8. Aka as hyaline membrane disease. Incidence: 10% of premies esp if <1500g. 44% if 500 to 1500g. Inversely proportional to GA and brith wt. 6% of all neonatal deathsPath: Surfactant defx from under-developed lungs, over compliant chest. Leads to progressive atelactasis, and failure to deveillp effective fx residual capacity (FRC). [Type II pneumocytes make surfatant. The TII pncytes are sensitive to asphyxia and insults]. Surfactant decreases surface tension. Without it the alveoli collapse with every expiration. By Normally 34th GA there is 2x more lecithin than sphyingomyelin in the amniotic fluid, so a L/S ratio less than 2 is a little predictive of HMD. Phosphatidylcholine levels are lowSigns and Symptoms: Difficulty in initiatingnl respiratoni, expiratory grunting or whining observed when the infant is not crying caused by closure of the glottis which is sometimes the only sign of disease. Sternal or intercostal retractions (2ry to decreased lung and increased cage compliance). Nasal flaring, cyanosis (if supplemental O2 is inadequate). Tachypnea or slow breathing if dss is severe. Edematous limbs from vascular permeability. Dgx: CXR shows Reticulanogranular pattern

Reticulogranular (net of granules) looks cloudy. Ground glass appearance, of HMD

12. Treatment: Prevention with steroids between 24-34 wks GA. Recuscitation (ABCs). Expansion of the lungs with Positive Pressure via intermittent positive pressure breaths or CPAP. The goal should be to maintain the aa pO2 between 50-70mmHg. Assisted ventilation can be weaned or stopped when the infant can maintain that range by himself without too much effort. Conservative fluid administration as you don’t want to overflow the lungs

Biggest risk factor is prematurity. 2M:F. Whites>Blacks but blacks are more likely to die from it. DM mom, 2nd born twin. Neonates younger than 33-38 weeks. Weight less than 2500g. Fetal asphyxia. Latter born twin. Protective Factors: HTN during pregnancy, premature rupture of membranes, subacute placental abruption, narcotic addicted mom’s.

13. Definition. Persistent pulmonary hypertension of the newborn is a condition resulting from elevated pulmonary vascular resistance (PVR) and altered pulmonary vasoreactivity, leading to right-to-left extrapulmonary shunting of blood across the foramen ovale and the ductus arteriosus, if it is patent. AKA persistent fetal circulation. PPHN is characterized by postnatal persistance of right-to-left ductal shunting or right-to-left atrial shunting or both. Results in cyanosis, which is often refractory to supplemental oxygen. These infants are often recognized shortly after birth because of their respiratory distress or cyanosis. There can be marked intercostal and sternal retractions and usually grunting respirations. Differential cyanosis (pink upper extremities, cyanotic lower extremities; greater oxygen saturation in the upper body than in the lower body; this is caused by right-to-left shunting of deoxygenated pulmonary arterial blood through a PDA) is pathognomonic of PPHN. With a right-to-left ductus shunt, there will also be a positive PO2 difference between the right radial artery and the descending aorta; a difference in PO2 of >10 to 15 mm Hg may be considered indicative of PPHN. Many patients, however, do not have differential cyanosis because there may be limited flow via the ductus arteriosus, or most of the right-to-left shunting is intrapulmonary or across the foramen ovale.

Incidence is <6/1000 births. Statistically UMC should see 30 per year or 2-3 per month.

Path: May be the result of 1) underdevelopment of the lung and its vascular bed (eg, congenital diaphragmatic hernia and hypoplastic lungs), 2) maladaptation of the pulmonary vascular bed to the transition occurring around the time of birth (eg, various conditions of perinatal stress, hemorrhage, aspiration, hypoxia, and hypoglycemia); and 3) maldevelopment of the pulmonary vascular bed in utero from a known or unknown cause. It is convenient to think in terms of this basic pathologic classification. Clinical manifestations of PPHN are often not attributable to a single physiologic or structural entity, and many disorders exhibit more than one underlying pathology. Often, even when there is evidence of perinatal or postnatal stress (eg, meconium aspiration), the underlying cause of PPHN had been secondary to an in utero process of some duration.

Preacinar arteries are already present in the lungs by 16 weeks' gestation; thereafter, respiratory units are added with further growth of the appropriate arteries. Muscularization of the peripheral pulmonary arteries is related to differentiation of pericytes and recruitment of fibroblasts and is influenced by numerous trophic factors (eg, neuropeptides, fibroblast growth factors, and insulin-like growth factors). The growth, differentiation, and adaptation of the pulmonary vascular bed are also influenced by changes that occur in the connective tissue matrix (eg, elastin and collagen). The lungs of infants with PPHN contain many undilated precapillary arteries, and pulmonary arterial medial thickness is increased. There may be extension of muscle in small and peripheral arteries that are normally nonmuscular. After a few days, there is already evidence of structural remodeling with connective tissue deposition.In the fetus, PVR is high, and only 5-10% of the combined cardiac output flows into the lungs, with most of the right ventricular output crossing the ductus arteriosus to the aorta. After birth, with expansion of the lungs, there is a sharp drop in PVR and pulmonary blood flow increases about 10-fold. We don’t know how that happens. Vasoconstrictive and vasodilatory stimuli are balanaced by various factors. Vasoconstrictive stimuli possibly include various products of arachidonic acid metabolism (eg, thromboxane, leukotrienes, and isoprostanes), Rho/Rho kinase, and the endothelins (ETs). The hemodynamic effect of the ETs are mediated by at least two receptors; ET-A and ET-B. There are at least three isoforms of endothelin. ET-1, the most studied of these, constricts pulmonary arteries from various animals. Intrapulmonary infusion of ET-1 has a biphasic response: initially dilating the vascular bed of the intact fetal lamb. This vasodilatory effect is transient and followed by a return to baseline tone when the infusion is continued. The biphasic response to ET-1 is likely due to initial activation of ET-B receptors (which stimulate release of nitric oxide), followed by activation of the ET-A receptors, which mediate vasoconstriction. Vice versa selective ET-A blockade causes fetal pulmonary vasodilatation, while upregulation of ET-1 contributes to pulmonary hypertension. RhoA is a GTPase, and rho-kinase is its effector protein. These have been identified as key regulators of vascular tone and structure. Rho-kinase phosphorylates and inactivates myosin light chain phosphatase, increasing calcium sensitivity of vascular smooth muscle, and thus promotes vasoconstriction. Prolonged treatment with rho-kinase inhibitors prevents the development of pulmonary hypertension in some animal models. There is an interaction

between the rho-kinase and the nitric oxide signaling pathway, and inhibition of rho-kinase also prevents vasoconstriction caused by inhibition of nitric oxide production. The fetal lung also produces a number of COX-dependent metabolites that function as pulmonary vasodilators (eg, PGI-2, PGE-1, and PGE-2). Nitric oxide (NO), a potent vasodilator, is synthesized from L-arginine by endothelial nitric oxide synthase (eNOS). NO stimulates soluble guanylate cyclase (sGC), which produces cGMP and causes vasodilation. cGMP, in turn, is hydrolyzed by cyclic nucleotide phosphodiesterases (PDEs), and manipulation of these control the intensity and duration of cGMP action. Various isoenzymes of PDE have been identified and inhibition of PDE-5 (by, eg, sildenafil) causes pulmonary vasodilation.In summary, for successful pulmonary circulatory transition to occur, various mechanical, physiologic, and biochemical factors, which maintain high fetal PVR, must be eliminated or reversed. Major events are the 1) replacement of the fluid-filled lung of the fetus with the air-filled postnatal lung, the increase in oxygen tension, and 2) the increase in pulmonary blood flow (which increases shear stress and thereby increases NO). At the same time, changes occur in 3) the synthesis and release of various biochemical modulators of vascular tone and there are interactions between the mechanical and biochemical events surrounding birth. Disturbances in this cascade of events may lead to PPHN. At the same time, manipulation of these pathways enables us to treat it.

Risk Factors: Lung Disease-Meconium aspiration, respiratory distress syndrome, pneumonia, pulmonary hypoplasia, cystic lung disease (cystic adenomatoid malforation, congenital lobar emphysema) diaphragmatic hernia, congenital alveolar capillary dysplasia. Systemic Disorders-Polycythemia, hypoglycemia, hypoxia, acidosis, hypocalcemia, hypothermia, sepsis; Congenital Heart Disease-Total Anomalous Venous Return, hypoplastic left heart, transient tricuspid atresia, coarctation of the aorta, severe aortic stenosis, endocardial cushion defect, ebstein anomaly, transposistion of great aa, cerebral vv malformx; Perinatal Factors-Asphyxia, perinatal hypoxia, maternal ingestion of aspirin/indomethacin; Misc-CNS disorders, neuromuscular dss, upper airway obstruction,

16. Symptoms and SignsSymptoms and signs include tachypnea, retractions, and severe cyanosis or desaturation unresponsive to supplemental O2. In infants with a right-to-left shunt via a patent ductus arteriosus, oxygenation is higher in the right brachial artery than in the descending aorta; thus cyanosis may be differential, ie, O2 saturation in the lower extremities is 5% lower than in the right upper extremity.The primary finding is respiratory distress with cyanosis (confirmed by demonstrating hypoxemia). This may occur despite adequate ventilation. Other clinical findings are highly variable and depend on the severity, stage, and other associated disorders (particularly pulmonary and cardiac diseases). Sometimes just tachypnea. Onset may be at birth or within 4-8 h of age. In addition, in an infant with pulmonary disease, PPHN should be suspected as a complicating factor when there is marked lability in oxygenation. These infants may have significant decreases in pulse oximetry (desats) readings with routine nursing care or minor stress (eg, movement or noise). Furthermore, a minor decrease in inspired oxygen concentration may lead to a surprisingly large decrease in arterial oxygenation (eg, the AaDO2 gradient changes more rapidly and is more labile than that seen in the normal course of progression of uncomplicated RDS or other pulmonary disease). Maybe a prominent right ventricular impulse, a single second heart sound, and a murmur of tricuspid insufficiency. In extreme cases, there may be hepatomegaly and signs of heart failure. CXR can be nl or show cardiomegaly. If there is no associated pulmonary disease, the film may show normal or diminished pulmonary vascularity. If there is also a parenchymal lung disorder, the degree of hypoxemia may be out of proportion to the radiographic measure of severity of the pulmonary disease. Thrombocytopenia has been reported to be present in as many as 60% of infants with PPHN. The specificity of this finding is unknown. Once the diagnosis is suspected, certain tests are either strongly suggestive or supportive of PPHN.

Dgx: Diagnosis of exclusion. Differential oximeter readings. In the presence of right-to-left shunting of blood via the PDA, the PaO2 in preductal blood (eg, from the right radial artery) is higher than that in the postductal blood (obtained from left radial, umbilical, or tibial arteries). Hence simultaneous preductal and postductal monitoring of oxygen saturation is a useful indicator of right-to-left shunting at the ductal level. However, it is important to note that PPHN cannot be excluded if no difference is found because the right-to-left shunting may be predominantly at the atrial level (or the ductus may not be patent at all). A difference >5% between preductal and postductal oxygen saturations is considered indicative of a right-to-left ductal shunt. A difference >10-15 mm Hg between preductal and postductal PaO2 is also considered suggestive of a right-to-left ductal shunt. Preductal and postductal oxygenation should be assessed simultaneously. Hyperventilation test. PPHN should be considered if marked improvement in oxygenation (>30 mm Hg increase in PaO2) is noted on hyperventilating the infant (lowering PaCO2 and increasing pH). When a "critical" pH value is reached (often ~7.55 or greater), PVR decreases, there is less right-to-left shunting, and PaO2 increases. This test may differentiate PPHN from cyanotic congenital heart disease (CHD does not respond to pH increase via hyperventilation). It has been suggested that infants subjected to this test should be hyperventilated for 10 min. Prolonged hyperventilation is not recommended esp in premature infants (see later

discussion). Radiography. Clear lung fields or only minor disease in the face of severe hypoxemia is strongly suggestive of PPHN, if cyanotic congenital heart disease has been ruled out. In an infant with significant pulmonary parenchymal disease, a chest film is of little help in diagnosing PPHN but needed to rule out other diseases eg pneumothorax or pneumopericardium. Echocardiography is often essential in distinguishing cyanotic congenital heart disease from PPHN. Furthermore, whereas all the other previously mentioned signs and tests are suggestive, echocardiography (together with Doppler studies) can provide confirmatory evidence that is often diagnostic. The first question that needs to be answered is whether the heart is structurally normal. Then the pulmonary artery pressure can be assessed indirectly by measuring the acceleration time of the systolic flow in the main pulmonary artery, by measuring the velocity of the tricuspid regurgitant jet, and by measuring ductal shunt velocities. A flattened interventricular septum, or one that is bowing into the left ventricle, also support the diagnosis of PPHN. Echocardiography (with Doppler) also provides information about shunting at the atrial and ductal levels. Echocardiography can also be used to assess ventricular output and contractility (both of which may be depressed in infants with PPHN).

17. The ascending aorta is labelled as AO.  The RV is enlarged and the LV is underfilled and "squashed".  This is common in severe PPHN. The top images on the left are taken in the parasternal long axis view.  http://www.adhb.govt.nz/newborn/guidelines/Cardiac/PPHNAndEchocardiography.htmhttp://www.yale.edu/imaging/echo_atlas/views/index.html

18. 1) Prevention: adequate ventilation of the asphyxiated infant can help prevent PPHN2) Initial therapies are directed toward correcting alveolar hypoxia, acidosis, and hypercarbia with administration of oxygen and buffer usually coupled with and assisted ventilation. These measures often restore normal pulmonary vasodilation and allow for alveolar recruitment. However, excessive mean airway pressures have adverse effects that can perpetuate lung injury (see Sec. 23.9). It is also important to note that although hyperventilation has become perhaps the most commonly used treatment of PPHN, it has never been prospectively demonstrated to reduce the morbidity or mortality of PPHN. Hyperventilation with 100% oxygen may, indeed, worsen pulmonary, neurologic, and ophthalmologic morbidity. In some infants with hypoplastic lungs or especially severe parenchymal lung disease, high-frequency oscillatory ventilation may permit adequate gas exchange with smaller tidal volumes and lower airway pressures. This "lung recruitment" ventilation strategy has been successful in the treatment of some infants with PPHN. If the heart and lungs cannot support gas exchange, use of extracorporeal membrane oxygenation may allow time for the lungs to recover and pulmonary hypertension to resolve. Although this technique has been successful in the treatment of a large number of infants, it remains an extremely expensive and invasive method of supportive care and has many complications (see Secs. 2.19.3 and 4.2.3 ). If the cause of PPHN is respiratory distress syndrome (RDS) from lack of endogenous surfactant in the near-term child, exogenous surfactant is now available to reverse atelectasis and the attendant alveolar hypoxia (see Sec. 2.16.1). Many other experimental therapies have been proposed to provide adequate gas exchange (see Sec. 2.19.1 and 2.19.5 ).

If treatment of the underlying lung disease is ineffective, or if there is PPHN with no underlying parenchymal disease, then direct attempts to dilate the pulmonary circulation should be made. Numerous vasodilators have been utilized in the setting of persistent pulmonary hypertension of the newborn. Many other vasodilators including nitroprusside, prostacyclin, isoproterenol, and chlorpromazine have also been given to neonates with PPHN. Unfortunately, none of these agents is a selective pulmonary vasodilator. They all decrease both pulmonary and systemic vascular resistance, and thus none of them can be expected to selectively restore the normal transition to gas exchange by the lungs. For this reason, the discovery that inhaled NO (iNO) was a potent and selective pulmonary vasodilator effective in patients with PPHN was a clinical breakthrough, and this is the current treatment of choice (see Sec. 2.19.4).

There are patients in whom PPHN persists, despite treatment with iNO, because of abnormalities of vascular development or function. In some of these patients there may be alterations in the content or activity of soluble guanylate cyclase in the lung, or there may be high concentrations of the cGMP-specific phosphodiesterase PDE-5. Therefore, inhibitors of PDE-5 such as zaprinast or dipyrimidole may prove to be useful with PPHN. Figure 2-58 demonstrates other therapeutic targets that have been tried or will be tried in the future. These include inhaled prostacyclin, calcium channel inhibitors, and even antagonists of endothelin and thromboxane receptors. Persistent pulmonary hypertension of the newborn is the persistence of or reversion to pulmonary arteriolar constriction, causing a severe reduction in pulmonary blood flow and right-to-left shunting. Symptoms and signs include tachypnea, retractions, and

severe cyanosis or desaturation unresponsive to O2. Diagnosis is by history, examination, chest x-ray, and response to O2. Treatment is with O2, alkalinization, inhaled nitric oxide, or, if medical therapy fails, extracorporeal membrane oxygenation.Etiology and PathophysiologyAffects term or postterm infants. The most common causes perinatal asphyxia or hypoxia (a history of meconium staining of amniotic fluid or meconium in the trachea is common); hypoxia triggers reversion to or persistence of intense pulmonary arteriolar constriction, a normal state in the fetus. Additional causes include premature ductus arteriosus or foramen ovale closure, which increases fetal pulmonary blood flow and may be triggered by maternal NSAID use; polycythemia, which obstructs blood flow; congenital diaphragmatic hernia, in which the left lung is severely hypoplastic, forcing most of the pulmonary blood flow through the right lung; and neonatal sepsis, presumably from production of vasoconstrictive prostaglandins by activation of the cyclo-oxygenase pathway by bacterial phospholipids. Whatever the cause, elevated pressure in the pulmonary arteries causes abnormal smooth muscle development and hypertrophy in the walls of the small pulmonary arteries and arterioles and right-to-left shunting via the ductus arteriosus or a foramen ovale, resulting in intractable systemic hypoxemia.

DiagnosisDiagnosis should be suspected in any near-term infant with arterial hypoxemia and/or cyanosis, especially one with a suggestive history whose O2 saturation does not improve with 100% O2. Diagnosis is confirmed by echocardiogram, which can confirm the presence of elevated pressures in the pulmonary artery using Doppler interrogation and simultaneously excludes congenital heart disease. Lung fields on x-ray may be normal or may demonstrate changes due to the underlying cause (eg, meconium aspiration syndrome, neonatal pneumonia, congenital diaphragmatic hernia).Prognosis and TreatmentAn oxygenation index (mean airway pressure [cm H2O] × fraction of inspired O2 [FIO2] × 100/PaO2) > 40 predicts mortality of > 50%. Overall mortality ranges from 10 to 80% and is directly related to the oxygenation index but also varies with underlying disorder. However, many survivors (perhaps 1/3) exhibit developmental delay, hearing deficits, and/or functional disabilities. This rate of disability may be no different from that of other infants with severe illness.Treatment with O2, which is a potent pulmonary vasodilator, is begun immediately to prevent disease progression. O2 is delivered via bag and mask or mechanical ventilation; mechanical distention of alveoli aids vasodilation. FIO2 should initially be 100% but can be titrated downward to maintain PaO2 between 50 and 90 mm Hg to minimize lung injury. Once PaO2 is stabilized, weaning can be attempted by reducing FIO2 in decrements of 2 to 3%, then reducing ventilator pressures; changes should be gradual, because a large drop in PaO2 can cause recurrent pulmonary artery vasoconstriction. High-frequency oscillatory ventilation expands and ventilates the lungs while minimizing barotrauma and should be considered for infants with underlying lung disease in whom atelectasis and ventilation/perfusion (V/Q) mismatch may exacerbate the hypoxemia of PPHN.

Inhaled nitric oxide relaxes endothelial smooth muscle, dilating pulmonary arterioles, which increases pulmonary blood flow and rapidly improves oxygenation in as many as 1/2 of patients. Initial dose is 20 ppm, titrated downward by effect.Extracorporeal membrane oxygenation (see Extracorporeal membrane oxygenation (ECMO)) may be used in patients with severe hypoxic respiratory failure defined by an oxygenation index > 35 to 40 despite maximum respiratory support.Normal fluid, electrolyte, glucose, and Ca levels must be maintained. Infants should be kept in a neutral thermal environment and treated with antibiotics for possible sepsis until culture results are known.http://online.statref.com.ezproxy.ttuhsc.edu/Document/Document.aspx?docAddress=yJerlS6GC3bEsTC0P6g46A%3d%3d&Scroll=1&Index=0&SessionId=13172CEFSBIAGUUG

20. Infants with air trapping may have a barrel-shaped chest and also symptoms and signs of pneumothorax, pulmonary interstitial emphysema, and pneumomediastinum. chest x-ray demonstrating hyperinflation with variable areas of atelectasis and flattening of the diaphragm. cultures of blood and tracheal aspirate should also be obtained. A. Postterm pregnancy. B. Preeclampsia-eclampsia. C. Maternal hypertension. D. Maternal diabetes mellitus. E. Abnormal fetal heart rate and non reassuring fetal heart rate tracing. F. Intrauterine growth retardation. G. Abnormal biophysical profile. H. Oligohydramnios. I. Heavy smoking, chronic respiratory or cardiovascular disease in the mother. J. Low five minute apgar score. K. Presence of fetal distress. L. Ethnicity

21. chest x-ray demonstrating hyperinflation with variable areas of atelectasis and flattening of the diaphragm.

22. Prognosis and TreatmentPrognosis is generally good, although it varies with the underlying physiologic stressors; overall mortality is slightly increased. Infants with meconium aspiration syndrome may be at greater risk of asthma in later life.Immediate treatment, indicated for all neonates delivered through meconium, is vigorous suctioning of the mouth and nasopharynx using a De Lee suction apparatus as soon as the head is delivered and before the neonate breathes and cries. If suction returns no meconium and the infant appears vigorous, observation without further intervention is appropriate. If the infant has labored or depressed respirations, poor muscle tone, or is bradycardic (< 100 beats/min), the trachea should be intubated with a 3.5- or 4.0-mm endotracheal tube. A meconium aspirator connected to a suction apparatus is attached directly to the endotracheal tube, which then serves as the suction catheter. Suction is maintained while the endotracheal tube is removed. Reintubation and continuous positive airway pressure are indicated for continued respiratory distress, followed by mechanical ventilation and admission to the neonatal ICU as needed. Because positive pressure ventilation enhances risk of pulmonary air-leak syndrome, regular evaluation (including physical examination and chest x-ray) is important to detect these complications; these should immediately be sought in any intubated infant whose BP, perfusion, or O2 saturation suddenly worsens.Additional treatments may include surfactant for mechanically ventilated infants with high O2 requirements, which can decrease the need for extracorporeal membrane oxygenation, and antibiotics (usually ampicillin and an aminoglycoside). Treatment of air-leak syndromes, a complication of air trapping, is discussed below.Intrapartum meconium aspiration can cause chemical pneumonitis and mechanical bronchial obstruction producing a syndrome of respiratory distress. Findings include tachypnea, rales and rhonchi, and cyanosis or desaturation. Diagnosis is suspected when there is respiratory distress after delivery through meconium-tinged amniotic fluid and is confirmed by chest x-ray. Treatment is vigorous suction immediately on delivery before the neonate takes his 1st breath, followed by respiratory support as needed. Prognosis depends on the underlying physiologic stressors.Etiology and PathophysiologyPhysiologic stress at the time of labor and delivery (eg, from hypoxia caused by umbilical cord compression or placental insufficiency or from infection) may cause the fetus to pass meconium into the amniotic fluid before delivery; meconium passage is noted in about 10 to 15% of births. During delivery, perhaps 5% of infants with meconium passage aspirate the meconium, triggering lung injury and respiratory distress, termed meconium aspiration syndrome. Postterm infants delivered through reduced amniotic fluid volume are at risk of more severe disease because the less dilute meconium is more likely to cause airway obstruction.The mechanisms by which aspiration induces the clinical syndrome probably include nonspecific cytokine release, airway obstruction, surfactant inactivation, and/or chemical pneumonitis; the underlying physiologic stressors also may contribute. If complete bronchial obstruction occurs, atelectasis results; partial blockage leads to air trapping on expiration, resulting in hyperexpansion of the lungs and possibly pulmonary air leak (see Pulmonary Air-Leak Syndromes) with pneumomediastinum or pneumothorax.

Continuing hypoxia may lead to persistent pulmonary hypertension of the newborn (see Persistent Pulmonary Hypertension of the Newborn).Infants may also aspirate vernix caseosa, amniotic fluid, or blood of maternal or fetal origin during delivery and can develop respiratory distress and signs of aspiration pneumonia on chest x-ray. Treatment is supportive; if bacterial infection is suspected, cultures are taken and antibiotics begun.

Symptoms and SignsSigns include tachypnea, nasal flaring, retractions, cyanosis or desaturation, rales, rhonchi, and greenish yellow staining of the umbilical cord, nail beds, or skin. Meconium staining may be visible in the oropharynx and (on intubation) in the larynx and trachea. Infants with air trapping may have a barrel-shaped chest and also symptoms and signs of pneumothorax, pulmonary interstitial emphysema, and pneumomediastinum (see Pneumomediastinum).

DiagnosisDiagnosis is suspected when a neonate demonstrates respiratory distress in the setting of meconium-tinged amniotic fluid and is confirmed by chest x-ray demonstrating hyperinflation with variable areas of atelectasis and flattening of the diaphragm. Fluid may be seen in the lung fissures or pleural spaces, and air may be seen in the soft tissues or mediastinum. Because meconium may enhance bacterial growth and meconium aspiration syndrome is difficult to distinguish from bacterial pneumonia, cultures of blood and tracheal aspirate should also be obtained.

The majority (94-97%) of infants born through meconium-stained fluid will not develop meconium aspiration syndrome, but when it does occur, infants are often critically ill. Meconium can block the airway and prevent the newborn's lungs from filling with oxygen, which is a vital step in normal transitioning. Meconium aspiration into the lungs can cause obstruction of the small airways and consequently areas of atelectasis, gas trapping, and overdistention in addition to a chemical pneumonitis. The infant born through meconium may have pulmonary hypertension and inadequate oxygenation and requires close observation and early initiation of treatment when appropriate.

Risk factors. The following factors are associated with an increased risk of meconium passage and subsequent tracheal aspiration:A. Postterm pregnancy. B. Preeclampsia-eclampsia. C. Maternal hypertension. D. Maternal diabetes mellitus. E. Abnormal fetal heart rate and non reassuring fetal heart rate tracing. F. Intrauterine growth retardation. G. Abnormal biophysical profile. H. Oligohydramnios. I. Heavy smoking, chronic respiratory or cardiovascular disease in the mother. J. Low five minute apgar score. K. Presence of fetal distress. L. Ethnicity. Black Americans and Africans have an increased risk when compared to other ethnic groups. Pacific Islander and indigenous Australian ethnicity also have increased risk. M. Homebirth. An increased risk of MAS was noted after a planned home birth.

Chemical pneumonitis. With distal progression of meconium, chemical pneumonitis develops, with resulting bronchiolar edema and narrowing of the small airways. Meconium at the alveolar level may inactivate existing surfactant. Uneven ventilation resulting from areas of partial obstruction, atelectasis, and superimposed pneumonitis causes carbon dioxide retention and hypoxemia.

23. Bronchopulmonary dysplasia is chronic lung injury in premature infants caused by supplemental O2 and prolonged mechanical ventilation.Bronchopulmonary dysplasia (BPD) is considered present when there is need for supplemental O2 in premature infants at 36 wk gestation who do not have other conditions that require O2 (eg, pneumonia, congenital heart disease). It is caused by high concentrations of inspired O2 typically in patients on prolonged mechanical ventilation. Incidence increases with degree of prematurity; additional risk factors include pulmonary interstitial emphysema, high peak inspiratory pressures, increased airway resistance and pulmonary artery pressures, and male sex. BPD is typically suspected when a ventilated infant is unable to wean from O2 therapy, mechanical ventilation, or both. Patients develop worsening hypoxemia, hypercapnia, and increasing O2 requirements. Chest x-ray initially shows diffuse haziness due to accumulation of exudative fluid; appearance then becomes multicystic or spongelike, with alternating areas of emphysema, pulmonary scarring, and atelectasis. Alveolar epithelium may slough, and macrophages, neutrophils, and inflammatory mediators may be found in the tracheal aspirate.Prognosis and TreatmentPrognosis varies with severity. Infants who still depend on mechanical ventilation at 36 wk gestation have a 20 to 30% mortality rate in infancy. Infants with BPD have a 3- to 4-fold increased rate of growth failure and neurodevelopmental problems. For several years, infants are at increased risk of lower respiratory tract infections (particularly viral) and may quickly develop respiratory decompensation if pulmonary infection occurs. The threshold for hospitalization should be low if signs of a respiratory infection or respiratory distress develop.Treatment is supportive and includes nutritional supplementation, fluid restriction, diuretics, and perhaps inhaled bronchodilators. Respiratory infections must be diagnosed early and treated aggressively. Weaning from mechanical ventilation and supplemental O2 should be accomplished as early as possible.Feedings should achieve an intake of > 120 calories/kg/day; caloric requirements are increased because of the increased work of breathing and to aid lung healing and growth.Because pulmonary congestion and edema may develop, daily fluid intake is often restricted to about 120 mL/kg/day. Diuretic therapy is sometimes used: chlorothiazide 10 to 20 mg/kg po bid plus spironolactone 1 to 3 mg/kg once/day or split into twice-daily doses. Furosemide (1 to 2 mg/kg IV or IM or 1 to 4 mg/kg po q 12 to 24 h for neonates and q 8 h for older infants) may be used for short periods, but prolonged use causes hypercalciuria with resultant osteoporosis, fractures, and renal calculi. Hydration and serum electrolytes should be monitored closely during diuretic therapy.Weeks or months of additional ventilator support and/or supplemental O2 may be required for advanced BPD. Ventilator pressures and fraction of inspired O2 (FIO2) should be reduced as rapidly as tolerated, but the infant should not be allowed to become hypoxemic. Arterial oxygenation should be continuously monitored with a pulse oximeter and maintained at ≥ 88% saturation. Respiratory acidosis may occur during ventilator weaning and treatment and is acceptable as long as the pH remains > 7.25 and the infant does not develop severe respiratory distress.Passive immunoprophylaxis with palivizumab, a monoclonal antibody to respiratory syncytial virus (RSV), decreases RSV-related hospitalizations and ICU stays but is costly and is indicated primarily in high-risk infants (see for indications). During RSV season

(November through April), children are given 15 mg/kg IM q 30 days until 6 mo after treatment of the acute illness. Infants > 6 mo should also be vaccinated against influenza.PreventionBPD often can be prevented by weaning infants to the lowest tolerated ventilator settings and completely off mechanical ventilation as soon as possible; early use of aminophylline as a respiratory stimulant may help preterm infants wean from intermittent mandatory ventilation. Prenatal corticosteroid administration, prophylactic surfactant administration in extremely low-birth-weight infants, early treatment of patent ductus arteriosus, and avoidance of large volumes of fluid also decrease BPD incidence and severity. When an infant cannot be weaned within the expected time, possible underlying conditions, including patent ductus arteriosus and nursery-acquired pneumonia, should be considered and treated.

24. CXR of ___ A recent summary of a National Institutes of Health workshop on BPD proposes a definition of the disease that includes oxygen requirement for more than 28 days, a history of positive pressure ventilation or continuous positive airway pressure, and gestational age. The new definition accommodates several key observations regarding the disease, as follows: (1) although most of these children were premature and had hyaline membrane disease, full-term newborns with such disorders as meconium aspiration or persistent pulmonary hypertension can also develop bronchopulmonary dysplasia; (2) some extremely preterm newborns require minimal ventilator support yet subsequently develop a prolonged oxygen requirement despite the absence of severe acute manifestations of respiratory failure; (3) newborns dying within the first weeks of life can already have the aggressive, fibroproliferative pathologic lesions that resemble bronchopulmonary dysplasia; and (4) physiologic abnormalities (increased airway resistance) and biochemical markers of lung injury (altered protease-antiprotease ratios, and increased inflammatory cells and mediators), which may be predictive of BPD, are already present in the first week of life.

Chest radiograph showing a diffuse, moderately coarse increase in lung density, which in a 2-month old ventilated ex-premie is most consistent with chronic lung disease (CLD)/bronchopulmonary dysplasia.

26. TreatmentA. Clinical CourseThe clinical course of infants with BPD ranges from a mild increased oxygen requirement that gradually resolves over a few months to more severe disease requiring chronic tracheostomy and mechanical ventilation for the first 2 years of life. In general, patients show slow, steady improvements in oxygen or ventilator requirements but can have frequent respiratory exacerbations leading to frequent and prolonged hospitalizations. Clinical management generally includes careful attention to growth, nutrition (caloric requirements of infants with oxygen dependence and respiratory distress are quite high), metabolic status, developmental and neurologic status, and related problems, along with the various cardiopulmonary abnormalities described in a later discussion.B. Corticosteroid TherapyShort courses of postnatal glucocorticoid therapy have been helpful in increasing the success of weaning from the ventilator. Longer courses of postnatal glucocorticoids have been linked to an increased incidence of cerebral palsy. Inhaled glucocorticoids may help reduce the need for systemic steroids, but the overall incidence of BPD has not been affected. Early use of surfactant therapy with adequate lung recruitment increases the chance for survival without BPD and can decrease the overall mortality and reduce the need for ventilation. Thus early interventions are important prior to the development of BPD to decrease morbidity and mortality. Inhaled corticosteroids together with occasional use of β-adrenergic agonists are commonly part of the treatment plan. Part of the rationale for the use of corticosteroids is to decrease lung inflammation and enhance responsiveness to β-adrenergic drugs, as in the treatment of severe asthma. β-Adrenergic agonists followed by chest physiotherapy are often used for the thick secretions that may contribute to airway obstruction or recurrent atelectasis.C. Airway EvaluationChildren with significant stridor, sleep apnea, chronic wheezing, or excessive respiratory distress need diagnostic bronchoscopy to evaluate for structural lesions (eg, subglottic stenosis, vocal cord paralysis, tracheal stenosis, tracheomalacia, bronchial stenosis, and granulomatous bronchial polyps). In addition, the contribution of gastroesophageal reflux and aspiration should be considered in the face of worsening chronic lung disease.D. Diuretic TherapySalt and water retention secondary to chronic hypoxemia, hypercapnia, or other stimuli may be present. Chronic or intermittent diuretic therapy is commonly used if rales or signs of persistent pulmonary edema are present, and clinical studies show acute improvement in lung function with this therapy. Unfortunately, diuretics often have adverse effects, including severe volume contraction, hypokalemia, alkalosis, and hyponatremia. Potassium and arginine chloride supplements are commonly required.E. Management of Pulmonary HypertensionInfants with BPD are at risk of developing pulmonary hypertension, and in many of these children even mild hypoxemia can cause significant elevations of pulmonary arterial pressure. To minimize the harmful effects of hypoxemia, the arterial oxygen saturation should be kept above 93%, with care to avoid hyperoxia during retinal vascular development. Electrocardiographic and echocardiographic studies should be performed to monitor for the development of right ventricular hypertrophy. If hypertrophy persists or if

it develops where it was not previously present, intermittent hypoxemia should be considered and further assessments of oxygenation pursued, especially while the infant sleeps. Infants with a history of intubation can develop obstructive sleep apnea secondary to a high-arched palate or subglottic narrowing. Barium swallow, esophageal pH probe studies, bronchoscopy, and cardiac catheterization will diagnose unsuspected cardiac or pulmonary lesions that contribute to the underlying pathophysiology, such as aspiration, tracheomalacia, obstructive sleep apnea, and anatomic cardiac lesions. Long-term care should include monitoring for systemic hypertension and the development of left ventricular hypertrophy.F. NutritionNutritional problems in infants may be due to increased oxygen consumption, feeding difficulties, gastroesophageal reflux, and chronic hypoxemia. Hypercaloric formulas and gastrostomies are often required to ensure adequate intake while avoiding overhydration. Influenza vaccination is recommended. With the onset of acute wheezing secondary to suspected viral infection, rapid diagnostic testing for RSV infection may facilitate early treatment. Immune prophylaxis of RSV reduces the morbidity of bronchiolitis in infants with BPD.G. VentilationFor children who remain ventilator-dependent, attempts should be made to maintain PaCO2 below 60 mm Hg—even when pH is normal—because of the potential adverse effects of hypercapnia on salt and water retention, cardiac function, and perhaps pulmonary vascular tone. Changes in ventilator settings in children with severe lung disease should be slow, because the effects of many of the changes may not be apparent for days. PrognosisSurfactant replacement therapy has had a significant effect on reducing morbidity and mortality from BPD. Infants of younger gestational age are surviving in greater numbers. Surprisingly, the effect of neonatal care has not decreased the incidence of BPD significantly, as 50% of survivors go on to develop this diagnosis. The disorder typically develops in the most immature infants, but the long-term outlook for most survivors is generally favorable. Long-term follow-up studies suggest that lung function may be altered for life. Hyperinflation and damage to small airways has been reported in children 10 years out from the first signs of BPD. In addition, these infants are at a higher risk for developing such sequelae as persistent airway hyperreactivity, exercise intolerance, pulmonary hypertension, increased risk for chronic obstructive pulmonary disease, and perhaps abnormal lung growth. As smaller, more immature infants survive, abnormal neurodevelopmental outcomes become more likely. The incidence of cerebral palsy, hearing loss, vision abnormalities, spastic diplegia, and developmental delays is increased. Feeding abnormalities, behavior difficulties, and increased irritability have all been reported. Finally, children with BPD frequently develop airway obstruction, hyperreactive airways, and decreased oxygen saturation during exercise. This should be taken into account for children residing at higher altitudes. A focus on good nutrition, prophylaxis against respiratory pathogens and airway hyperreactivity, and attention to school performance continue to provide the best outcomes. Patience, continued family support, attention to developmental issues, and speech and physical therapy help to improve the long-term outlook.

27. 77. Bronchopulmonary DysplasiaIntroductionI. Definition. Classic bronchopulmonary dysplasia (BPD) is a neonatal form of chronic pulmonary disorder that follows a primary course of respiratory failure (eg, respiratory distress syndrome [RDS], meconium aspiration syndrome) in the first days of life. A "new" form of BPD has been described in extremely low birthweight infants. This occurs in infants who initially had none or modest initial ventilatory and oxygen needs.BPD is defined as persistent oxygen dependency up to 28 days of life. The severity of BPD-related pulmonary dysfunction in early childhood is more accurately predicted by an oxygen dependence at 36 weeks' postconceptional age (PCA) in infants <32 weeks' gestational age (GA) and at 56 days of age in infants with older GA. BPD is thus classified at this later postnatal age and is graded according to the type of respiratory support required to maintain a normal arterial oxygen saturation (>89%).A. Mild BPD. Infants who have been weaned from any supplemental oxygen.

B. Moderate BPD. Infants who continue to need up to 30% oxygen.

C. Severe BPD. Infants whose requirements exceed 30% and/or include continuous positive airway pressure or mechanical ventilation.

II. Incidence. The incidence of BPD is influenced by many risk factors, the most important of which is lung maturity. The incidence of BPD increases with decreasing birthweight and affects ~30% of infants with birthweights <1000 g. There is a large variability in rates reported among centers in part related to differences in clinical practices, such as criteria used for the management of mechanical ventilation.III. Pathophysiology. A primary lung injury is not always evident at birth. The secondary development of a persistent lung injury is associated with an abnormal repair process and leads to structural changes such as arrested alveolarization and pulmonary vascular dysgenesis.A. The major factors contributing to BPD are as follows:

1. Inflammation is central to the development of BPD. An exaggerated inflammatory response (alveolar influx of numerous proinflammatory cytokines as well as macrophages and leukocytes) occurs in the first few days of life in infants in whom BPD subsequently develops.

2. Mechanical ventilation. Volutrauma/barotrauma is one of the key risk factors for the development of BPD. Minimizing the use of mechanical ventilation by the use of early nasal continuous positive airway pressure (NCPAP) and noninvasive ventilatory support (nasal intermittent positive pressure ventilation) has led to lesser rates of BPD.

3. Oxygen exposure. Classic BPD observed prior to the availability of exogenous surfactant treatment was always associated with prolonged exposure (>150 h) to an FIO2 >60%. Hyperoxia can have major effects on lung tissue such as proliferation of alveolar type II cells and fibroblast, alterations in the surfactant system, increases in inflammatory cells and cytokines, increased collagen deposition, and decreased alveolarization and

microvascular density. Today, exposure to prolonged high oxygen is limited. Nevertheless, aiming for arterial oxygen saturation in the range 85-93% rather than >92% has led to a decrease in the need for supplemental oxygen at 36 weeks PCA in this postsurfactant era.

B. Pathologic changes. Compared with the presurfactant era, lungs of infants currently dying from BPD have normal-appearing airways, less fibrosis, and more uniform inflation. However, these lungs have deficient septation, leading to fewer and larger alveoli with possible reduced pulmonary capillarization that may lead to pulmonary hypertension.

IV. Risk factors. Major risk factors are prematurity, white race, male gender, chorioamnionitis, tracheal colonization with ureaplasma, and the increased survival of the extremely low birthweight infant. Other risk factors are RDS, excessive early intravenous fluid administration, symptomatic PDA, sepsis, oxygen therapy, vitamin A deficiency, and a family history of atopic disease.V. Clinical presentation. BPD is usually suspected in infants with progressive and idiopathic deterioration of pulmonary function. Infants in whom BPD develops often require oxygen therapy or mechanical ventilation beyond the first week of life. Severe cases of BPD are usually associated with poor growth, pulmonary edema, and a hyperreactive airway.VI. DiagnosisA. Physical examination

1. General signs. Worsening respiratory status is manifested by an increase in the work of breathing, an increase in oxygen requirement, or an increase in apnea-bradycardia, or a combination of these.

2. Pulmonary examination. Retractions and diffuse rales are common. Wheezing or prolongation of expiration may also be noted.

3. Cardiovascular examination. A right ventricular heave, single S2, or prominent P2 may accompany cor pulmonale.

4. Abdominal examination. The liver may be enlarged secondary to right-sided heart failure or may be displaced downward into the abdomen secondary to lung hyperinflation.

B. Laboratory and radiologic studies. These studies are intended to rule out differential diagnosis such as sepsis or patent ductus arteriosus (PDA) during the acute nature of the disease and to detect problems related to chronic lung disease or its therapy.

1. Arterial blood gas levels frequently reveal carbon dioxide retention. However, if the respiratory difficulties are chronic and stable, the pH is usually subnormal (pH ≥7.25).

2. Electrolytes. Abnormalities of electrolytes may result from chronic carbon dioxide

retention (elevated serum bicarbonate), diuretic therapy (hyponatremia, hypokalemia, or hypochloremia), or fluid restriction (elevated urea nitrogen and creatinine), or all three.

3. Urinalysis. Microscopic examination may reveal the presence of red blood cells, indicating a possible nephrocalcinosis as a result of prolonged diuretic treatment.

4. Chest radiograph. Radiographic findings may be quite variable. Most frequently, BPD appears as diffuse haziness and lung hypoinflation in infants who were very immature at birth and have persistent oxygen requirements. In other infants, a different picture is seen reminiscent of that originally described by Northway: streaky interstitial markings, patchy atelectasis intermingled with cystic area, and severe overall lung hyperinflation. Because those findings persist for a prolonged period, new changes (such as a secondary infection) are difficult to detect without the benefit of comparison to previous radiographs. (See Figure 10-16 for an example of BPD.)

5. Renal ultrasonography. Radiologic studies of the abdomen should be considered during diuretic therapy to detect the presence of nephrocalcinosis. It should be performed when red blood cells are present in the urine.

6. Other studies. Electrocardiography and echocardiography are indicated in nonimproving or worsening BPD. Electrocardiograms and echocardiograms could detect cor pulmonale and/or pulmonary hypertension, manifested by right ventricular hypertrophy and elevation of pulmonary artery pressure with right axis deviation, increased right systolic time intervals, thickening of the right ventricular wall, and abnormal right ventricular geometry.

VII. ManagementA. Prevention of BPD

1. Prevention of prematurity and RDS. Therapies directed toward decreasing the risk of prematurity and the incidence of RDS include improving prenatal care and antenatal corticosteroids.

2. Reducing exposure to risk factors. Successful measures should include minimizing exposure to oxygen, ventilation strategies that minimize the use of excessive tidal volume (above 4-6 mL/kg), prudent administration of fluids, aggressive closure of PDA, and adequate nutrition. Early surfactant replacement therapy may be beneficial, but the avoidance of intubation and mechanical ventilation with the initiation of continuous positive airway pressure (CPAP) shortly after birth may prove to be the most effective preventive strategy.

3. Vitamin A is known to be important in epithelial cell differentiation and repair, and extremely low birthweight infant have low blood levels. A multicenter randomized trial has shown that vitamin A supplementation, 5000 IU administered intramuscularly three

times per week for 4 weeks, significantly reduced the rate of BPD. In this study, one additional infant survived without BPD for every fifteen extremely low birthweight infants treated.

4. Caffeine. Methylxanthines decrease the frequency of apnea and allow for shorter duration of mechanical ventilation leading to a reduced rate of BPD.

5. Inhaled nitric oxide (iNO). Inhaled nitric oxide has been shown in animal models to reduce pulmonary vascular tone and prevent lung inflammation that ensues mechanical ventilation. Recently, two randomized multicenter trials were performed to assess the efficacy of iNO for BPD prevention. Results have been equivocal with a possible beneficial effect within certain subgroups divided according to birthweight or onset of treatment.

B. Treatment of BPD. Once BPD is present, the goal of management is to prevent further injury by minimizing respiratory support, improving pulmonary function, preventing cor pulmonale, and emphasizing growth and nutrition.

1. Respiratory support

a. Supplemental oxygen. Maintaining adequate oxygenation is important in the infant with BPD to prevent hypoxia-induced pulmonary hypertension, bronchospasm, cor pulmonale, and growth failure. However, the least required oxygen should be delivered to minimize oxygen toxicity. Arterial oxygen saturation (SaO2) should be monitored during the infant's various activities, including rest, sleep, and feeding. The optimal oxygen saturation level has not been established, and whether the level should exceed the range between 90% and 94% is controversial. Nonfrequent blood gas measurements are important for the assessment of trends in pH, PaCO2, and serum bicarbonate, but they are of limited use in monitoring oxygenation because they provide information about only one point in time.

b. Positive-pressure ventilation. Mechanical ventilation should be used only when clearly indicated. Problems with air trapping can be significant; thus a ventilatory strategy using a slower rate with longer inspiration and expiration times than when ventilated for RDS should be implemented. Similarly inspiratory pressure needs to be limited at the expense of tolerating PaCO2 in excess of 50-60 mm Hg. Nasal CPAP can be useful as an adjunctive therapy after extubation.

2. Improving lung function

a. Fluid restriction. Restricting fluid to 120 mL/kg/day is often required. It can be accomplished by concentrating proprietary formulas to 24 cal/oz. Increasing the caloric density further, to 27-30 cal/oz may require the addition of fat (eg, medium-chain triglyceride oil or corn oil) and carbohydrate (eg, Polycose) to avoid excessive protein intake.

b. Diuretic therapy. See Chapter 132.

(i) Furosemide (1-2 mg/kg every 12 h, orally or intravenously) is a potent diuretic that is particularly useful for rapid diuresis. It is associated with side effects such as electrolyte abnormalities, interference with bilirubin-albumin binding capacity, calciuria with bone demineralization and renal stone formation, and ototoxicity. When used as a chronic medication, Na+ and K+ supplementation are often required.

(ii) Bumetanide (0.015-0.1 mg/kg daily or every other day, orally or intravenously). When administered orally, 1 mg of bumetanide (Bumex) has a diuretic effect similar to that of 40 mg of furosemide. Whereas furosemide's bioavailability is 30-70%, bumetanide's bioavailability is >90%. Bumetanide produces side effects similar to those of furosemide, except that it may produce less ototoxicity and less interference with bilirubin-albumin binding.

(iii) Chlorothiazide and spironolactone. When used in doses of 20 mg/kg/day (chlorothiazide) and 2 mg/kg/day (spironolactone), a good diuretic response can often be achieved. Although less potent than furosemide, this combination is often better suited for chronic management because it has relatively fewer side effects. It may be the diuretic combination of choice when the calciuric effect of furosemide has led to the development of nephrocalcinosis.

c. Bronchodilators

(i) β2-Agonists. (See Table 7-5.) Inhaled β2-agonists produce measurable acute improvements in lung mechanics and gas exchange in infants with BPD exhibiting symptoms of increased airway tone. Their effect is usually time limited. Because of their side effects (eg, tachycardia, hypertension, hyperglycemia, and possible arrhythmia), their use (albuterol, 0.2 mg/kg/dose nebulized as needed every 2-8 h) should be limited to the management of acute exacerbations of BPD. Xopenex (levalbuterol, 0.1 mg/kg/dose nebulized as needed every 8 h) is a nonracemic form of albuterol recently introduced in pediatric and adult populations. Its experience in newborns is limited. Its potential advantages are better and longer efficacy; hence lower doses have a therapeutic effect, enabling a significant reduction in the adverse effects associated with racemic albuterol. If bronchodilators are being used long term, a frequent reevaluation of their benefit is essential.

(ii) Anticholinergic agents. (See Table 7-5.) The best studied and most available inhaled quaternary anticholinergic is ipratropium bromide (nebulized Atrovent, 175 mcg, diluted in 3 mL of normal saline over 10 min every 8 h). Its bronchodilatory effect is more potent than that of atropine and similar to that of albuterol. Combined albuterol and ipratropium therapy has a larger effect than either agent alone. Unlike atropine, systemic effects do not occur because of its poor systemic absorption.

(iii) Theophylline. The beneficial actions of theophylline include smooth airway muscle dilation, improved diaphragmatic contractility, central respiratory stimulation, and mild

diuretic effects. It appears to improve lung function in BPD when levels are maintained at >10 mcg/mL. Side effects are fairly common and may include central nervous system (CNS) irritability, gastroesophageal reflux, and gastrointestinal irritation. Prevention of apnea rather than bronchodilation is the major reason for infants with BPD to receive a methylxanthine treatment.

d. Corticosteroids. Although very efficient, the use of postnatal steroids should be limited to severe cases of BPD with a low chance of survival because of impaired gas exchange. Parents should be informed that the use of postnatal steroids could be associated with impaired brain and somatic growth and increased incidence of cerebral palsy. The initiation of steroid therapy in the first day increases the incidence of gastrointestinal perforation in particular when associated with concomitant indomethacin administration. Other side effects include infection, hypertension, gastric ulcer, hyperglycemia, adrenocortical suppression, lung growth suppression, and hypertrophic cardiomyopathy. Because of the central role of inflammation and relative adrenal insufficiency in the pathogenesis of BPD, steroids can be very effective both for prophylaxis or treatment of severe cases. Various steroid regimens have been proposed.

(i) Dexamethasone (DXM), 0.25 mg/kg twice daily for 3 days and then gradually tapered by a 10% dose decrease every 3 days for a total course of 42 days, is one of the original regimens that has proven efficacious in the treatment of BPD. Because of the concern about the possible neurologic adverse effects, many other regimens of shorter duration or dosage have been used, and no standards have been accepted.

(ii) Methylprednisolone (Solu-Medrol), a corticosteroid with much weaker genomic activity than DXM, has almost similar nongenomic activity and thus possibly fewer CNS and somatic side effects. In a pilot study, methylprednisolone, 0.6, 0.4, 0.2 mg/kg/dose every 6 h for 3 days, followed by betamethasone, 0.1 mg/kg orally every other day for a total of 21 days, was found to have similar beneficial effects and fewer side effects (eg, periventricular leukomalacia, hyperglycemia) than DXM. These findings still need to be confirmed by large randomized controlled trials.

(iii) Hydrocortisone, 5 mg/kg/day divided every 6 h for 1 week, then gradually tapered for the following 2 to 5 weeks. In contrast to infants treated with dexamethasone, when compared with nontreated preterm infants, hydrocortisone-treated infants showed no difference in neurocognitive or motor outcome, or in the incidence of brain abnormalities on magnetic resonance imaging, in long-term follow-up studies at 5-8 years.

(iv) Prednisolone, 2 mg/kg per day orally divided twice per day for 5 days, then 1 mg/kg per dose orally daily for 3 days, and then 1 mg/kg per dose every other day for three doses has been used to wean from oxygen therapy prior to discharge home.

(v) Nebulized corticosteroids (beclomethasone, 100-200 mcg 4 times/day) produced fewer side effects than oral or parenteral forms but seems to be much less efficacious in the treatment of BPD.

3. Growth and nutrition. Because growth is essential for recovery from BPD, adequate nutritional intake is crucial. Infants with BPD frequently have high caloric needs (120-150 kcal/kg/day or more) because of increased metabolic expenditures. Concentrated formula is often necessary to provide sufficient calories and prevent pulmonary edema. In addition, specific micronutrient supplementation, such as antioxidant therapy, may also enhance pulmonary and nutritional status.

C. Discharge planning. Oxygen can often be discontinued before discharge from the neonatal intensive care unit. However, home oxygen therapy can be a safe alternative to long-term hospitalization. The need for home respiratory, heart rate, and oxygen monitoring must be decided on an individual basis but is generally recommended for infants discharged home on oxygen. Synagis (palivizumab, humanized monoclonal antibodies against respiratory syncytial virus [RSV]) should be given monthly (15 mg/kg intramuscularly) throughout the RSV season. All parents should be instructed in cardiopulmonary resuscitation.

D. General care. Care plans for older infants with BPD should include adapting their routine for home life and involving the parents in their care. Immunizations should be given at the appropriate chronologic age. Periodic screening for chemical evidence of rickets and echocardiographic evidence of right ventricular hypertrophy is recommended. Assessment by a developmental specialist and occupational or physical therapist, or both, can be useful for prognostic and therapeutic purposes.

VIII. Prognosis. The prognosis for infants with BPD depends on the degree of pulmonary dysfunction and the presence of other medical conditions. Most deaths occur in the first year of life as a result of cardiorespiratory failure, sepsis, or respiratory infection or as a sudden, unexplained death.A. Pulmonary outcome. The short-term outcome of infants with BPD, including those requiring oxygen at home, is surprisingly good. Weaning from oxygen is usually possible before their first birthday, and they demonstrate catch-up growth as their pulmonary status improves. However, in the first year of life, rehospitalization is necessary for ~30% of patients for treatment of wheezing, respiratory infections, or both. Although upper respiratory tract infections are probably no more common in infants with BPD than in normal infants, they are more likely to be associated with significant respiratory symptoms. Most adolescents and young adults who had moderate to severe BPD in infancy have some degree of pulmonary dysfunction, consisting of airway obstruction, airway hyperreactivity, and hyperinflation.

B. Neurodevelopmental outcome. Children with BPD appear to be at an increased risk for adverse neurodevelopmental outcome compared with comparable infants without BPD. Neuromotor and cognitive dysfunction appears to be more common. In addition, children with BPD may be at higher risk for significant hearing impairment and retinopathy of prematurity. They are also at risk for later problems, including learning disabilities, attention deficits, and behavior problems.http://library.med.utah.edu/WebPath/PEDHTML/PED216.html interstitial fibrosis of BPD, large alveoli

30. Current mechanical ventilators possess a wide, and potentially confusing, array of modes, settings, and capabilities. All of them, however, control three variables: trigger, limit, and cycle.CO2 (ventilation) movement is determined by minute ventilation=RR x VT. So that increasing RR or Vt increases CO2 removal and lowers PaCO2Things that affect CO2A. Minute Ventilation. Minute Ventilation is affected by:

1. RR – The higher the frequency, the bigger the VT. RR is affected by: a. Expiratory timeb. Inspiratory timec. E:I ratio

2. Tidal Volume (Vt) – is affected by: a. Inspiratory time – Short inspiratory times cause short tidal volumesb. Pressure gradient – is affected by: increasing the pressure gradient

increases Vti. PEEP increases --> decreased VT. ii. PIP increases causes increase in VT.

c. Time Constant – Is affected by: i. Resistanceii. Compliance

B. Low Vt can cause high PaCO2 (hypercapnia). Hypercapnia caused by hypoventilation can be managed by mechanical ventilationOxygenation depends mostly on the P(Mean airway Pressure) and FiO2 (MAP>FiO2). Hypoxemia can be due to V/Q mismatch, shunting, diffusion abl, and hypoventilation. V/Q mismatches from poorly ventilated/perfused alveoli cause hypoxemia. Hypoxemia from shunting (eg PDA, PPHN, TOF) does not respond to O2 supplementation or mech vent unless the shunt is reversed. Hypoxemia from lung disease eg impaired diffusion or hypoventilation responds well to O2 supplementation or mech vent. Things that affect Oxygenation: A. Mean Airway Pressure – MAP = K(PIP – PEEP) x (Ti/Ti+Te) + PEEP. K=constant on the irway pressure curve. MAP is affected by:

1. PIP increases causes increases in MAP2. PEEP increases causes increases in MAP3. I:E Ratio increases (esp increasing I time) increases MAP 4. Inspiratory Flow increases cause increase in K which causes an increase in

MAP5. Rate increases cause increase in MAP

B. FiO2 – is affected by: C. Limitations: 1. PEEP and PIP affect MAP more than I/E ratio. That is, to make the same change in MAP, increases in PIP and PEEP enhance oxygenation more than adjusting the I:E ratio. 2. The effectiveness of PEEP is reached at 6cmH2O. 3. High MAPs cause lung overdistention, R to L shunts in the lungs by redistributing the blood flow to poorly ventilated areas, or decreasing CO. 4. Long Ti increase the risk for pneumothorax

Greater effects on arterial oxygenation are achieved through adjustment of either FIO2 or mean airway pressure (Paw), both of which can be readily manipulated with a mechanical ventilator.

31. An essential concept in mechanical ventilation is the distinction between two key processes, ventilation and oxygenation. The primary purpose of ventilation is to excrete carbon dioxide. The minute ventilation (VE) is the total amount of gas exhaled per minute= rate x tidal volume (VT). Minute ventilation has two components, alveolar ventilation (VA) and dead space ventilation (VD). Under normal conditions, approximately two thirds of VE reaches the alveoli and takes part in gas exchange (VA); the remaining third moves in and out of the conducting airways and nonperfused alveoli (VD). Thus, the ratio of dead space to tidal volume (VD/VT) is normally 0.33. The amount of CO2 excreted is directly related to the amount of alveolar ventilation and inversely proportional to the partial pressure of CO2 in the alveoli (PACO2). During spontaneous breathing, VE is regulated by the brain stem respiratory center. The brain stem respiratory center responds primarily to changes in plasma pH and in the partial pressure of CO2 in arterial blood (PaCO2). In the face of normal CO2 production (~ 200 ml/min) and normal minute ventilation (6 L/min), alveolar ventilation amounts to approximately 4 L/min and corresponds to a PaCO2 of 40 mm Hg. Respiratory rate and tidal volume can be set independently, and the mode of ventilation can be set to allow additional spontaneous breathing if necessary. In most cases, the primary goal is maintenance of a near-normal PaCO2. The physician must be cognizant of factors that might increase CO2 production (e.g., fever, sepsis, injury, and overfeeding) or VD (e.g., lung injury, ARDS, and massive pulmonary embolism), any of which would increase the VE requirements in a ventilated patient.Greater effects on arterial oxygenation are achieved through adjustment of either FIO2 or mean airway pressure (Paw), both of which can be readily manipulated with a mechanical ventilator.

33. 2. Mask oxygen is not suitable for infants because of poor control and lack of monitoring of oxygen supply.3. Nasal cannulas are well suited for infants needing low concentrations of oxygen. Delivery can be controlled by flowmeters delivering as little as 0.025 L/min. Flow rates of >1 L/min may impart distending airway pressure. Table 7-3 gives approximate percentages of nasal cannula oxygen based on flow rates of 0.25-1.0 L/min at blended FIO2 settings of 40-100%. Pulse oximeter monitoring is recommended while nasal cannulas are in use.Minute Ventilation = RR x Vt; where Vt is the tidal volume. Minute ventilation is the volume of air/gas ventilated in one minute expressed as L/min. Normal minute ventilation in newborns is 240ml/min-360mL/min. Normal Vt is 5-7cc/kg

35. A mask, nasal prongs, or an endotracheal tube can be used to apply CPAP. It improves PaO2 by stabilizing the airway and allowing alveolar recruitment. CO2 retention may result from excessive distending airway pressure.1. Mask CPAP is rarely used in the newborn.[Table 7-3. Nasal Cannula Conversion Table]2. Nasal CPAP prongs are the most commonly applied means of delivering CPAP and are used for respiratory assistance in an infant with mild RDS. The prongs are also used postextubation to maintain airway and alveolar expansion in the process of weaning from mechanical ventilation and recovery from respiratory diseases. This treatment maintains upper airway patency and, as such, is useful in infants with apnea of infancy. CPAPs may range from 2 to 8 cm H2O, although 2-6 cm H2O is most often used. Overdistention of the airway can lead to excessive CO2 retention or air leak (pneumothorax). Gastric distention may be a complication of nasal CPAP, and an orogastric tube for decompression should be used. Infants can be fed by nasogastric tube during nasal CPAP therapy with close monitoring of abdominal girth.3. Nasopharyngeal CPAP is an alternative to nasal prongs. An endotracheal tube is passed nasally and advanced to the nasopharynx. A ventilator or CPAP device is used to deliver continuous distending pressure as with nasal prongs. This approach is slightly more secure in active infants and may cause less trauma to the nasal septum.4. Nasal ventilation. Using a ventilator for the generation of CPAP allows for the addition of a "bump rate." Breath rates of 10-15/min with peak pressures set to 10 cm H2O above CPAP are well tolerated. Nasal ventilation seems to be particularly helpful in managing apnea. Some newer ventilators allow for synchronized nasal ventilation.

36. It improves PaO2 by stabilizing the airway and allowing alveolar recruitment. CO2 retention may result from excessive distending airway pressure.

37. High-frequency ventilation refers to a variety of ventilatory strategies and devices designed to provide ventilation at rapid rates and very low VTs. The ability to provide adequate ventilation in spite of reduced VT (equal to or less than dead space) may reduce the risk of barotrauma. Rates during high-frequency ventilation are often expressed in hertz (Hz). A rate of 1 Hz (1 cycle/s) is equivalent to 60 bpm.Furthermore, because rapid changes in ventilation or oxygenation may occur, continuous monitoring is highly recommended. Optimal use of these ventilators is evolving, and different strategies may be indicated for a particular lung disease.A. Definitive indications for high-frequency ventilation support1. Pulmonary interstitial emphysema (PIE). A multicenter trial has demonstrated HFJV to be superior to conventional ventilation in early PIE as well as in neonates who fail to respond to conventional ventilation.2. Severe bronchopleural fistula. In severe bronchopleural fistula not responsive to thoracostomy tube evacuation and conventional ventilation, HFJV may provide adequate ventilation and decrease fistula.3. Hyaline membrane disease. High-frequency ventilation has been used with success. It is usually implemented at the point of severe respiratory failure with maximal conventional ventilation (a rescue treatment). Earlier treatment has been advocated. No advantages have yet been demonstrated for a very early intervention (in the first hours of life) when infants are pretreated with surfactant.4. Patients qualifying for ECMO. Pulmonary hypertension with or without associated parenchymal lung disease (eg, meconium aspiration, pneumonia, hypoplastic lung, or diaphragmatic hernia) can result in intractable respiratory failure and high mortality unless the patient is treated by ECMO. The prior use of high-frequency ventilation among ECMO candidates has been successful and eliminated the need for ECMO in 25-45% of cases.B. Possible indications. High-frequency ventilation has been used with success in infants with other disease processes. Further study is needed to develop clear indications and appropriate ventilatory strategies before this treatment can be recommended for routine use in infants with these diseases.1. Pulmonary hypertension.2. Meconium aspiration syndrome.3. Diaphragmatic hernia with pulmonary hypoplasia.4. Postoperative Fontan procedures.C. High-frequency ventilators, techniques, and equipment. Three types of high-frequency ventilators in the United States are high-frequency jet ventilators (HFJVs), high-frequency oscillatory ventilators (HFOVs), and high-frequency flow interrupters (HFFIs).2. High-frequency oscillatory ventilators. The HFOV generates VT less than or equal to dead space by means of an oscillating piston or diaphragm. This mechanism creates active exhalation as well as inspiration. The SensorMedics 3100A HFOV (SensorMedics Inc., Yorba Linda, CA) is currently approved by the FDA for use in neonates.a. Indications. Respiratory failure: High-frequency oscillatory ventilation is indicated when conventional ventilation does not result in adequate oxygenation or ventilation or requires the use of very high airway pressures. Like other forms of high-frequency ventilation, success is more likely when increased airway resistance is not the

dominant pulmonary pathophysiology or when parenchymal disease is homogeneous. Some clinicians advocate high-frequency oscillatory ventilation as the primary method of assisted ventilation in premature infants with RDS.c. Procedure(b) Settings(i) Frequency is usually set at 15 Hz for premature infants with RDS. Larger infants, or those with a significant component of increased airway resistance (meconium aspiration), should be started at 5-10 Hz.(ii) MAP is set higher (2-5 cm H2O) than on the previous conventional ventilation. If overdistention or air leaks were present prior to initiation of high-frequency oscillatory ventilation, a lower Paw should be considered.(iii) Amplitude (analogous to PIP on conventional ventilation) is regulated by the power of displacement of the piston. This power is increased until there is visible chest wall vibration.(c) After high-frequency oscillatory ventilation has been initiated, careful and frequent assessment of lung expansion and adequate gas exchange are necessary. Air trapping is a continuous potential threat in this form of treatment. Signs of overdistention, such as descended and flat diaphragms and small heart shadow, are monitored with frequent chest radiographs.d. Management(i) If PaO2 is low, an increase in Paw may be necessary. Chest radiographs may be helpful in determining the adequacy of lung expansion.(ii) If Paco2 is high:(a) If oxygenation is also poor, the Paw may be too high or too low, resulting in either hyperinflation or widespread collapse, respectively. Again, chest radiographs are necessary to differentiate between these two conditions.(b) If oxygenation is adequate, the amplitude (power) should be increased.e. Weaning(i) In the absence of hyperinflation, FIO2 is weaned prior to for adequate PaO2. Below 40% FIO2, wean exclusively.(ii) Paw should be weaned as the lung disease improves with the goal of maintaining optimal lung expansion. Excessively aggressive early weaning of may result in widespread atelectasis and the need for significant increases in and FIO2.(iii) Amplitude should be weaned for acceptable PaCO2.(iv) Frequency is usually not adjusted during weaning. A decrease in frequency is necessary when signs of lung overdistention cannot be eliminated by a reduction in .(v) The neonate may be switched to conventional ventilation at a low level of support or may be extubated directly from an HFOV

1. High-frequency jet ventilators. The HFJV injects a high-velocity stream of gas into the endotracheal tube, usually at frequencies between 240 and 600 bpm and VTs equal to or slightly greater than dead space. During HFJV, expiration is passive. The only FDA-approved HFJV is the Life Pulse (Bunnell, Inc., Salt Lake City, UT) ventilator, discussed here.Indications. Mostly used for PIE, the Life Pulse HFJV has been used for the other indications described for all types of high-frequency ventilation.

d. Management. Management of high-frequency jet ventilation is based on the clinical course and radiographic findings.(i) Elimination of CO2. Alveolar ventilation is much more sensitive to changes in VT than in respiratory frequency during high-frequency ventilation. As a result, the delta pressure (PIP minus PEEP) is adjusted to attain adequate elimination of CO2, whereas jet valve "on time" and respiratory frequency are usually not readjusted during HFJV.(ii) Oxygenation. Oxygenation is often better during HFJV than during conventional mechanical ventilation in neonates with PIE. However, if oxygenation is inadequate and if the infant is already on 100% oxygen, an increase in usually results in improved oxygenation. It can be accomplished by:(a) Increasing PEEP.(b) Increasing PIP.(c) Increasing background conventional ventilator (either rates or pressure).(iii) Positioning of infants. Positioning infants with the affected side down may speed resolution of PIE. In bilateral air leak, alternating placement on dependent sides may be effective. Diligent observation and frequent radiographs are necessary to avoid hyperinflation of the nondependent side.

38. An "oscillator," or "high frequency oscillatory ventilator" (HFOV), is a new type of ventilator that came into use in the 1990's. The equipment shown here is the Sensor-Medics 1000A, a popular brand. Unlike traditional ventilators, which essentially inflate and deflate the baby's lungs like a set of billows, the oscillator keeps the lungs open with a constant positive end-expiratiory pressure ("PEEP") and vibrates the air at a very high rate (up to 600 times per second). The vibration helps gases to quickly diffuse in and out of the baby's airways without the need for the "bellows" action which may damage delicate lung structures. Although oscillators are not appropriate for every disorder and situation, there is no doubt that because of their incredible power, oscillators have made it easeir to care for the very sickest babies with certain types of lung problems.

39. The decision to initiate mechanical ventilation is complex. The severity of respiratory distress, severity of blood gas abnormalities, natural history of the specific lung disease, and degree of cardiovascular and other physiologic instabilities are all factors to be considered. Because mechanical ventilation may result in serious complications, the decision to intubate and ventilate should not be taken lightly.1. Bag-and-mask or bag-to-endotracheal tube handheld assemblies allow for emergency ventilatory support. Portable manometers are always required for monitoring peak airway pressures during hand-bag ventilation. Bags may be self-inflating or flow-dependent, anesthesia-type bags. All handheld assemblies must have pop-off valves to avoid excessive pressures to the infant's airway.2. Conventional infant ventilators. Conventional mechanical ventilation delivers physiologic tidal volumes at physiologic rates via an endotracheal tube. Modern microprocessor controlled ventilators provide numerous modes of ventilation, which vary in the degree to which patient effort controls the ventilator. These modes are critically dependent on the function of flow and/or pressure sensors for accurate performance. The very rapid respiratory rates and small tidal volumes encountered in some neonates may prevent the use of patient-triggered or controlled ventilator modes. Table 7-4 gives basic ventilator setting changes and expected blood gas responses.[Table 7-4. Changes in Blood Gas Levels Caused by Changes in Ventilator Settings]

A. Pressure Controlled ventilators – A constant flow of gas passes through the ventilator. Intermittently the expiratory relief valve closes and the gas flows to the infant. Pressure is limited to the desired magnitude. When the expiratory relief valve has been closed for the preset period of time, the valve opens and inspiration ceases. Pressure controlled ventilation is usually used with the technique of intermittent mandatory ventilation, which allows spontatneous breathing between ventilator breaths. Examples of pressure controlled ventilators include the Bear Cub, Dragger, Healthdyne, Infant Star and Sechrist 100B.

B. Volume Controlled ventilators – A preset volume of gas is delivered to the system (patient + ventilator circuit). When this gas has been delivered by the piston, inspiration is terminated. Examples are Bird, VIP, Newport Breeze and Siemens Servo 300.

D. Other kinds of Mechanical ventilation1. Patient initiated mechanical ventilation

2. patient triggered ventilation aka Assist/Control – (in Pressure controlled conventional ventilation the ventilator breath is triggered at a preset frequency, but patient is allowed to take spontaneous breaths) In A/C uses spontaneous respiratory efforts to trigger the ventilator. Once the vent detects an inspiratory effortit delivers a ventilator breath of predetermined settings (PIP, time, flow). Not good for pts with weak effort. 3. Synchronized intermittent Mandatory Ventilation – synchrony is achieved by matching the ventilator frequency to the spontaneous resp or by simply ventilating at high rates. 4. Proportional Assist Ventilation – matches the onset and duration of inspiratory and expiratory support. Ventilatory support is in proportion to the volume or flow fo the spontaneous breath. So the ventilator can selectively decrease the elastic or resistive work of breathing. The magnitude can be be adjusted depending on the patients needs. When compared with conventional and patient triggered vent, proportional assist vent reduces vent pressures while maintaining or improving gas exchange.

40. Questions 1. SIMV stands for: a. . . . . a. synchronized intermittent mandatory ventilation . . . . . b. simplified intermittent mechanical ventilation . . . . . c. synchronized interspersed mechanical ventilation 2. Name 2 prerequisites for extubation. Coughing or gag intact. NPO. Minimized sedation. Adequate oxygenation on 40% FiO2 with CPAP less than or equal to 4. Availability of personnel to reintubate if necessary. Availability of equipment to reintubate if necessary. 3. True/False: The ventilator FiO2 should never be reduced below 40%. False4. True/False: There are very specific, pediatric evidence based protocols that will guide you, step by step, on ventilation management. False5. Minute ventilation = respiratory rate x _______ RR6. Physiologic PEEP is (in mmHg): a. . . . . a. 3-4 . . . . . b. 1-2 . . . . . c. 5-6 7. A good indicator of adequate tidal volume is: d . . . . . a. good chest rise . . . . . b. adequate breath sounds . . . . . c. oxygen saturation = 100% . . . . . d. a and b 8. As compliance worsens in a child receiving pressure controlled mechanical ventilation, the TV delivered to the patient will: b . . . . . a. increase . . . . . b. decrease 9. If the patient has the ABG: pH 7.28, pCO2 50, pO2 120, BE -3, which of the following ventilator changes would NOT be a good idea: d . . . . . a. decrease the FiO2 . . . . . b. decrease the I-time . . . . . c. decrease the PEEP . . . . . d. decrease the rate

41. PEEP, MAP increase intrathoracic pressure and may impede venous return/CO. Too high a rate risks hyperventilation and respiratory alkalosis along with inadequate expiratory time and autoPEEP; too low a rate risks inadequate minute ventilation and respiratory acidosis. The inspiratory flow rate can be adjusted in some modes of ventilation (ie, either the flow rate or the I:E ratio can be adjusted, not both). A/C ventilation is the simplest and most effective means of providing full mechanical ventilation. In this mode, each inspiratory effort beyond the set sensitivity threshold triggers delivery of the fixed tidal volume. If the patient does not trigger the ventilator frequently enough, the ventilator initiates a breath, ensuring the desired minimum respiratory rate. SIMV also delivers breaths at a set rate and volume that is synchronized to the patient's efforts. In contrast to A/C, however, patient efforts above the set respiratory rate are unassisted, although the intake valve opens to allow the breath. This mode remains popular, despite the fact that it neither provides full ventilator support as does A/C nor facilitates liberating the patient from mechanical ventilation. Pressure control ventilation is similar to A/C; each inspiratory effort beyond the set sensitivity threshold delivers full pressure support maintained for a fixed inspiratory time. A minimum respiratory rate is maintained.In pressure support ventilation, a minimum rate is not set; all breaths are triggered by the patient. Pressure is typically cut off when back-pressure causes flow to drop below a certain point. Thus, a longer or deeper inspiratory effort by the patient results in a larger tidal volume. This mode is commonly used to liberate patients from mechanical ventilation by letting them assume more of the work of breathing. However, no studies indicate that this approach is more successful. In pressure controlled ventilation, a PIP (peak inspiratory pressure) and an inspiratory time (IT) duration determines the inspiratory cycle. The advantage of a pressure ventilator is that it should help protect the lungs from excessive pressures. However, tidal volume (TV) may then be compromised. So, as a child's lung compliance worsens (decreases), the TV delivered will decrease for a given PIP. Similarly, if volume ventilation is chosen, the peak pressure will change based upon changes in lung compliance. SIMV (synchronized intermittent mandatory ventilation) pressure support: This method synchronizes the ventilator breaths with the patient's inspiratory efforts, thereby preventing the stacking of a ventilator breath on top of a spontaneous breath. Pressure support is the provision of a specified amount of positive pressure to assist the patient's own respiratory effort. IMV (intermittent mandatory ventilation): The ventilator delivers mandatory positive pressure breaths at a set rate. The patient may have unassisted spontaneous breaths between ventilator breaths, but the ventilator breaths are not synchronized with the patient's breaths. In choosing a TV or PIP, the most important tenant to remember is, in general, to use a volume or pressure that causes good visible chest rise and air entry on auscultation. One could increase the mean airway pressure by increasing the PEEP, the inspiratory time, or the PIP. Increasing the tidal volume (TV) on a volume ventilator, in essence, increases the PIP so this also increases the MAP.

42. a. PEEP (positive end-expiratory pressure) is common to all modes of continuous mandatory ventilation (CMV). PEEP is usually generated with a continuous flow through the ventilator circuit, which allows for untriggered spontaneous ventilation. In most cases, PEEP will be set at 3-5 cm H2O. Use of higher PEEP is often appropriate in conditions of alveolar collapse, but it must be balanced with the risk of overdistending the lung during inspiration.b. Ventilator modes. Various modes of mechanical ventilation are determined by the parameters that are set by the clinician to determine the characteristics of the mechanical breath and the circumstances under which it is delivered. Not all modes are available on every ventilator, and subtle differences between the same mode may exist between different manufacturers. The characteristics of each breath are as follows:(i) Length of breath (Ti)(a) Time cycled. Each mechanical breath lasts for a controlled set time.(b) Flow cycled. Each breath lasts until inspiratory flow falls below a threshold.(ii) Size of breath (VT)(a) Volume limited. Each mechanical breath is the same volume; the pressure used may vary.(b) Pressure limited. A set pressure is reached with each mechanical breath, the VT delivered may vary. This mode uses a continuous flow through the ventilator circuit, allowing for spontaneous respiration to occur without ventilator action.(c) Pressure control. As in pressure-limited ventilation, the clinician specifies the desired peak pressure; however the flow rate through the circuit is variable. Ventilator action is necessary for every breath.(d) Volume assurance/guarantee. Ventilator automatically adjusts set pressure to deliver target VT.(iii) Frequency of mechanical breaths(a) IMV (intermittent mandatory ventilation). Breaths are delivered at set intervals without regard to patient effort.(b) SIMV (synchronized IMV). The set rate determines time frames during which the ventilator will deliver a breath in response to a patient trigger or will deliver a mandatory breath if no trigger is sensed. The minimum and maximum ventilator rates are equal.(c) A/C (assist/control). Each patient trigger results in a ventilator breath. If no trigger is sensed, a minimum set rate is delivered. Maximum rate may be much higher than minimum. Excessive trigger sensitivity may lead to auto-cycling and much greater rates than needed.(d) Support or assist. Each patient trigger results in a breath. No mandatory backup rate.(iv) The previous sets of parameters are often combined to yield the following modes:(a) IMV. Usually refers especially to nontriggered, pressure-limited, time-cycled ventilation. Use: In absence of reliable patient trigger.(b) SIMV. May be either volume or pressure limited, time cycled. Use: Prevents hyperventilation from auto-cycling.(c) Pressure control. Pressure limited (usually with a decreasing flow rate during inspiration), time cycled, A/C. Use: Provides well-tolerated support in patients with easily sensed respiratory effort.

(d) Volume control. Volume-limited, time-cycled, A/C. Use: As in pressure control, but may result in more consistent VT.(e) Pressure support. Pressure-limited, flow-cycled, support. Use: In addition to SIMV, especially during weaning.(v) Patient triggers. The advanced patient-regulated ventilation modes available with modern microprocessor-controlled ventilators depend on reliable detection of patient respiratory effort. In the smallest premature infants, it is difficult to separate flow or pressure changes due to inspiratory effort from those due to measurement error or leaks.(vi) Flow determinations by pneumotach or mass airflow sensors. Measurements vary with gas composition, temperature, and humidity, although not significantly. Large errors may be expected with anesthesia gases or heliox. It is also subject to error with fluid contamination or air leaks. Placement between the patient's endotracheal tube and the circuit gives greatest sensitivity.(vii) Pressure. Pressure triggers may be confused by ringing within the circuit, especially with rainout in the tubing.(viii) Neural. Using a bipolar esophageal lead placed at the level of the diaphragm, phrenic nerve impulses to the diaphragm can be detected and used to trigger mechanical breaths. This new technology is promising but not yet adequately studied in neonates.