EDUCATION SERIES CareSource CLINICAL Nurse Education Program Ross

Neonatal Respiratory System

Vicky L. Armstrong, RNC, MSN Neonatal Respiratory System is one segment Clinical Nurse Specialist of the Clinical Education Series published by Perinatal Outreach Program Ross Products Division, Abbott Laboratories Inc., Children’s Hospital for nurses and physicians. Each segment consists Columbus, Ohio of a teaching reference and accompanying visual aids in chart and 35-mm slide form.

CONTENTS EMBRYOLOGY AND Embryology and System Development SYSTEM DEVELOPMENT Transition From Intrauterine to Extrauterine Life There are five stages in the embryonic development Resuscitation of the Infant With Respiratory Distress of normal lung growth: embryonic, pseudoglandu- Differential Diagnosis lar, canalicular, terminal sac, and alveolar. As shown History and Respiratory System Assessment in Figure 1, the embryonic stage occurs from Common Neonatal Respiratory Disorders conception to week 5, with the major event being • Respiratory Distress Syndrome (RDS) the formation of the proximal airways. The lung bud • Transient Tachypnea of the Newborn (TTNB) appears and begins to divide, the pulmonary vein • Meconium Aspiration Syndrome (MAS) develops and extends to join the lung bud, and the • Pneumonia trachea develops. In stage 2, the pseudoglandular • Persistent Pulmonary Hypertension stage, formation of the conducting airways occurs of the Newborn (PPHN) (weeks 6-16). Cartilage appears and the main bronchi • Air-Leak Syndrome form. Formation of new bronchi is complete and the • Congenital Diaphragmatic Hernia (CDH) capillary bed is formed. During the canalicular stage • Apnea of Prematurity (weeks 17-24), the major feature is formation of acini • Bronchopulmonary Dysplasia (BPD) (gas-exchanging sites). There is an appearance of Special Concerns With the Premature Infant cuboidal cells, the capillaries invade the terminal air Related Nursing Care sac walls, type II alveolar cells appear, and the airway References changes from glandular to tubular and increases in Additional Readings length and diameter. The alveolar sacs are formed and there is development of gas-exchange sites in

Figure 1. The five phases of the process of tracheobronchial airway development. n = number of branches. Reproduced, with permission, from Elliott and Leuthner: Anatomy and development of the lung, in Hansen TN, Cooper TR, Weisman LE (eds): Contemporary Diagnosis and Management of Neonatal Respiratory Diseases, ed 2. © 1998, Handbooks in Health Care Co, p 2.

© 2002 Ross Products Division, Abbott Laboratories 1 the terminal sac stage (weeks 25-37). In the alveolar, alveolar epithelial cells. These cells begin to appear or final, stage (week 37-postnatal), expansion of in the lung between 20 and 24 weeks of gestation. the surface area occurs. This stage continues up to 8 years after birth. TRANSITION FROM INTRAUTERINE The surface of the lung is lined by a layer of fluid TO EXTRAUTERINE LIFE that creates an air-liquid interface. Surface-tension forces act on air-liquid interfaces, causing a water The transition from intrauterine to extrauterine droplet to bead up. A surface-active compound environment and from fetal to postnatal life begins called surfactant reduces the surface tension and with the clamping of the and the allows the droplet to spread out into a thin layer. infant’s first breath. In the lungs, the surface-tension forces tend to cause In utero, fetal circulation (Figure 2) depends on the the alveoli to collapse. Surfactant is needed to lower placenta and three fetal ducts: the ductus venosus, the surface tension within these alveoli to prevent the foramen ovale, and the ductus arteriosus. The their collapse at the end of expiration. Surfactant is placenta allows for the exchange of gases, nutrients, a surface-active agent composed of phospholipids and metabolic waste products. It is a low-resistance (including lecithin and sphingomyelin), cholesterol, circuit that maintains a low fetal systemic vascular lipids, and proteins and is synthesized in type II resistance, while the pulmonary fetal circuit maintains a high pulmonary vascular resistance. Subsequently, the increased pulmonary To head vascular resistance and low systemic vascular resistance promote right-to-left To arm To arm shunting through the fetal ducts. The ductus Aorta Superior vena cava Ductus arteriosus venosus allows part of the oxygenated

Pulmonary artery blood carried by the umbilical vein to Left atrium bypass the liver. Oxygenated blood Foramen ovale entering the heart flows through the Right atrium foramen ovale into the left atrium, then Right Lung Left Lung perfuses the brain and the heart via the Right ventricle carotid, subclavian, and coronary arteries. Hepatic vein The ductus arteriosus directs blood from Left ventricle the main pulmonary artery to the descend- Ductus venosus Liver ing aorta. Fetal admixture at the foramen ovale and ductus arteriosus lowers fetal Inferior vena cava arterial oxygen tension to ~ 25-35 mm Hg. The low fetal oxygen tension helps to Renal arteries & veins maintain pulmonary artery vasoconstric- Umbilical vein tion, allowing blood to bypass the lung Portal vein Aorta and flow instead through the foramen ovale and ductus arteriosus. Umbilical Umbilicus arteries In summary, fetal blood flows from the placenta via the umbilical vein, bypasses the liver via the ductus venosus, and enters the inferior vena cava. From the Hypogastric arteries inferior vena cava, blood enters the right

Umbilical cord atrium, where the majority of it is shunted To left leg through the foramen ovale into the left Arterial blood Placenta atrium. Blood continues into the left Bladder Venous blood ventricle, where it mixes with blood Mixed arterial-venous blood returning from the pulmonary veins, and is then injected into the ascending aorta. From the ascending aorta, it supplies the carotid, subclavian, and coronary arteries before mixing with blood shunted across Figure 2. The fetal circulation.

2 the ductus arteriosus. The remainder of the blood saturations and decreasing carbon dioxide levels, entering the right atrium mixes with blood from the resulting in an increase in pulmonary blood flow. superior vena cava and continues into the right Decreasing prostaglandin levels also will facilitate the ventricle and pulmonary arteries. Most of this reversal of the pulmonary vasoconstriction. Removal blood shunts across the ductus arteriosus into of the placental circuit by the clamping of the the descending aorta. umbilical cord results in increasing systemic vascular resistance. Simultaneous cardiovascular changes Once the infant is delivered and the transition to include the closing of fetal shunts. The ductus extrauterine life begins, respiratory and cardiovas- venosus functionally closes as the umbilical cord is cular changes occur independently but simulta- clamped. Functional closure of the foramen ovale neously. Fetal lung fluid is replaced by air, so the occurs at birth from the changing atrial pressures liquid-liquid interface of alveoli becomes an air-liquid and increasing systemic vascular resistance. The left interface and surface tension forces begin. Surfactant atrial pressure is now greater than the right atrial decreases the surface tension with the first breath pressure. With increasing arterial oxygen tension and arterial oxygen tension rises, resulting in and decreasing levels of prostaglandin E, the ductus reversal of hypoxemia-induced pulmonary vaso- arteriosus closes functionally at 15-24 hours of age constriction. The pulmonary vascular resistance but does not close anatomically for 3-4 weeks (see begins to decline as a result of increasing oxygen Tables 1 and 2).

Table 1. Summary of Main Transitional Events RESUSCITATION OF THE INFANT From Fetal to Neonatal Circulation WITH RESPIRATORY DISTRESS Loss of fetal lung fluid Anticipation is a key component of the successful Secretion of surfactant resuscitation of a distressed newborn. Maternal or Establishment of functional residual capacity fetal conditions that place a newborn at risk for respiratory depression/distress at birth must be Fall in pulmonary vascular resistance recognized. According to the American Academy of Rise in systemic vascular resistance Pediatrics (AAP) and the American Heart Association (AHA), “Every newborn has a right to a resuscitation Closing of fetal shunts performed at a high level of competence. The proper Increasing pulmonary blood flow

Table 2. Transition From Fetal to Neonatal Circulation* First Period of Reactivity Period of Relative Inactivity Second Period of Reactivity (early reactivity) (deep sleep) (secondary reactivity) Time Course Birth to 30-45 minutes 45 minutes to 2-4 hours 3-4 hours thereafter CNS Alert, eyes open; vigorous, Somnolent, eyes closed; Hungry; progresses normally active crying; increased tone difficult to arouse or interest; through wake, feed, quiet alert, and highly responsive to stimuli decreased tone and general drowsy, and deep sleep in responsiveness; can be cyclic fashion awakened only briefly Color Ruddy with acrocyanosis Pale, no cyanosis Pink, no cyanosis Heart Rate High (140-160 BPM) and Low (90-120 BPM) and Varies with wake/sleep cycle very reactive briefly reactive Respiratory Rate High (40-60 BPM), mild Low (20-40 BPM), no Varies with wake/sleep cycle retractions, moist rales retractions, no rales; occasional periodic breathing Blood Pressure Should rise slowly but steadily through all stages Bowel Sounds Active bowel sounds; belly Inactive bowel sounds; less Active bowel sounds; air distended; may pass meconium distention; belly easily palpated swallowing and distention and urine with crying

*Adapted from Molteni RA: Neonatal Respiratory Distress Clinical Education Aid. © 1992 Ross Laboratories, p 3.

3 equipment must be immediately available at delivery, Resuscitation Procedure and healthcare professionals must be skilled in Mastery of neonatal resuscitation skills is necessary resuscitating a newborn and capable of working for performing successful resuscitation. The smoothly as a team” (Bloom et al, 1994, p O-1). AAP/AHA NRP is a national program that provides health care professionals with the knowledge and Resuscitation Equipment skills to resuscitate newborn infants by using a Resuscitation equipment should be available, ready standardized approach. to use, and functional at all times, and should The American Academy of Pediatrics and the include: American Heart Association have developed a new • Radiant warmer bed (prewarmed) algorithm for resuscitation of the newly born infant. • Stethoscope The revised NRP algorithm follows the basics of the • Bulb syringe previous algorithm, but now includes three levels of • DeLee suction catheter post-resuscitation care: routine care, supportive care, • Meconium aspirator and ongoing care. Evaluation continues to be based • Wall suction primarily on respirations, heart rate, and color, and • Suction catheters (6F, 8F, 10F) the valuation-decision-action cycle. (See the Textbook • Resuscitation bag with a manometer of Neonatal Resuscitation for algorithm.) • Laryngoscope with Miller 0 and Miller 1 blades • Straight blades; extra bulbs and batteries • Endotracheal tubes (2.5, 3.0, 3.5, 4.0, 4.5 internal DIFFERENTIAL DIAGNOSIS diameter mm) • Stylet The differential diagnosis for neonatal respiratory • Tape (to secure endotracheal tube) distress is very broad (see Tables 4 and 5). The • #8 feeding tube; 20-mL syringe practitioner must carefully review the maternal • Face masks (newborn, premature sizes) history, observe the infant’s disease course, and • Oxygen source with flowmeter and tubing assess the results of the physical examination. Laboratory tests and radiologic findings are Medications recommended in the AAP/AHA Neonatal adjuncts to the differential diagnosis. ® Resuscitation Program (NRP) and in NeoFax (Young and Mangum, 1997) should also be readily available, including intravenous or umbilical vessel cannulation materials (see Table 3).

Table 3. Medications for Neonatal Resuscitation* Medication Indication Dose Route Administration Epinephrine HR<60 despite 30 seconds 1:10,000 concentration 0.1-0.3 mL/kg ETT or IV Administer as of assisted ventilation & quickly as possible another 30 seconds of coordinated chest compressions and ventilations Volume No response to resuscitation Use normal saline 10 mL/kg IV, Administer over Expander Evidence of blood loss (recommended), umbilical vein 5-10 minutes ringer’s lactate, O-negative blood Sodium Suspected or proven severe 4.2% solution 2 mEq/kg IV, Administer slowly Bicarbonate metabolic acidosis umbilical vein (no greater than (Do not administer (4 mL of 1 mEq/kg/min) if lungs are not 4.2% solution) adequately ventilated)

(Do not give per endotracheal tube)

*Naloxone is not necessary during ACUTE stage of resuscitation, so is no longer discussed under resuscitation medications. Adapted from Kattwinkel J (ed): Textbook of Neonatal Resuscitation, ed 4. © 2000 American Academy of Pediatrics and American Heart Association.

4 COMMON NEONATAL RESPIRATORY With the hypoxemia and resulting acidosis there DISORDERS is increased pulmonary vascular resistance and vasoconstriction, leading to pulmonary RESPIRATORY DISTRESS SYNDROME (RDS) hypoperfusion and additional hypoxemia. Respiratory distress syndrome (RDS) is caused by a Clinical Presentation primary absence or deficiency of surfactant. The usual clinical presentation is seen within Endogenous surfactant prevents increased surface 6 hours after birth and includes the following: tension, which can lead to alveolar collapse. Nasal flaring An attempt to decrease airway Incidence (Moïse and Hansen, 1998; Cifuents et al, 1998) resistance and take in more 40,000 infants per year oxygen 14% of low-birth-weight infants Grunting An attempt to maintain functional 60% of infants of < 29 weeks’ gestational age residual capacity Inversely proportional to gestational age Retractions A reflection of noncompliant Infants at Risk/Predisposing Factors or stiff lungs and compliant Premature infants chest wall Male infants Tachypnea An attempt to maintain minute Infants of diabetic mothers—surfactant ventilation and prevent lung production can be inhibited due to the collapse infant’s hyperinsulinemic state Hypoventilation A result of muscle fatigue —surfactant production can be Diminished A reflection of decreased decreased due to transient fetal distress breath sounds air entry Pathophysiology Edematous A result of altered vascular The absence or deficiency of surfactant results in extremities permeability increased alveolar surface tension, leading to alveolar Cyanosis A result of increasing hypoxemia collapse and decreased lung compliance (stiff lungs). With decreased lung compliance, greater and greater Arterial blood gases demonstrate hypoxemia in room negative pressure must be generated to inflate the air, hypercarbia, and mixed acidemia. With mild RDS, lung with each succeeding breath. Widespread the chest radiograph shows a ground-glass, reticulo- alveolar collapse, or atelectasis, results in mismatches granular appearance (diffuse alveolar atelectasis of ventilation and perfusion (V/Q ratio) and surrounding open bronchi), air bronchograms hypoventilation. Collapsed areas of the lung may (aerated bronchioles), and decreased lung volumes continue to receive capillary blood flow, but gas (diffuse atelectasis). With severe RDS, a “whiteout” exchange does not occur. Intrapulmonary shunting pattern is seen on the chest film, with little aeration causes further hypoxemia. Hypercarbia also and with the heart border obscured or fuzzy. develops, which leads to respiratory acidosis. Hypoxia at the cellular level results in anaerobic metabolism and, subsequently, metabolic acidosis. Table 5. Extrapulmonary Disorders Vascular Metabolic Neuromuscular Table 4. Pulmonary Disorders Persistent Acidosis Cerebral edema Common Less Common pulmonary or hemorrhage Hypoglycemia hypertension Respiratory distress syndrome Pulmonary hypoplasia Drugs Hypothermia Congenital Transient tachypnea Upper airway obstruction Muscle disorders heart disease Meconium aspiration syndrome Rib-cage abnormalities Spinal cord Hypovolemia, problems Pneumonia Space-occupying lesions Phrenic nerve Air-leak syndrome Pulmonary hemorrhage damage

5 HISTORY AND RESPIRATORY SYSTEM ASSESSMENT

Table 6. History Table 7. Respiratory System Assessment (continued) Mother Prenatal history and care Other Respiratory Findings Family illnesses Expiratory Audible, forced expiration through a partially Age grunt closed glottis -related complications Delays expiration and increases gas exchange Medications by increasing end-expiratory pressure Substance abuse Nasal flaring Increased size of nares with respiration to Gravida, para, abortions, living children decrease airway resistance Blood type, antibody screening Stridor High-pitched crowing sound caused by Intrapartum Intrapartal complications narrowing of glottis or trachea Time of rupture of membranes Wheeze High-pitched, continuous lung sounds (spontaneous or artificial) similar to dry whistling sound produced by Description of amniotic fluid air passing through a narrowed lumen (clear, foul-smelling, meconium-stained) Chest Shape/Symmetry Onset and duration of labor (spontaneous or induced) Barrel-shaped Suggests increased chest volume . Medications chest eg, transient tachypnea of the newborn, Evidence of fetal distress meconium aspiration syndrome, persistent Method of delivery: pulmonary hypertension Vaginal (especially forceps, Bell-shaped Suggests decreased chest volume vacuum extraction) chest eg, respiratory distress syndrome, Cesarean pulmonary hypoplasia Chest wall Results from volume differences between Infant Apgar scores asymmetry two sides of thoracic cavity Resuscitative interventions eg, atelectasis, , unilateral Gestational-age examination pulmonary emphysema, cystic lung disease General physical examination Auscultation of Breath Sounds

Table 7. Respiratory System Assessment Assess air movement and quality of breath sounds: Normal breath Bronchovesicular (expiration equals Color sounds inspiration) Pink Reddish-pink hue of skin, nailbeds, and Adventitious Rales mucous membranes breath sounds Rhonchi Cyanosis Blue discoloration of skin, nailbeds, and Wheeze mucous membranes Pleural friction rub Acrocyanosis Peripheral cyanosis of hands and feet Plethora Ruddy color Pallor Pale, white skin Type of Breathing The clinical course of RDS is variable but self- Apnea Cessation of breathing for > 20 seconds, limiting. There is progressive worsening over the usually with color changes and bradycardia first 2 to 3 days, as evidenced by increasing oxygen Periodic Intermittent cessation of respiration; usually requirements and poor lung performance. Postnatal respirations pauses between breaths < 15 seconds surfactant production begins at ~ 48-72 hours of Dyspnea Labored or difficult breathing age and results in improved lung compliance Bradypnea Abnormally slow respiratory pattern; and decreasing respiratory distress. This recovery 20-30 BPM of slower, deeper respirations phase is usually preceded by a period of sponta- Tachypnea Respiratory rate > 60 BPM neous diuresis. Respiratory Effort Chest movement Depth of respiration, symmetry, synchrony Paradoxical Inward pull of lower thorax and bulging of respiratory abdomen with each breath effort Retractions Inward pull of chest wall on inspiration

(continued) 6 Management Synchronized intermittent mandatory ventilation Management begins with preventive measures. and assist/control mode ventilation are referred to as Administration of antenatal steroids results in patient-triggered ventilation. Synchronized intermit- accelerated maturity of the fetal lungs. The incidence tent mandatory ventilation uses airway flow, airway and severity of RDS are decreased in infants whose pressure, changes in chest wall impedance, or mothers received corticosteroids 24-48 hours before abdominal movements to detect the onset of delivery. Corticosteroids are most effective when inspiratory efforts. Spontaneous breaths trigger the infants are less than 34 weeks’ gestational age and ventilator to maintain the rate. During episodes of the drug is administered for at least 24 hours but apnea, controlled breaths occur at the preset rate. no longer than 7 days before delivery. There appears In the assist/control mode, a spontaneous breath to be an additive effect in the improvement of lung triggers a mechanical breath. This mode also delivers function with the combined use of antenatal steroids controlled breaths at the preset rate during apnea. and postnatal surfactant. Patient-triggered ventilation has been shown to improve gas exchange and reduce asynchrony The goals of treating RDS are to prevent alveolar between infant-generated and ventilator-generated collapse, optimize tissue oxygenation and carbon breaths. dioxide elimination, minimize oxygen consumption, and provide supportive care. Administration of Prognosis (Moïse and Hansen, 1998; Bhutani, 1996) oxygen, continuous positive airway pressure, and Most infants with RDS recover without further positive-pressure ventilation may be needed to problems, usually within 3 to 5 days. With severe provide adequate tissue oxygenation, relieve hypoxic RDS, the requirement for assisted ventilation, the vasoconstriction, and reduce right-to-left shunting. development of complications such as air leaks, Arterial blood gases, pulse oximetry, and transcuta- patent ductus arteriosus, or the beginnings of neous oxygen monitors provide information needed bronchopulmonary dysplasia may delay recovery for to maintain the arterial oxygen tension within an days, weeks, or even months. Mortality is inversely acceptable range. Positive end-expiratory pressure, proportional to gestational age. The incidence of provided by either nasal prongs or tracheal chronic lung disease is < 10% in infants with a intubation, can be used to prevent atelectasis by birth weight > 1000 g to ~ 50% in infants with maintaining alveolar distention throughout the a birth weight < 1000 g. respiratory cycle. Sedatives and analgesics may be given if the infant’s respiratory efforts interfere with TRANSIENT TACHYPNEA OF THE effective positive-pressure ventilation (see Table 8). NEWBORN (TTNB) Supportive care includes maintaining a neutral thermal environment, hydration, and circulatory The most commonly cited cause of transient tachy- support; antibiotics; and standard neonatal care. pnea of the newborn (TTNB) is delayed absorption of fetal lung fluid. Other treatments for RDS include surfactant replacement therapy, high-frequency ventilation, and Infants at Risk/Predisposing Factors patient-triggered ventilation. Term or near-term infants Precipitous delivery Surfactant replacement therapy has become a Cesarean delivery, especially in the absence of labor standard treatment. It improves oxygenation and stabilizes alveoli with a resultant reduction in the Pathophysiology severity of RDS. Commercial preparations used in In utero, the fetal lungs are filled with fluid. During surfactant replacement therapy are usually given as normal vaginal delivery, the fluid is usually forced a liquid bolus into the endotracheal tube, with the out by the thoracic squeeze. The remainder of the dose divided into aliquots and administered with the fluid in the lungs is cleared by the pulmonary veins infant in different positions. and lymphatic system. With a precipitous or cesarean delivery, absence of the gradual chest compression High-frequency ventilation, including high-frequency that occurs during normal vaginal birth causes fluid oscillation and high-frequency jet ventilation, to be retained. Accumulation of this interstitial fluid appears to produce adequate gas exchange at lower interferes with forces that tend to keep the bronchi- peak airway pressures while potentially reducing oles open and eventually causes the bronchioles to barotrauma and the development of chronic lung collapse (air trapping). Air trapping and hyperinfla- disease. It uses small tidal volumes at near or less tion can increase pulmonary vascular resistance and than anatomic dead space at rapid rates. lead to potential persistent pulmonary hypertension.

7 Clinical Presentation response to asphyxia and may inhale meconium into The clinical presentation can be difficult to distin- the airway. With the infant’s first breath, meconium guish from that of other neonatal disorders such as can be aspirated into the lungs. This aspirated thick bacterial pneumonia, sepsis, and RDS. The onset meconium can result in: of symptoms is usually 0.5-6 hours after birth; • Partial airway obstruction (a ball-valve obstruc- respiratory rates up to 120-140 BPM are the most tion), leading to air trapping and overdistention common symptom. Grunting, nasal flaring, and of the airways, with alveolar rupture and air leaks retractions may occur with varying severity. Arterial • Complete airway obstruction, leading to small blood gases reveal hypoxemia in room air, mild airway atelectasis hypercarbia, and mild to moderate acidosis. Chest • Inflammatory response of the tracheobronchial radiographs show hyperinflation (from air trapping) epithelium to meconium, leading to chemical and streaky infiltrates (interstitial fluid along the pneumonitis bronchovascular space) from the hilum. • Possible surfactant displacement or inactivation of endogenous surfactant Management Treatment of TTNB consists of supplemental oxygen Uneven pulmonary ventilation with hyperinflation

(usually < 40% fractional inspiratory oxygen [FiO2]), of some areas and atelectasis of others leads to pulse oximetry and/or transcutaneous monitoring, ventilation-perfusion mismatches and, subsequently, antibiotics (if infection is suspected), a neutral hypercarbia and hypoxemia. Hypoxemia may worsen thermal environment, and general supportive pulmonary vasoconstriction, resulting in further neonatal care. Oral feedings should be delayed hypoxemia and acidemia, and set up a vicious cycle. to prevent aspiration from high respiratory rates. Clinical Presentation Prognosis Usually infants with MAS have a history of fetal Although TTNB is self-limiting and usually clears distress and meconium-stained fluid. Respiratory within 1 to 3 days, it is a diagnosis of exclusion made distress can range from mild to severe, with varying after the infant has recovered. Infants generally degrees of cyanosis, tachypnea, retractions, grunting, recover completely without any residual respiratory nasal flaring, and coarse rales and rhonchi. The chest problems. appears barrel-shaped (increased anteroposterior diameter) from gas trapping. Arterial blood gases MECONIUM ASPIRATION SYNDROME (MAS) may reflect varying degrees of hypoxemia, hyper- carbia, and acidosis. The chest radiograph shows Meconium aspiration syndrome (MAS) is the most coarse, patchy areas of decreased aeration (atelec- common aspiration syndrome causing respiratory tasis) and areas of hyperaeration (air trapping). distress in newborns. Meconium-stained fluid is Later, chemical pneumonitis can become apparent present in 9% to 20% of all deliveries, but not all on the chest film. meconium-stained infants develop MAS. Management Incidence (Orlando, 1997) Treatment of infants at risk for MAS begins with ~ 520,000 infants per year are meconium-stained preventive management. Infusion of saline into the ~ 26,000 infants per year develop MAS amniotic sac (amnioinfusion) has been used to ~ 1,000 infants per year die from MAS dilute the meconium and correct the oligohydram- Infants at Risk/Predisposing Factors nios often associated with meconium-stained Term, postterm infants amniotic fluid. Amnioinfusion may also decrease the Term or postterm small-for-gestational age infants risk of cord compression and acidemia, which could Any event causing fetal distress, such as: stimulate passage of meconium. Another preventive • Reduced placental or uterine blood flow intervention, nasopharyngeal and oral suctioning, • Maternal hypoxia and/or anemia should be instituted as soon as the head is delivered • Placental or umbilical cord accidents and before the thorax is delivered. After delivery, a person skilled in neonatal resuscitation and Pathophysiology intubation should provide direct tracheal suctioning Meconium is normally retained in the fetal gut until before the infant begins breathing. This is usually postnatal life, but passage of meconium occurs in necessary if the meconium is thick or particulate, response to fetal distress (hypoxic bowel stimula- and the infant is depressed. tion). The rectal sphincter tone or muscle may relax after vagal reflex stimulation and release meconium Additional treatment is required for infants who into the amniotic fluid. The fetus begins gasping in develop MAS. Because meconium in the alveoli can injure type II alveolar epithelial cells and interfere

8 with endogenous surfactant production, surfactant limited to broad-spectrum antibiotics for suspected replacement therapy may improve oxygenation. infection, correction of metabolic abnormalities, Respiratory status should be constantly monitored maintenance of fluid balance, a neutral thermal with pulse oximetry or transcutaneous monitoring, environment, and minimal stimulation. Sedatives frequent blood gases, and clinical assessment to and analgesics may be given if the infant’s respiratory determine the need for oxygen and positive-pressure efforts interfere with effective positive-pressure ventilation. Supportive care includes but is not ventilation (see Table 8). Potential complications

Table 8. Sedatives, Analgesics, and Muscle Relaxants for Neonates Dose Side Effects (Young and Mangum, 1997) (Alexander and Todres, 1998; Young and Mangum, 1997) Sedatives Lorazepan 0.05-0.1 mg/kg/dose Respiratory depression IV slow push Hypotension Midazolam 0.05-0.15 mg/kg/dose over at least 5 minutes Respiratory depression IV, IM Hypotension Continuous IV infusion: 0.01-0.06 mg/kg/hour Seizure, seizurelike activity following rapid bolus administration Chloral hydrate 25-75 mg/kg/dose CNS, respiratory, myocardial depression PO or PR and bladder atony Dilute oral preparation or give after a feeding Direct hyperbilirubinemia Cardiac arrhythmias Do not use in patients with significant liver or kidney disease Analgesics Morphine 0.05-0.2 mg/kg/dose Respiratory depression IV, IM, SQ Hypotension Urine retention Continuous IV infusion: Decreased gut motility Loading dose first— Tolerance and withdrawal 100 mcg/kg over 1 hour followed by (prolonged administration) 10-15 mcg/kg/hour (weaning regimen needed) Reversed with naloxone Fentanyl 1-4 mcg/kg/dose IV Fewer respiratory and cardiovascular effects than with morphine Continuous IV infusion: With large, rapid boluses: 1-5 mcg/kg/hour Muscle rigidity Seizure activity Hypotension Bradycardia Tolerance and significant withdrawal with continuous infusion > 5 days (weaning regimen needed) Reversed with naloxone Muscle Relaxants Pancuronium 0.1 mg/kg/dose IV Tachycardia bromide (0.04-0.15 mg/kg/dose), as needed for paralysis Hypotension Usual dosing interval: 1-2 hours Peripheral edema Continuous IV infusion: 0.05-0.2 mg/kg/hour Increased salivation Reversed with atropine or glycopyrrolate followed by neostigmine

Vecuronium 0.1 mg/kg/dose IV Few cardiovascular effects bromide (0.03-0.15 mg/kg/hour), as needed for paralysis Usual dosing interval: 1-2 hours

IV = intravenously, IM = intramuscularly, PO = orally, PR = rectally, SQ = subcutaneously

9 associated with MAS include air-leak syndrome, Incidence (Carey and Trotter, 1997) chemical pneumonitis, persistent pulmonary 1% of term neonates hypertension, and end-organ damage. 10% of preterm neonates Other treatment interventions for MAS depend on Infants at Risk/Predisposing Factors the disease progression and may include high- Premature infants frequency ventilation (discussed in RDS section), Prolonged rupture of membranes > 24 hours nitric oxide, and extracorporeal membrane Excessive intrapartum manipulation oxygenation (ECMO). Maternal fever Nitric oxide, a potent pulmonary vasculature dilator, Maternal viral, bacterial, or other infection appears to be an effective adjunct therapy for persist- Prolonged labor ent pulmonary hypertension and may reduce the Maternal urinary tract infection need for ECMO. Inhaled nitric oxide can selectively Amnionitis lower pulmonary artery pressure and improve oxy- Immature immune system genation without causing adverse effects on cardiac Pathophysiology performance or systemic blood pressure. It enhances Transmission occurs transplacentally, intrapartally, or gas exchange by improving ventilation-perfusion postnatally. Pathologic organisms include but are mismatching and decreasing intrapulmonary not limited to those listed in Table 9. Transplacental shunting. But nitric oxide is not without problems. pneumonia can develop from aspiration or ingestion Progressive atelectasis and decreased cardiac per- of infected amniotic fluid or from transmission of formance can limit its effectiveness. Potential toxici- organisms from an infected mother across the ties include both methemoglobinemia and direct placenta to the fetus. Intrapartum pneumonia results lung injury from nitric dioxide. Therefore, nitric from colonization of the infant by ascension of the oxide administration is still considered experimental organism after rupture of the membranes or by the and is reserved for extremely sick newborns. infant’s passage through the birth canal. Postnatal ECMO is a process of prolonged cardiopulmonary pneumonia usually develops from hospital-acquired bypass that provides cardiorespiratory support until or nosocomial sources such as unwashed hands and the lungs recover. It is used with infants who have open skin lesions, as well as contaminated equip- reversible lung disease and who have not responded ment, nutritional products, or blood products. to maximal medical therapy. ECMO is often used to Clinical Presentation treat infants with predictably fatal pulmonary failure A high index of suspicion of pneumonia is the key from diseases such as MAS and infants with a birth to early diagnosis. The clinical presentation is often weight > 2 kg with RDS, pneumonia and sepsis, and nonspecific and includes temperature instability, persistent pulmonary hypertension. ECMO can be apnea, tachycardia, tachypnea, grunting, nasal performed by either venoarterial or venovenous flaring, retractions, lethargy, poor peripheral techniques. It has significant complications, so perfusion, and poor feeding. Skin lesions may be selection criteria must be established to determine found in infants with congenital pneumonia caused candidates who would die if conventional therapies by herpes simplex virus, Candida sp, or T pallidum. were used.

Prognosis (Orlando, 1997) Table 9. Pneumonia: Pathologic Organisms Meconium aspiration syndrome is usually resolved by 1 week of life for infants who do not require Transplacental Intrapartum Postnatal Nosocomial assisted ventilation, but may persist in infants Cytomegalovirus Herpes Staphylococcus aureus simplex virus requiring prolonged assisted ventilation. The Rubella Staph epidermidis outcome depends on the severity of the asphyxial C trachomatis insult and the extent of lung damage caused by T pallidum Herpes simplex virus Group B the disease and its potential complications. Toxoplasma gondii Candida sp streptococci Varicella Cytomegalovirus PNEUMONIA Escherichia coli Enterovirus Group B streptococci Neonatal pneumonia can be caused by bacterial, Klebsiella sp viral, protozoan, fungal, or other pathogens such as Listeria Enteroviruses Treponema pallidum or Chlamydia trachomatis. monocytogenes It can occur as a primary infection or as part of a Respiratory syncytial generalized infection. virus

10 A shocklike syndrome is often seen in the first 7 days Incidence (Walsh and Stork, 2001) of life with early-onset group B β-hemolytic strepto- 0.43 to 6.82 per 1,000 live births coccus (GBS) sepsis. Bacterial and viral cultures, rapid viral screening tests, and antigen tests (latex Infants at Risk/Predisposing Factors agglutination, counterimmunoelectrophoresis) Near-term, term, or postterm infants should be performed on infants with suspected Maladaptation of the pulmonary vascular bed— pneumonia. A Gram’s stain of tracheal aspirate may functional pulmonary vasoconstriction with be useful if done during the first 8 hours of life, but normal structural development and anatomy it may not differentiate overt pulmonary infection (eg, MAS, cold stress, asphyxia, sepsis) from early colonization. A complete blood count Maldevelopment of the pulmonary vascular bed— with differential and platelets is a useful adjunct abnormal pulmonary vascular structure resulting diagnostic test. The chest radiograph may show in excessive muscularization (eg, fetal ductal patchy opacifications, unilateral or bilateral alveolar closure, congenital heart disease) infiltrates, pleural effusions, and/or changes in lung Underdevelopment of the pulmonary vascular bed— volume. GBS pneumonia is difficult to differentiate decreased cross-sectional area of pulmonary from RDS on a chest radiograph. vascular bed secondary to hypoplasia (eg, Potter’s syndrome, diaphragmatic hernia) Management For an infant with suspected bacterial pneumonia, Pathophysiology broad-spectrum antibiotics, such as ampicillin and an The neonatal pulmonary vasculature is sensitive to aminoglycoside, should be started immediately and changes in arterial oxygen tension (PaO2) and pH. adjusted, if necessary, once the organism has been With hypoxemia and acidemia, the pulmonary identified. Some viral pneumonias can be treated vasculature constricts, resulting in increased with pharmacologic agents such as acyclovir or pulmonary vascular resistance. High pulmonary vidarabine for herpes simplex virus and ribavirin vascular resistance promotes blood flow away from for respiratory syncytial virus (RSV). Supportive the lungs through the ductus arteriosus into the treatment is needed for respiratory problems, systemic system and results in right-to-left shunting. hematologic instability, and acid-base imbalance. It also maintains higher right-sided pressures in the Oxygen and positive-pressure ventilation may be heart. When right atrial pressure is greater than left required in addition to volume expanders, blood atrial pressure and pulmonary artery pressure is products, and vasopressors if the infant is in shock. greater than systemic pressure, blood flow follows With continued deterioration, the infant may require the path of least resistance through the foramen newer treatment options, including granulocyte ovale and ductus arteriosus, again bypassing the transfusion, intravenous immunoglobulins, colony- lungs. This promotion of right-to-left shunting results stimulating factors, high-frequency ventilation, in hypoxemia due to venous admixture. The cycle inhaled nitric oxide, and extracorporeal membrane repeats as hypoxemia increases pulmonary vascular oxygenation. resistance, resulting in further intrapulmonary shunting, hypoxemia, and pulmonary Prognosis (Speer and Weisman, 1998) vasoconstriction. Overall mortality from sepsis, both related and unrelated to pneumonia, ranges from 5% to 10% in Clinical Presentation term infants and is as high as 67% in infants with a Clinical presentation is variable due to the different birth weight < 1500 g. etiologies of PPHN. Respiratory distress and cyanosis worsen despite high concentrations of inspired PERSISTENT PULMONARY HYPERTENSION oxygen. Arterial blood gases demonstrate severe OF THE NEWBORN (PPHN) hypoxemia, normal or mildly elevated arterial carbon dioxide tension (PaCO2), and metabolic acidosis. Persistent pulmonary hypertension of the newborn There is no classic chest radiograph finding for (PPHN) has been described as the persistence of the PPHN; rather, the x-ray reflects the underlying lung cardiopulmonary pathway seen in the fetus, but disease. It may show a prominent main pulmonary without the passage of blood through the placenta. artery segment, mild to moderate cardiomegaly, and It is characterized by high resistance in the pulmo- variable prominence of the pulmonary vasculature nary arteries, which produces an obstruction (normal or decreased vascular markings). of blood flow through the lungs and right-to-left shunting through the ductus arteriosus and/or fora- men ovale. PPHN may be idiopathic or secondary to another disorder such as MAS or sepsis.

11 The diagnostic work-up for PPHN may include a vascular resistance, and volume expanders can be hyperoxia/hyperventilation test and/or preductal and used to keep the systemic pressure normal or above postductal PaO2 tests. With the hyperoxia/hyperventi- normal in an attempt to reduce the pulmonary and lation test, the infant is placed in 100% FiO2 and systemic pressure gradient, thereby decreasing right- hyperventilated at rates > 100 BPM. An increase in to-left shunting. Tolazoline, a vasodilator, dilates the

PaO2 from < 50 mm Hg before the test to > 100 mm pulmonary arteries, which results in decreased Hg after the test is indicative of PPHN. Preductal pulmonary vascular resistance. Because of its serious and postductal blood is sampled to demonstrate a side effects, such as significant hypotension, gastro- right-to-left shunt through the ductal arteriosus. intestinal , thrombocytopenia, and renal Blood is drawn simultaneously from a preductal dysfunction, tolazoline should be used with caution. site (right radial or either temporal artery) and a Sedatives, analgesics, and muscle relaxants are used postductal site (umbilical, femoral, or posterior tibial when the infant’s respiratory efforts interfere with artery). In the hypoxemic infant, ductal shunting positive-pressure ventilation (see Table 8). Support- is demonstrated with a PaO2 difference > 15 to ive care includes continuous monitoring of arterial 20 mm Hg between the preductal and postductal blood pressure, pulse oximetry, maintenance of fluid sites. Pulse oximetry also demonstrates an arterial and electrolyte balance, and provision of a neutral oxygen percent saturation (SaO2) difference between thermal environment, hematologic support, and the right arm and the rest of the body and supports minimal stimulation. the diagnosis of PPHN. Diagnosis of PPHN can be made by demonstration of a shunt by two-dimen- Prognosis (Wearden and Hansen, 1998) sional echocardiogram. The prognosis varies according to disease etiology and severity. Improvement should be seen after Management 3 to 5 days. The goal of treatment is to correct hypoxemia and acidosis and promote pulmonary vascular dilation. AIR-LEAK SYNDROME Treatment consists of positive-pressure ventilation, pharmacologic support, supportive care, and Air leaks develop from alveolar rupture and the perhaps the use of high-frequency ventilation, nitric escape of air into tissue in which air is not normally oxide, and ECMO. Alkalosis, with either mechanical present (pleura, mediastinum, pericardium, or ventilation or a bicarbonate infusion, produces extrathoracic areas). pulmonary vasodilation. This subsequently Incidence (Miller et al, 1997) decreases pulmonary vascular resistance and The incidence of air-leak syndrome varies with the improves pulmonary perfusion and oxygenation. underlying lung disease as well as with resuscitation This approach is not without risks, as mechanical and ventilation methods: hyperventilation can impede venous blood return 5% to 20% incidence in infants with RDS, with and and reduce cardiac output, which further reduces without the use of assisted ventilation oxygenation. Induced hypocarbia can also diminish 20% to 50% incidence in term infants with MAS cerebral blood flow. Also, alkali infusion increases carbon dioxide production, which may lead to use of Infants at Risk/Predisposing Factors increased ventilator settings. Infants with hypoplastic lungs, RDS, MAS, or congenital malformations A more conservative approach attempts to minimize Infants who require ventilatory assistance or barotrauma while maintaining PaO2 between 50 and vigorous resuscitative efforts 70 mm Hg and PaCO2 between 40 and 60 mm Hg. Infants who have undergone thoracic surgery The appropriate peak inspiratory pressure for either ventilatory approach is then determined by the Pathophysiology infant’s chest excursion. Air leaks develop from abnormal distribution of gas and subsequent alveolar overdistention and rupture. Nitric oxide or ECMO may be needed if an infant Air ruptures out of the alveoli and moves along the does not respond to maximal medical treatment pulmonary blood vessels or peribronchial tissues. (see section describing ECMO and nitric oxide). The escaping air flows toward the point of least Pharmacologic management includes a variety of resistance. The location of the air leak determines agents. Vasopressors, which increase systemic which air-leak syndrome develops:

12 Pulmonary interstitial Air that is trapped in and the catheter can be left in place until a chest emphysema (PIE) interstitial space tube is inserted. A chest (thoracostomy) tube and chest drainage system will restore negative pressure Air that has traveled along and expand the lung. Local anesthesia with 1% the pulmonary blood xylocaine and an analgesic should be given for vessels and entered the pain relief. mediastinum Pneumothorax Air that has escaped directly CONGENITAL DIAPHRAGMATIC into the pleural space HERNIA (CDH) Tension pneumothorax Free pleural air that A congenital diaphragmatic hernia (CDH) is the compresses the lung herniation of the abdominal contents into the chest Air that has entered the through a defect in the diaphragm. Ninety percent space between the heart of these hernias occur on the left side and in the and the pericardial sac posterolateral portion of the diaphragm. Pneumoperitoneum Air that has traveled down- Incidence (Guillory and Cooper, 1998; Cifuents et al, 1998) ward into the abdominal 1:2000 to 1:5000 live births cavity and entered the Occurs more often in males than in females peritoneal space via the Infants at Risk/Predisposing Factors postmediastinal openings None in the diaphragm Pathophysiology Air embolism Thought to arise when air Closure of the diaphragm occurs at 8 to 10 weeks’ ruptures out of alveoli into gestational age. If closure is delayed, the bowel small pulmonary veins can move into the thoracic cavity and result in a diaphragmatic hernia. The stomach as well as the Clinical Presentation and Management small and large bowel, spleen, and liver can also The clinical presentation of air-leak syndrome is out- herniate into the chest. The presence of the lined in Table 10. abdominal contents in the thorax does more Transillumination provides a preliminary diagnosis than just cause lung hypoplasia by compression. for pneumothorax. It works by placing a high-inten- Decreased numbers of bronchial generations and sity, fiber optic light source over the chest wall and alveoli are seen, and the pulmonary artery is small. comparing the ring of the light bilaterally. Normal Increased muscularization of the pulmonary arteries lung and pleura are dense, so light is absorbed. The is also present. Both the bronchial and vascular presence of air pockets produces light around the changes restrict pulmonary blood flow, which can fiber optic light. However, negative transillumination result in persistent pulmonary hypertension. does not rule out pneumothorax. The definitive Clinical Presentation diagnosis for air leaks is a chest radiograph, either an A history of polyhydramnios is frequently associated anteroposterior (A-P) view or an A-P and a lateral with CDH, because the thoracic location of the view. The chest radiograph will identify the location intestine interferes with the intrauterine flow of and extent of air outside the tracheobronchial tree. amniotic fluid. Severity of signs and symptoms and A nitrogen washout can be used to treat pneumo- age at onset depend on the extent of lung hypo- mediastinum or nontension pneumothorax. The plasia and the degree of interference with ventila- infant is placed in 100% oxygen for 6 to 12 hours to tion. Clinical presentation includes a scaphoid establish a diffusion gradient between the pleural air abdomen, barrel-shaped chest, cyanosis, dyspnea, and the pleural capillaries so that air is more rapidly retractions, shifted heart sounds, and decreased or absorbed by the capillaries. Nitrogen washout is not absent breath sounds on the affected side. Chest and recommended for preterm infants because of the abdominal radiographs show loops of bowel in the relationship between high oxygen concentrations in chest (although these may not be evident until the the blood and retinopathy of prematurity. Tension infant has swallowed adequate air), sparse or absent pneumothoraces require emergency treatment. abdominal bowel gas, a mediastinal shift, and a Needle aspiration can be used to remove air quickly markedly elevated or indistinct diaphragm.

13 Table 10. Air-Leak Syndrome: Types, Symptoms, Diagnoses, Management

Air Leak Clinical Presentation Chest Radiograph Findings General Management Pulmonary interstitial Increased oxygen requirements Small dark bubbles of air outside Positive-pressure ventilation

emphysema CO2 retention the tracheobronchial tree but High-frequency ventilation Increased noncompliant lung trapped within the lung tissue Optional: selective main stem bronchus intubation Pneumomediastinum Generally asymptomatic “Spinnaker sail sign”: thymus Usually none required Tachypnea gland lifted by the mediastinal air Bulging sternum “Angel wing sign”: both lobes of thymus lifted Pneumothorax If symptomatic, see: May not show any changes, or Usually no specific management • Tachypnea may show air in pleural space Optional: nitrogen washout • Grunting outlining the visceral pleura • Retractions • Cyanosis Tension Tachypnea Pocket of air impinging on Needle aspiration pneumothorax Grunting/retractions the lung Chest tube placement Cyanosis Mediastinal shift may/may not Hypotension be evident Decreased breath sounds Chest asymmetry Shift in point of maximal impulse Distended abdomen Pneumopericardium Distant/absent heart sounds Dark circle surrounding the heart Needle aspiration Bradycardia Decreased heart size Optional: pericardial tube Diminished/absent pulses placement Marked hypotension Cyanosis and/or pallor Reduced EKG voltage Pneumoperitoneum Distended abdomen Dark layer over the abdomen Usually none required Pulmonary function may be Blurring or obscuring of normal Optional: insertion of soft compromised bowel pattern catheter into the peritoneum Air embolism Catastrophic Bizarre picture of intracardiac and No effective treatment Sudden cyanosis intravascular air Circulatory collapse Air-blood mixture crackles and pops with each heartbeat Air-blood mixture aspirated from the umbilical artery catheter

Management interventions include establishing intravenous Immediate recognition of the defect in the delivery access and providing a neutral thermal environment. room is a key component in management of an Elevating the head of the bed and positioning the infant with a congenital diaphragmatic hernia. infant so that the affected side is down allows for Bag-and-mask ventilation should be avoided to maximal expansion of the unaffected lung. Sedatives, prevent the accumulation of air in the stomach and analgesics, and muscle relaxants are used for pain bowel, which will compromise respiratory expansion relief and asynchrony of infant- and ventilator- and worsen respiratory function. Instead, immediate generated breaths (see Table 8). The definitive intubation and ventilation, using the lowest possible treatment is surgical correction of the hernia. The pressure, should be instituted. A large double-lumen development of pulmonary hypertension is frequently orogastric tube placed to low, intermittent suction seen postoperatively (see section on management of prevents stomach and bowel distention. Other pulmonary hypertension).

14 Prognosis (Miller et al, 1997) Pathophysiology Infants with CDH continue to have a high mortality Apnea of prematurity is a diagnosis of exclusion rate (from 20% to 60%). Pulmonary hypoperfusion when other underlying causes of apnea have been on the affected side may persist for years as the ruled out for infants of < 37 weeks’ gestational age. number of bronchi and alveoli remains reduced It has been related to neuronal immaturity of brain and increased muscularization of the pulmonary stem function, which controls respirations. In blood vessels continues. For survivors, gastro- addition, the central responsiveness to carbon esophageal reflux can be a long-term problem dioxide is blunted in preterm infants. A diminished after surgical repair. response to peripheral chemoreceptors located in both the aortic arch and the carotid arteries has APNEA OF PREMATURITY also been noted. These receptors sense changes in PaO2, pH, and PaCO2 that affect the regulation of Apnea is a cessation of respiration lasting 15 to respirations and relay them to the respiratory center 20 seconds and associated with bradycardia and/or in the brain. Upper airway obstruction contributes color changes. It can be obstructive, central, or to apnea because the negative pressure generated mixed. With obstructive apnea, respiratory efforts are during inspiration may result in pharyngeal and observed, but there is blocked air flow from collapse laryngeal collapse. of the upper airway. Central apnea involves the cessation of both respiratory efforts and air flow, Clinical Presentation with no airway obstruction. The most common Cessation of respiratory effort with cyanosis, pallor, classification in preterm infants is mixed apnea, , or bradycardia is noted. Frequent which involves a pause in respiratory effort preceded swallowing-like movements in the pharynx during or followed by airway obstruction at the upper apnea can be a problem, because swallowing directly airway level. inhibits the respiratory drive.

Incidence (Adams, 1998) Management ~ 25% incidence in preterm infants Treatment of the infant with apnea of prematurity 75% incidence in infants with a birth weight < 1000 g begins with assessment and monitoring (see Table 12). Tactile stimulation, oxygen administration, and/or Infants at Risk/Predisposing Factors bag-and-mask ventilation can be used to stimulate Premature infants an infant who is experiencing an apneic episode. Contributing factors shown in Table 11 The standard long-term treatment for apnea of prematurity is the use of methylxanthines, specifi- Table 11. Factors Contributing to Apnea cally theophylline, aminophylline, and caffeine, Sepsis which act on the brain stem respiratory neurons to exert a central stimulatory effect. Other effects Intracranial hemorrhage include improved sensitivity to carbon dioxide Prostaglandin E infusion response, increased diaphragmatic contractions, increased catecholamine activity, enhanced resting Gastroesophageal reflux pharyngeal muscle tone, and decreased diaphragm Poor thermoregulation fatigue. Doxapram, a peripheral chemoreceptor stimulator, has also been used for infants with Antepartum narcotics or general anesthesia apnea; it increases both minute ventilation and Metabolic disorders tidal volume. However, doxapram contains benzyl Anatomic abnormalities alcohol and requires continuous infusion, so it is not recommended for newborns. Anemia of prematurity Seizure activity Electrolyte abnormalities

15 Infants who fail to respond to methylxanthines Incidence (Oellrich, 1997; Verklan, 1997) or who continue to have apnea while on these ~ 20% in preterm infants with RDS medications may respond to continuous positive 5% in infants with a birth weight > 1500 g airway pressure (CPAP), which increases functional 1 to 3 cases per 1,000 live births residual capacity and stabilizes the chest wall. CPAP ~ 7,000 new cases reported annually is beneficial to infants with mixed and obstructive apnea, but not central apnea. Infants who fail to Infants at Risk/Predisposing Factors respond to medications and CPAP require positive- Preterm infants pressure ventilation. Supportive care includes Term infants (infrequent) provision of a neutral thermal environment, use of Early gestational age and low birth weight (risk pulse oximetry and/or transcutaneous monitoring, inversely proportional) and positioning to prevent flexing of the neck. Oxygen toxicity Barotrauma Prognosis (Menendez et al, 1996) Nutritional deficiencies Apnea of prematurity usually resolves by a post- Infection conceptional age of 34 to 52 weeks. Some infants Patent ductus arteriosus may require home monitoring after discharge from the hospital. Pathophysiology Lung injury from oxygen toxicity, barotrauma, and BRONCHOPULMONARY DYSPLASIA (BPD) other contributory factors produces an inflammatory reaction, capillary leak, abnormal lung repair, and There is no consensus about the definition of airway obstruction. A pattern of constant and bronchopulmonary dysplasia (BPD), but current recurring lung injury, repair, and scarring occurs. definitions agree that it is a chronic neonatal This produces cellular, airway, and interstitial respiratory problem with a multifactorial cause. changes, including inflammation, atelectasis, emphysema, inactivation of surfactant, pulmonary edema, decreased lung compliance, increased airway resistance, ventilation/perfusion mismatch, over-

Table 12. Apnea Monitoring Type of Monitor Characteristics/Capabilities Problems Impedance Detects changes in electrical impedance as size of Unable to detect obstructive apnea monitoring with thorax increases and decreases during respiration Obstruction may not trigger a respiratory alarm EKG electrodes Heart rate may not decrease with episode of apnea Sensitivity level usually set so monitor will sound in presence of shallow respirations (false alarm) Pulse oximetry Continuous measurement of hemoglobin saturation Decreased accuracy during hypoperfusion, hypothermia, and active movement Three-channel Assesses respiratory effort, heart rate, pulse oximetry Motion and cardiogenic artifacts can interfere with pneumocardiogram Overnight or 24-hour recording respiratory signals Two-channel Assesses respiratory effort, heart rate Motion and cardiogenic artifacts can interfere with pneumocardiogram Continuous recording on memory chip x 2-3 weeks respiratory signals Allows analysis of apnea, bradycardia, or both Polysomnography Expanded sleep study Involves use of transducers and electrodes EEG, ECG, EMG, chest wall, and abdominal movement

analysis, end-tidal CO2, oxygen saturation, continuous esophageal pH determination, nasal air flow Inductance Uses chest and abdominal belts to monitor respirations Belt slippage plethysmography Detects obstructive apnea and decreases false alarms Changes in body position

16 distention, air trapping, and increased production of With mild BPD, chest radiograph findings are mucus. These pulmonary function disturbances lead identical to those for RDS. As BPD progresses, to hypoxemia, hypercarbia, and some degree of coarse, irregular-shaped densities and air cysts start bronchial hyperactivity. Bronchial hyperactivity and to develop. With advanced BPD, the lungs appear airway smooth-muscle hypertrophy (which decreases bubbly (air cysts continue to enlarge) and are lumen size) cause bronchospasms or constrictions. extensively hyperinflated, emphysema has prog- The hypoxemia or ongoing marginal oxygenation ressed considerably, and cardiomegaly (indicating induces pulmonary artery vasoconstriction, vascular right-sided heart failure) is present. muscular hypertrophy, and hypertension, resulting in pulmonary hypertension and subsequently Management increasing stress of the right-sided cardiac function. The treatment goals for BPD are to promote growth and to heal the infant’s lungs. Oxygen administration Clinical Presentation and positive-pressure ventilation are both the cause The most common alteration of pulmonary function of and the treatment for BPD. Adequate oxygen- in infants with BPD is increased airway resistance. ation is required to prevent recurrent hypoxemia In addition to low pulmonary compliance, this and reduce pulmonary hypertension. This applies resistance results in increased work of breathing, whether the infant is awake or asleep, crying or feed- hypoventilation, and retention of carbon dioxide. In ing. The lowest possible ventilator settings should be infants with mild chronic lung disease, there is an used and weaning should be accomplished slowly, initial need for positive-pressure ventilation, which based on the infant’s tolerance. Ventilator settings must be maintained longer than was anticipated, can be reduced on the basis of acceptable blood followed by days or weeks of oxygen supplementa- gases of PaO2 55 to 70 mm Hg, PaCO2 50 to 60 mm tion. Retractions, crepitant rales, and diminished Hg, and pH > 7.25. Oxygen saturation should breath sounds occur. In the early phase of moderate be maintained between 90% and 95% to assure to severe BPD, oxygen and ventilatory pressure adequate tissue oxygenation and to avoid the requirements increase relentlessly. Chest radiographs effects of chronic hypoxemia (such as pulmonary show progressive overdistention of the lungs. hypertension and cor pulmonale). Hyperoxia is to Clinically, a barrel-shaped chest is noted, and the be avoided, as it may worsen the BPD. Hemoglobin infant demonstrates lability with handling and acute should be maintained at 12 to 15 g/dL to maximize episodes of bronchospasms. Generally, if respiratory oxygen delivery to the tissues. support can be decreased during the 1st month of life, the subsequent course of BPD is relatively Pharmacologic management is critical for infants benign. But if increased support is needed at this with BPD. Excessive interstitial fluid accumulates time, a severe, protracted course is usual. BPD often in the lung and can result in deterioration of becomes a progressive disease if it persists beyond pulmonary function, adding to the existing hyp- 1 month of age. Growth failure is prominent and oxemia and hypercarbia. Pharmacologic manage- osteopenia is common. Right-sided cardiac failure, ment includes diuretics, bronchodilators, and bronchospasms, inspiratory stridor, overproduction steroids (see Table 14). Diuretic therapy decreases of airway secretions, and systemic hypertension excessive lung fluid. Bronchodilator and systemic are common in infants with progressive BPD methylxanthines have been used for both reactive (see Table 13). airway disease and airway hyperreactivity. Cortico- steroids promote weaning from the ventilator and decrease the inflammatory response, thereby Table 13. Overall Signs and Symptoms improving pulmonary function. of Bronchopulmonary Dysplasia Optimal nutrition is required for growth, for lung Rapid and shallow respirations Crackles healing, and as compensation for increased oxygen Increased work of breathing Decreased air entry and calorie consumption. Since optimal nutrition is often limited by increased caloric demands, fluid Hyperinflated chest Atelectasis restriction, feeding intolerance, and gastroesophageal Hypoxemia Hypercarbia reflux, a high-calorie, nutrient-dense feeding is advisable. Adequate vitamin A is critical for normal Pulmonary hypertension with Intercostal/substernal growth and differentiation of epithelial cells, and right-sided cardiac failure retractions appropriate intake of minerals and vitamin D is necessary to prevent the development of rickets.

17 Table 14. Pharmacologic Management of Infants With Bronchopulmonary Dysplasia Medication Effects Side Effects Diuretics (Decrease interstitial fluid and pulmonary edema) Furosemide Decrease interstitial pulmonary edema Electrolyte imbalance Lowers pulmonary vascular resistance and Dehydration improves ventilation-perfusion ratios Ototoxicity Renal stone formation Thiazide Diuretics Decrease interstitial pulmonary edema Electrolyte imbalance • Chlorothiazide Improve pulmonary function Dehydration • Hydrochlorothiazide Decrease airway resistance Hyperglycemia • Used in combination Increase pulmonary compliance Glycosuria with spironolactone, a potassium-sparing drug Bronchodilators (Improve pulmonary mechanics) Inhaled: Increase surfactant production Tachycardia • Albuterol Decrease pulmonary edema Tremors • Terbutaline sulfate Enhance mucociliary transport Hypertension • Cromolyn sodium Overall: increase lung compliance and decrease Irritability • Isoetharine airway resistance Gastrointestinal disturbances • Isoproterenol • Ipratropium bromide Systemic: • Methylxanthines Caffeine citrate Decreases pulmonary resistance Rare Stimulates central nervous system Increases inspiratory drive Improves skeletal muscle and diaphragm contractility and increases lung compliance

Aminophylline Actions as noted for caffeine citrate Vomiting, tachycardia, gastroesophageal reflux, Theophylline Increase surfactant production electrolyte abnormalities, tremors, agitation

• Albuterol Decreases pulmonary resistance/adjunct Tachycardia, tremors, hypertension, irritability, • Terbutaline sulfate to methylxanthine gastrointestinal disturbances, hypokalemia (albuterol)

Corticosteroids (Promote weaning from ventilator and decrease inflammatory response)

Dexamethasone Improves pulmonary status, probably by decreasing Hypertension tracheobronchial and alveolar inflammation and Hyperglycemia decreasing pulmonary edema Gastrointestinal complications (perforated gastric Facilitates gas exchange and duodenal ulcers, upper GI hemorrhage) Increases lung compliance Restlessness and/or irritability Diminishes airway resistance

18 Table 15. Premature Infants: Special Respiratory The environment surrounding the infant is impor- Considerations tant for recovery from BPD. Minimizing agitation to Concern/Condition Impact/Result prevent the hypoxemia and bronchospasms that often accompany agitation is essential. Sedation may Brain respiratory May lack sufficient maturity to be needed in addition to evaluation of noise, light, control center consistently regulate respirations; and touch to avoid overstimulation, which has a therefore, may experience periodic negative effect on weight gain, respiratory function, breathing and apnea and development. Compliant (immature) Insufficient breathing and chest wall retractions Prognosis (Adams and Wearden, 1998; Barrington and Finer, 1998) Survival to discharge is inversely related to duration Noncompliant lungs Increased work for respiratory of ventilation. Improvement in pulmonary function muscles, leading to increased work occurs slowly over 1 to 3 years. Morbidities include of breathing and retractions but are not limited to chronic respiratory difficulties, Surfactant deficiency Collapsed alveoli plus prolonged or recurrent hospitalizations, increased intrapulmonary shunting, incidence of neurodevelopmental disabilities, and resulting in hypoxemia growth restriction. Overall mortality ranges from Pulmonary vascular Not as well developed as in term 25% to 40%, with most deaths related to infection or smooth muscle infants, so fall in pulmonary vascu- cardiopulmonary failure associated with pulmonary lar resistance occurs more rapidly hypertension or cor pulmonale. Immaturity of terminal Poor gas exchange air sacs and associ- SPECIAL CONCERNS ated vasculature WITH THE PREMATURE INFANT Immaturity of Inspiratory difficulty diaphragm and other The clinician or bedside caregiver should be alert muscles of respiration to special concerns with the premature infant, as outlined in Table 15 (Donovan et al, 1998; Whitaker, 1997). Peripheral Blunted response; therefore, can chemoreceptors experience apnea (in aortic arch and carotid arteries) Muscle fiber type Muscles may be more susceptible distribution to fatigue Ductus arteriosus Ductal smooth muscle does not have a fully developed constrictor response to oxygen Ductal tissue exhibits increased dilatory response to prostaglandins Persistently high circulating levels of prostaglandins May remain patent, shunting blood away from systemic organs Lower hemoglobin Limited oxygen-carrying capacity

19 RELATED NURSING CARE percentage every hour and with changes Document oxygen administration temperature • Document ventilator settings and alarm limits NURSING DIAGNOSIS: every shift and with changes Impaired Gas Exchange • Assess and document blood gas results as ordered Notify physician/practitioner of results PATIENT OUTCOME • Maintain pulse oximetry (oxygen saturation) or Infant will maintain adequate gas exchange and transcutaneous monitor (transcutaneous and effective breathing pattern, as evidenced by: partial pressure of oxygen [TcPO2] and carbon RR 40-60 BPM dioxide pressure [TcPCO2]) HR 110-160 BPM Pulse oximetry: Clear and equal breath sounds Note probe site and change PRN Mild to no retractions Place probe so light source and photodetector Lack of nasal flaring and grunting are opposite one another Pink color Shield probe from ambient light, especially Blood gases within normal limits if phototherapy is in use Set monitor alarms according to unit policy Document readings every hour and PRN INTERVENTIONS Transcutaneous monitor: • Assess for signs of impaired gas exchange/ Position probe on a flat, well-perfused area respiratory distress every hour and as Change probe position every 4 hours and PRN necessary (PRN) Preferred temperature range: 43ºC for preterm Nasal flaring infants, 44ºC for term infants Expiratory grunt Set monitor alarms according to unit policy Tachypnea Document readings every hour and PRN Cyanosis • Maintain end-tidal CO2 monitoring if ordered Retractions—note type and degree • Provide chest physiotherapy as ordered Type: suprasternal, substernal, intercostal, Monitor O2 saturation, heart rate, respiratory subcostal rate, signs and symptoms of distress on an Degree: mild, moderate, severe ongoing basis to assess tolerance of procedure • Auscultate breath sounds and note adventitious Percussion: 1 to 2 minutes over area to be sounds every 1 to 2 hours and PRN drained Air movement Emphasize atelectatic area Equality—compare and contrast each side Do not percuss over liver or spleen of chest Vibration: Use padded electric toothbrush Clarity—clear, rales, rhonchi or vibrator • Maintain a patent airway: Base duration on infant’s tolerance Small roll under shoulders • If chest tube required: With endotracheal tube (ETT): Assist with transillumination process Suction PRN Assist with needle aspiration of chest Assess and document ETT size and position— Assist with chest tube placement: note insertion depth (mark located at Administer analgesic infant’s lips) Monitor vital signs during procedure Use ETT adaptor or closed suction system Place chest tube to chest drainage system at to allow suctioning without removing infant 15 to 20 cm H2O pressure from ventilator Note bubbling activity With nasal continuous positive airway pressure Document tolerance to procedure (NCPAP): • If chest tube in place: Keep infant calm; swaddle if necessary (crying Maintain tube stability: releases pressure through mouth) Tape all connections securely Maintain patency of nares and nasal prongs Secure tubing from infant to bed to relieve Guard against pressure necrosis tension at insertion site • Administer oxygen in correct amount and by Assess for kinks in tubing correct route of delivery Do not strip/milk chest tube; this generates Analyze and document inspired oxygen extremely high pressures

20 Bubbling activity slows several hours after • Suction PRN (most units have a minimal chest tube placement and usually stops after suctioning protocol) 72 hours Use appropriate-sized suction catheters If no bubbling noted for 24 hours, place chest Wear protective goggles and mask (if not using a tube to underwater seal (provides an outlet closed suctioning system) for any reaccumulated air after suction is Use sterile technique and follow unit suctioning discontinued); do not clamp tube protocol After discontinuing chest tube, use an Document amount, characteristics, and color occlusive dressing (such as petrolatum gauze) of secretions for 48 hours Document auscultatory findings of breath Keep occlusive dressing at bedside for sounds before and after suctioning application at insertion site if chest tube • Assess patient tolerance of suctioning procedure becomes dislodged • Initiate appropriate interventions to minimize Assess and document amount of chest tube hypoxia (bag ventilation presuctioning or drainage every hour or every shift postsuctioning) Assess and document bubbling activity every Determine degree of hypoxia by pulse oximeter hour and PRN or transcutaneous monitor readings and time to Reposition infant every 2 to 4 hours to return to baseline facilitate removal of air Note degree of bradycardia, if any, and time to Elevate head of bed return to baseline • Reposition infant every 2 to 4 hours Note any other physiologic changes • Provide cluster care with minimal handling • Allow infant to rest after suctioning procedure and • Assess infant’s response to and tolerance of before other major stress activities handling and procedures to determine • Reposition infant every 2 to 4 hours and PRN appropriate nursing care • Maintain adequate hydration • Administer sedatives, analgesics, and muscle relaxants as ordered ADDITIONAL NURSING DIAGNOSES Assess response to medications • Maintain neutral thermal environment These include but are not limited to: • Provide support to family High risk for injury: intraventricular hemorrhage, air leaks, other, related to treatment for respiratory NURSING DIAGNOSIS: disorders Ineffective Airway Clearance Alteration in comfort: pain, related to chest tube placement and other procedures PATIENT OUTCOME High risk for fluid volume deficit: related to Infant will have an adequately clear airway, as disease process, fluid loss, and IV administration evidenced by: Clear and equal breath sounds High risk for fluid volume excess: related to renal Respiratory rate 40-60 BPM inability to excrete any volume overload and to Pink color iatrogenic fluid volume excess Unlabored respirations Altered nutrition: less than body requirements, related to increased caloric expenditures and INTERVENTIONS decreased nutritional intake • Assess respiratory status every 2 hours and PRN Knowledge deficit: related to lack of parental • Provide chest physiotherapy and administer understanding of the disease process aerosol medications as ordered • Assess need for suctioning on the basis of: Quality of breath sounds Current condition Blood gas results General clinical appearance: chest movement, color Oxygen saturation readings

21 REFERENCES Rodriquez RJ, Martin RJ, Fanaroff AA: Respiratory distress syndrome and its management, in Fanaroff AA, Martin RJ (eds): Neonatal-Perinatal Adams JM: Control of breathing in neonates, in Hansen TN, Cooper TR, Medicine, ed 7. St. Louis: Mosby, 2002, pp 1001-1011. Weisman LE (eds): Contemporary Diagnosis and Management of Speer ME, Weisman LE: Acute, acquired parenchymal lung disease: Neonatal Respiratory Diseases, ed 2. Newtown, Pa: Handbooks in Pneumonia, in Hansen TN, Cooper TR, Weisman LE (eds): Contem- Health Care Co, 1998, pp 213-222. porary Diagnosis and Management of Neonatal Respiratory Diseases, Adams JM, Wearden ME: Bronchopulmonary dysplasia, in Hansen TN, ed 2. Newtown, Pa: Handbooks in Health Care Co, 1998, pp 130-133. Cooper TR, Weisman LE (eds): Contemporary Diagnosis and Verklan MT: Bronchopulmonary dysplasia: Its effects upon the heart and Management of Neonatal Respiratory Diseases, ed 2. Newtown, Pa: lungs. Neonatal Netw 1997;16(8):5-12. Handbooks in Health Care Co, 1998, pp 150-165. Walsh MC, Stork EK: Persistent pulmonary hypertension of the newborn. Alexander SM, Todres ID: The use of sedation and muscle relaxation in Clinics in Perinatology 2001;28(3):609-627. the ventilated neonate. Clin Perinatol 1998;25:63-78. Wearden ME, Hansen TN: Acute, acquired parenchymal lung disease: Bancalari EH: Neonatal chronic lung disease, in Fanaroff AA, Martin RJ Persisent pulmonary hypertension of the newborn, in Hansen TN, (eds): Neonatal-Perinatal Medicine, ed 7. St. Louis: Mosby, 2002, pp Cooper TR, Weisman LE (eds): Contemporary Diagnosis and 1057-1070. Management of Neonatal Respiratory Diseases, ed 2. Newtown, Pa: Barrington KJ, Finer NN: Treatment of bronchopulmonary dysplasia: A Handbooks in Health Care Co, 1998, pp 100-109. review. Clin Perinatol 1998;25:177-202. Whitaker KB: Comprehensive Perinatal and Pediatric Respiratory Care, Bhutani VK: Differential diagnosis of neonatal respiratory disorders, in ed 2. Albany, NY: Delmar, 1997. Spitzer AR (ed): Intensive Care of the Fetus and Newborn. St Louis: Young TE, Mangum OB: Neofax®: A Manual of Drugs Used in Neonatal Mosby, 1996, pp 494-506. Care, ed 10. Raleigh, NC: Acorn, 1997. Carey BE, Trotter C: Neonatal pneumonia. Neonatal Netw 1997; 16(5):65-71. Carlo WA, Fiore JMD: Assessment of pulmonary function, in Fanaroff AA, ADDITIONAL READINGS Martin RJ (eds): Neonatal-Perinatal Medicine, ed 7. St. Louis: Mosby, 2002, pp 991-1001. Anand KJS: Analgesia and sedation in ventilated neonates. Neonatal Respir Dis 1995;5(5):1-10. Carlo WA, Martin RJ, Fanaroff AA: Assisted ventilation and complications of respiratory distress, in Fanaroff AA, Martin RJ (eds): Neonatal- Bhatt DR, Reber DJ, Wirtschafter DD, et al (eds): Neonatal Drug Perinatal Medicine, ed 7. St. Louis: Mosby, 2002, pp 1011-1025. Formulary, ed 4. Los Angeles: NDF, 1997. Cifuents J, Haywood JL, Ross M, Carlo WA: Assessment and management Calhoun LK: Pharmacologic management of apnea of prematurity. of respiratory dysfunction, in Kenner C, Lott JW, Flandermeyer AA (eds): J Perinat Neonatal Nurs 1996;9(4):56-62. Comprehensive Neonatal Nursing: A Physiologic Perspective, ed 2. Carey BE, Trotter C: Bronchopulmonary dysplasia. Neonatal Netw Philadelphia: WB Saunders, 1998, pp 252-267. 1996;15(4):73-77. Donovan EF, Schwartz JE, Moles LM: New technologies applied to the Carey BE, Trotter C (series eds): Radiology Basics Part III: TTN, management of respiratory dysfunction, in Kenner C, Lott JW, meconium aspiration, and neonatal pneumonia. Neonatal Network Flandermeyer AA (eds): Comprehensive Neonatal Nursing: A Physiologic 2000;19(4):37-50. Perspective, ed 2. Philadelphia: WB Saunders, 1998, pp 268-289. Cole CH, Fiascone JM: Strategies for prevention of neonatal chronic lung Elliott SJ, Leuthner SR: Anatomy and development of the lung, in disease. Seminars in Perinatology 2000;24(6):445-462. Hansen TN, Cooper TR, Weisman LE (eds): Contemporary Diagnosis and Management of Neonatal Respiratory Diseases, ed 2. Newtown, Pa: Cooper TR: Chronic pulmonary insufficiency of prematurity, in Hansen Handbooks in Health Care Co, 1998, pp 1-5. TN, Cooper TR, Weisman LE (eds): Contemporary Diagnosis and Management of Neonatal Respiratory Diseases, ed 2. Newtown, Pa: Guillory C, Cooper TR: Diseases affecting the diaphragm and chest wall, Handbooks in Health Care Co, 1998, pp 149-150. in Hansen TN, Cooper TR, Weisman LE (eds): Contemporary Diagnosis and Management of Neonatal Respiratory Diseases, ed 2. Newtown, Pa: DeBoer SL, Stephens D: Persistent pulmonary hypertension of the Handbooks in Health Care Co, 1998, pp 188-197. newborn: Case study and pathophysiology review. Neonatal Netw 1997;16(1):7-13. Kattwinkel J (ed): Textbook of Neonatal Resuscitation, ed 4. Dallas: American Academy of Pediatrics and American Heart Association, 2000. Donn SM, Nicks JJ: Special ventilatory technologies and modalities: 1. Patient triggered ventilation, in Goldsmith JP, Karotkin EH (eds): Menendez AA, Alea OA, Beckerman RC: Control of ventilation and Assisted Ventilation of the Neonate, ed 3. Philadelphia: WB Saunders, apnea, in Goldsmith JP, Karotkin EH (eds): Assisted Ventilation of the 1996, pp 215-228. Neonate, ed 3. Philadelphia: WB Saunders, 1996, pp 69-81. Doyle P: Bronchopulmonary dysplasia and corticosteroid therapy: A case Miller MJ, Fanaroff AA, Martin RJ: Respiratory disorders in preterm and review. Neonatal Netw 1996;15(6):35-40. term infants, in Fanaroff AA, Martin RJ (eds): Neonatal-Perinatal Medicine, ed 7. St. Louis: Mosby, 2002, pp 1025-1048. Few BJ: Pulmonary critical care problems, in Curley MAQ, Smith JB, Moloney-Harmon PA (eds): Critical Care Nursing of Infants and Moïse AA, Hansen TN: Acute, acquired parenchymal lung disease: Children. Philadelphia: WB Saunders, 1996, pp 619-655. Hyaline membrane disease, in Hansen TN, Cooper TR, Weisman LE (eds): Contemporary Diagnosis and Management of Neonatal Folsom MS: Amnioinfusion for meconium staining: Does it help? MCN Respiratory Diseases, ed 2. Newtown, Pa: Handbooks in Health Care Co, Am J Matern Child Nurs 1997;22:74-79. 1998, pp 79-95. Gannon BA: Theophylline or caffeine: Which is the best for apnea of pre- Molteni RA: Neonatal Respiratory Distress Clinical Education Aid. maturity? Neonatal Network 2000;19(8):33-36. Columbus, Ohio: Ross Laboratories, 1992. Gardner MO, Goldenberg RL: Use of antenatal corticosteroids for fetal Oellrich RG: Complications of positive pressure ventilation, in Askin DF maturation. Curr Opin Obstet Gynecol 1996;8:106-109. (ed): Acute Respiratory Care of the Neonate, ed 2. Petaluma, Calif: NICU Gibson E: Apnea, in Spitzer AR (ed): Intensive Care of the Fetus and Ink, 1997, pp 135-181. Newborn. St Louis: Mosby, 1996, pp 470-481. Orlando S: Pathophysiology of acute respiratory distress, in Askin DF Gnanaratnem J, Finer NN: Neonatal acute respiratory failure. Current (ed): Acute Respiratory Care of the Neonate, ed 2. Petaluma, Calif: NICU Opinion in Pediatrics 1999;12:227-232. Ink, 1997, pp 31-56.

22 Goetzman BW, Milstein JM: Pharmacologic adjuncts 1, in Goldsmith JP, Rozycki ZHJ, Sysyn GD, Marshall MK, et al: Mainstream end-tidal carbon Karotkin EH (eds): Assisted Ventilation of the Neonate, ed 3. Philadel- dioxide monitoring in the neonatal intensive care unit. Pediatrics phia: WB Saunders, 1996, pp 291-304. 1998;101:648-653. Greenough A: Meconium aspiration syndrome: Prevention and treat- Sansoucie DA, Cavaliere TA: Transition from fetal to extrauterine ment. Early Hum Dev 1995;41:183-192. circulation. Neonatal Netw 1997;16(2):5-12. Hagedorn MI, Gardner SL, Abman SH: Respiratory diseases, in Meren- Snapp B: Lung physiology and surfactant replacement therapy. stein GB, Gardner SL (eds): Handbook of Neonatal Intensive Care, ed 4. Mother Baby J 1998;3(2):13-17. St Louis: Mosby, 1998, pp 437-499. Speer ME, Hansen TN: Acute, acquired parenchymal lung disease: Hicks MA: A systematic approach to neonatal pathophysiology: Transient tachypnea of the newborn, in Hansen TN, Cooper TR, Understanding respiratory distress syndrome. Neonatal Netw 1995;14(1):29-35. Weisman LE (eds): Contemporary Diagnosis and Management of Neonatal Respiratory Diseases, ed 2. Newtown, Pa: Handbooks in Jobe, AH, Ikegami M: Prevention of bronchopulmonary dysplasia. Health Care Co, 1998, pp 95-100. Current Opinion in Pediatrics 2001;13:124-129. Theobald K, Botwinski C, Albanna S, McWilliam P: Apnea of prematurity: Johnson KE, Cooper TR, Hansen TN: Acute, acquired parenchymal lung Diagnosis, implications for care, and pharmacologic management. disease: Meconium aspiration syndrome, in Hansen TN, Cooper TR, Neonatal Network 2000;19(6):17-24. Weisman LE (eds): Contemporary Diagnosis and Management of Turner BS: Nursing procedures, in Askin DF (ed): Neonatal Respiratory Diseases, ed 2. Newtown, Pa: Handbooks in Acute Respiratory Health Care Co, 1998, pp 121-130. Care of the Neonate, ed 2. Petaluma, Calif: NICU Ink, 1997, pp 183-212. Kanto WP Jr, Bunyapen C: Extracorporeal membrane oxygenation: Verma RP: Respiratory distress syndrome of the newborn infant. Obstet Gynecol Surv Controversies in selection of patients and management. Clin Perinatol 1995;50:542-555. 1998;25:123-136. Walsh WF, Hazinski TA: Bronchopulmonary dysplasia, in Spitzer AR (ed): Kattwinkel J: Surfactant: Evolving issues. Clin Perinatol 1998;25:17-32. Intensive Care of the Fetus and Newborn. St Louis: Mosby, 1996, pp 641-656. Katz AL, Wiswell TE, Baumgart S: Contemporary controversies in the Wandstrat TL: Neonatal respiratory pharmacotherapy, in Askin DF (ed): management of congenital diaphragmatic hernia. Clin Perinatol 1998;25:219-248. Acute Respiratory Care of the Neonate, ed 2. Petaluma, Calif: NICU Ink, 1997, pp 245-280. Kenner C: Complications of respiratory management, in Kenner C, Lott Wyatt TH: Pneumothorax in the neonate. JW, Flandermeyer AA (eds): Comprehensive Neonatal Nursing: A J Obstet Gynecol Neonatal Nurs Physiologic Perspective, ed 2. Philadelphia: WB Saunders, 1998, 1995;24:211-216. pp 290-305. Kenner C, Amlung SR, Flandermeyer AA (eds): Protocols in Neonatal Nursing. Philadelphia: WB Saunders, 1998. King P: The pulse oximeter: A key assessment tool. Mother Baby J 1996;1(2):29-33. Kinsella JP, Abman SH: Controversies in the use of inhaled nitric oxide therapy in the newborn. Clin Perinatol 1998;25:203-218. Korones SB: Complications: Bronchopulmonary dysplasia, air leak syndrome and retinopathy of prematurity, in Goldsmith JP, Karotkin EH (eds): Assisted Ventilation of the Neonate, ed 3. Philadelphia: WB Saunders, 1996, pp 327-352. Koszarek K: Nursing assessment and care for the neonate in acute respiratory distress, in Askin DF (ed): Acute Respiratory Care of the Neonate, ed 2. Petaluma, Calif: NICU Ink, 1997, pp 57-91. Loper DL: Physiologic principles of the respiration system, in Askin DF (ed): Acute Respiratory Care of the Neonate, ed 2. Petaluma, Calif: NICU Ink, 1997, pp 1-30. Mariani GL, Carlo WA: Ventilatory management in neonates: Science or art? Clin Perinatol 1998;25:33-48. Miller JC (ed): Pediatric Dosing Handbook and Formulary. Hudson, Ohio: Lexi-Comp, 1997. Moïse AA, Gest AL, Garcia-Prats JA, et al: Respiratory therapy: General considerations, in Hansen TN, Cooper TR, Weisman LE (eds): Contemporary Diagnosis and Management of Neonatal Respiratory Diseases, ed 2. Newtown, Pa: Handbooks in Health Care Co, 1998, pp 223-281. Morin FC III, Davis JM: Persistent pulmonary hypertension, in Spitzer AR (ed): Intensive Care of the Fetus and Newborn. St Louis: Mosby, 1996, pp 506-516. Noerr B: Midazolam (Versed). Neonatal Netw 1995;14(1):65-67. Quinn W, Sandifer L, Goldsmith JP: Pulmonary care, in Goldsmith JP, Karotkin EH (eds): Assisted Ventilation of the Neonate, ed 3. Philadelphia: WB Saunders, 1996, pp 101-123.

23 EDUCATION SERIES CareSource CLINICAL Nurse Education Program Ross Pediatrics

Neonatal Respiratory System

Tension Pneumothorax

Sternal Retraction Normal Respiratory Tract

Interstitial Emphysema

Normal Lung Tissue Cyanosis

Congenital Diaphragmatic Hernia

© 2003 Abbott Laboratories 61534/MARCH 2003 LITHO IN USA