e6 219 Merin RG, Kumazawa T, Luka NL Dose dependent depression of cardiac function and metabolism by inhalation anesthetics in chronically instrumented dogs Recent Adv Stud Cardiac Struct Metab 1976;1[.]
e6 219 Merin RG, Kumazawa T, Luka NL Dose-dependent depression of cardiac function and metabolism by inhalation anesthetics in chronically instrumented dogs Recent Adv Stud Cardiac Struct Metab 1976;11:473-480 220 Merin RG, Kumazawa T, Luka NL Myocardial function and metabolism in the conscious dog and during halothane anesthesia Anesthesiology 1976;44(5):402-415 221 Zink J, Sasyniuk BI, Dresel PE Halothane-epinephrine-induced cardiac arrhythmias and the role of heart rate Anesthesiology 1975;43(5):548-555 222 Baigel G Volatile agents to avoid ventilating asthmatics Anaesth Intensive Care 2003;31(2):208-210 223 Beach FX, Williams NE Bronchial lavage in status asthmaticus A long term review after treatment Anaesthesia 1970;25(3): 378-381 224 Henke CA, Hertz M, Gustafson P Combined bronchoscopy and mucolytic therapy for patients with severe refractory status asthmaticus on mechanical ventilation: a case report and review of the literature Crit Care Med 1994;22(11):1880-1883 225 Durward A, Forte V, Shemie SD Resolution of mucus plugging and atelectasis after intratracheal rhDNase therapy in a mechanically ventilated child with refractory status asthmaticus Crit Care Med 2000;28(2):560-562 226 Leiba A, Bar-Yosef S, Bar-Dayan Y, et al Early administration of extracorporeal life support for near fatal asthma Isr Med Assoc J 2003;5(8):600-602 227 Mikkelsen ME, Woo YJ, Sager JS, Fuchs BD, Christie JD Outcomes using extracorporeal life support for adult respiratory failure due to status asthmaticus ASAIO J 2009;55(1):47-52 228 Extracorporeal Life Support Organization Registry International Summary, January 2019 229 Bellomo R, McLaughlin P, Tai E, Parkin G Asthma requiring mechanical ventilation A low morbidity approach Chest 1994; 105(3):891-896 230 Kearney SE, Graham DR, Atherton ST Acute severe asthma treated by mechanical ventilation: a comparison of the changing characteristics over a 17 yr period Respir Med 1998;92(5):716-721 231 Rampa S, Allareddy V, Asad R, Nalliah RP, Allareddy V, Rotta AT Outcomes of invasive mechanical ventilation in children and adolescents hospitalized due to status asthmaticus in United States: a population based study J Asthma 2014:1-8 232 Bohn D, Kissoon N Acute asthma Pediatr Crit Care Med 2001; 2(2):151-163 233 Stein R, Canny GJ, Bohn DJ, Reisman JJ, Levison H Severe acute asthma in a pediatric intensive care unit: six years’ experience Pediatrics 1989;83(6):1023-1028 e7 Abstract: Patients with severe acute asthma exacerbations should be promptly and aggressively managed in the emergency department with inhaled b-agonist agents, inhaled ipratropium bromide, oxygen, and a systemic corticosteroid Patients who fail to improve or who further deteriorate should be admitted to the intensive care unit for escalation of therapy and a higher level of monitoring Standard treatments include administration of intravenous fluids, oxygen, b-agonist agents by intermittent or continuous nebulization, ipratropium bromide, parenteral corticosteroids, and intravenous infusion of a b2-agonist agent Other therapies available in the intensive care unit include intravenous infusions of magnesium sulfate and methylxanthine agents, and breathing helium-oxygen mixtures Failure to respond to treatment can lead to further deterioration and the development of respiratory failure, necessitating noninvasive ventilatory support or even intubation and mechanical ventilation When needed, ventilation should be initiated with a strategy that avoids dynamic hyperinflation Select patients may benefit from inhalational anesthetic agents for bronchodilation, bronchoscopy to relieve airway obstruction or atelectasis resulting from mucous plugging, or extracorporeal life support Aggressive medical treatment and a mechanical ventilation strategy that minimizes dynamic hyperinflation result in low morbidity and near-zero mortality rates in patients with critical or nearfatal asthma Key Words: Critical asthma, near-fatal asthma, corticosteroids, b-agonist, magnesium sulfate, ketamine, mechanical ventilation 51 Neonatal Pulmonary Disease THOMAS M RAFFAY AND RICHARD J MARTIN PEARLS • Both pulmonary and nonpulmonary disorders must be considered as leading to neonatal respiratory distress • It is important to distinguish respiratory disorders from the normal neonatal cardiorespiratory transition Common disorders are transient tachypnea of the newborn, respiratory distress syndrome, and persistent pulmonary hypertension of the newborn • Increased use of noninvasive positive pressure ventilator techniques has reduced the need for endotracheal intubation • Bronchopulmonary dysplasia remains a major chronic problem affecting approximately 40% of extremely low-birthweight infants Effective gas exchange within the lung requires both adequate ventilation and perfusion This is dependent on an effective cardiorespiratory transition from fetal to postnatal life that includes strong respiratory drive Consequently, a wide range of pulmonary and nonpulmonary derangements can lead to respiratory insufficiency Lung expansion, clearance of lung fluid, and cardiopulmonary changes following cord clamping lead to increased systemic vascular resistance and decreasing pulmonary vascular resistance, with resultant decreased shunting across the ductus arteriosus and foramen ovale In the first hours following birth, adequate functional residual capacity (FRC) is achieved, intrapulmonary shunting decreases, and a regular rhythmic, modulated respiratory pattern should be established Any disruption in this cardiopulmonary transition may manifest as respiratory distress in the form of tachypnea (.60 breaths/min), cyanosis, expiratory grunting, chest retractions, and nasal flaring parturition, such as vasopressin and glucagon, may contribute to this process The pulmonary circulation also plays a key role in fetal lung fluid clearance Interstitial liquid drains directly into the circulation, and the dramatic increase in pulmonary blood flow occurring after birth enhances reabsorption of liquid from fetal airspaces It is estimated that lung fluid approximates to 20 to 30 mL/kg near term.4 In the hours to days leading up to delivery, net lung fluid accumulation diminishes and, during labor, reabsorption predominates As a result, extravascular lung liquid volume (i.e., liquid within the airspaces and interstitium) decreases Any excess fluid remaining within the airspaces at the time of delivery is further resorbed as air entry into the lungs displaces liquid from the airways into the interstitium Excessive residual extravascular liquid can impair gas exchange as interstitial liquid pressure compresses small airways, leading to atelectasis and gas trapping Excess liquid remaining within airspaces will impair alveolar gas exchange The onset of breathing increases the surface area for liquid reabsorption and is associated with the opening of pores through which liquid can readily enter the interstitium Drainage of interstitial liquid is generally complete by the end of initial neonatal transition (4–6 hours) Interstitial liquid appears to be directly absorbed into the microcirculation in a process governed by Starling forces; the contribution of lymphatic drainage appears to be negligible Retention of liquid in airspaces and interstitium leads to impaired gas exchange and respiratory distress, with variable clinical presentations manifest by tachypnea and mild to moderate hypoxemia The chest radiograph may show linear streaks of interstitial fluid radiating from the hilum on opaque areas similar in appearance to neonatal pneumonia or surfactant-deficient respiratory distress syndrome (RDS) The latter should resolve within approximately 24 hours if lung fluid is retained This clinical picture is often termed retained fetal lung liquid or transient tachypnea of the newborn (TTN) Acute Respiratory Disorders Transient Tachypnea of the Newborn The mechanisms of fetal lung liquid production and reabsorption involve active ion transport and hormonal regulation1 (Fig 51.1) Chloride ions enter the developing terminal air sac epithelium from the basolateral membrane via an Na/K/2Cl cotransporter (the transporter on which furosemide acts) Transepithelial (reabsorptive) movement of lung fluid at the time of birth involves passive movement of sodium through epithelial sodium channels (ENaC),2 which are inactive during fetal life and are activated during parturition by adrenergic stimulation Although b-adrenergic agents such as terbutaline and epinephrine enhance Na ion trafficking and liquid reabsorption, in animal studies b-adrenergic blockade does not inhibit the reabsorption of lung liquid during spontaneous labor and delivery.3 Additional hormones of 568 CHAPTER 51 Neonatal Pulmonary Disease Fetus Na/K/2Cl 569 Newborn Capillaries aC EN Chloride channels Na+ H2O Cl– H2O Fetal lung liquid Alveolus H2O Cl– Na+ H2O Na+ Na+ Cl– Lymphatics Cl– H2O K+ Na+ Na/K/2Cl K+ K+ • Fig 51.1 Mechanism of fetal and neonatal lung fluid transport Cl, Chloride; ENaC, epithelial sodium channel; H2O, water; K, potassium; Na, sodium (Data from Guglani L, Lakshminrusimha S, Ryan RM Transient tachypnea of the newborn Pediatr Rev 2008;29:e59–65 Copyright Satyan Lakshminrusimha.) Delayed fetal lung liquid clearance represents the most common type of respiratory disorder in the neonate It occurs in an estimated 3.6 to 5.7 per 1000 term infants and in up to 10 per 1000 preterm infants Infants who are born precipitously or by cesarean delivery, those who are male, and those born to mothers with diabetes are at highest risk for this disorder.5–7 The differential diagnosis includes neonatal pneumonia and meconium aspiration syndrome Definitive diagnosis is often retrospective once the respiratory signs resolve, most often within to days, and requires minimal interventions Preterm infants who have a TTN-like presentation may be mistakenly assumed to have surfactant-deficient RDS In both instances, supportive treatment is similar, although surfactant therapy is not indicated for infants with TTN Lung ultrasound has been reported to be useful in making the distinction.8 Most infants can be treated with supplemental oxygen alone, administered via cannula or continuous positive airway pressure (CPAP) Supplemental oxygen is usually necessary for not more than 24 to 48 hours, but tachypnea may persist for several days In addition, reactive airway disease is more likely to develop later in life in newborns who present with transient respiratory distress.9 Surfactant-Deficient Respiratory Distress Syndrome A seminal study by Avery and Mead10 in 1959 demonstrated that hyaline membrane disease, now termed respiratory distress syndrome (RDS) of the newborn is caused by a lack of pulmonary surfactant in preterm newborns The phospholipids, proteins, genes, and cellular processes of surfactant biosynthesis and recycling were subsequently elucidated RDS is primarily a disease of prematurity The incidence of RDS decreases with increasing gestational age, with occurrence in approximately 60% of babies born at less than 28 weeks of gestation, 30% born between 28 to 34 weeks, and 5% born after 34 weeks.11–13 Risk factors for RDS include prematurity, male sex, maternal gestational diabetes, perinatal asphyxia, and multiple gestations Surfactant-deficient alveoli are more prone to collapse, leading to diffuse atelectasis and the classic ground-glass appearance of chest radiographs There is reduced compliance, atelectasis, and intrapulmonary shunting Infants with surfactant deficiency have stiff, noncompliant lungs and require significant distending pressure for lung expansion and adequate ventilation Affected neonates exhibit tachypnea, respiratory muscle (diaphragmatic, subcostal, and intercostal) retractions, and expiratory grunting Complications include pulmonary air leak, pulmonary hemorrhage, intracranial hemorrhage, and chronic lung disease Infants who require prolonged intubation and mechanical ventilation also are at risk for subglottic injury, including subglottic stenosis and tracheomalacia Before the availability of exogenous surfactant therapy, the mortality rate from RDS exceeded 20% Currently, infants treated in neonatal intensive care units (NICUs) rarely succumb to RDS unless they are extremely preterm or suffer severe complications Pulmonary surfactant disperses at the air-liquid interface of alveoli, reduces surface tension at this interface, and prevents alveolar collapse at end expiration Pulmonary surfactant consists of 90% lipids and 10% proteins Phospholipids (including phosphatidylcholine and phosphatidylglycerol) are enriched surfactants produced by alveolar type pneumocytes The lipids are synthesized in the endoplasmic reticulum and transferred into lamellar bodies (LBs) via an adenosine triphosphate–binding cassette transporter A3 (ABCA3) pathway.14–16 The hydrophobic surfactant apoproteins (SP-B and SP-C) are assembled into LBs and secreted into the alveolar space with lipids via G-protein coupled receptor (GPR 116)17,18 at the epithelial surface Under the influence of extracellular calcium ions, the LBs then unwind and 570 S E C T I O N V Pediatric Critical Care: Pulmonary interact with hydrophilic surfactant proteins (SP-D and SP-A) to form a tubular myelin mesh, which spreads into the surfactant film surface monolayer Surfactant is also recycled and catabolized or reused Maintenance of the surface film is a dynamic process The unique surface tension–lowering property of surfactant is principally due to dipalmitoyl phosphatidylcholine, a disaturated phospholipid in which acyl groups are tightly interlaced as the film is compressed during exhalation Maternal glucocorticoid therapy has reduced the incidence of RDS in preterm infants Treatment with exogenous intratracheal surfactant has significantly reduced the clinical severity of RDS and improved survival Over the last decade, standard practice comprises rapid initiation of CPAP and withholding intubation (and accompanying surfactant instillation) until a threshold of supplemental oxygen (e.g., 30%–40%) is reached Use of an intratracheal catheter to administer surfactant shows promise as an alternative to endotracheal intubation.19 Mutations in the genes encoding SP-B, SP-C, and ABCA3 can cause refractory respiratory failure and chronic interstitial lung disease in full-term infants despite mechanical ventilation and surfactant replacement.20 SP-B mutations (often autosomal recessive) can result in a complete loss of SP-B Affected patients almost always present with respiratory failure in the neonatal period and usually die (without lung transplantation) in the first few months of life SP-C mutations are inherited as an autosomaldominant disorder, can present in infancy or later childhood, and are variable in severity ABCA3 mutations are inherited as autosomal-recessive disorders and can present as a neonatal form or much later in life as chronic childhood interstitial lung disease.14 Molecular genetic diagnosis can identify affected infants and help predict fatal outcome Pulmonary Air Leak Syndromes Pulmonary air leak syndrome encompasses a spectrum of entities, including pneumothorax, pneumomediastinum, pneumopericardium, and pulmonary interstitial emphysema (PIE) Subcutaneous emphysema and pneumoperitoneum are rarer forms As a group, pulmonary air leaks are more common during the neonatal period than at any other time of life The two most common types of air leak, pneumothorax and pneumomediastinum, occur spontaneously in 1% to 2% of term neonates and are apparently symptomatic only in an estimated 10% of these newborns Preterm infants with surfactant-deficiency RDS historically had reported rates of air leaks in excess of 30%; these rates fell rapidly with the advent of surfactant therapy in the 1980s but still remain at about 5%.21 Infants who have meconium aspiration or hypoplastic lungs have much higher air leak rates Air leak initiates as rupture of an overdistended alveolus Overdistention may be due to generalized air trapping or uneven distribution of air After rupture of the alveolus or terminal airspace, air escapes into the lung interstitium and tracks along the perivascular connective tissue sheaths toward the hilum If air leaks into the intrapleural space, pneumothorax results If the leak is at the hilar pleural reflection, pneumomediastinum occurs; air leak at the pericardial reflection results in pneumopericardium Rarely, air can dissect into the soft-tissue planes of the neck, causing subcutaneous emphysema, or across the diaphragmatic apertures and into the peritoneal abdominal space, leading to a pneumoperitoneum In the past, pulmonary air leaks most commonly occurred as a result of excessive ventilatory pressures due to either overly aggressive mechanical ventilation (barotrauma) or air trapping caused by partial airway obstruction by meconium or other debris (ball valving) More recently, air leaks are more commonly seen during the recovery phase of acute respiratory disease, when lung compliance dramatically improves and pressure-limited ventilation leads to excessive tidal volumes (volutrauma) This phenomenon explains the clinical observations that air leaks tend to occur during the recovery phase of RDS and why the incidence of air leaks actually increased during early trials of surfactant therapy Both observations underscore the need to closely monitor ventilatory volumes and wean pressure aggressively as compliance improves Moreover, evidence indicates that volume-limited ventilation may be a safer mode for neonatal mechanical ventilation even during the recovery phase of acute neonatal respiratory disease Pneumomediastinum is one of the most common air leaks and, considering the pathways by which air will track, is often the harbinger of further air leaks Infants with isolated pneumomediastinum generally display few or no signs other than chest radiograph low-density widening of the mediastinum On an anteroposterior view of the chest radiograph, air may form a lucency around the heart, whereas on a lateral view, air lifts the lobes of the thymus away from the cardiac silhouette (spinnaker sail sign) Pneumothorax is a clinically common and more worrisome form of pulmonary air leak The initial signs of pneumothorax result from lung compression and diminished lung compliance If compromise is minimal, the infant will maintain minute ventilation simply by increasing ventilatory rate (tachypnea) An additional sign may be increased use of accessory muscles (retractions) in an effort to improve tidal volume If positive pressure within the pleural space builds to the point of vascular compromise (i.e., tension pneumothorax), cardiac return will decrease and the heart rate will rise to compensate for diminished stroke volume Eventually, blood pressure may fall; if oxygen delivery cannot be maintained, bradycardia and cardiopulmonary arrest may ensue Pneumopericardium is a rare but often life-threatening form of pulmonary air leak The clinical signs closely resemble those of tension pneumothorax, with the addition that diminished heart sounds are invariably present Mortality may be as high as 80% Diagnosis is suspected if an infant experiences acute circulatory collapse; it is confirmed by lucency around the heart on the radiograph or by return of air on pericardiocentesis using an angiocatheter and syringe Pneumoperitoneum occurs when air dissects from the chest through a foramen of the diaphragm This condition is generally benign and causes little clinical difficulty It can, however, be confused with perforation of a viscus Pneumoperitoneum is often distinguishable from bowel perforation by a clinical history of a prior pneumomediastinum or pneumothorax, especially when there is an absence of gastrointestinal (GI) signs Pneumoperitoneum usually requires no treatment PIE is a more severe manifestation of the same pathophysiologic process that leads to other air leak syndromes In this instance, air accumulates in the interstitial space rather than tracking toward the hilum The chest radiograph may show a variable number of cystic or linear lucencies in the lung fields.22,23 This air accumulation produces compression of the airways and vasculature, making ventilation more difficult There should be a high degree of suspicion for air leaks in a patient who has a sudden, unexpected cardiovascular deterioration Transillumination of the relatively translucent neonatal chest wall using an intensely focused light source may be a quick and useful tool for diagnosing a large pneumothorax Immediate aspiration of the air, preferentially with a large-bore angiocatheter, ... intensive care unit include intravenous infusions of magnesium sulfate and methylxanthine agents, and breathing helium-oxygen mixtures Failure to respond to treatment can lead to further deterioration... 40% of extremely low-birthweight infants Effective gas exchange within the lung requires both adequate ventilation and perfusion This is dependent on an effective cardiorespiratory transition from... result, extravascular lung liquid volume (i.e., liquid within the airspaces and interstitium) decreases Any excess fluid remaining within the airspaces at the time of delivery is further resorbed