired in the ICU
			Critical Illness Neuropathy and Myopathy
			Mononeuropathies Which Develop in ICU
		Our Recent Experience Using EMG in the ICU
		References
	43: Movement Disorders in the ICU
		Introduction
		Hyperkinetic Movement Disorders
			Dystonia
				Acute Dystonic Reactions Secondary to Drugs
				Spasmodic Dysphonia/Adductor Laryngeal Breathing Dystonia (ALBD)
				Status Dystonicus
				Sudden Withdrawal of Intrathecal Baclofen
			Chorea, Athetosis and Ballismus
			Myoclonus
			Tremor
		Akinetic-Rigid Movement Disorders
			Primary and Neurodegenerative Akinetic-
			Secondary Akinetic-Rigid Movement Disorders
				Neuroleptic Malignant Syndrome
		Parkinsonism–Hyperpyrexia Syndrome
		Malignant Hyperthermia
		Serotonin Syndrome
		Tetanus
		Strychnine Toxicity
		Rabies
		References
Index